Metal-Mediated and Metal-Catalyzed Reactions of Isocyanides

Review pubs.acs.org/CR

Metal-Mediated and Metal-Catalyzed Reactions of Isocyanides Vadim P. Boyarskiy,* Nadezhda A. Bokach,* Konstantin V. Luzyanin,* and Vadim Yu. Kukushkin* Institute of Chemistry, Saint Petersburg State University, 198504 Stary Petergof, Russian Federation S Supporting Information *

3.5. Metal−B Bond 3.6. Metal−Si Bond 3.7. Metal−N Bond 3.8. Metal−P Bond 3.9. Metal−As Bond 3.10. Metal−Sb Bond 3.11. Metal−O Bond 3.12. Metal−Metal Bond 4. Electrophilic Addition to CNR Ligands 5. 1,3-Dipolar Cycloaddition to Ligated Isocyanides 5.1. Comparison of Metal-Mediated Cycloaddition to CNR and NCR Species 5.2. Cycloaddition of Propargyl-allenyl AnionType Dipoles 5.3. Cycloaddition of Allyl Anion-Type Dipoles 6. Reductive Coupling of Isocyanides at Metal Centers 7. Oxygenation and Sulfuration of CNR Species Involving Metal Centers 7.1. Metal-Mediated Oxygenations of CNR Species 7.2. Metal-Catalyzed Oxygenation of CNR Species 7.3. Other Metal-Mediated Oxidations of Isocyanides 7.4. Sulfuration of Metal-Bound Isocyanides 8. Cleavage of the CN−R Single Bond at Metal Centers 8.1. Cyanation of Metal Centers via Dealkylation of CNR Species 8.2. Metal-Catalyzed Cyanation of Aromatics and Olefins 9. Reactions of Isocyanides with Acidic α-H Atom Involving Metal Centers 9.1. Deprotonation of α-C−H of Coordinated Isocyanides and Metal-Mediated Reactions 9.2. Metal-Catalyzed Conversions of Isocyanides with Acidic α-H 9.2.1. Formal [2 + 3] Dipolar Cycloaddition Accompanied by C−O Bond Formation 9.2.2. Formal [2 + 3] Dipolar Cycloaddition Accompanied by C−N Bond Formation 9.2.3. Formal [2 + 3] Dipolar Cycloaddition Accompanied by C−C Bond Formation 9.2.4. Other Cyclization Reactions 10. Miscellaneous 11. Final Remarks and Outlook

CONTENTS 1. Introduction 2. Nucleophilic Addition to Metal-Activated Isocyanides 2.1. Addition of Monofunctional Nucleophiles 2.1.1. Addition of N-Nucleophiles 2.1.2. Addition of O-Nucleophiles 2.2. Addition of Functionalized Nucleophiles Accompanied by Intramolecular Cyclization 2.3. Intramolecular Cyclization of Functionalized CNR Species 2.4. Addition of Ambident Nucleophiles 2.5. Additions of Other Nucleophiles 3. Insertions of CNR Species into Metal−Element Bond 3.1. General Consideration of the Metal-Mediated Insertions 3.1.1. Background 3.1.2. Primary Insertion Products 3.1.3. Insertion Chemoselectivity 3.1.4. Driving Forces of the Insertion 3.1.5. Insertion Mechanisms 3.1.6. Reversibility of Isocyanide Insertion 3.1.7. Previous Reviews on Isocyanide Insertions 3.2. Metal−H Bond 3.3. Metal−C Bond 3.3.1. Reactions of Group 3 Metal Complexes 3.3.2. Reactions of Group 4 Metal Complexes 3.3.3. Reactions of Group 5 Metal Complexes 3.3.4. Reactions of Group 6 Metal Complexes 3.3.5. Reactions of Group 7 Metal Complexes 3.3.6. Reactions of Group 8 Metal Complexes 3.3.7. Reactions of Group 9 Metal Complexes 3.3.8. Reactions of Group 10 Metal Complexes 3.4. MetalC Bond © XXXX American Chemical Society

B D D D I J L M P Q Q Q Q Q Q R R R S U U X AC AI AJ AJ AK AL AY

AZ AZ AZ BB BC BC BD BD BE BF BF BF BG BH BI BI BJ BJ BK BK BK BN BO BO BP BP BQ BR BS BT BU

Received: July 14, 2014

A

DOI: 10.1021/cr500380d Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews Associated Content Supporting Information Author Information Corresponding Authors Notes Biographies Acknowledgments Dedication Abbreviations Radicals in Alphabetical Order Other Abbreviations in Alphabetical Order References

Review

odor, high reactivity and versatile chemistry of these species generously reward fearless researchers, and reactions of CNRs play an important role not only in the academic area, but also in numerous industrial processes. In particular, in organic chemistry, isocyanides are highly potent reagents for the development of multicomponent reactions (MCRs; for reviews on MCRs published after the year 2000, see Table 1), including, for example, the generation of heterocyclic systems or natural product-like compounds. Their importance in MCRs accounted for the diversity of bond-making processes and the high degrees of chemo-, regio-, and stereoselectivity reached in many reported cases. In organometallic chemistry, metal-mediated processes often allow the performance of certain CNR reactions, which are not feasible without the involvement of metal centers, and, in particular, isocyanide ligands are useful for the generation of acyclic (ADCs) and heterocyclic (NHCs) aminocarbenes (for recent reviews on this approach, see refs 1−9) with their avalanche-like increasing application in organometallic catalysis. Moreover, isocyanides are commonly employed for insertions into various metal−element bonds, producing libraries of useful species. In catalysis, isocyanides are involved in a variety of metal-catalyzed (mostly Pd-catalyzed) organic transformations10−12 (Table 2) furnishing species with high synthetic potential. In polymer chemistry, CNR species bearing sterically unhindered substituents R could be efficiently polymerized by application of transition metal catalysts to the so-called isocyanide polymers that are in turn applied for the development of some functional materials.13,14 Last, in the rapidly growing field of material chemistry, isocyanides play a role as an alternative to thiol stabilizers for nanoparticles,15−17 enabling their use in a wide range of applications including gas storage. Since the Chugaev times, the isocyanide chemistry involving metal species experienced a tremendous growth. However, it is of note that in all of the years of isocyanide research, no single review article has covered the entirety of reactions involving metal centers. Yet, individual types of metal-mediated reactions are regularly reviewed (for publications that appeared up to the year 2000, see Supporting Information Table A1; and after the year 2000, see Table 3). The most relevant reviews cover nucleophilic and electrophilic additions (Table 3, entries 1 and 2), isocyanide insertions into particular M−element bonds (Table 2), palladium-catalyzed organic transformations of CNRs (Table 2, entries 10−12), MCRs involving metal centers (Table 1), and reactions of isocyanoacetates including those occurring at metal centers.9,18 The first two surveys by Michelin, Guedes da Silva, and Pombeiro19,20 (Table 3, entries 1 and 2) dealt with nucleophilic addition to metal-activated CNR species giving aminocarbenes19 and electrophilic addition20 involving metal centers. In these two reviews published in 2001, a number of reactivity patterns, for example, application of metal-mediated and metal-catalyzed reactions in organic synthesis, isocyanide insertions, dipolar cycloadditions, oxygenation and sulfuration of CNR ligands, and the R−C bond cleavage, were either out of the reviews’ scope or treated briefly. Furthermore, a number of intriguing transformations, for example, coupling with heterocycles, addition of nucleophiles and dipoles to yield novel types of aminocarbene and aminocarbene-like ligands, as well as new types of insertions into metal−carbon bond in isocyanides, were discovered already after the appearance of these reviews. In the past decade, as a result of increasing interest in the conversions of CNR species in various fields of chemistry, the

BV BV BV BV BV BV BW BW BW BW BW BX

1. INTRODUCTION A timely subtitle to this Review focused on conversions of isocyanides at metal centers could have been “a platinum jubilee of the first metal-mediated reaction involving platinum”. Indeed, a “platinum jubilee” is in many cultures associated with an event’s centennial. In the year 2015, the chemistry community marks a century since Professor Lev Aleksandrovich Chugaev (Chart 1) Chart 1. Lev Aleksandrovich Chugaev (Center) along with His Assistants at the Chemical Laboratory Lecture Theater of Saint Petersburg Universitya

a

It was in Saint Petersburg that in 1915, jointly with his coworker Mariya Skanawy-Grigorjewa, he conducted the experiments on reactions of CNMe with platinum complexes and obtained platinum carbene species formed via nucleophilic addition of hydrazine to PtIIactivated methylisocyanide [Tschugajeff (Chugaev), L.; SkanawyGrigorjewa, M. J. Russ. Chem. Soc. 1915, 47, 776].

of Saint Petersburg University observed for the first time a reaction of CNR species involving metal centers. In Chugaev’s experiments, an aqueous solution of the platinum(II) complex K2[PtCl4] was treated with CNMe, giving the [Pt(CNMe)4]2+ complex followed by addition of hydrazine. The procedure led to the isolation of a bright orange solid that, many years after, was recognized as the first synthetically generated carbene formed via PtII-mediated addition of N2H4 to CNMe ligands. The story of the discovery of metal carbenes has received much attention in the literature (see, for instance, refs 1−5). Chugaev’s studies opened a broad research field of metalmediated and metal-catalyzed reactions of CNRs and stimulated further interest in these species that are considered stable carbenes. Although isocyanides are often treated as persona non grata in many chemical laboratories because of their horrible B


Chemical Reviews

Review

Table 1. Reviews and Textbook Considerations on MCRs of Isocyanides Catalyzed by Transition Metal Species Published after the Year 2000 entry

year

1

2003

J. Zhu

author(s)

2

2006

A. Dömling

3

2008

Ch. Hulme, Y.-S. Lee

4 5

2009 2011

L. El Kaim, L. Grimaud S. Sadjadi, M. M. Heravi

6

2011

M. M. Heravi, S. Moghimi

7

2012

8 9

2012 2013

S. S. van Berkel, B. G. M. Bögels, M. A. Wijdeven, B. Westermann, F. P. J. T. Rutjes R. Ramon, N. Kielland, R. Lavilla T. Vlaar, E. Ruijter, B. U. W. Maes, R. V. A. Orru

scope

refs

review covers MCR-based syntheses of heterocycles; transition metal-catalyzed syntheses of indoles and Ncyanoindoles are reported; 90 refs progress in MCR chemistry for the period 2000−2006 is summarized; applications in drug discovery and natural product synthesis are considered; several examples of the enantioselective metal-mediated and metal-catalyzed reactions were reviewed; 315 refs MCR-based synthesis of imidazo[1,2-x]-heterocycles and their therapeutic application were reported; some Sc-catalyzed reactions are described; 61 refs MCRs with iminium derivatives were reviewed including Lewis-acid catalyzed reactions; 127 refs a review on application of isocyanides for generation of various heterocyclic systems; few examples of metalcatalyzed reactions are also provided; 98 refs a comprehensive review devoted to catalytic (involving nontransition and transition metals, acids, or bases) MCR-based reactions; transition metals allow the improvement of reaction conditions, the achievement of better yields, and better stereoselectivities; 165 refs recent advances in the field of asymmetric MCRs with a focus on stereoselective α-additions of isocyanides; there are several examples of processes catalyzed by chiral complexes; 117 refs

21

MCRs catalyzed by transition metals species; 135 refs MCRs based on Pd-catalyzed insertion of CNR; palladium-catalyzed oxidative isocyanide insertive processes are also considered; 61 refs

28 11

22 23 24 25 26 27

Table 2. Reviews and Textbook Considerations on Isocyanide Insertions Published after the Year 2000 entry

year

author(s)

1 2

2002 2003

S. Dixon, R. J. Whitby Y. Ito, M. Suginome

3

2003

M. Gómez

4

2004

M. Suginome, Y. Ito

5

2005

6

2005

S. A. Cummings, J. A. Tunge, J. R. Norton N. Jeong

7

2007

8

2010

9 10 11

2012 2013 2013

12

2013

A. Antiñolo, S. Garcı ́a-Yuste, A. Otero, E. Villaseñor Y. Ito, M. Murakami J. M. P. Lauzon, L. L. Schafer S. Lang T. Vlaar, E. Ruijter, B. U. W. Maes, R. V. A. Orru G. Qiu, Q. Ding, J. Wu

scope

refs

insertions of CNR species into Zr−C bonds; number of refs is not provided in Chemical Abstracts survey covering palladium-catalyzed successive insertion of isocyanides leading to oligomeric and polymeric materials; number of refs is not provided in Chemical Abstracts review covering syntheses, structure, spectroscopic, and reactivity details for (alkyl)(monocyclopentadienyl)niobium and -tantalum complexes in insertion processes; 183 refs review covering transition metal-mediated polymerization of isocyanides including selective polymerization of 1,2diisocyanobenzenes using chiral organopalladium complexes as initiators; 102 refs survey covering insertions of CNR species into Zr−C, Zr−H, and Zr−Si bonds; number of refs is not provided in Chemical Abstracts reactions of isocyanides with Rh−C bonds as synthetic method (RhI-catalyzed [2 + 2+1] and [4 + 1] carbocyclization reactions); 98 refs review covering insertion of isocyanides in the Nb−X (X = H, C, and P); 55 refs

29 14 30 13 31 32 33

a review published in Japanese on the use of coordinated isocyanide insertions in organic syntheses; number of refs is not provided in Chemical Abstracts comprehensive review on isocyanide insertions into Ta−C bond giving tantalaaziridines; 76 refs this tutorial review covers insertions of CNR species into Pd−C bond; 50 refs mini-review covering Pd-catalyzed insertion of CNR; 92 refs

34

a review generally focused on the C−element (C−O, C−S, C−Si, C−H) insertions known in metal-free organic chemistry; it is dedicated to the recent advances in Lewis (Brønsted) acid-catalyzed isocyanide insertions into C−X (X = O, S, Si) and B−Si, and transition-metal-enabled isocyanide insertions into Y−H (Y = C, O, S, N, Si, P), S−S, and Si− Si bonds; 70 refs

12

number of investigations has increased to the point where the subject cannot be dealt within a single review article, and various excellent surveys considering specific aspects of CNR reactivity emerged in the literature (Table 2). For instance, a review by Qiu, Ding, and Wu12 (Table 2, entry 13) is devoted to a broad field of isocyanide insertions with a particular emphasis on the C−element (C−O, C−S, C−Si, C−H) insertions known in metal-free organic chemistry. Less attention is given to metalinvolving reactions (40 references for publications on the subject since 2000). Moreover, in the overwhelming majority of cases, this subject is limited to palladium-catalyzed organic synthesis that is also discussed in a tutorial review by Lang10 (Table 2, entry 11) and a mini-review by Orru et al.11 (Table 2, entry 12) published almost simultaneously with the survey by Qiu et al.12 (Table 2, entry 13). In this Review, all stoichiometric CNR insertions published after the year 2000 will be treated comprehensively (more than 150 references), while examples of palladium-catalyzed organic transformations will be inspected

35 10 11

selectively and restricted to studies published after the three reviews10−12 discussed above. Importantly, our consideration will not simply focus on encyclopedic listing of the available data. Instead, we shall aim to analyze the major driving forces and mechanisms of the insertion, which will certainly facilitate and stimulate further research activity in this field. Furthermore, in a view of recent reports highlighting metal involved MCRs of CNR species (Table 1) and reactions of CNRs bearing acidic α-H atom,9,18 we shall consider only a small portion of reports on these reactions that appeared in the past few years. In view of the emerging importance of metal-mediated and metal-catalyzed reactions of CNR species for organometallic, organic chemistry, and catalysis, a comprehensive critical review in this area would be timely. This Review will concentrate on isocyanide involvement in a variety of metal-mediated and metalcatalyzed transformations. The essential goals of this Review are 2-fold: (i) to attempt, based on recent advances, to systematize and explain many diverse data on metal-mediated and metalC


Chemical Reviews

Review

Table 3. Reviews and Textbook Considerations on Organometallic Chemistry of Isocyanide Species Published after the Year 2000 entry

year

author(s)

1

2001

R. A. Michelin, M. F. C. Guedes da Silva, A. J. L. Pombeiro

2

2001

A. J. L. Pombeiro, M. F. C. Guedes da Silva, R. A. Michelin

3

2001

A. J. L. Pombeiro

4

2001

P. D. Harvey

5

2002

M. L. Kuznetsov

6

2004

M. Suginome, Y. Ito

7

2005

8

2008

M. Basato, R. A. Michelin, M. Mozzon, P. Sgarbossa, A. Tassan L. M. Slaughter

9

2008

R. J. Angelici, M. Lazar

10

2009

M. Lazar, R. J. Angelici

11

2011

S. Sadjadi, M. M. Heravi

12

2012

V. G. Nenajdenko (Ed.)

13

2012

D. Moderhack

14

2012/ 2013

L. M. Slaughter, V. P. Boyarskiy, K. V. Luzyanin, V. Yu. Kukushkin

scope

refs

a comprehensive review is mostly devoted to nucleophilic additions to CNR species ligated to electron-poor metal centers; particular attention is given to reactions with haloalcohols and haloamines, three-membered heterocycles (oxirane, aziridine, thiirane), reactions of functionalized and α-deprotonated isocyanide complexes; 152 refs a comprehensive review is dedicated to electrophilic β-additions to the N atom of an isocyanide coordinated to a low-valent electron-rich metal center to accomplish aminocarbynes; the protoninduced C−C coupling of isocyanide ligands is also considered; 109 refs the review analyzes the coordination chemistry of hydrogen isocyanide (CNH), the syntheses of its complexes, electronic and structural features, H-bond formation, deprotonation (to give cyanide, isocyanotrifluoroborate, or isocyanotriphenylborate species), protonation to form the aminocarbyne CNH2 species, addition (with epoxides), multicomponent cycloaddition and condensation reactions in organic syntheses; 94 refs a comprehensive review is dedicated to the preparation and investigation of the reactivity of metal complexes bearing diisocyanide ligands; 82 refs theoretical studies of transition metal complexes with isocyanides and nitriles; this review includes consideration of electronic structures of complexes and the nature of coordination bonds and spectroscopic properties of ligands; theoretical data on reactivities and mechanisms of ligand reactions are given for nitrile but not for isocyanide species; 121 refs the review covers reports on transition metal-mediated polymerization of isocyanides, from mechanistic studies to functionalized polymer synthesis; particular focus is given to asymmetric polymerization, which leads to the formation of optically active, rigid rod helical poly(isocyanide)s; 102 refs this review covers the preparation of complexes with NHC ligands starting from corresponding functionalized isocyanides via the intramolecular cycloaddition; 56 refs a review on catalytic properties of some chelating bis(acyclic diaminocarbene) ligands that can be prepared by addition of diamines or hydrazines to coordinated isocyanide ligands; 82 refs survey on reactions of isocyanides (decomposition, oxidation, polymerization, electrophilic and nucleophilic additions) adsorbed on metal surfaces that reflect their reactivity modes in metal species; it also considers applications of isocyanide adsorption to the stabilization of metal nanoparticles, the functionalization of metal electrodes, and the creation of conducting organic− metal junctions in molecule-scale electronic devices; 68 refs a review that includes comparisons of isocyanide binding modes in transition metal complexes and isocyanide adsorption on metal surface; 71 refs a review on application of isocyanides for generation of various heterocyclic systems; a few examples of metal-catalyzed reactions are also provided; 98 refs a nice collection of tutorial reviews on various aspects of isocyanide chemistry; it mostly focused on metal-free organic transformations; some chapters include considerations of metal-mediated and metal-catalyzed conversions of CNR species such as oxidations, sulfuration, isocyanide−nitrile rearrangement (Chapter 2), examples of metal-mediated conversions of isocyanoacetic acid derivatives (Chapter 4), ligand properties of isocyanoarenes for low-valent metal species (Chapter 14), and acyclic carbenes derived from metal-bound isocyanides (Chapter 15) a review on N-isocyanide species and their organic chemistry; a few examples of metal-mediated reactions (e.g., nucleophilic addition and insertion) are also provided; 128 refs reviews on catalytic properties of ADC metal species and their application for transformations of organic substrates; they include consideration of routes for ADCs preparation by, in particular, nucleophilic addition to metal-bound isocyanides; L. M. Slaughter (ref 1) − 179 refs; V. P. Boyarskiy, K. V. Luzyanin, V. Yu. Kukushkin − 110 refs (ref 3) and 65 refs (ref 43)

19

20

36

37 38

13

39 6 40

41 25 9

42 1, 3, and 43

2.1. Addition of Monofunctional Nucleophiles

catalyzed conversions of isocyanides and to give a general outlook of reaction routes, mechanisms, and driving forces; and (ii) to underline the potential of metal-involved conversions of CNR in synthetic organometallic and organic chemistry and draw attention to the emerging putative targets.

2.1.1. Addition of N-Nucleophiles. 2.1.1.1. Addition of Amines (sp3-N Donor Centers). Ruiz et al.44 studied the reaction of the mixed-ligand carbonyl/isocyanide complexes fac-[Mn(CNR)(CO)3(bpy)]+ (1, R = Ph, 2-Cl-6-MeC6H3, Naph) with excess H2NMe (Scheme 1). The nucleophilic attack proceeds exclusively at the isocyanide ligand affording the acyclic diaminocarbene derivatives fac-[Mn(ADC)(CO)3(bpy)]+ (2; CH2Cl2, RT, 3 min; 70−82%; see Figure 1 for X-ray structure of fac-[Mn{C(NHMe)(NH(2-Cl-6-MeC6 H 3 ))}(CO) 3 (bpy)]ClO4). The reasons for the chemoselectivity can be understood taking into account the higher electrophilic activation of the CN triple bond as compared to CO. In the following studies (see below),45 the same group additionally rationalized the chemoselectivity by the instability of the carbamoyl derivatives at RT when compared to appropriate diaminocarbene. In 2, the carbene ligands can be deprotonated by KOH yielding the corresponding neutral formamidinyl (ADC−H) derivatives fac-[Mn(ADC−H)(CO)3(bpy)] (3). The deprotonation of 2 occurs at the N(H)aryl group rather than at the N(H)Me residue, due to

2. NUCLEOPHILIC ADDITION TO METAL-ACTIVATED ISOCYANIDES These nucleophilic addition reactions studied before the year 200019 were surveyed in an excellent review written by Michelin, Pombeiro, and Guedes da Silva. In this section, we concentrate on reports published after the year 2000 and up to now. To make this coverage comprehensive, we also discuss some works that were published before 2000 but not considered in the previous reviews. The experimental data are categorized on the basis of donor center of the attacking nucleophile, and in the framework of each subsection, similarly to section 3, the consideration goes along with the increase of metal group number in the Periodic Table. D


Chemical Reviews

Review

Scheme 1. Reaction of fac-[Mn(CNR)(CO)3(bpy)]+ with H2NMe

isocyanide complex. In contrast to the addition to carbonyl ligand, the formation of diaminocarbene by the addition of the amine to the isocyanide is irreversible. Inspection of the IR data45 indicates that both isocyanide and carbonyl ligands in the starting complexes are potentially activated toward the nucleophilic attack by the amine. In fact, they show νCO frequencies well above 2000 cm−1, and values of ΔνCN = νCN(coordinated) − νCN(free) for the isocyanide ligand are above 40 cm−1, which appear to be the threshold values of susceptibility to nucleophilic attack of carbonyl and isocyanide ligands, respectively.19 Nevertheless, the experimental results show that in this case the addition of the amine to the carbonyl ligand located in a trans position with respect to the isocyanide ligand is clearly favored and led to the selective formation of the carbamoyl species at −30 °C. The authors demonstrated that the carbamoyl complexes of manganese(I) are unstable at RT and decompose to give the starting manganese species that are then attacked by H2NMe at the isocyanide ligand to afford the diaminocarbene. In the extension of this work,46 the corresponding iron(II)−ADC species were prepared upon attack of H2NMe on one isocyanide in [CpFe(CO)(CNXyl)2](ClO4). The reaction of the phosphine-tethered isocyanide iron(II) complex [CpFe(CO)(PNC)]I (6, PNC = CNCH2CH2CH2PR12, R1 = But, Ph; for other nucleophilic additions to this complex, see sections 2.1.2.2 and 2.2) with primary and secondary amines (CH2Cl2, RT, overnight, Scheme 2) proceeds Scheme 2. Reaction of [CpFe(CO)(PNC)]I with Amines

Figure 1. View of the molecular structure of fac-[Mn{C(NHMe)(NH(2-Cl-6-MeC6H3))}(CO)3(bpy)]ClO4 as a representative example of 2. Thermal ellipsoids are drawn at the 50% probability level.

exclusively at the isocyanide ligand affording the corresponding acyclic diaminocarbene complexes [(Cp)Fe(CO)(PNHCX)]I (7, 90−93%).47 Inspection of the absorptions due to the isocyanide (average νCN = 2090 cm−1) and carbonyl (average νCO = 2000 cm−1) moieties clearly indicates that the carbonyl ligand is deactivated toward a nucleophilic attack. The reaction of [Ir(ttp)(CNCH2Ph)2](BF4) (tpp = mesotetratolylporphyrine) with H2NR1 (R1 = Bun, CH2Ph) was studied.48 When 1 equiv of H2NCH2Ph was used, the reaction (CHCl3, 40 °C, overnight) led to the monocarbene complex [Ir(tpp){C(NHCH2Ph)2}(CNCH2Ph)](BF4) (73%); the reaction with H2NBun is given in a scheme of ref 48, but details are not provided in the experimental part. When 10-fold excess of H2NR1 was used, the nucleophilic attack on both isocyanide ligands in the starting complex occurred furnishing the corresponding bis-carbenes, whose yields were not given. The mixed 1,1-ethylenedithiolato/isocyanide complexes [M(CNR)2{η2-S2CC{C(O)Me}2}] (7, M = Pd, Pt; R = But, Xyl) react with diethylamine (CHCl3, RT, 15 h) furnishing the aminocarbene species [M{C(NEt2)(NHR)}(CNR){η2-S2C C{C(O)Me}2}] (8, 89−98%) due to the addition of HNEt2 to one isocyanide ligand (Scheme 3).49 The same compounds were formed even in the presence of a large excess of amine, regardless of the nature of the isocyanide. When excess NH3 was used in place of HNEt2 (THF, RT, 75 min), the generation of the complexes [M{C(NH2)(NHBut)}(CNBut){η2-(S,S′)S2CC{C(O)Me}2}] (9, 83−92%) or [M{C(NH2)(NHXyl)}2{η2-

the more acidic character of the former, and it is proved to be fully reversible. Indeed, the addition of 1 equiv of HBF4 to 3 brings about the formation of starting diaminocarbene complexes 2. It is worth mentioning that the formation of formamidinyl complexes via the two-step reaction of coordinated isocyanides with amines followed by the subsequent deprotonation of the diaminocarbene intermediate is well-known in the literature (see ref 19 and references therein). The same formamidinyl derivatives can also be prepared via the direct insertion of isocyanides (section 3) in the metal−nitrogen bond of amido complexes. In the related work,45 the chemoselectivity of the coupling between fac-[Mn(CNR)(CO)3(bpy)]+ (1, R = Me, But, CH2Ph, Ph, Xyl) and the amines H2NMe and H2NCH2CH2CH2Br (for nucleophilic addition accompanied by intermolecular cyclization of the latter, see section 2.2) was evaluated. When the reaction was performed at RT (CH2Cl2, 1 h), the nucleophilic attack of H2NMe proceeds exclusively at the isocyanide ligand affording the diminocarbene derivatives fac-[Mn(ADC)(CO)3(bpy)]+ (2, 72−87%; Scheme 1). At −30 °C, the chemoselectivity is inverted, and the addition of the amine proceeds at the carbonyl ligand giving MnI carbamoyl complexes, that is, fac-[Mn(CNR){C(O)NHMe}(CO)2(bpy)]+ (4). The formation of carbamoyl derivative is reversible; hence, the removal of excess H2NMe under vacuum results in the regeneration of the starting E


Chemical Reviews

Review

species of 14 (CHCl3, 50−60 °C, 6−7 h) leading to palladium(II) complexes 15 featuring the unusual chelating C,C-(iminiumbenzoyl)carbene ligands (65−68%; Scheme 5, see Figure 2 for X-ray structure of [PdCl2{C,C-C(NHXyl)C6H4{NHC(NHXyl)}-2}]).

Scheme 3. Reactivity of [M(CNR)2{η2-S2CC{C(O)Me}2}] toward Amines

Scheme 5. PdII-Mediated Intramolecular Nucleophilic Addition

(S,S′)S2CC{C(O)Me}2}] (10, 91−94%) was observed.49 The authors49 report that the nucleophilic attack on the second isocyanide ligand becomes only possible when small and sterically unhindered nucleophile, NH3, is used. The reaction of the mixed NHC−isocyanide complexes cis/ trans-[PdBr2(Pri2-bimy)(CNR)] (11; Pri2-bimy is diisopropylbenzimidazol-2-ylidene) with 2,6-dimethylaniline leads to NHC−ADC palladium(II) complex 12 (CHCl3, RT, overnight), obtained in a very low isolated yield (Scheme 4).50

Figure 2. View of the molecular structure of [PdCl2{C,C-C( NHXyl)C6H4{NHC(NHXyl)}-2}] as a representative example of 15. Thermal ellipsoids are drawn at the 50% probability level.

Scheme 4. Reaction of trans-[PdBr2(Pri2-bimy)(CNR)] with H2NXyl

The reaction of one isocyanide ligand in cis-[PdCl2(CNR)2] (16, R = But, 2,6-Et2C6H3, 2,6-Pri2C6H3, 2,6-di(cyclohex-2-ene1-yl)-4-MeC6H2) with the primary and secondary amines HNR1R2 (R1, R2 = H, alkyl, cycloalkyl, benzyl, aryl; THF, RT, 12 h; 10 examples, Scheme 6) results in the generation of the Scheme 6. Reactivity of cis-[PdCl2(CNR)2] toward Amines

corresponding diaminocarbene derivatives 17 (21−96%).54 The second isocyanide ligand does not react under any of the studied conditions presumably due to its insufficient electrophilic activation. The reaction of the arenediethynylgold(I)−isocyanide complex [(Bu t NC)AuCC(1,3-(C 6 HMe 3 -2,4,6))CCAu(CNBut)] with HNEt2 leads to the corresponding aminocarbene derivatives [{(Bu t NH)(Et 2 N)}CAuCC(1,3-(C 6 HMe 3 2,4,6))CCAuC{(NHBut)(NEt2)}] (CH2Cl2, RT, 2.5 h; 72%).55 Reasons for the inertness of the CC moieties were not provided, although in previous studies56,57 it was also observed that the amines do not react with the alkynes at the gold(I) center. In the other work,58 the reaction of the (isocyanide)AuI complexes [AuX(CNPh)] or [Au(NCS)(CNMe)] with HNMe(CH2CH2O)nMe (n = 1−11) or HNEt2 afforded the (diaminocarbene)AuI derivatives [AuX{C(NHPh)(MeN(CH2CH2O)nMe)}] (CH2Cl2, RT, 3 h; X = Br, Cl; 45%) and [(NCS)Au{C(NHMe)(NEt2)}]2 (CH2Cl2, RT, 3 h; 78%).

Attempts to improve the yield of 12 by extending the reaction time, increasing the reaction temperature, or using an excess of the nucleophile were unsuccessful, and the treatment typically results in substitution of the isocyanide with the amine giving 13. The authors stated that in this case, palladium(II)-centered ligand substitution is preferred over the nucleophilic attack on the coordinated isocyanide; similar reactivity was previously observed with hydrazine, which is a widely used bifunctional nucleophile to generate chelating acyclic diaminocarbene ligands.51,52 Moreover, it is believed50 that the insufficient electron susceptibility of the coordinated isocyanide in the starting complex caused by the strong σ-donating and poor πaccepting nature of the NHC ligand is the principal reason for the low reactivity of the isocyanide species (Scheme 4). Vicente and co-workers53 disclosed the palladium(II)mediated intramolecular nucleophilic addition of the pendant amine moiety of the iminiumacyl ligand to CNR (R = But, Xyl) F


Chemical Reviews

Review

Echavarren, Espinet et al.62 studied the reaction between the (isocyanide)AuI complexes [AuCl(CNR)] [R = But, Tol, Xyl, 4C6H4CO2H, 4-C6H4CO2Et] and several primary amines H2NR1 (R1 = Me, Bun, Pri, Heptn, Tol) or HNEt2 leading to the series of the diaminocarbene complexes [AuCl{C(NHR)(NHR1)}] (THF, 15 min, 51−85%) and [AuCl{C(NHR)(NEt2)}] (THF, 15 min, 79−98%). In the related work, Hashmi and coworkers63 found that the reaction of [AuCl(CNR)] with various primary and symmetrical secondary amines afforded a broad family of the (diaminocarbene)AuI species (CH2Cl2, RT, 15 min, 42−99%; 21 examples). Espinet et al.64 reported the reaction of isocyanide gold(I) complexes with chiral amines or diamines leading to mononuclear (22; Figure 3b, 78−86%) and dinuclear (23; Figure 3c, 50−82%) gold(I) complexes featuring chiral acyclic diaminocarbene ligands. Both reactions proceed (CH2Cl2 or THF, RT) with retention of the absolute configuration of the chiral centers. In the related study, Slaughter and co-workers reported65 the preparation of gold(I) complexes containing chiral 2-isocyanobinaphthyls and their reaction with achiral (Pri2NH) or chiral ((S-PhMeCH)2NH) amines producing species having chiral acyclic diaminocarbene ligands (24; Figure 3d; 61−85%). In the recent studies,66 palladium(II) complexes containing respective chiral diaminocarbene ligands were prepared upon nucleophilic addition of amino acid esters to one isocyanide in either cis-[PdCl 2 (CNR) 2 ] or trans[PdI2(CNR)2]. Reaction of the cyclometalated gold(III) complex [AuCl2(pap-C1,N)] (25, pap = 2-(2-pyridylamino)phenyl) with an equimolecular amount of the different isocyanides CNR (R = Naph, Cy, Xyl; CH2Cl2, RT, 2 h) leads to complexes featuring bidentate arylaminocarbene ligands 26 (35−94%, Scheme 8).67 The authors of ref 67 suggested that the reaction

Reaction of the gold(I) isocyanide complex [AuX(CNC5H4N4)] (18) with primary (H2NMe) or secondary (HNEt2) amines gave the respective diaminocarbene derivatives of the type [XAuR{C(NRR1)(NHC5H4N-4)}] (X = C6F5, C6H2(2,4,6CF3)3) (19; CH2Cl2, RT, 15 min; 60−82%, Scheme 7).59 Scheme 7. Reaction of [AuX(CNC5H4N-4)] with HNEt2 or 1,4-(H2N)2C6H4

Single-crystal X-ray diffraction studies indicated that, in some of the complexes, the NHC5H4N-4 moiety forms supramolecular macrocycles supported by hydrogen-bond interactions, either with the N−H groups of other molecules or with water. The corresponding reaction of the starting isocyanide complex with the diamine 1,4-(H2N)2C6H4 as a nucleophile provided dimeric gold(I) diaminocarbene 20 (64%, Scheme 7).59 In a related work,60 the isocyanide in the complexes [AuX(CNC5H4N-2)] (X = Cl, C6F5, FMes) reacts with H2NMe or HNEt2 producing the aminocarbene species [AuX{C(NR1R2)(NHC5H4N-2)}].60 In the other study,61 the gold(I) complexes [AuX(CNR)] (X = Cl, C6F5, Br, I) with crown ether-functionalized isocyanide CNR (R = benzo-15-crown-5) were obtained. They were further transformed into the diaminocarbene derivatives [AuCl{C(NHR1)(NHR)}] (21, Figure 3a) upon treatment with the corresponding primary amine H2NR1 (R1 = Me, Bun; CH2Cl2, RT, 30 min) and isolated in 16% (for R1 = Bun) or 60% (R1 = Me) yields. The yields of the reaction are apparently controlled by steric factors, and low product yield was observed for the bulkier n-butyl isocyanide.

Scheme 8. Reaction of [AuCl2(pap-C1,N)] with Isocyanides

proceeds through the nucleophilic attack of the amine nitrogen (NH) of the cyclometalated ligand on the carbon of the uncomplexed CNR followed by the displacement of the pyridine N atom with the aminocarbene formed. However, the authors of this Review, as a possible alternative, suggest another mechanism that involves the decoordination of the pyridine substituents of the cyclometalated ligand via the replacement with the isocyanide and subsequent intramolecular nucleophilic addition to the metal-activated CNR by the NH moiety of the C-bound amine. 2.1.1.2. Addition of Imines and Related Nucleophiles (sp2-N Donor Centers). The reaction between cis-[PtCl2(CNXyl)2] and HNCPh2 in dry chloroform results in the addition of benzophenone imine to one isocyanide ligand (Scheme 9) to yield the amino(imino)carbene cis-[PtCl2{C(NCPh2)N(H)Xyl}(CNXyl)] (28).68 The formulation of 28 is based on the coherent NMR and ESI−MS data. This adduct is not stable in solution at RT in the presence of water traces from undried solvents leading to the diaminocarbene cis-[PtCl2{C(NH2)N(H)Xyl}(CNXyl)], which

Figure 3. Gold diaminocarbene complexes 21−24. G


Chemical Reviews

Review

Scheme 9. Metal-Mediated Addition of Imines to cis[MCl2(CNR)2]

Scheme 10. Metal-Mediated Addition of 1,3Diiminoisoindoline to Isocyanides

is, formally, the product of the addition of ammonia to one isocyanide ligand in cis-[PtCl2(CNXyl)2].68 The reaction between one isocyanide in cis-[MCl2(CNR)2] (27, M = Pd, Pt) and various unsubstituted or substituted 3iminoisoindolin-1-ones proceeds under reflux conditions in CHCl3 for 2 h (Scheme 9).69,70 The subsequent workup provides aminocarbene complexes 29 (Figure 4), which were isolated in

secondary amide functionality of the 1,3-diiminoisoindoline to the metal. The corresponding reaction of cis-[PdCl2(CNR)(PPh3)] (32) and 1,3-diiminoisoindoline (1 equiv) in CHCl3 under reflux for 4 h (Scheme 11) affords the mixed ADC/phosphine species cis[PdCl{C(NCa(C6H4CNHNb))N(H)R}(PPh3)](Ca−Nb) in good to moderate yields (33; R = Cy 84%; But 76%; CMe2CH2CMe3 75%). Scheme 11. Metal-Mediated Addition of 1,3Diiminoisoindoline to 33

No reaction between cis-[PdCl2(CNXyl)(PPh3)] with 1,3diiminoisoindoline was observed, presumably due to the insufficient thermal stability of the starting isocyanide complex that is decomposed prior the addition.71 A nucleophilic addition of indazole or 5-methylindazole to one isocyanide in cis-[PdCl2(CNCy)2] (27; refluxing CHCl3, ca. 6 h, Scheme 12) afforded aminocarbene species 34 (72−83%).72 Indazoles bearing electron-withdrawing substituents, for example, 3-chloroindazole, 5-nitroindazole, and 6-nitroindazole, do not react with 27. No conversion of the second isocyanide into the carbene was achieved even with a 4-fold excess of indazole or 5-

Figure 4. View of the molecular structure of cis-[PdCl{C(N Ca(C6H4CONb))N(H)Cy}(CNCy)](Ca−Nb) as a representative example of 29. Thermal ellipsoids are drawn at the 50% probability level.

good (80−85% for the palladium complexes) to moderate (60− 65% for the platinum species) yields. Attempts to perform similar nucleophilic attack on the remaining isocyanide ligand were unsuccessful; the low reactivity toward the subsequent addition is explained by lowering of the electron susceptibility of the second isocyanide species caused by the strong σ-donating and poor πaccepting nature of the ADC ligand previously formed. In the related study, 71 the reaction between cis[PdCl2(CNR)2] and 1,3-diiminoisoindoline in CHCl3 under reflux for 4 h (Scheme 10) provided aminocarbene species 30 (R = Cy, 82%) or 31 (R = But 78%, Xyl 84%, CMe2CH2CMe3 79%) that are derived from the addition of 2 or 1 equiv of 1,3diiminoisoindoline to the isocyanide, respectively. The reasons for the formation of different products from the same reaction are so far not clear. It is worth mentioning that the obtained aminocarbene ligands are additionally stabilized through the chelating effect, that is, due to coordination of the

Scheme 12. Metal-Mediated Addition of Indazoles to CNCy

H


Chemical Reviews

Review

Scheme 14. Nucleophilic Addition of H2N(H)NC(O)R1

methylindazole under reflux of the reaction mixture for 1 day. This reaction represents the first example for the addition of aromatic azaheterocycles, where the pyrrole-type NH center plays the role of a nucleophilic site, to metal-bound isocyanides, although such addition is known for the isoelectronic nitrile ligands and gives imine species.73−77 2.1.1.3. Addition of Hydrazides and Hydrazones (Mixed sp3/sp2-N Donor Centers). Metal-mediated reaction between equimolar amounts of cis-[MCl2(CNR)2] (27, M = Pd, Pt) and benzophenone hydrazone (CHCl3, reflux, 8 h) afforded the aminocarbene species cis-[MCl2{C(N(H)NCPh2)N(H)R}(CNR)] (35, 80−85%, Scheme 13; see Figure 5).78,79 The

acting as a strong σ-donor ligand deactivates the remaining isocyanide species preventing the nucleophilic addition. 2.1.2. Addition of O-Nucleophiles. 2.1.2.1. Addition of Water/Hydroxide. Fehlhammer and co-workers reported83 the reaction between the isocyanide complexes [PtCl(CNR)(PPh3)2](BF4) [37, R = CH2CO2Et, CH2Ph, Cy, CH2SO2(4MeC6H4)] and hexafluoroacetone-sesquihydrate, (F3C)2CO· 1.5H2O, in the presence of a stoichiometric amount of NEt3 that gives the carbamoyl complexes [PtCl{C(O)NHR}(PPh3)2] (38, 80%, Scheme 15).

Scheme 13. Nucleophilic Addition of H2N−NCPh2

Scheme 15. Addition of OH− to Isocyanide in [PtCl(CNR)(PPh3)2](BF4)

In this process, (F3C)2CO·1.5H2O plays a role of the stoichiometric source of OH−, while the corresponding reaction with excess OH− (e.g., from KOH/MeCN or NaOH/H2O) did not bring the formation of the isolable products. The authors83 believe that any carbamoyl complexes formed are too labile in the presence of excess hydroxide. 2.1.2.2. Addition of Alcohols. The reaction of [CpFe(CO)(PNC)]I (5; PNC = CNCH2CH2CH2PR2, R = But, Ph; for other nucleophilic additions to this complex, see sections 2.1.1.1 and 2.2) with alkoxides (THF, RT, 16 h, Scheme 16) yields respective ylidene complexes (39, 89−93%).47

Figure 5. View of the molecular structure of cis-[PtCl2{C(N(H)N CPh2)N(H)Xyl}(CNXyl)] as a representative example of 35. Thermal ellipsoids are drawn at the 30% probability level.

reaction proceeds only at one isocyanide ligand with any ratio between the reagents, while the second isocyanide remains intact. In the related studies by the same group,80,81 the scope of the reaction was extended to the other hydrazones H2N−N CR1R2 [R1/R2 = 9H-fluorenyl; R1 = H, R2 = 2-(OH)C6H4] and to the isocyanide 2-Cl-6-MeC6H3NC; the reaction yielded the structurally related complexes cis-[MCl 2 {C(N(H)N CR1R2)N(H)R}(CNR)]. The reaction between one isocyanide ligand in cis[PdCl2(CNR)2] (27, R = Cy, But) and the carbohydrazides H2N(H)NC(O)R1 [R1 = Ph, 4-ClC6H4, 3-NO2C6H4, 4NO2C6H4, 4-CH3C6H4, 3,4-(MeO)2C6H3, naphth-1-yl, fur-2-yl, 4-NO2C6H4CH2, Cy, 1-(4-fluorophenyl)-5-oxopyrrolidin-3-yl, (pyrrolidin-1-yl)C(O)] (refluxing CHCl3, 4 h; Scheme 14) led to cis-[PdCl2{C(NHNHC(O)R1)N(H)R}(CNR)] (36; 80− 95%).82 The addition of H2NN(H)SO2Ph to cis-[PdCl2(CNR)2] (R = Cy, But, Xyl, 2-Cl-6-MeC6H3) occurs similarly to afford the aminocarbenes cis-[PdCl 2 {C(NHNHSO 2 Ph)N(H)R}(CNR)] (60−90%).82 No subsequent addition to the second isocyanide was accomplished under studied conditions. It is believed that the ADC formed after the addition to the first isocyanide ligand

Scheme 16. Reaction of the Iron(II) Complex [CpFe(CO)(PNC)]I with Alkoxides

I


Chemical Reviews

Review

Inspection of the resonances due to the isocyanide (average νCN = 2090 cm−1) and carbonyl (average νCO = 2000 cm−1) moieties indicates that the carbonyl is deactivated toward a nucleophilic attack, and it justifies the fact why the reaction proceeds exclusively at the isocyanide species. It is reported19 that when the νCO frequencies are higher than 2000 cm−1 (this value is considered as a threshold for susceptibility to nucleophilic attack on carbonyl), the nucleophilic attack occurs at the CO ligand. Further protonation of the above-mentioned ylidene complexes affords the corresponding acyclic oxyaminocarbene complexes 40 (87−93%, Figure 6).

Scheme 18. Generation of Heterocyclic Aminocarbene Complexes via the Addition of Haloalcohols, Haloamines, or Three-Membered Heterocycles to Complexed Isocyanides

A proposed mechanism for the reaction of metal-bound isocyanides with haloalcohols or haloamines leading to cyclic aminocarbene (Scheme 18) entails initial nucleophilic attack on the isocyanide carbon atom to give an imidoyl intermediate. The latter then undergoes intramolecular cyclization to give the final heterocyclic carbene product. The reaction is generally limited to the formation of five-membered heterocyclic structures at PdII and PtII centers, although several examples of other metals and other heterocyclic structures have emerged in recent years. Thus, the reactions of the iron(II) complexes [CpFe(CO)(CNR)]I [5, R = (CH2)3P(But)2, (CH2)3PPh2; for other nucleophilic additions to this complex, see sections 2.1.1.1 and 2.1.1.2)] with 2-chloroethyl and 3-chloropropylamine followed by intramolecular cyclization afforded the five- and sixmembered cyclic (diamino)carbene complexes [CpFe(CO)(NHC)]I (43; 81−83%), respectively (Scheme 19).47 The Figure 6. View of the molecular structure of [CpFe(CO{C(NHex2)NHCH2CH2CH2PPh2}]I as a representative example of 40. Thermal ellipsoids are drawn at the 50% probability level.

Scheme 19. Reactions of the Isocyanide Iron(II) Complexes [CpFe(CO)(CNR1)]I with Functionalized Nucleophiles Leading to the Corresponding (NHC)Fe Species

In the other study,61 the gold(I) complexes [AuCl(CNR)] (41) bearing the crown ether-functionalized isocyanide CNR (R = benzo-15-crown-5) reacted with methanol (reflux, 24 h), accomplishing the corresponding oxyaminocarbene derivative [AuCl{C(OMe)(NHR)}] (42; 53%, Scheme 17). Scheme 17. Reaction of [AuCl(CNR)] with Methanol

corresponding cyclic oxyamino carbene complexes [CpFe(CO)(NHC)]Cl (44; 90−91%) are formed by the concerted reactions of [CpFe(CO)(CNR)]I with lithium 2-chloroethoxide and 3chloropropoxide followed by the intramolecular cyclization.47 The reaction between one isocyanide ligand in cis[PdCl2(CNR)2] [16, R = 2,6-Et2C6H3, 2,6-Pri2C6H3, 2,6di(cyclohex-2-ene-1-yl)-4-MeC6H2] with a number of 2(chloroethyl)ammonium salts (R1 = alkyl, cycloalkyl, R2 = H, R3 = H, Ph, seven examples; THF, RT, 12 h; Scheme 20) in the presence of Et3N gives the corresponding N-heterocyclic carbene derivatives 45 (52−86%, Figure 7).54 The second isocyanide species does not react under any of the studied conditions

2.2. Addition of Functionalized Nucleophiles Accompanied by Intramolecular Cyclization

Addition of functionalized nucleophiles, for example, haloalcohols, haloamines, or three-membered heterocycles, to metalbound isocyanides leading to heterocyclic aminocarbene complexes5,7,8,84 was extensively reviewed19 in the year 2001. These reactions are summarized in Scheme 18. J


Chemical Reviews

Review

metal(II) species. Consequent CN ring opening of the aziridine moiety followed by the intramolecular attack of the nucleophilic imino nitrogen on the adjacent methylene group of aziridine leads to the cyclic aminocarbene species. For the related addition of oxirane, the ring opening precedes the nucleophilic attack by the oxygen center on the isocyanide carbon atom. Recently, Ruiz et al.88 reported the reaction of the cationic manganese(I) isocyanide complexes fac-[Mn(CNR)(CO)3(bpy)]+ (1, for other additions to this complex, see section 2.1.1.1) with different functionalized nucleophiles such as propargylamines and propargylic alcohols (Scheme 22). The

Scheme 20. Reactions of cis-[PdCl2(CNR)2] with 2(Chloroethyl)ammonium Salts

Scheme 22. Intramolecular Hydroamination of the Alkyne Residue in fac-[Mn(CNR)(CO)3(bpy)]+

Figure 7. View of the molecular structure of cis[PdCl2{Ca(NPriCH2CH2)NbC6H3Pri2-2,6}(CNC6H3Pri2-2,6)](Ca− Nb) as a representative example of 45. Thermal ellipsoids are drawn at the 50% probability level.

reaction brings about the formation of the complexes fac[Mn(NHC)(CO)3(bpy)]+ (48, 78%; 49, 63−70%) featuring newly formed NHC ligand (imidazoline-2-ylidene, imidazolidine-2-ylidene, or corresponding N,O-heterocyclic analogues). A plausible mechanism at least formally includes an intramolecular hydroamination of the alkyne residue and consists of the initial nucleophilic attack of the amine or the alcohol to the isocyanide followed by an intramolecular cyclization. In the other study,89 the reaction of amino acid esters with isocyanides activated by d8 metal centers, AuI, PdII, and PtII (CH2Cl2, RT, 36 h, see Scheme 23 for gold(I)-mediated

presumably due to the insufficient electrophilic activation. Similar reactions at the platinum(II) center led85 to the corresponding mixed NHC/isocyanide platinum complexes. Hashmi and colleagues86,87 described the preparation of gold(I) complexes bearing the unsymmetrically substituted Nheterocyclic carbene ligands 48 (60−99%, Scheme 21) that were Scheme 21. Generation of Gold(I) Complexes Bearing Unsymmetrically Substituted NHCs

Scheme 23. Reaction of Amino Acid Esters with (RNC)AuI Species

obtained from the corresponding gold−isocyanides 47 (R = But, 2,6-Pri2C6H3, Mes) upon the nucleophilic attack of 2chloroethylammonium chlorides (in the presence of Et3N, THF, or CH2Cl2, RT; R1 = Pri, Ad; R2 = H, Ph) followed by the intramolecular cyclization. Similar reactions at palladium(II) and platinum(II) centers led to the corresponding metal-NHCs.86 This approach was extended87 toward the preparation of chiral NHCs by employing chloroethylammonium chlorides bearing chiral substituents. For the reaction of metal-bound isocyanides with threemembered heterocycles (Scheme 18), the following mechanism was proposed. Thus, in case of reaction with aziridine or thiirane, the initial attack of the entering amine on the electrophilic isocyanide carbon atom produces an intermediate imino−

process), led to compounds 51 featuring N-heterocyclic oxocarbene ligands (42−92%; 11 examples). In the case of gold(I), the isocyanide complexes were generated in situ from the corresponding uncomplexed CNR (R = Xyl, 2,6-Et2C6H3, 2,6Pri2C6H3, 2-Naph) and the [AuCl(tht)] precursor (50, tht = tetrahydrothiophene). The initial nucleophilic attack by the NH center of the amino acid ester (R1 = alkyl, cycloalkyl, R2 = H, alkyl; five examples) on the isocyanide carbon leads to ADC ligands that are subject to an intramolecular cyclization with K


Chemical Reviews

Review

elimination of MeOH giving target NHCs. In the cases of bisisocyanide PdII and PtII complexes, the reaction involves only one isocyanide ligand, whereas the second remains intact.

Scheme 25. Intramolecular Cyclization of the in Situ Formed 2-Aminophenyl Isocyanide Ligand

2.3. Intramolecular Cyclization of Functionalized CNR Species

These reactions at least formally represent the intramolecular nucleophilic attack leading to heterocyclic structures, and the reports published before the year 2000 were surveyed by Michelin, Pombeiro, and Guedes da Silva.19 In this section, our attention is mostly focused on recent reports in the field, although to make this Review comprehensive, we also discuss a small amount of early reports that were not covered by Michelin et al.19 The fluoride-catalyzed hydrolysis of the Si−O bonds in [CpFe{CNC6H4(OSiMe3)-2}3]Cl (52) occurs at RT in MeOH and leads to an intramolecular cyclization of the isocyanide ligands furnishing the unusual complex 53 (yield is not given) bearing simultaneously a 2-hydroxyphenyl isocyanide, a benzoxazol-2-yl, and 1,2-dihydrobenzoxazol-2-ylidene ligands (Scheme 24).90 Thus, all three possible intermediates for the As an amplification of the latter study,101 the reduction of the nitro or azido groups of the isocyanides in the complexes [M(CO)3(dppe)(CNR)] (M = Mo, W; R = 2-N3CH2CH2, 2N3C6H4, or 2-NO2C6H4) was studied. The reduction of these functionalities attached to the isocyanide ligands by the Zn/ NH4Cl (used for azidoethyl or azidophenyl isocyanides) or Raney-nickel/hydrazine hydrate (applied for nitrophenyl isocyanide) systems yields exclusively the complexes bearing the 2amino-functionalized isocyanides. The usually unstable 2-aminofunctionalized isocyanides are stabilized by π-back-bonding, which deactivates the isocyanide carbon atom for an intramolecular nucleophilic attack by the primary amine. Michelin and colleagues102 observed the reduction of the 2(azidomethyl)phenyl isocyanide in [M(CO)5(CNR)] (M = Cr, Mo) with PPh3 that leads to six-membered NHCs. In the same study, the isocyanide in [W(CO)5(CNC6H4-2-CH2I)] was treated with NH 2 Me, and this reaction results in the corresponding N-methylated NHC species isolated in 29% yield. Treatment of [ReBr(CO)5] (58) with CNC6H4(OSiMe3)-2 (2.2 equiv, reflux THF−benzene, overnight) results in complexes with two NHC ligands 59 (90%, Scheme 26, Figure 8). It is

Scheme 24. Intramolecular Cyclization of [CpFe{CNC6H4(OSiMe3)-2}3]Cl

conversion of isocyanide CNC6H4(OSiMe3)-2 into the corresponding N-heterocyclic carbene were formed. Oxidation of 53 with I2 in MeOH brings about the full conversion of the isocyanides into the three ylidenes. In related works,91−97 Hahn and colleagues undertook a comprehensive evaluation of factors controlling the cyclization of β-functionalized isocyanides into N-heterocyclic carbenes, driving forces of the hydrolytic cleavage of functionalized isocyanides and stability of intermediate hydroxyphenylisocyanides at such metal centers as chromium(0),93 tungsten,94 and rhenium(I, III, or V).95 Effects including π-back bonding of the ancillary ligands, the presence of bases, and the effect of their strength were studied. The reduction of the azide moiety of CNR in the [M(CO)5(CNR)] (54, M = Cr, W; R = 2-azidophenyl) complexes using tertiary phosphines (PMe3, PPh3) to accomplish 2-triphenylphosphiniminophenyl isocyanide species (55, Scheme 25) was observed.98,99 Compounds 55 undergo hydrolysis with H2O/HBr to afford the complexes with the unstable 2-aminophenyl isocyanide ligands (56) that spontaneously cyclize by intramolecular nucleophilic attack of the primary amine at the isocyanide carbon atom to yield fivemembered NHCs, that is, 2,3-dihydro-1H-benzimidazol-2ylidene complexes 57 (65−85%). In the other study by the same group,100 metallic tin and hydrazine hydrate were used as reducing agents to generate the corresponding β-aminofunctionalized isocyanides. With hydrazine hydrate, the reduction was incomplete, giving rise to complexes with 2-hydro-3hydroxy-1H-benzimidazol-2-ylidene instead of the expected 2,3dihydro-1H-benzimidazol-2-ylidene.

Scheme 26. Intramolecular Cyclization of ReI-Bound Isocyanides

believed that this reaction involves the initial coordination of the isocyanide, splitting of the O−SiMe3 bond, followed by intramolecular nucleophilic attack on the isocyanide carbon by the oxygen center.103 In the same study, the addition of 2bromoethanol, 2-bromoethylamine, thiirane, and diethoxyethanamine to one isocyanide in cis,cis-[Re(CO)2(CNC6H4Cl4)2(bpy)]Br was studied, and it brings about the corresponding L


Chemical Reviews

Review

NHC ligand. Deprotonation of the latter led to iron(II) complexes bearing the macrocyclic [11]ane-P2CNHC ligand. Similar results were obtained at a rhenium(I) metal center.107,108 The reduction of the 2-(azidomethyl)phenyl isocyanide, CNC6H4(CH2N3)-2 (CNAzi), in the complexes trans-[MCl(CNAzi)(PPh3)2][BF4] and [MCl2(CNAzi)2] (M = Pt, Pd) with PPh3 and H2O (CH2Cl2, RT, 24 h) led to the heterocyclic carbene species trans-[MCl{CN(H)C 6 H 4 -2-CH 2 N(H)}(PPh3)2]+ (M = Pt, 63, 52−67%, M = Pd, 64, 71−88%; Figure 9a).109,110 In the related study,111 a base-promoted cyclization of

Figure 8. View of the molecular structure of [ReBr{Ca(O(C6H4NbH2))}2(CO)3](Ca−Nb) as a representative example of 59. Thermal ellipsoids are drawn at the 50% probability level.

NH,NH-, NHO-, or NHS-heterocyclic carbene ligands (21− 57%). In the subsequent work,104 the same group of authors reported that the reaction of [Re(CO)3(phen)(NCMe)](OTf) or [Re(CO)3(phen)(PR1R22)](OTf) with CNC6H4(OSiMe3)-2 furnishes the corresponding NHO-heterocyclic carbene species. The reduction of the azido group of the coordinated 2azidoethyl isocyanide in ruthenium(II) complexes 60 with Zn/ NH4Cl/H2O generates the 2-aminoethyl isocyanide ligand that cyclizes intramolecularly furnishing a metal-bound NH,NH-Nheterocyclic carbene species 61 (94%; Scheme 27).105

Figure 9. Complexes obtained via intramolecular cyclization of βfunctionalized isocyanides.

Scheme 27. Intramolecular Cyclization of the in Situ Prepared 2-Aminophenyl Isocyanide

the arsonium-substituted isocyanides CNC6H4{(CH2As+R3)2}I− at platinum(II) centers provided metal-indolidin-2-ylidene derivatives. The corresponding cyclization of 2-azidoethyl,112 2-azidophenyl,113 or 2-azidopropyl114 isocyanides at the platinum(II) center led to complexes obtaining five- or six-membered cyclic diaminocarbenes (for example, see Figure 9b). The intramolecular cyclization of 2-(trimethylsiloxymethyl)phenyl isocyanide, CN C6H4(CH2OSiMe3)-2, was observed at platinum(II) and palladium(II) centers (MeOH, RT, 24 h), and it gives the corresponding cyclic aminooxycarbene derivatives (66, 75%; 67, 72%; Figure 9c) in the presence of a catalytic amount of fluoride ions in MeOH.115 In related studies, cyclization of 2-(trimethylsiloxy)phenyl isocyanide in platinum(II)116 and iridium(III)117 complexes led to the corresponding five-membered cyclic aminooxycarbene derivatives. Hahn and co-workers118,119 described platinum(II)-mediated cyclization of β,β′-dihydroxyphenyl-1,4-diisocyanide (in acetonitrile, RT, 48 h, Scheme 28) upon reaction of 68 with the isocyanide leading to dimeric (69, 42%) and rectangular tetrameric structures supported by the formed NH,O-NHC ligands. A similar reaction was also observed117 for iridium(III) complexes featuring β,β′-dihydroxyphenyl-1,4-diisocyanide ligands. Vicente et al.120 reported the base-promoted transformation of the iminoacyl isocyanide complex trans-[Pd{C(NXyl)C 6 H 4 NHC(O)NHTol-2}I(CNXyl) 2 ] (70) (Tol-2 = 2MeC6H4; in acetone/CH2Cl2, RT, 16 h; Scheme 29) that yields iminoacyl amido carbene C,N,C-chelate 71 (58%, Figure 10).

Deprotonation of the latter results in an intramolecular nucleophilic attack of the amido nitrogen atoms at the fluorinated phenyl groups of the diphosphine ligand to afford a complex with facially coordinated macrocyclic [11]ane-P2CNHC species 62 (70%). Similar cyclizations at ruthenium(II) core were observed in the related studies.105 The same group106 described the cyclization of the structurally related iron(II) complex [CpFe(P∧P)(CNR)]X (P∧P = 1,2bis{bis(2-fluorophenyl)phosphanyl}benzene, X = Br, PF6) bearing 2-azidoethyl isocyanide ligands CNCH2CH2N3 upon the reduction with PPh3 at the azido function followed by hydrolysis of the iminophosphorane formed with HBr. This reaction afforded iron(II) complex with the above-mentioned

2.4. Addition of Ambident Nucleophiles

Slaughter and colleagues121 observed the coupling of isocyanide ligands in cis-[PdCl2(CNC6H4CF3-4)2] (72) with trans-N,N′M


Chemical Reviews

Review

Scheme 28. Platinum(II)-Mediated Cyclization of β,β′Dihydroxyphenyl-1,4-diisocyanide

Scheme 30. Reaction of cis-[PdCl2(CNC6H4CF3-4)2] with trans-N,N′-Dimethyl-1,2-diaminocyclohexane

chelate is thermally stable under dinitrogen, but in air it undergoes a slow oxidation to the corresponding bis(amidine) complex 74.

Scheme 29. Cyclization of trans-[Pd{C( NXyl)C6H4NHC(O)NHTol-2}I(CNXyl)2]

Figure 11. View of the molecular structure of cis-[PdCl2{C(((NMe)2Cy-1,2)NHC6H4CF3-4)2}] as a representative example of 73. Thermal ellipsoids are drawn at the 50% probability level.

In the related study,122 reaction of cis-[PdCl2(CNC6H4CF34)2] with N,N′-bis[(R)-1-phenylethyl]-1,3-diaminopropane (Scheme 31) afforded enantiomerically pure C1-symmetric Scheme 31. Reaction of cis-[PdCl2(CNC6H4CF3-4)2] with N,N′-Bis[(R)-1-phenylethyl]-1,3-diaminopropane

Figure 10. View of the molecular structure of [Pd{κ3C,N,C-C( NXyl)C6H4NC(O)N(Tol-2)C(NHXyl)-2}(CNXyl)] as a representative example of 71. Thermal ellipsoids are drawn at the 50% probability level.

bis(ADC)PdII complex 75 (acetonitrile, RT, 2 d; 41%). A related process with N,N′-bis[(R)-1-(1-naphthyl)ethyl]-1,3diaminopropane led to decomposition products, while the reaction of 72 with the racemic N,N′-bis[1-(1-naphthyl)ethyl]1,3-diaminopropane provided an achiral Cs-symmetric bis(ADC)PdII complex (20%) that is derived exclusively from the

dimethyl-1,2-diaminocyclohexane (Scheme 30) leading to onestep formation of the first chiral bis(acyclic diaminocarbene) complex 73 (CH2Cl2, RT, 2 h; 65%, Figure 11). The obtained N


Chemical Reviews

Review

(R,S) diamine. These studies were further extended123 toward other chiral diamines. The palladium-mediated addition of phenylhydrazine to methylisocyanide6,51 proceeds at RT in water and brings about the formation of complex 76 (45%) featuring formally deprotonated chelating aminocarbene ligand (Scheme 32).

monodentate aminohydrazinocarbene ligand and the unreacted arylisocyanide. Upon heating, this complex partially converted into a chelating bis(ADC) complex, while in solution, an equilibrium between the monocarbene and bis(carbene) complexes was established.123 It was also reported125−128 that the reaction of cis-[PdCl2(CNR)2] and H2NNR1R2 (R1/R2 = Ph; R1 = H, R2 = 4-NO2C6H4) proceeds at one isocyanide ligand and leads to complexes featuring monodentate aminocarbene ligands (refluxing DCE or CHCl3, 4−8 h; 85−95%). Metal-mediated nucleophilic addition of N-phenylbenzamidine, HNC(Ph)NHPh, to one or two isocyanide ligands in cis[MCl2(CNR)2] (27, M = Pd, Pt) proceeds with different regioselectivity upon varying R group (Scheme 33).129 When R = Xyl (route A, Scheme 33), N-phenylbenzamidine is first coordinated to a metal by the HNC moiety giving the complex 79. Subsequent nucleophilic attack of the uncoordinated NPh center of the benzamidine on isocyanide ligands gives complexes [MCl{C(N(Ph)C(Ph)NH)NXyl}(CNXyl)] (80; refluxing CHCl3, 4 h; 65−85%). Attack of N-phenylbenzamidine (2 equiv) on cis-[MCl2(CNR)2] produces complexes containing the two equal aminocarbene-like ligands [MCl{C(N(Ph)C(Ph)NH)NXyl}2] (refluxing CHCl3, 8 h; 45−65%). For R = But (route B, Scheme 33), HN C(Ph)NHPh is coordinated to a metal by the NPh center to afford the intermediate complex 81; the subsequent addition occurs via the HNC center of the nucleophile to furnish [MCl{C(NC(Ph)NPh)NBu t }(CNBu t )] (82, reflux, CHCl3, 4 h; 65−85%). Reaction with 2 equiv of N-phenylbenzamidine produces bis-chelate [MCl{C(NC(Ph)NPh) NBut}2] (refluxing CHCl3, 8 h; 45−65%). With R = Cy, the reaction loses regioselectivity, and the addition of N-phenylbenzamidine proceeds via both nucleophilic centers of the latter affording a mixture of two products. The substituent Rdependent reactivity was explored using theoretical (DFT) methods and interpreted as a result of the steric repulsions in one of the regioisomers of the addition products, when R = Cy and But. Metal-mediated coupling between equimolar amounts of cis[PdCl2(CNR)2] (27, R = Cy, Xyl, 2-Cl-6-Me-C6H3) and H2NC5H3R1N (R1 = H, NH2) leads (CHCl3, RT, 12 h) to diaminocarbene species 83 (60−75%, Scheme 34).130 Addition of 83 to starting 27 (1:1 molar ratio) in the presence of excess

Scheme 32. Palladium-Mediated Addition of Phenylhydrazine to Isocyanides

Further protonation of 76 with HCl led to Chugaev-type chelating bis(carbene)Pd complex 77 (86%). When CNPri was used as a reactant, the addition gives 78 (41%) featuring two monodentate aminohydrazinocarbene ligands. The authors6,51 believe that the monodentate carbene species of 78-type are likely to be the intermediates in the formation of chelating species 77. Steric reasons are accounted for by the observed reactivity difference between CNMe and CNPri, and the complexes with the bulkier CNPri do not cyclize into the corresponding chelating aminocarbenes. In the related studies,6,52,124 the same authors observed that the palladium-mediated reaction of H2NNH2 or MeNHNH2 with several CNRs (R = Me, Pri, But, Cy) brings about the formation of a series of complexes bearing chelating aminocarbene ligands. Slaughter et al.123 also demonstrated that the reaction of 72 with N,N′-diphenylhydrazine proceeds at one isocyanide ligand only and affords a complex bearing one

Scheme 33. Regioselective Metal-Mediated Nucleophilic Addition of N-Phenylbenzamidine

O


Chemical Reviews

Review

Scheme 34. Addition of H2NC5H3R1N to Isocyanide in cis[PdCl2(CNR)2]

Scheme 35. Addition of Phosphorus Ylides to [AuCl(CNR)]

It was also demonstrated that arsenic ylide and nucleophiles featuring a polarized CC bond, R1R2CC(H)R3 (Scheme 36), add to the isocyanide ligand in [AuCl(CNPh)] (toluene, Scheme 36. Addition of Arsenic Ylide and En(di)amines to [AuCl(CNPh)]

solid K2CO3 (CHCl3, 40 °C, 12 h) led to dinuclear complexes 84 (65−75%, Figure 12). Generation of 84 proceeds via a cascade

−10 °C, 1 d for arsenic ylide; toluene, 35 °C, 1−8 h for R1R2C CR3) affording acyclic aminocarbene complexes 88 (40%) and 89 (87−95%), correspondingly. Riera et al.133 found that deprotonation of the imidazole ligand in rhenium complexes 90 with 1 equiv of K(NSiMe3)2 (THF, −78 °C) immediately affords complexes 91 (85% and 75% for R = Me and Mes, respectively) as a result of intramolecular nucleophilic attack of the C-nucleophile onto the isocyanide moiety (Scheme 37).

Figure 12. View of the molecular structure of a representative dinuclear carbene complex of type 84. Thermal ellipsoids are drawn at the 50% probability level.

reaction including addition of the amino group of a 2aminopyridine to the metal-activated isocyanide, ring-closure, and reaction of the formed ADC complex with the yet unreacted starting material. In the subsequent work by the same group,131 addition of 2aminopyrazine gave structurally related binuclear complex, whereas the addition of 4-acetyl-3-amino-5-methylpyrazole provided only a mononuclear aminocarbene species.

Scheme 37. Imidazole−Isocyanide C−C Coupling at ReI Center

2.5. Additions of Other Nucleophiles

Alcarazo et al.132 reported the reaction between the isocyanide gold complexes 85 and substituted phosphorus ylides Ph3P C(H)R1 leading (toluene, 35−45 °C) to substitution 86 and addition 87 products in different ratios depending on the electronic properties of the ylide employed and the substituent in isocyanide (Scheme 35). The use of sterically demanding isocyanides decreases the yield of 87 (74−98% for R = Ph, R1 = COMe, CO2Et, CN, CONMe2, 2-Py; 12−37% for R = Xyl, R1 = COMe, CO2Et, CN, CONMe2) and increases the outcome of the substitution product (86:87 ratio determined by 31P NMR: ca. 2:98 for R = Ph, R1 = COMe, CO2Et, CN, CONMe2, 2-Py and 23:77−75:25 for R = Xyl, R1 = CO2Et, CN, CONMe2). The ligand-exchange process is also favored by using nonstabilized ylides as nucleophiles (86:87 ratio determined by 31P NMR: 76:24 for R, R1 = Ph; 98:2 for R = Xyl, R1 = 2-Py).

Complexes 91 react with HOTf (toluene, 30 min, RT) resulting in protonation of the iminoacyl nitrogen and formation of carbene complexes 92 (85% and 76% for R = Me and Mes, respectively). P


Chemical Reviews

Review

3.1.3. Insertion Chemoselectivity. Similarly to carbon monoxide, the dominant part of CNR insertions is associated with insertions into M−C bonds, such as metal−alkyl, −vinyl, −allyl, −alkyne, −aryl, and −hetaryl. If a complex bears simultaneously alkyl and allyl ligands, the reaction may proceed initially at the M−alkyl bond, but it could also occur at the M− allyl bond, and the chemoselectivity depends on the substituents of the carbon chains.148 Cyclopentadienyl ligands are usually inert in these reactions, although some exceptions are known (see, for instance, ref 149). Insertions into M−H, M−N, or other M−X bonds are much less common as compared to those observed for M−C bonds, and this is accounted for by the relative strength of the corresponding metal−element bonds. Numerous cases of competitive insertion involving complexes having various M−X bonds, whose energies are estimated, support this statement. Indeed, the insertion usually occurs at the weakest bond. Thus, for example, titanium complexes bearing both alkyl and amide ligands150−152 react with CNRs initially at the Ti−C bond (D°298 = 423 kJ/mol153) followed by the insertion into the Ti−N bond (D°298 = 476 kJ/mol153). Theoretical DFT calculations support the idea that the insertion into the Ti−C bond is more thermodynamically favorable than the reaction centered at the Ti−N bond.10,150 In this regard, it is of interest to compare the competitive CNR reactivity toward M−C and M−O bonds. For early transition metal centers, such as Ti154 or Ta,155 the insertion into a M−C bond is more favorable, while for late transition metals, for example, platinum, the insertion occur at the Pt−O bond.156 These reactivities correlate with the relative strengths of the corresponding bonds153 (Ti−C (D°298 = 423 kJ/mol), Ti−O (D°298 = 672 kJ/mol), Pt−C (D°298 = 598 kJ/mol), Pt−O (D°298 = 392 kJ/ mol). However, exceptions from the general trend were reported, and, for instance, for an average Ti−Cl bond, the D°298 value (405 kJ/mol153) is smaller than for the average Ti−N bond (D°298 = 476 kJ/mol153), but CNRs insert into the Ti−N bond.150 3.1.4. Driving Forces of the Insertion. The bulkiness of isocyanide species plays one of the key roles in controlling their insertions. Reports, where inhibition or the complete stopping of the insertion upon increase of the steric hindrance of the R group of CNR was indicated, are large in number.151,152,157,158 It is noteworthy that the effect of bulkiness of the R moiety is more pronounced for 3d metal centers than for 4d and 5d metals having larger radii.151,152,157 A spatial accessibility of M−X bonds also plays a significant role, and, for example, the insertion into metal−alkyl bond is substantially more common for the primary,159 rather than for secondary alkyls. Furthermore, the insertion is inhibited on going from methyl to more bulky benzyl and then to the highly sterically encumbered trimethylsilyl group.160 Steric properties of other unreacting ligands in complexes also play a role either inhibiting the insertion by spatial hindrance161 or making unfavorable coordination of CNR147 that precedes the insertion. The role of electronic effects on the insertion is less obvious than that of steric effects. Thus, one group158 states that the increase of electron density on a metal center facilitates the insertion, while the opposite finding was reported by another group.162 We anticipate that most likely both groups are right despite the obtained contrasting results. Actually, the insertion involves the neutral isocyanide and anionic ligands, and, therefore, electronic effects on the insertion could be opposite depending on the nature of a metal center and its ligand environment.

3. INSERTIONS OF CNR SPECIES INTO METAL−ELEMENT BOND 3.1. General Consideration of the Metal-Mediated Insertions

3.1.1. Background. Undoubtedly, the most common reaction of isocyanides involving metal centers is the insertion into a metal−element bond (Scheme 38). In the literature, this Scheme 38. Insertions of CNR and CO into a Metal−Element Bond M−Xa

a

X is an anionic ligand.

process is named in different ways, insertion (a term that will be used in this Review), 1,1-insertion, migratory insertion, and also isocyanide migration. The reasons for the different terminology are considered below in the discussion of the insertion mechanisms. The CNR insertions are important not only in the chemistry of transition metal complexes for production of libraries of various organometallic compounds, but also in organic synthesis. Furthermore, these reactions comprise an intermediate stage in many metal-catalyzed processes, such as the generation of azaheterocyclic systems or polymerization of CNR species (section 3.3.8.2). Basic driving forces for isocyanide insertions are similar to those established to the well-studied insertions of CO into metal−element bonds (Scheme 38) insofar as isocyanide and carbon monoxide ligands are isoelectronic. Another group of ligands relevant to isocyanides is nitriles. However, insertions of NCR into a metal−element bond, as compared to insertions of CNR species (see, for example, articles and reviews12,134−146) are observed much less often, and, when it does occur, it leads to 1,2insertion products. 3.1.2. Primary Insertion Products. Usually, the insertion results in generation of metal-bound η1- or η2-imidoyl (or, in other words, iminoacyl) ligands whose binding modes depend on the nature of metal centers (Scheme 38). Inspection of both experimental and relevant theoretical reports suggests that the early transition metals usually favor the η2-coordination, which is related with lesser valence electrons at these metal centers and, appropriately, with more pronounced tendency for binding η2-4electron ligands. It should be noted that in the vast majority of cases, acyl ligands, formed by the CO insertion into an early transition metal−element bond, are also η2-coordinated.147 However, for imidoyl ligands, this coordination pattern is, in general, more common because of the greater basicity of the N relative to the O atom. Late transition metals (group 8−10 metals) usually favor the η1-coordination of imidoyl ligands. If CNR inserts into a M−vinyl bond, the resulting α,β-unsaturated imidoyl ligand is able to form the η3-coordination mode by the three C atoms.142 Q


Chemical Reviews

Review

Scheme 39. Mechanisms of CO and CNR Insertions

Scheme 40. Double and Multiple Insertions of Isocyanides into a Metal−Element Bond

(CNR)n−C oligomers and polymers is quite common for the isocyanide chemistry (Scheme 40).13,14,149,173−176 It is worth mentioning that disagreements between the terms double insertion and bis-insertion are not unusual. In this Review, under “double insertion” we understand insertion of two CNR species into one M−X bond, while the bis-insertion means insertion of two CNR species into two M−X bonds (Scheme 41).

3.1.5. Insertion Mechanisms. Insertion of isocyanides into M−X bonds mainly proceeds through initial coordination of the carbon lone pair to a metal center followed by a rapid insertion into the adjacent metal−carbon bond. In contrast to the CO insertion, whose mechanism involves anionic ligand migration to the C atom of carbon monoxide ligand, the CNR insertion usually occurs as the true insertion of the isocyanide C atom into a M−X bond (Scheme 39). This general principle is supported experimentally, for a Co complex,163 and confirmed theoretically, for Ti and Zr,147 Ta,164 and Pt.165 Although mechanisms for CO and CNR insertions are different, some authors, based upon the analogy between CO and CNR ligands and without studying the mechanism, apply the generic terms “migratory insertion” or simply “migration” to isocyanide species. 3.1.6. Reversibility of Isocyanide Insertion. Insertions of both CO and CNR ligands are reversible, and in both cases the major driving force of the direct reaction is the favorable enthalpy change due to formation of a C−X bond in newly formed acyl or imidoyl ligands. In the case of the CNR insertion, some experimental data favor the insertion reversibility,166 but the equilibrium of this reaction is substantially more shifted to the reaction products than in the case of the CO insertion (see, e.g., refs 147 and 167). To the best of our knowledge, no report of the reversing of the isocyanide insertion, even under drastic conditions, has been published to date,168 although an interchange between the coordinated and the inserted CNBut162 or CNXyl ligands169 has been observed by Vicente and colleagues who, as a possible rationale of this phenomenon, proposed extrusion of an inserted isocyanide. One should notice that this extrusion has precedents in the chemistry of metalbound NCR species.170,171 If both CNR and CO ligands are bound to the same metal center forming ArM(CNR)(CO) species (M = Ru), isocyanide undergoes the insertion, while carbon monoxide remains intact.172 This selective isocyanide insertion is rationalized by the stronger CO bond in carbon monoxide than the CN bond in isocyanides. Thermodynamics also explain why the double insertion into M−C bonds, accomplishing M−CO−CO−C moieties, is not characteristic for carbon monoxide. On the contrary, the double or even multiple insertion giving M−

Scheme 41. A Simplified Scheme Indicating the Difference between Double- and Bis-insertion

3.1.7. Previous Reviews on Isocyanide Insertions. The broad area of isocyanide insertion into particular M−element bonds was previously covered in a number of reviews10−14,29−35 published over the years (Table 2). In particular, a recent article by Qiu, Ding, and Wu12 (Table 2, entry 13) is devoted to isocyanide insertions with a particular emphasis on the C− element (C−O, C−S, C−Si, C−H) reactions known in metalfree organic chemistry. Less attention is given to metal involving reactions (40 refs for publications on the subject since the year 2000). Moreover, in the overwhelming majority of cases, this subject is limited to palladium-catalyzed organic synthesis that is also discussed in reviews by Lang10 (Table 2, entry 11) and Orru et al.11 (Table 2, entry 12) published almost simultaneously with the survey by Qiu et al.12 In this Review, all noncatalytic CNR insertions published after the year 2000 will be treated comprehensively, while examples of palladium-catalyzed organic transformations will be inspected selectively and restricted to studies published after the appearance of the two reviews discussed in the previous paragraph. Importantly, our consideration will not simply focus on encyclopedic listing of the available data. Instead, we shall aim R


Chemical Reviews

Review

Scheme 45. Insertion of CNBut into Ln−H Bonds of 95

to analyze the major driving forces and mechanisms of the insertion, which are certain to facilitate and stimulate further research activity in this field. The classification of the section is based upon the type of anionic ligands X− (Scheme 41) followed by division by metal group in the Periodic Table. Isocyanides insert into M−M or M−M′ bonds giving bridged μ2-CNR ligands (Scheme 42) and also into MC carbene Scheme 42. Insertion of an Isocyanide into a Metal−Metal Bond That Could Also Be Treated as Coordination

Scheme 43. Insertion of an Isocyanide into M−Carbene Bond That Could Also Be Treated as Cycloaddition

Hydrozirconation of three isocyanides takes place when a suspension of oligomeric hydrozirconation reagent 97 was treated with CNR (R = But, Cy, Xyl; Scheme 46).179 The alkyl Scheme 46. Insertion of CNR into the Zr−H Bond

bonds furnishing metallacyclopropanes (Scheme 43). These two reactions could formally be classified as coordination and cycloaddition, respectively, but as they are relevant to the isocyanide insertion into M−X bonds, these processes are also considered in the end of this section.

isocyanides react at RT for 1 h in benzene to furnish 98 (Figure 13); CNXyl is the least reactive species of this series, and its insertion requires heating at 50 °C for 3 h.

3.2. Metal−H Bond

Isocyanide insertions into M−H bonds are not widespread, but it is still well documented that transition metal hydrides react with isocyanides forming mainly η1- or η2-formimidoyl complexes. Although isocyanide insertions into terminal M−H bonds are known, these reactions in the most reported cases involve bridged hydride species, M−(μ-H), and insertions usually occur under mild conditions. Most likely, CNR easily splits the M(μH)M bridge forming M(H)(CNR) species followed by the insertion giving formimidoyl complexes. It is noteworthy that often the insertion into a M−H bond (see below) is preferable when a metal center, apart from M−H, has other bonds such M− C, M−N, M−P, M−O (see below). In this section, consideration will follow increasing group number for any particular metal center in the Periodic Table. The isocyanide CNBut inserts into the Y−H bonds in bridged hydride complex 93 at RT in a toluene solution to form η2-Nalkylformimidoyl complex 94 in excellent yield already after 10 min (Scheme 44).177 The same isocyanide, CNBut, inserts readily into the Ln−H bonds (Ln = Y, Er, Gd) of organolanthanide hydrides 95. This reaction proceeds at RT in THF solution giving 96 that bears the bridging μ-(N-alkylformimidoyl) species (Scheme 45).178

Figure 13. View of the molecular structure of 98 (R = But) as a representative example of complexes derived from the isocyanide insertion into M−H bonds. Thermal ellipsoids are drawn at the 30% probability level.

Addition of either 1 equiv or an excess of CNBut to zirconium hydride complex 99 brings about the formation of rather unstable insertion product 100 (toluene, RT, 30 min, 53%; Scheme 47)180 that was characterized by 1H and 13C NMR spectroscopy. This compound easily decomposes at ambient temperature in the solid state or in a solution over a few hours to give an intractable mixture of products.

Scheme 44. Insertion of CNBut into the Y−H Bond of 93

Scheme 47. Insertion of CNBut into the Zr−H Bond

S


Chemical Reviews

Review

formimidoyl complex 109 obtained in ca. 40% yield (Scheme 51). Further addition of CNBut to 109 was studied by 1H NMR spectroscopy in C6D6, and it led quantitatively to 110. Complex 110 was found to be unreactive toward excess CNBut. When 108 was allowed to react with slightly more than 3 equiv of CNBut, 110 was isolated as pale yellow crystals in 62% yield. Compound 111 featuring the Mo−Mo unit reacts with CNBut accomplishing μ-η2-formimidoyl derivative 112 (THF, RT, 85%; Scheme 52)185 that was characterized by microanalyses, IR, and NMR spectroscopies. Another Mo2 complex, but having the MoMo triple bond, 113, reacts at RT with CNBut giving insertion product 114 (Scheme 53; yield is not given)186 featuring the formimidoyl ligand HCNBut. An X-ray diffraction study of the But derivative of 114 revealed that this ligand displays η2-bridged coordination mode. The replacement of molybdenum with tungsten affects significantly the reactivity of similar dinuclear species and the nature of the corresponding isocyanide derivatives.187 The addition of 1 equiv of the isocyanide to ditungsten hydride 115 (Scheme 54) yields, in all cases, formimidoyl intermediates 116. The latter species are kinetic products, which than rearrange to more stable (in accord with the DFT calculations) bridged isomers. These reactions take place rapidly in CH2Cl2 solutions producing two types of bridged formimidoyl derivatives, symmetrical 117a,b (RT, 1 min, 93−96%, Figure 14) or asymmetrical 117c (0 °C, 45 min, yield not given) complexes. While compounds 117a,b are stable in solution at RT, 117c underwent isomerization at RT furnishing aminocarbyne 118 (toluene, 90 °C, 4 h, 79%). The reaction of 115 with excess CN(4-MeOC6H4) gave aminocarbene-iminoacyl complex 119 (CH2Cl2, RT, 1 h, 62%; Scheme 55) derived from the N−C coupling of the formimidoyl and isocyanide ligands, whereas the analogous reaction with CNXyl accomplished aminocarbyne complex 120 (CH2Cl2, RT, 1 h, 90%) having the terminal bent isocyanide ligand. Treatment of a benzene solution of silylimide tungsten hydride 121 with CNBut (2.2 equiv) for 1.5 h at 23 °C leads to generation of 122 in 62% yield (Scheme 56).188 In this case, the complexed HCNBut exhibits the η1, rather than the η2coordination pattern. η1-Coordinated formimidoyl ligand in 124 forms upon the insertion of CNBut into the Ru−H bond of 123 (toluene, 25 °C, Scheme 57).189 The authors noted that satisfactory separation of 124 was not achieved, but 124 appeared to be reasonably longlived in solution at RT, and it was characterized by 31P, 1H, and 13 C NMR spectroscopy, but the yield was not established. Generally group 9 and 10 metal hydrides react with CNR species to form rather labile formimidoyl complexes. In many instances, these species undergo further transformations that are accompanied by liberation of the newly formed ligand. Hence, these processes are applied in metal-catalyzed systems. In particular, Hirai and Han reported a direct and selective palladium-catalyzed synthesis of α-iminophosphine oxides 125 and rhodium-catalyzed formation of bis-(diarylphosphinoyl)aminomethanes 126 (Scheme 58).190 In case of 125, the reaction between Ar2P(O)H (Ar = Ph, 4-CF3C6H4, 4-ClC6H4, 4MeOC6H4) and CNR (R = Xyl, 4-(Et2N)C6H4, Cy, ButCH2C(Me)2) is catalyzed by Pd2(dba)3,191 and the reaction proceeds in a toluene solution at 60 °C for 12−24 h accomplishing 125 in 70−99% yields. The proposed mechanism includes the isocyanide insertion into the Pd−H bond of hydride palladium complex 127 (Scheme 59).

Interaction of a benzene solution of tantalum hydride 101 with CNXyl proceeds at RT for 14 h and accomplishes insertion product 102 that was isolated in 77% yield (Scheme 48).181 Scheme 48. Insertion of CNXyl into the Ta−H Bond

The 1H and 13C NMR spectroscopy data favor the η2coordination mode of the formimidoyl ligand. Reaction of 103 with 1 equiv of CNBut gave complex 105 featuring the tantallaziridine moiety (CH2Cl2, from −98 °C to RT over 1 h, then 15 min at RT, 50%; Scheme 49).182 It is believed that the reaction pathway includes generation of intermediate 104 resulting from insertion. Scheme 49. Insertion of CNBut into the Ta−H Bond

A similar reaction of 106 bearing the tridentate [OSO]-type ligand brings about generation of tantallaziridine species 107 (C6D6, RT, immediate reaction, 100%; Scheme 50).183 The increased reactivity of the Ta−(μ-H) bond toward CNR in comparison with a Ta−C bond was observed by Kawaguchi and colleagues.184 In accord with their report, treatment of 108 with 1 equiv of CNBut in THF yielded, after workup, Scheme 50. Insertion of CNR into the Ta−H Bond of 106

T


Chemical Reviews

Review

Scheme 51. Insertion of CNBut into the Ta−H Bond

Scheme 52. Insertion of CNBut into the Mo−H Bond of 111

Scheme 53. Insertion of CNBut into the Mo−H Bond of 113

Scheme 54. Insertion of CNR into the W−H Bond of 115 Figure 14. View of the molecular structure of 117a as a representative example of symmetrical bridged formimidoyl derivatives. Thermal ellipsoids are drawn at the 50% probability level.

Although the rhodium-catalyzed reaction (Scheme 58; X = Cl, Br, I) was thought to proceed in a similar way, it requires higher temperature and longer reaction time (80 °C, 4 d) and gave bisphosphinoyl product 126. 3.3. Metal−C Bond

3.3.1. Reactions of Group 3 Metal Complexes. 3.3.1.1. Scandium. Mindiola et al. reported192 that CNXyl inserts into the Sc−C bond of the pincer-like aryl complexes (128 and 131, Scheme 60) to generate iminoacyl species 129 and 132, respectively. These complexes are involved in further transformations forming an unusual indoline scandium species after reaction with another isocyanide molecule (Scheme 60). Thus, treatment of U


Chemical Reviews

Review

coordination of the pyridine moiety and ring expansion, (C) intramolecular cyclization, and (D1) [3,5]-migration of the Me carbocation giving 130 (in the first case). For 132, no Me migration occurs and the process stopped at 133 (A−D2, Scheme 61) probably due to the chelating effect of the CH NAr group or, in other words, entropic reasons.192 The same group also demonstrated that scandium imide complex 134 facilitates activation of the C−H bonds in pyridine and assists its functionalization with isocyanides at both 2- and 2,6-positions to give mono- and bis-iminosubstituted pyridines.192 The catalytic process proceeds at 90 °C (Scheme 62) and includes the insertion. In the case of Ar = Xyl, complex 128 (which is formed upon C−H activation) reacted with 2 equiv of CNXyl to give a mixture of products, thus preventing this substrate from entering the catalytic cycle. However, in the case of Ar = 2,6-Pri2C6H3, treatment of 128 with CNAr gave 135 that does not react with excess isocyanide under applied conditions, therefore implying that an ArNCHPy (Ar = 2,6-Pri2C6H3) could be prepared catalytically using pyridine as a substrate. 3.3.1.2. Lanthanides. Insertion of isocyanides into a M−C bond of rare earth metal acetylenides found an application in organic catalysis. Thus, Komeyama and colleagues193 described a coupling between various monoalkyl or monoaryl acetylenes and alkyl or aryl isocyanides that proceeds efficiently (53−95%) in the presence of the rare earth metal silylamide catalysts and npentyl amine (cyclohexane, RT, 24 h; Scheme 63). The proposed mechanism (Scheme 64) includes the isocyanide M−C monoinsertion during the main catalytic cycle and polyinsertion as a side-reaction. Bimetallic Y/Ru complex 138 bearing a bridging phosphinomethyl ligand interacts with CNBut via insertion of the isocyanide into the reactive Y−CH2 bond (C6D6, 20 °C, 64%) (Scheme 65).194 This reaction afforded complex 139 featuring a new ligand scaffold that includes a bridging (η2-iminoacetyl)phosphine ligand at the binuclear Y/Ru core. 3.3.1.3. Actinides. Coupling of isocyanides with terminal alkynes described above (see reactions of Lanthanides in this section) can be catalyzed by uranium and thorium species. Thus, complexes 140a−c catalyzed the coupling of isocyanide and terminal acetylenes via insertion of the isocyanide terminal carbon atom into a metal−acetylide or a metal−imine bond (Scheme 66; R1 = But, Pri, TMS, Ph; R2 = But, n-C5H11).157,195 The reaction proceeds in toluene or benzene at 90−100 °C in J. Young Teflon valve-sealed NMR tubes for 18−48 h.195 Thorium complex 140c exhibits the best catalytic activity; 1 mol % of this catalyst affords the coupling products, 1-aza-1,3-enynes (137), in 80−90% yields after 18 h. This reaction proceeds via an actinide−carbon bond formation followed by insertion of one (or more) molecules of the isocyanide into the An−C bond (Scheme 67). The authors argue157 that insertion of isocyanides is the ratedetermining step in the generation of 1-aza-1,3-enynes. Therefore, less sterically hindered n-pentyl isocyanide is more reactive than those with But or Pri. Evans et al.196−199 employed the isocyanide insertions into an U−C bond for generation of organometallic species, which were obtained in excellent yields and characterized by spectroscopic and X-ray data. Thus, treatment of monoaryl uranium(IV) complex 141 with CNBut in a toluene solution at RT for 1 d gives η2-imidoyl complex 142 (99%; Scheme 68).196 The reactivity of CNBut with the U−Calkynyl bonds in Cp*2U(CCPh)2 (143) was also studied.197 Only 1 equiv of CNBut undergoes insertion

Scheme 55. Reaction of Isocyanides with W2 Complex 115

Scheme 56. Insertion of CNBut into the W−H Bond of 121

Scheme 57. Insertion of CNBut into the Ru−H Bond of 123

Scheme 58. Metal-Catalyzed Reaction of the Isocyanides and the Diaryl Phosphine Oxides

Scheme 59. Postulated Mechanism for the R2P(O)H Addition to the Isocyanides

128 with 2 equiv of CNXyl (toluene, 70 °C, 12 h) leads to 130 (35%) that is formed via intermediate generation of 129 (Scheme 60).192 Similarly, complex 131 gives 133 (37%). NMR data indicate that iminoacyl complex 129 was formed quantitatively.192 It was isolated in 78% yield after treatment of 128 with 1 equiv of CNXyl at 90 °C. The proposed mechanism192 for generation of 130 and 133 from insertion products 129 and 132 includes (A) nucleophilic attack of the isocyanide at the acylimine carbon, (B) V


Chemical Reviews

Review

Scheme 60. Insertion of CNXyl into Sc−CAryl Bonds

Scheme 61. Proposed Mechanism for Generation of 130 and 133

interesting features of these dihaptoiminoacyl species was continued later by the same group.198 Heating a toluene solution of 146 at 110 °C for 12 h led to rearrangement affording generation of 147 (55%). In case of less hindered complex 148, spectroscopic and analytical data indicate that there is an initial insertion of one isocyanide to form iminoacyl complex 149 followed by coordination of second isocyanide to generate isocyanide adduct 150. After 12 h, another insertion occurs to form 151, and this complex was characterized by X-ray crystallography.199

into the U−C bond of 143 to yield iminoacyl uranocene 144 (Et2O, RT, 12 h, 97%). The isocyanide CNBut also reacts with the U−CAlkyl bonds of uranium(IV) complex 145197 giving bis(tethered iminoacyl) actinide metallocene 146 (Scheme 69; yield was not reported), in contrast to the monoinsertion that occurs with complex 143 (Scheme 68).197 The larger bond angles in 145 in comparison with Cp*2UR2 (143) appear to allow the bis-insertion in the isocyanide reaction, and this suggests that the tethered systems have the potential to deliver enhanced reactivity. The study of the W


Chemical Reviews

Review

Scheme 65. Insertion of CNBut into Y−CH2 Bond

Scheme 62. Catalytic Cycle of PyH Functionalization via the CNAr Insertion into the Sc−CAryl Bond

hindrance in the methyl titanium complex. However, slow reaction proceeded when 1 equiv of CNXyl was added to a toluene solution of 156 and heated at 75 °C for 1 d. The insertion into the Ti−Me bond initially gives iminoacyl complex 157 that inserts another CNXyl molecule into the Ti−NMe2 bond affording after the rearrangement 159 (Figure 15), which was the sole product when excess CNXyl (4 equiv) was added and the reaction mixture was heated at 120 °C for 1 d. Pure compound 157 could not be isolated, whereas 159 was isolated as a red crystalline solid (86%) and identified by elemental analyses, NMR spectroscopy, and X-ray crystallography (Figure 15). Otero, Fandos, and colleagues154 studied the different behavior of structurally similar complexes 160 and 162 upon their treatment with isocyanides. Thus, the insertion of CNBut into the titanium−carbon bond of 160 furnishes the iminoacyl derivative (161a) as the only product (53%; Scheme 73). In the same way, the reaction of CNXyl with 160 led to iminoacyl complex 161b, which was isolated in 71% yield. Surprisingly, complex 162 does not react with isocyanides at RT, and upon increasing the temperature only a mixture of its decomposition products was detected. The authors indicated the high kinetic inertness of the Ti−Me bond in 162 toward the insertion processes, but no further explanation was provided. Titanium(III) alkyl complexes are also reactive in the insertion (Scheme 74; R = Et, Bun, Bui, neo-C5H11, n-C6H13; R′ = But, Xyl).201 Isocyanides undergo the quantitative insertion into titanium−carbon bonds of the alkyl groups of 163 to provide good to excellent yields (47−96%) of the corresponding series of crystalline paramagnetic titanium(III) η2-iminoacyl derivatives 164. Azatitanacyclobutene complexes 165a,b were shown to undergo facile Ti−C bond insertions (Scheme 75). It allowed Mountford, Gade, and colleagues202 the synthesis (toluene, RT, overnight, quantitative yields) and full characterization of the intermediates of the three-component iminoamination of alkynes and yielding α,β-unsaturated β-iminoamines. The observed selectivity was rationalized after a DFT study, whose results indicate that the Ti−C bond is less stable than the Ti−N bond (E of the σ-NLMOTi−C = −8.4 eV; E of the σ-NLMOTi−N = −10.3 eV).

Scheme 63. Coupling between Terminal Alkynes and Isocyanides

3.3.2. Reactions of Group 4 Metal Complexes. 3.3.2.1. Titanium. An interaction of CNBut with titanium complex 152 was reported by Martins et al. (Scheme 70).150 The reaction was carried out in a C6D6 solution at RT for 4−5 min; the product was identified by 1H and 13C NMR spectroscopy. On the basis of NMR data, the isocyanide exclusively inserts into the Ti−C bond accomplishing η2-iminoacyl complex 153 with quantitative yield. Accordingly to DFT calculations, it is due to the weakness of the Ti−Me bond as compared to both Ti−NMe2 and μ-(η5-indenyl) bonds. The insertion of the CNH ligand, taken as a model for the DFT calculations, into the Ti−C bond is largely more favorable from a kinetic (Ea = 1.0 kcal/mol) as well as from a thermodynamic point of view (ΔE = −38.2 kcal/mol) than the insertion of CNH into the Ti−N bond (Ea = 7.9 kcal/ mol and ΔE = −26.6 kcal/mol). The same group also indicated the preference of the insertion into the Ti−C bond in titanium tris(ketimide) complex 154 to furnish 155 (Scheme 71).200 Facile isocyanide insertion into a Ti−Me bond was studied theoretically by De Angelis et al., who performed DFT calculations for the reaction of [calix[4]c(OMe)2(O)2TiMe2] and CNMe.147 The calculations disclosed that the ratedetermining step for the reaction is the coordination of CNMe to the electron-deficient titanium center, rather than the insertion into the Ti−Me bond. A higher reactivity of the Ti−Me bond as compared to the Ti− NMe2 bond in 156 (Scheme 72) was demonstrated by Royo and colleagues.151,152 Thus, no reaction was observed for 156 and CNBut because of the bulky character of the But group and spatial

Scheme 64. Proposed Mechanism of Rare Earth Metal-Catalyzed Generation of 1-Aza-1,3-enyne 137

X


Chemical Reviews

Review

Scheme 66. Coupling of Isocyanides with Terminal Alkynes Catalyzed by Actinide Species

Scheme 67. Plausible Mechanism of the Formation of 1-Aza-1,3-enynes 136 Including Byproducts

Scheme 68. CNBut Insertion into Different U−C Bonds of Uranium(IV) Complexes

Scheme 70. Insertion of CNBut into the Ti−C Bond of 152

Scheme 71. Insertion of CNMes into the Ti−C Bond of 154

Scheme 69. CNBut Insertion into the U−C Bonds of Uranium(IV) Complexes

Y


Chemical Reviews

Review

Scheme 72. Insertion of CNXyl into the Ti−C Bond of 156

Scheme 75. Insertion of the Isocyanides into the Ti−C Bond of Azatitanacyclobutene Complexes

(OMe)2(O)2ZrMe2] is reported in ref 147, and these characteristics were compared to those for the isoelectronic carbon monoxide. The rate-determining step is the coordination of CNMe (or CO, correspondingly) to the metal center. The insertion of CNMe leads to η2-bound iminoacyl ligand, formed via a labile η1-isomer. The much higher stability of the insertion product for CNMe as compared to that for CO is consistent with the broad experimental evidence that isocyanide deinsertion is an extremely rare process, while it is rather common for CO. A number of papers are devoted to steric aspects of the insertion into different hindered Zr−C bonds. Thus, Otero et al. reported insertions of a bulky isocyanide in alkylzirconocenes 170, bearing asymmetric ansa ligands, to yield η2-iminoacyl complexes 171 (THF, RT, 18 h, 75−84%) (Scheme 76; R = CH2Ph, CH2SiMe3; R′ = Me, Pri, SiMe3).203 Scheme 76. Reaction of CNXyl with 170 Figure 15. View of the molecular structure of 159 as a representative example of complexes originating from the consistent insertion into the Ti−Me and the Ti−NMe2 bonds. Thermal ellipsoids are drawn at the 50% probability level.

Scheme 73. Insertion of the Isocyanides into the Ti−C Bond of 160 In the subsequent work, the Otero group studied the reactivity of ansa-zirconocene dialkyl complexes 172, bearing the chiral carbon atom at the bridge (Scheme 77; R = Pri, Bun, But, Ph), Scheme 77. Reaction of CNXyl with Chiral Complexes 172

Scheme 74. Insertion of the Isocyanides into Ti−C Bonds of Titanium(III) Alkyl Complexes toward isocyanide insertion reactions conducted under the same conditions (THF, RT, 2 h).204 These complexes insert only one molecule of CNXyl to yield η2-iminoacyl methyl complexes 173 (79−86%). Dzhemilev and colleagues studied205 the CNCy insertion into the Zr−R bond of 174 that furnishes η2-iminoacyl complexes 175 (Alk = Et, 75%; Alk = Bun, 79%) formed at the same diastereomeric ratio as in the starting zirconocene alkyl chlorides (toluene, RT, immediate reaction; Scheme 78). Sita et al.159 reported the first example of insertion into a secondary alkyl group of an early transition metal complex that is

3.3.2.2. Zirconium. The main features of the isocyanide insertion into various Zr−C bonds agree well with those verified for Ti−C bonds. A summary of the energetics for coordination of CNMe and its insertion into the Zr−Me bond of [calix[4]cZ


Chemical Reviews

Review

monoaddition products or compounds derived from the insertion into the Zr−N bond were detected (Scheme 81).

Scheme 78. Reaction of CNCy with Chiral Complexes 174

Scheme 81. Reaction of the Dialkyl Zirconium Complexes with CNXyl

not stabilized by ancillary bonding interactions. The insertion of CNBut into the Zr−C bonds of 176 occurs in essentially quantitative yield (n-pentane, 25 °C, R = H, Me) and gives the corresponding η2-iminoacyl complexes 177 (Figure 16), where the secondary alkyl group structure was preserved (Scheme 79). Royo and colleagues also compared isocyanide (CNXyl, CNBut) insertions into the Zr−Me and Zr−CH2Ph bonds of complexes 182a,b (Scheme 82).151 The Zr−CH2Ph bond is sterically more protected and less reactive than the Zr−Me bond. Therefore, only CNXyl reacted with 182a, and the reaction proceeds at rather high temperature (60 °C, 4 h, 86%) in toluene. The steric hindrance of the more sterically encumbered CNBut isocyanide may explain the absence of reaction with the benzyl zirconium complex. The Zr−Me bond in 182b interacts with both isocyanides, but CNXyl reacts at RT (12 h, 93%) and CNBut only at 50 °C (12 h, 91%). The authors also compared Ti−C and Zr−C bond reactivities in the isocyanide insertion reactions (Schemes 72 and 82).151,152 The Zr−C bond is more reactive because methyl zirconium complex 182b interacts with CNXyl at RT and with more hindered CNBut (at 50 °C for 12 h), whereas the corresponding methyl titanium complex 156 reacts only with CNXyl at 120 °C (Scheme 72). The authors argue that the lack of reactivity of the benzyl titanium complex in comparison with the higher reactivity observed for the zirconium derivative demonstrates that these insertion reactions are sterically controlled. The reactivity of triamidoamine-supported zirconium complex 184 was examined toward a variety of small and polar substrates including, in particular, CNBut (Scheme 83).207 The observed insertion into the Zr−C bond of 184 is facile and produces one atom ring-expanded product 185 (benzene, 12 h, 82%), whereas the Zr−N bonds remain intact. The reaction of CNBut with the cyclobutylene-bridged bis(cyclopentadienyl) (186)- and bis(2-indenyl) (187)-zirconocene dimethyl and diphenyl complexes was conducted in a toluene solution under kinetically and thermodynamically controlled conditions (Scheme 84).208 The reaction of zirconocene complexes 186 or 187 with CNBut was carried out at −78 °C in toluene-d8; it is kinetically controlled and leads to insertion products 188 and 189, respectively. When the reaction is thermodynamically controlled (RT, from 10 min to 1 h), each of the complexes reacts cleanly to give a monoinsertion product (190 or 191) as a mixture of two stereoisomeric (syn- and anti-, the ratio varies from 1:2 to 2:1 depending on the starting complex; overall yields 56−70%). The authors determined the activation parameters for the intramolecular rearrangement of the kinetic “N-outside” (188, 189) to the thermodynamic “N-inside” (190, 191) η2-iminoacyl metallocene isomers in the temperature range from −70 to −19 °C. The rearrangement of the “N-outside” to “N-inside” isomers of the cyclobutylene bis(cyclopentadienyl)Zr-(η2-iminoacyl) systems (188-syn/anti to 190-syn/anti) is much faster than the one for the corresponding bis(2-indenyl) species (189-syn/anti to 191-syn/anti). The authors assume that it is probably due to

Figure 16. View of the molecular structure of 177 (R = H) as a representative example of η2-iminoacyl complexes. Thermal ellipsoids are drawn at the 50% probability level.

Scheme 79. CNBut Insertion into the Secondary Alkyl Zr−C Bonds

The reaction of dialkyl complexes 178 (R = Me, CH2Ph, CH2SiMe3) with 1 equiv of CNXyl at RT (5 h) in Et2O gave the corresponding iminoacyl compounds (87−91%).160 The insertion proceeds easier for less bulky alkyl ligands following the order Me > CH2Ph > CH2SiMe3. Diastereoselective insertion into the less hindered Zr−R bond was observed (Scheme 80). The same authors reported206 that exclusively bis(iminoacyl) complexes 181a,b (a, R = Me, 3 h, 80%; b, R = CH2Ph, overnight, 65%) could be isolated when dialkyl zirconium species 180 were treated with CNXyl in toluene at RT. Under these conditions, no Scheme 80. Diastereoselective Insertion into the Zr−C Bond

AA


Chemical Reviews

Review

Scheme 82. Zr−Me versus Zr−CH2Ph Bond at the Isocyanide Insertions

were formed, and these species could be considered as enediamido complexes. With regard to the mechanism, it is not clear if a (2−3η)butatriene complex (metallacyclopropane) or the internally η2complexed alkyne (zirconacyclopropene) is reacting directly. The fact that typical zirconacyclopropenes do not insert isocyanide molecules into their Zr−C bonds is contradictory to the latter suggestion. Thomson and Schafer studied the reaction of zirconium dibenzyl complex 194 with two isocyanides, CNXyl and CNBut (Scheme 86).167 The bis-insertion of CNXyl was observed for 194, resulting in the η2-iminoacyl complex 195 (toluene, RT, few minutes, 52%). The latter undergoes thermal coupling to form enediamido species 196 (toluene, 110 °C, overnight, 81%). Insertion of CNBut leads to vinylamido complex 198 (toluene, RT, almost immediately, 86%), which is presumably generated from a transient η2-iminoacyl intermediate (197) via a 1,2hydrogen migration. The inability to controllably insert 1 equiv of the isocyanide is indicative, as the authors believe, of the extremely electrophilic nature of 194. Dibenzylzirconium(IV) complexes 199 and 201 bearing asymmetric guanidinate ligands and their different reactivity toward the insertion of CNXyl were studied (Scheme 87).161 Thus, more hindered complexes 199 are only involved in a single insertion to yield 200 (a toluene solution, 50 °C, 16 h, 89% and 91% yields), whereas 202 (95%) is obtained by reaction with both Zr−C bonds in 201 (toluene, RT). These results indicate that steric effects resulting from the coordination mode of the guanidinate ligands play a decisive role in the insertion of the aryl isocyanide. Some reports were devoted to syntheses of organic compounds via reactions of isocyanides with complexes featuring Zr−C bonds. In particular, Whitby and colleagues described that the insertion of cyclopropyl carbenoids into alkenylzirconocenes gives allylzirconium species, which react with protons and isocyanides to afford alkenylcyclopropanes (Scheme 88).210 Thus, the insertion of CNBun into norcarane-allyl-zirconocene 203 occurred stereo- and regioselectively to give aldehyde 205 after the acid-catalyzed hydrolysis. Later, the same group extended this method onto zirconocycles 206−208 (Scheme 89).211 The insertion of CNBut into the Zr−C bonds of the cycles in a THF solution at 0 °C for 30 min followed by the hydrolysis with 2 M aq HCl (RT, 1 d) afforded aldehydes 209−210 in moderate yields (48−56%), while aldehyde 211 (31%) was isolated in poorer yield because of the concomitant generation of ketone 212 (30%). Remarkably, the selective insertion into the more hindered side of α-substituted system 206 occurred, and the regiochemistry is consistent with the mechanism suggested in Scheme 90. Zirconocene-mediated multicomponent coupling of silicontethered diynes, nitriles, and isocyanides leads to azaindoles or dihydropyrrolo[3,2-c]azepines.212 The overall process proceeds via mono (in case of the sterically encumbered CNBut) or double (for the less sterically hindered CNCy and CNXyl) isocyanide

Scheme 83. Zr−C versus Zr−N Bond at the Isocyanide Insertion in 184

Scheme 84. Kinetic and Thermodynamic Controls in the Reaction of 186 or 187 with CNBut

steric hindrance in the corresponding transition states by building up unfavorable interactions between the large rotating σ-moieties and the covering phenylene groups of the indenyl ligands of the rigid bent metallocene frameworks. The isocyanide CNBut undergoes the insertion into 1zirconacyclopent-3-ynes 192a−c to furnish substituted 1zircona-2,5-diazacyclopent-3-enes with an anellated cyclobutene (193a−c) (Scheme 85).209 In the first step (toluene, 50 °C, 12 h), 2 equiv of CNBut was inserted into the Zr−C bonds of the zirconacycle. After subsequent rearrangement, the corresponding substituted 1-zircona-2,5-diazacyclopent-3-enes (193a−c) Scheme 85. Bis-insertion of CNBut into the Zr−C Bonds of 192a−c

AB


Chemical Reviews

Review

Scheme 86. Bis-insertion of CNRs into the Zr−C Bonds of 194

toluene solution of 218 at RT to generate 220a or 220c, correspondingly, in more than 90% yields. Rosenthal et al. demonstrated a double insertion of CNBut into the Hf−Cfulvene bond of complex 221 (Scheme 94).209 The reaction proceeds in an n-hexane/THF (10/1) solution at RT for 16 h and gives 222 in a rather low yield (29%). The structure of 222 was verified by X-ray crystallography. Unfortunately, the authors do not discuss chemoselectivity, and the question why do CNRs choose the Hf−C bond for the insertion remains unanswered. Waterman and Don Tilley compared the isocyanide insertion into Hf−C and Hf−P bonds.214 Thus, treatment of phosphide methyl complex 223 with CNXyl (benzene, RT) afforded the Hf−C bond insertion product 224 isolated in 92% yield, whereas the Hf−P bonds in both 223 and 225 remain intact under these conditions (Scheme 95). 3.3.3. Reactions of Group 5 Metal Complexes. Although reactivity of niobium and tantalum complexes featuring Nb−C and Ta−C bonds toward isocyanide insertion seems to be similar, usually these reactions are studied separately for niobium and tantalum species. Only a few reports are devoted to reactions of both Nb and Ta complexes with CNRs. In particular, new iminoacyl derivatives of dinuclear niobium and tantalum imido complexes are formed via isocyanide insertions to the alkyl precursors215 (Scheme 96). Thus, the reaction of alkyl dinuclear bis(imido) complexes 225 with CNXyl gives dimers 226 (M = Nb, Ta, R = CH2SiMe3, C6H4 = 1,3-C6H4; 1,4-C6H4; hexane, RT, 20 min, 72−78%) that originate from the insertion of four CNXyl molecules into the M−C σ-bonds at both metal centers of 225. There was no evidence for the formation of the product derived from the insertion of one CNXyl on each metal center or two CNXyl on one metal center, even when the reaction was carried out in deficiency of the isocyanide. In a relevant reaction, half-sandwich complexes 229 (R = Me, CH2Ph, CH2SiMe3, C6H4 = 1,3-C6H4; 1,4-C6H4; 91−94%) and 230 (C6H4 = 1,4-C6H4; 49%) were prepared via the insertion of CNXyl into Nb−C bonds of alkyl precursors 227 and 228, respectively (hexane, RT, 20 min). Attempts to insert the second isocyanide on any of the metal centers of 227 and 228 failed. The reactions of trialkyl imido compounds 231 (R = Me, CH2CMe3, CH2CMe2Ph, CH2Ph, CH2SiMe3) with 2 equiv of CNXyl bring about the insertion into the two metal−alkyl bonds, and this synthesis furnishes a series of alkyl imido bis(iminoacyl)

Scheme 87. Insertion of CNXyl into the Zr−C Bonds of 199 and 201

Scheme 88. Functionalization of Norcarane-allyl-zirconocene 203

insertion into the Zr−C bond of zirconocyclic intermediates 213 (benzene, RT, 1 h; Scheme 91). Iminoacyl complexes 214 and 215 were isolated in good yields and identified, whereupon they were successfully converted in the next step of the multicomponent coupling. 3.3.2.3. Hafnium. Royo and colleagues found206 that dialkylhafnium complexes 216 react easily with CNXyl, similarly to dialkyl zirconium complexes 180 (see above), giving only the bis(iminoacyl) complexes 217 (toluene, RT, 70−80%; Scheme 92). Hafnium complex 218 reacts immediately in a toluene solution at RT with 1 equiv of CNXyl to give monoinsertion product 219 (Scheme 93)213 that was isolated and characterized. The structure of 219 was established by 1H (including NOE method) and 13C NMR, and IR spectroscopies. Addition of a second equivalent of CNXyl or CNPri to 219 at RT results in the exclusive formation of the bis(η2-iminoacyl) products 220a and 220b, respectively. Finally, the bis(iminoacyl) complexes were prepared by addition of 2 equiv of CNXyl or CNPri to the AC


Chemical Reviews

Review

Scheme 89. Functionalization of Zirconocycles 206−208

Scheme 90. Plausible Mechanisms of the Insertion

Scheme 91. Mono or Double Isocyanide Insertion into the Zr−C Bonds of 213

An equimolar amount of CNXyl reacts with olefin−hydride complex 233 (Scheme 98) at RT to form initially ethyl isocyanide derivative 234a, which evolves rapidly at RT with the insertion of the second isocyanide into the Nb−C bond to yield iminoacyl compound 235a. Compound 234a could not be isolated in pure form, but as a part of a mixture with 233 and 235a. However, 235a could be prepared and isolated as an individual compound by the reaction of 233 with 2 equiv of CNXyl (hexane, RT, 16 h, 90%). The reaction of CNBun with

derivatives 232 (anhydrous toluene, RT, 12 h, 77−84%; Scheme 97).216 All 13C and 15N NMR data are consistent with an iminoacyl ligand η1-C bound to Nb or Ta metal centers, which corresponds to a pseudo tetrahedral geometry of 232. 3.3.3.1. Niobium. Otero and colleagues reported the synthesis and characterization of new allylniobocene complexes and studied their reactivity as well as the reactivity of the olefinhydride species toward aliphatic and aromatic isocyanides217 (Schemes 98, 99). AD


Chemical Reviews

Review

Scheme 94. Double Insertion of CNBut into the Hf−Cfulvene Bond of 221

Scheme 92. Reaction of the Dialkylhafnium Complexes with CNXyl

Scheme 95. CNXyl Insertion into the Hf−C Bond of Phosphide Methyl Complex 223

233 also gave a mixture of products, alkyl compound 234b and iminoacyl complex 235b. With an excess of CNBun, further reactions gave a mixture of unidentified products. The isocyanide CNBut promotes the insertion of the olefin into the Nb−H bond of 233, giving 234, and no further reaction was observed even with an excess of isocyanide or when the reaction was performed at higher temperatures. In the case of allylniobocene derivatives 236 (Scheme 99), even at 80 °C the reaction with CNBut was not observed. Nevertheless, the complexes rapidly reacted with CNBun giving mixtures of unidentified products. Complex 236b reacts with 2 equiv of CNXyl at RT to give initially η1-allyl isocyanide derivative 237b, which undergoes an insertion reaction of another CNXyl furnishing iminoacyl derivative 238b (16 h, 85%). In contrast, 236a did not react with CNXyl at RT, and the reaction had to be carried out at 80 °C to obtain the corresponding η1-iminoacyl compound 238a (90%). Under these conditions, the corresponding intermediate η1-allyl derivative 237a was not detected. However, the reaction of 237a, obtained by a distinctive synthetic route, with an equimolar amount of CNXyl gives iminoacyl complex 238a. Comparison between reactivity of tert-butylimido and polyhedral oligomeric silsesquioxane (POSS) niobocene alkyl derivatives in the insertion processes was undertaken (Scheme 100).218 Although alkylimido compounds 239 react with CNXyl to give expected iminoacyl derivatives 240 (hexane or C6D6, RT, 1 h, 69−86%), as a result of an insertion, the reaction of alkylsilsesquioxanyl complex 241 leads to azaniobacyclopropane 242 (hexane, RT, 30 min, 80%), whose formation involves insertion of the isocyanide into one Nb−methyl bond to give an iminoacyl intermediate, followed by nucleophilic attack of the second methyl group on the iminoacyl carbon atom to give the imine ligand. Isocyanide phosphido complexes 243a−c (a, R = H; R′ = CO2Me; b, R = Me; R′ = CO2Me; c, R = R′ = CO2But) were treated with such alkynes as methyl propiolate, methyl 2butynoate, or di(tert-butyl) 2-butynedioate, and this reaction furnishes unusual heteroniobacycles 245a−c (THF, 0 °C, 10

min, 80−85%; Scheme 101).219,220 The DFT calculations indicate that the generation of 245 could be understood in terms of the mechanism depicted in Scheme 101. The first step involves a 1,2-insertion of the alkyne into the Nb−P bond to give phosphinoalkenyl species 244a−c. In the second step, which occurs in the reaction with both polarized and electron-poor alkynes, a new intermediate is formed by insertion of the isocyanide ligand into the Nb−C bond; the latter subsequently undergoes ring closure by coordination of the phosphine group. The insertion reactions of new monoguanidinate-supported dibenzyl niobium complexes 246 (R = But, Br, MeO) and 247 with isocyanides were studied (Scheme 102).221 The reaction of 246 and 247 with CNBut conducted in an NMR tube accomplishes 248 and 249, respectively, rapidly and in almost quantitative yield. On a preparative scale, the products were synthesized in a toluene solution at RT for 10 min and isolated in 38−51% yields. The analogous reaction with CNXyl, taken instead of CNBut, results in 250 and 251 generated via a proposed 1,2-hydrogen shift from an iminoacyl intermediate that is structurally similar to those obtained from the insertion of CNBut (Scheme 103). The mixture of the dibenzyl niobium complex and CNXyl in an NMR tube was transformed (50 °C, 16 h; ca. 100%) into a single product 250. In the case of 247, however, a 1:1 mixture of isomers was obtained. In preparative scales, the products were obtained in a toluene solution at 50 °C for 16 h (38−43%). 3.3.3.2. Tantalum. The insertion of the isocyanides CNR′ at RT occurs slowly and selectively into the Ta−CH2 bonds of

Scheme 93. Reaction of Hafnium Complex 218 with CNR

AE


Chemical Reviews

Review

Scheme 96. Reaction of the Dinuclear Nb−Alkyl and Ta−Alkyl Complexes with CNXyl

Scheme 100. Reactivity of tert-Butylimido and POSS Niobocene Alkyl Derivatives toward CNXyl

Scheme 97. Reaction of the Trialkyl Imido Nb and Ta Species with CNXyl

Scheme 98. Reaction of the Olefin−Hydride Nb Species with CNR

zwitterionic species 252 to form N-out isomers 254 as the only kinetic products (THF, 1−2 h, 83−91%; Scheme 104).158 By comparison, insertion of the same isocyanides into a Ta− Me bond of nonzwitterionic analogues 253 occurs much more rapidly, again to form N-out isomers 255, and this process is kinetically controlled (−78 °C up to RT, THF or CH2Cl2, 30 min, 79−89%). The difference in the rates is attributed to the

presence of a ground-state α-agostic interaction in the zwitterionic compounds that could not be realized in the dimethyl complex. All of the N-out isomers formed undergo thermal and irreversible conversion to the corresponding N-in isomers 256 and 257 (THF or CD3CN, 65−110 °C, 61−91%). Kinetic studies indicated that the rate is decreased as the steric

Scheme 99. Reaction of the Allylniobocenes with CNXyl

AF


Chemical Reviews

Review

Scheme 101. Reactions of Alkynes with Phosphido Niobocenes Bearing the CNXyl Ligand

Scheme 102. Reactions of the Guanidinate-Supported Dibenzyl Niobium Complexes with CNBut

Similarly, the reaction of dimethyl complex 261 with 1 equiv of CNXyl produces alkenylamido imido methyl derivative 262, which, with one additional equivalent of the isocyanide, gives imido η2-iminoacyl methyl compound 263 (Scheme 106). Dichloro complex 264 reacts with 1 equiv of CNXyl or CNBut in toluene giving a mixture of dichloro(imido) tantalum complex 266 and the s-trans-vinylazacumulenes formed in a 1:1 ratio (Scheme 107). The generation of these compounds probably takes place via the ligation of the isocyanide to the metal center of 264 followed by the insertion of the new ligand into the Ta− C(sp2) bond. Resulting metallacyclic species 265 transforms into dichloro(imido) complex 266 and the s-trans-vinylazacumulenes by a formal retro cycloaddition. Alkyl complexes 267a−c (a, R = X = Me; b, R = X = CH2Ph; c, R = CH2Ph, X = Cl) immediately reacted at RT with 1 equiv of CNXyl furnishing η2-iminoacyl compounds 268a−c by insertion of the CNXyl ligand into the Ta−C bond (toluene, RT, 1 h, 87− 91%; Scheme 108),223 and further insertion was not observed. The reaction of monocyclopentadienyl Ta complex featuring an auxiliary dialkoxide ligand (269) with CNXyl yields dicationic aminocarbene complex 271 (toluene, RT, 5 d, 31%) instead of the expected neutral insertion product (Scheme 109).155 The authors assume that the reaction proceeds through initial displacement of the triflate ligand by the isocyanide and subsequent protonation of generated cationic iminoacyl 270. The mechanism of this transformation was supported by DFT calculations, but no intermediates were observed experimentally. Tribenzyl tantalum imido compound 272 undergoes insertion of two CNXyl species to form bis-iminoacyl 273 (benzene, 75 °C, 2 h, 99%) (Scheme 110) that was characterized by NMR, but not by X-ray method.224 The authors did not succeed in establishing the iminoacyl ligand coordination mode insofar as the NMR method cannot distinguish between these two isomers and attribution of η2-pattern in Scheme 110 is hypothetical. Mashima et al. described173 the insertion of CNXyl into the Ta−C bond of homoenolate complex 274 yielding 275 (toluene,

Scheme 103. Reactions of the Guanidinate-Supported Dibenzyl Niobium Complexes with CNXyl

bulk of the isocyanide substituent R′ increased and that the rates were faster for the series with the more electron-donor C5H4Me ancillary ligand. Furthermore, the isomerization rates for the zwitterionic N-out compounds (254) were higher than those found in the nonzwitterionic series (255). Gómez and colleagues studied the reactivity of alkyl azatantalacyclopentene derivatives toward isocyanides and the intramolecular rearrangement detected in the resulting species (Schemes 105 and 106).222 The treatment of 258 in a toluene solution with 2 equiv of CNXyl (50 °C) or CNBut (RT) affords imido η2-iminoacyl derivatives 260 via simultaneous elimination of s-trans-vinylazacumulenes from corresponding intermediates 259 (Scheme 105). AG


Chemical Reviews

Review

Scheme 104. Reaction of the Ta−C Bonds with Isocyanides

Scheme 105. Reactivity of Alkyl Azatantalacyclopentene Derivatives toward Isocyanides

Scheme 107. Reaction of Dichloro Azatantalacyclopentene Derivatives with Isocyanides

Scheme 108. Reaction of the Ta−C Bonds of 267 with CNXyl Scheme 106. Reaction of 261 with CNXyl

Scheme 109. Interaction between 269 and CNXyl

Scheme 110. Reaction of the Ta−C Bonds of Tribenzyl Tantalum Imido Compound 272 with CNXyl

RT, overnight, 80%), which possesses a metallacyclic structure with the exocyclic ketene imine moiety (Scheme 111). Thus, 3 equiv of CNXyl inserted consecutively into the Ta−C bond of 274 to give 275 because the coordinated carbonyl moiety was released by the first coordination of the isocyanide. The insertion involves three isocyanide molecules, and at least two of them insert into the Ta−C bond. Reactions of some monocyclopentadienyltantalum complexes bearing the tridentate [OSO]-type ligand were reported.225 Insertion into the methyl groups of 276 was not observed upon the reaction with isocyanides. In contrast, complex 277 reacted

Scheme 111. Insertion of CNXyl into the Ta−C Bond of 274

AH


Chemical Reviews

Review

slowly with 1 equiv of CNXyl or CNBut to furnish 278 (toluene, 100 °C, 24 h, 99%) and 279 (THF, 65 °C, 96 h, 11%), respectively (Scheme 112). When the reaction of 277 with

of the cation; the presence of the hydrogen bonds was confirmed by spectroscopic and structural techniques. 2-Methylallyl and 2-butenyl tantalum complexes 283a and 283b react with CNXyl in 1:1 or 1:2 molar ratios (Scheme 114)

Scheme 112. Reaction between CNXyl and Dimethyl Ta Complexes 276−277

Scheme 114. Reaction of the 2-Methylallyl and 2-Butenyl Ta Compounds with CNXyl

at RT in toluene for 12 h to give bis(iminoacyl) compounds 284 (77−80%) formed as a result of bis isocyanide insertion into the two different Ta−C bonds of 283.227 Complex 283a reacts with 1 equiv of CNXyl, leading to a mixture in which the dominant product is di(2-methylallyl) imido iminoacyl derivative 285a together with small amounts of bis(iminoacyl) complex 284a and the starting material. 3.3.4. Reactions of Group 6 Metal Complexes. In contrast to group 4 and group 5 metal complexes, the isocyanide insertion promoted with any of one group 6 metal centers are rather poorly studied. In the past decade, only a few reports on the insertion involving group 6 metals were published. Therefore, this section is not divided into separate parts, and Cr, Mo, and W compounds are discussed together. Treatment of molybdenum metallacyclopentane complex 286 (pentane solution, RT, overnight) with 4 equiv of CNBut228 results in the formation of 287 and iminocyclopentane (Scheme 115), while the addition of 5 equiv of CNXyl to 286 gives

CNBut was carried out, 280 was detected in the reaction mixture; the 1H NMR data support the presence of the azatantalacyclopropane moiety in its structure. The mechanism of this reaction was studied by the DFT method.164 The presence of both a cyclopentadienyl and the tridentate ligand complicates a usually simple reaction, and the insertion is accompanied by the fac → mer rearrangement of the tridentate ligand. Two routes have been explored for the overall insertion process, depending on the order of the fac → mer and insertion steps. However, electronic effects of the phenyl substituents can favor one of the pathways. The same group synthesized and characterized a series of new cationic aminocarbene tantalum complexes 282a−c183,226 obtained by the insertion of CNXyl into the methyl groups of the related neutral triflate complexes 281 (toluene, 100 °C, 24 h, 55−81%; Scheme 113). Complexes 282a,b having a triflate

Scheme 115. Reactions of Mo Metallacyclopentane Complex 286 with Isocyanides

Scheme 113. Reaction between CNXyl and Methyl Ta Complex 281

iminocyclopentane and the isocyanide insertion into the amido Mo−N bonds followed by a 1,3-silatropic shift forming 288 (see section 3.7). The authors indicate that complex 286 contains both Mo−C and Mo−N bonds, but the Mo−N bonds are either inert (in the case of CNBut insertion) or react after the insertion into the Mo−C bond (in the case of CNXyl). Reasons for this behavior were not discussed.

counterion are stable even in air, while complex 282c is stable in apolar solvents such as benzene or toluene but decomposes rapidly when dissolved in CDCl3 and more slowly when the solvent is CD3CN. This stabilizing behavior was accounted for by the establishment of hydrogen bonds between the electronegative atoms of the anion and the amine and hydroxyl protons AI


Chemical Reviews

Review

The insertion of CNMe into the W−C bond of 291 (R = nC5H11) was studied by the DFT method,230 and the obtained data indicate that the CNMe insertion into the metal−alkyl linkage is, in fact, the alkyl migration to CNMe. In comparison with the allyl group, the alkyl (n-C5H11) migration to CNMe is more favorable both kinetically and thermodynamically. The authors also proposed the mechanism for the reversible transformation 293a to 293b. 3.3.5. Reactions of Group 7 Metal Complexes. To the best of our knowledge, in the past 15 years the isocyanide insertion into group 7 metal−carbon bonds did not attract the attention of researchers. The early works were devoted to the insertion of CNAr into benzyl Mn−CH2231 and Re−CH2232 bonds. In the case of the Mn−CH2 bond, a complex mixture of products is formed upon the reaction of 294 with 1 equiv of CNXyl (THF, RT, 18 h; Scheme 118). After separation, double isocyanide insertion species 295 (Figure 17) was isolated in 12% yield.

The addition of excess CNXyl to tungsten complex 289 in toluene afforded 290 (RT, 3 d, 57%; Scheme 116) featuring an Scheme 116. Reactions of Tungsten Complex 289 with CNXyl

η2-iminoacyl group. Even in the presence of excess CNXyl, further insertion of CNXyl does not proceed.173 It was noted without explanations that, in contrast to the Ta analogue 272 (section 3.3.3) where reaction with two isocyanides was observed, the tungsten complex inserts only one CNXyl. Exposure of the tungsten mixed allyl-(substituted alkyl) complexes 291 to isocyanides leads to generation of 292a bearing β,γ-unsaturated η2-iminoacyl ligands that, as believed, originate from the insertion of isocyanides into the W−allyl linkages (Scheme 117). Thus, for instance, reaction of 291 (R = CH2SiMe3) with CNXyl (0.90−0.95 equiv) in Et2O solution at RT for 2 h produces the corresponding 292a in 80% yield. Complexes 292a isomerize to afford 292b with conjugated α,βunsaturated η2-iminoacyl ligands at gentle warming of 292a or upon their chromatography on Al2O3.148 In contrast to these observations, the treatment of 291 featuring the n-alkyl ligands (R = n-C5H11, n-C7H15, n-C8H17) with CNXyl (benzene, RT, 1−20 h) produces complexes 293a bearing η2-iminoacyl ligands.229 The latter species arise from the insertion of the isocyanide into the W−C(alkyl) moieties; η3 → η1 haptotropic shifts and CNXyl ligation precedes the insertion. Compounds 293a then undergo a subsequent intramolecular nucleophilic attack to form metallacyclic compounds 293b containing aminocarbene ligands. Interestingly, the conversion of 293a to 293b does not proceed to completion but rather continues only until equilibrium between the isomeric complexes is established. The difference in the reactive mode of allyl-nalkyl229 and allyl-(substituted alkyl)148 complexes 291 is remarkable; however, no explanations of this interesting phenomenon were provided.

Scheme 118. Double Insertion of CNXyl into the Benzyl Mn− CH2 Bond

Rhenium complexes 296 afforded five-membered metallocycles 297 as a result of the CNTol ligand insertion and the C−H bond activation (toluene, reflux, 1 h, 48−65%; Scheme 119).232 It is noticeable that the isocyanide insertion into the Re−CH2 bond prevailed over the CO insertion into the same bond, and this reactivity pattern agrees well with the relative ability of CNAr and CO ligands to insert into M−C bonds (see section 3.1). 3.3.6. Reactions of Group 8 Metal Complexes. 3.3.6.1. Iron. Reaction of bridged isocyanide iron complex 298 with alkynes proceeds under UV irradiation and affords 299 (Et2O, 2.5−9 h, 55−64%; neither temperature, nor irradiation wavelength were provided) (Scheme 120; R = Me, Et, Ph, 4MeC6H4, CH2OH, SiMe3; R′ = H, Me, Et, Ph).233 Formally, this reaction can be regarded as the insertion into the metal− isocyanide bond, but in fact it is the insertion of the alkyne and

Scheme 117. Reactions of the Mixed Allyl−(Alkyl) W Complexes with CNR′

AJ


Chemical Reviews

Review

Scheme 121. Insertion of CNBut into the Ru−Ph Bond

changes for the insertion of CNH into the Ru−Ph bond were also calculated. The combination of experimental and computational studies leads the authors to the conclusion that the insertion of the isocyanide into the Ru−Ph bond of 302 is thermally disfavored. Trapping the insertion products by the added PMe3 drives the reaction toward 303. 3.3.7. Reactions of Group 9 Metal Complexes. 3.3.7.1. Cobalt. The neutral C-bound iminiumacetyl ligand is formed upon acidification of an aqueous solution of [Co(CN)5(Me)]3− (304) (AcOH/H2O, RT, 5 d, 72%; Scheme 122).163 The insertion of cis hydrogen isocyanide, CNH, was

Figure 17. View of the molecular structure of 295 as a representative example of the double isocyanide insertion into M−C bonds. Thermal ellipsoids are drawn at the 30% probability level.

Scheme 119. Insertion of CNTol into the Benzyl Re−CH2 Bond

Scheme 122. Isotope Distributions in the Pentacyano(iminiumacetyl)cobaltate(III) Anion upon a Migratory Insertion of the cis-CNH Ligand

Scheme 120. Alkyne−Isocyanide Coupling in Di-iron Complex 298

studied by 1H, 13C, 15N, and 59Co NMR using the labeled 13C- or N-cyanide. The reaction was shown to be a migratory insertion of cis CNH as evidenced by the isotope distribution in the final product 306. 3.3.7.2. Rhodium. The system based on the combination of [Cp*RhCl(μ-Cl)]2 and Cu(OAc)2·H2O catalyzes the annulation of N-benzoylsulfonamides involving isocyanides that provides 3(imino)isoindolinones (dichloroethane, 130 °C, 20 h, 40− 81%).234 The plausible mechanism of this transformation is depicted in Scheme 123 (R = n-C5H11, Cy, Xyl, 2-Cl-6-MeC6H3; R′ = H, 2-F, 3-MeO, 4-Me, 4-F, 4-MeO, 2,3-(CH)4). The authors argue that the cycle originates from the generation of five-membered rhodacycle 307 via the C−H activation. Subsequently, isocyanides coordinate to the rhodium 15

therefore we shall not consider this process in detail. Compounds 299 (R = R′ = Me or Et) exist as a mixture of cis and trans isomers (with reference to the mutual Cp position), whereas the others exhibit exclusively the cis geometry. Complex 298 reacts with 2 equiv of HCCCO2Me under UV irradiation giving 300 (Et2O, 6 h, 56%). 3.3.6.2. Ruthenium. Gunnoe et al. reported172 on the experimental and computational studies that probe reactions of isocyanides with the ruthenium(II) complex 301 with tris(pyrazolyl)borate ligand, [HB(Pz)3]−. The reaction of 301 with CNBut (THF, 90 °C, 21 h) forms 302, derived from the acetonitrile ligand substitution. Complex 302 is generated in essentially quantitative 1H NMR yield, but it was isolated in 33% yield (Scheme 121). Neither extended thermolysis, nor photolysis of 302 in C6D6 or CD3CN affords the isocyanide insertion into the Ru−Ph bond. Complex 302 was heated to 100 °C in benzene in a J. Young NMR tube in the presence of PMe3. Under these conditions, the formation of 303 in equilibrium with both 302 and uncoordinated PMe3 was observed. Free energy

Scheme 123. Rhodium-Catalyzed Annulation of NBenzoylsulfonamide Involving Isocyanides

AK


Chemical Reviews

Review

accomplish complexes 316−318 derived from the insertion of one isocyanide molecule into the Pd−C bond (the ortho substituent X is Ac, CN, or CHCH2) (Scheme 126).

center to form 308 followed by insertion of CNR into the Rh−C bond. The reactivity of rhodium(III) cationic complex 309 in the isocyanide insertion depends on the nature of CNR (Scheme 124).235 Thus, in the case of CNBut, insertion was not observed,

Scheme 126. Species Derived from the Insertion of One CNXyl Molecule into the Pd−C Bond

Scheme 124. Insertion of CNRs into the Rh−C Bond of 309

and complex 310 originating from the substitution was the only species isolated, even if a large excess of the isocyanide was employed (CHCl3, reflux, several days, 71%). When excess of CNXyl was used, this isocyanide apart from replacing the MeNH2 ligand is also capable of inserting into the Rh−C bond to give imino(iminoacyl) complex 311 (a molar ratio between the reactants is 1:12, CHCl3, reflux, 1 d, 62%). 3.3.8. Reactions of Group 10 Metal Complexes. 3.3.8.1. Metal-Mediated Insertions. 3.3.8.1.1. Metal-Mediated Insertions Involving Palladium Centers. Vicente and colleagues conducted detailed studies120,174,236−256 on the reaction between CNBut or CNXyl with different ortho-substituted aryl palladium(II) complexes 312 (Scheme 125).

In the case of the (2-X-aryl)palladium(II) complex bearing PPh3 as the only neutral ligand (319, 320; Scheme 127), the Scheme 127. Triple Insertion of CNXyl with ortho-Substituted Aryl PdII Complexes

Scheme 125. Reaction of CNRs with ortho-Substituted Aryl Palladium(II) Complexes

Vicente’s group used different ortho-substituents, which are capable of chelating the metal center: amino derivatives (e.g., X = NH2,239,245,246,254 CH2NH2,241,244 CH2CR2NH2,237,238,249,256 NPPh3,242 NCO,243 and NHC(O)NH2120), phenols (X = OH),251 thioethers (X = SAr),247 carbonyl and carboxyl compounds (X = COZ, 174,236,252a CH 2 COZ, 240 and CH2CH2COZ252b), oximes (X = C(R)NOH,249 and CH2C(R)NOH253), amidoxime (X = C(NH2)NOH),250 nitriles (X = CN),174 and some unsaturated species (X = CHCHR)2.174 The first stage of the reaction was the CNR insertion to form the corresponding (arylimidoyl)palladium(II) complexes 313, which then usually converted into a variety of products involving cyclization of the ortho-substituents. As a rule, CNXyl is more reactive than CNBut in the insertion; in the latter case, substitution rather than the insertion was observed in many instances.241,242,257 The reactivity of CNXyl depends on the nature of the ortho substituent and the nature of other supporting ligands, and also on the reaction conditions.174 Thus, 2-X-arylpalladium(II) complexes featuring bpy (314, 315) react with CNXyl to

reactions with CNXyl in a 1:3 molar ratio led to 321, in which PPh3 was substituted by CNXyl, but only when the reactions were stopped almost immediately after mixing the reactants. When these reactions were carried out at a longer reaction time and at a 1:4 molar ratio, complexes 322 (Figure 18) derived from triple insertion were isolated. The studied reaction of (2-O(H)C-aryl)palladium(II) complex 323 with CNXyl led to complex mixtures. Only in one case, reaction of 323 (N∧N is bpy) with CNXyl in a 1:5 molar ratio between the reactants (acetone, RT, 16 h) were the authors able to isolate 324 (34%) resulting from the triple insertion of CNXyl followed by a nucleophilic attack at the formyl carbon of the nitrogen of the initially inserted isocyanide (Scheme 128). Later, the generation of monoinserted species 327 and 328 (Scheme 129; N∧N is bpy) and decomposition of the resulting complexes furnishing N-heterocyclic compounds were described by the same group.236 ortho-Palladated phenol derivatives 329 are also reactive in both isocyanide and alkyne/isocyanide sequential insertion AL


Chemical Reviews

Review

Scheme 130. Reaction of 329 and 331 with Isocyanides

Figure 18. View of the molecular structure for 322 (X = CN) as a representative example of an isocyanide triple insertion into M−C bonds. Thermal ellipsoids are drawn at the 50% probability level.

Scheme 128. Triple Inserted Products of the Reaction between 323 and CNXyl

Scheme 131. Synthesis of Tetrahydroisoquinolines

Scheme 129. Insertion Products of the Reaction of 325 and 326 with Isocyanides

The different behavior between palladacycles 343a (R = CO2Me, X1 = H, X2 = OH) and 343b (R = H, X1 = OMe, X2 = OMe) toward the isocyanide insertion (CH2Cl2, RT, 2−4 h; Scheme 133) was reported by Oliva-Madrid et al.249 The authors believe that the increased nucleophilicity of the aryl C atom bonded to the palladium(II) center in 343b favors the insertion of the isocyanide into the Pd−C bond to furnish 345, while the treatment of 343a with CNXyl results in the bridge splitting to accomplish 344. Complex 346 was treated with 1 equiv of AgClO4 (MeCN, RT) and then, after the halide abstraction, with 2 equiv of CNXyl to furnish insertion product 347 as a mixture of the Z and E isomers (Scheme 134).239 The reactivity of palladated phenylacetamides toward CNXyl was reported.240 The reaction 348 featuring 4,4′-(But)2bpy (N∧N) ligand with 1 equiv of CNXyl results in the isocyanide insertion to achieve complex 349 (CH2Cl2, RT, 1 h, 78%; Scheme 135). However, analogous iminoacyl derivatives could not be isolated when starting from tmeda derivatives 350 (N∧N = tmeda) because they immediately decompose giving palladium black, (tmedaH)[I], and the C−N coupling products (351a,b; CH2Cl2 or CHCl3, RT or reflux, 58% and 80%, respectively) or the C−O coupling products (352c; CHCl3, reflux, 24 h, 98%; Scheme 136). The reactions of 350a (N∧N = tmeda; R = H) and 350b (N∧N = tmeda, R = Me) with 3 equiv of CNXyl bring about

(Scheme 130).251,255 Initially aryl palladium complex 329b reacts with dimethyl acetylenedicarboxylate giving 331b (CH2Cl2, 3 d, 82%), whereupon the resulting species reacts with the isocyanide affording metal-free organic compound 332 (CH2Cl2, 1 h, 57%) or palladium complex 333 (1 equiv of TlOTf, CH2Cl2, 6 h, 72%). The six-membered cyclopalladated (S)-phenylalanine methyl ester 334 was employed as a starting material for the synthesis of tetrahydroisoquinolines 337 (Scheme 131).237 The first step consists of the coordination of an isocyanide (CNR, R = But, Xyl) to the ortho-metalated fragment to give 335 (acetone, RT, 10 min), while the second step is the insertion into the Pd−C bond furnishing iminoacyl complex 336 (acetone, RT, 15 min). The latter complex was suspended in toluene and refluxed for 7 h, affording tetrahydroisoquinoline 337. In addition, Vicente and colleagues developed238 a similar synthesis of amidines and amidinium salts bearing isoquinoline, benzo[g]isoquinoline, and β-carboline heterocyclic moieties (toluene, reflux, 7 h, 47−92%; Scheme 132). AM


Chemical Reviews

Review

Scheme 132. Synthesis of Amidines and Amidinium Salts

Scheme 133. Different Routes for the Reaction between 343a,b and CNXyl

Scheme 136. Reactivity of 350 (N∧N = tmeda) toward CNXyl

Scheme 137. Reactivity of 350 (N∧N = tmeda) toward Excess of CNXyl Scheme 134. Reactivity of CNXyl toward 346

the coordination of the acetamide group and consequently rules out any coupling process such as that observed in the equimolecular reaction (Scheme 136). The formation of coupling products was explored for the reactions of complexes 354 with CNXyl (Scheme 138; a, N∧N = tmeda, R, R′ = H; b, N∧N = tmeda, R = Me, R′ = H; c, N∧N = tmeda, R, R′ = Me; d, N∧N = 4,4′-(But)2bpy, R = Me, R′ = H). In the case of NH2 derivative 354a, the 1:1 reaction led to a quite unstable complex that was not characterized. However, the 1:2 reaction (CH2Cl2, RT, 2.5 h) led to C−N coupling product 351a formed in essentially quantitative yield. The authors argue that the unstable compound from the former reaction is an insertion product and the second equivalent of CNXyl favors generation of heterocycle 351a by displacing one of the N atoms of tmeda ligand, which can then act as a base. In contrast, the reactions of N(H)Me and NMe2 derivatives 354b−d with 2 equiv of CNXyl produced the insertion of one CNXyl into the Pd−C bond and the displacement of the O-bound amide group by the second

t

Scheme 135. Reactivity of 348 (N∧N = 4,4′-(Bu )2bpy) toward CNXyl

generation of 353 (CH2Cl2, RT, 30 min, 92% for 350a as a starting compound, the yield when 350b is the starting material is not reported) (Scheme 137), which originates from the displacement of the chelating ligands by the two isocyanides and the insertion of the third CNXyl into the Pd−C bond. The occupancy of both positions cis to the iminoacyl ligand prevents AN


Chemical Reviews

Review

Pd−C bond and the subsequent intramolecular C−N coupling. Treatment of dimethylamino derivative 360b with 3 equiv of CNXyl gives palladium complex 363b, resulting from the displacement of tmeda ligand by two isocyanides and the insertion of the third isocyanide into the Pd−C bond. Complex 363b was also obtained when only 1 equiv of isocyanide was employed, leaving a part of starting complex 360b unreacted. Neutral (365) and cationic (364, N∧N = 4,4′-(But)2bpy) cyclopalladated complexes derived from phenylacetone oxime also inserted isocyanides easily (Scheme 141).253 When 364 was

Scheme 138. Reactivity of 354a−d toward Excess CNXyl

Scheme 141. Reactivity of Cyclopalladated Phenylacetone Oxime Complexes 364 and 365 toward Isocyanides

CNXyl accomplishing 355b−d (CH2Cl2, RT, 2.5 h, 66% of 355b, the yields of 355c and 355d are not indicated). Such behavior is also characteristic for homologues of palladated phenylacetamides, complexes 356 (a, R = R′ = H; b, R = Me, R′ = H; c, R = R′ = Me).252b These species react with 3 equiv of CNXyl at RT forming imidoyl complexes 357 (CH2Cl2, 15 min, 74−79%; Scheme 139). In the case of 356a, the reaction proceeds deeper upon heating (CHCl3, reflux, 24 h) with formation of demetalated products 358a (47%) and 359a (18%). Scheme 139. Reactivity of 356 (N∧N = tmeda) toward Excess of CNXyl reacted with 2 equiv of CNR (R = But, Xyl), compounds 366 were isolated, probably by decomposition of the expected iminobenzoyl complexes. When 1 equiv of the isocyanide was employed, in both cases a significant lowering of the yield was observed. Compounds 366 were also obtained when 365 was used instead of 364, but 366 was not purified because of some difficult-to-separate byproducts, and, consequently, the yield is not given. Isocyanides are capable also of inserting into Pd−CAlkyl bonds. Thus, zwitterionic complex 367 reacts with excess CNXyl to give insertion product 368 (CH2Cl2, RT, 1 h, 74%, Scheme 142).258 Scheme 142. Reactivity of Pd−Calkyl Bond in 367 toward CNXyl The reaction of ortho-palladated phenylbenzamides 360a,b with isocyanides (CH2Cl2, RT, 0.5−6 h) demonstrated similar features (Scheme 140).252a Compound 360a reacted with 1 equiv of CNXyl or CNBut forming palladium black, (tmedaH)[I], and 3-XylNH-2-Me-isoindolin-1-one (361a) or 3-ButNH-2Me-isoindolin-1-one (362a), respectively. These products derived from the insertion of an isocyanide molecule into the Scheme 140. Reactivity of 360a,b toward Isocyanides Eight-membered cyclic amidines 370 are obtained from thermal decomposition of eight-membered palladacycles 369 via a similar insertion (R, R′ = (H, CO2Et), 2,3-norbornadiyl; acetone, RT; toluene, reflux, 4−12 h, 38−70%; Scheme 143).259 Monoacetonyl palladium(II) isocyanide complexes 372 and 373, obtained from 371, were transformed into the C-palladated β-ketoenamine complexes (374, 375) resulting from the insertion of one isocyanide followed by a β-ketoimine to βketoenamine tautomerization (Scheme 144).260 Depending on the reagents ratio, complex 371 forms either monomeric (373) or dimeric (372) species. When the reaction is conducted at a 1:1 AO


Chemical Reviews

Review

Scheme 143. Synthesis of Eight-Membered Cyclic Amidines Involving the Insertion of CNXyl into Pd−CAlkyl Bonds

Scheme 145. Insertions of Isocyanides into the Pd−C Bond of the Dinuclear Pd−Fe Complexes

Scheme 144. Synthesis of β-Ketoenamine Palladium(II) Complexes

after 1 h, but instead complex 384 was isolated in good yield. Furthermore, double insertion product 385 was obtained in almost quantitative yield by the insertion of 1,2-bis(2isocyanophenoxy)ethane into the Pd−Me bond of 378. Thienyl palladium 386 (Scheme 147) and thienylene-bridged dipalladium 390 (Scheme 148) complexes underwent insertion of one or more CNXyl molecules into their Pd−C bonds.176 Thus, treatment of 386 with 1 equiv of CNXyl furnished iminoacyl complexes 387 (CH2Cl2, RT, 16 h, 69−89%), and a 3fold excess of CNXyl led to iminoacyl complexes 388 (CH2Cl2, RT, overnight, 74%). Cyclization reactions of 387 upon treatment with 3 equiv of CNXyl (CH2Cl2, RT, 16 h, 82%) or cyclization reaction of 388 by the action of 1 equiv of CNXyl (CH2Cl2, RT, 16 h, 82%) accomplished triiminoacyl complex 389, which was also obtained by the reaction of 2,5dibromothiophene (acetone, 0 °C, 30 min, RT, 3 h, 85%) or 386 (CH2Cl2, RT, overnight, 85%) with a 4-fold excess of CNXyl with or without added [Pd2(dba)3]·dba. Similarly, complexes 490a,b (Scheme 148; a, N∧N = bpy; b, N∧N = 4,4′-(But)2bpy) were reacted with 2 equiv of CNXyl to furnish iminoacyl complexes cis-cis-391a,b (CH2Cl2, RT, 16 h, 52−55%), and an 8fold excess of CNXyl afforded tetraiminoacyl complex 392 (CH2Cl2, RT, overnight, 50%). Palladium-mediated coupling of two aryl iodides and two isocyanide species led to α-diimines formed via intermediate generation of 393 (Scheme 149).261 Thus, when Pd2(dba)3 was treated with an ArI (1.5 equiv to Pd) and CNXyl (3.0 equiv to Pd) in toluene at 26 °C for 1 d, oxidative addition of ArI and the isocyanide insertion took place to give 393 (48−83%). Conducting this reaction at 100 °C leads to metal-free αdiimines 394 (32−43%) formed via reductive coupling. The treatment of dimeric cyclopalladated compound 395 with CNBut in a molar ratio 1:2, respectively, in refluxing chloroform for 4 d, produced a significant amount of palladium(0) (Scheme 150)262 along with N-tert-butylphenanthridine-6-amine 396 that was isolated in 88% yield. This uncomplexed phenanthridine was formed by a monoinsertion of CNBut into the C−Pd σ-bond of 395 followed by a reductive elimination of palladium(0) in the corresponding iminoacyl intermediate complex.

molar ratio between 371 and CNBut or CNXyl under mild conditions (MeCN, 0 °C, 5 min), dimeric monoacetonyl palladium(II) isocyanide complexes 372 are formed (74− 81%). The latter transforms, after the isocyanide insertion followed by the tautomerization, into dimeric β-ketoenamine product 374 (CHCl3, 40−45 °C, 1−13 h, 68−71%). With 2-fold excess of the isocyanide and at lower temperatures the authors synthesized monomeric monoacetonyl palladium(II) isocyanide derivatives 373 (CH2Cl2, −10 °C for CNBut or −78 °C for CNXyl, 68−71%). These species form monomeric β-ketoenamine compounds 375 upon heating (CHCl3, 40 °C, 5−14.5 h, 61−81%). The higher yields of 375 in the reaction of 371 were achieved by using the one-step process (2 equiv of CNR, CHCl3, 40 °C, 4−14 h, 75−80%). The obtained data indicate that the coordination of the isocyanide is not a rate-determining step and the insertion of CNBut is hindered as compared to the insertion of CNXyl. Isocyanides insert into the Pd−C bond of heterodinuclear Fe− Pd alkoxysilyl complexes 376−378 (CH2Cl2, 0 °C or RT, from 10 min to 1 h, from good to essentially quantitative yield) (Schemes 145 and 146)175 as well as their mononuclear palladium analogues.138 Thus, the insertion at 376 and 377 proceeds rapidly, and even multiple insertions could be achieved for 378 already at room temperature (Scheme 146). The formation of six-membered C,N-chelated complex 380 was observed upon stoichiometric treatment of 377 with either CNPh or CNXyl (yields were not provided). Iminoacyl compound 381 was formed as the major product upon stoichiometric addition of o-anisyl isocyanide to the Pd− Me bond of 378 in CH2Cl2 (64%; Scheme 145). The addition of 2 equiv of 2-MeOC6H4NC (Scheme 146) afforded a mixture containing the expected double insertion product 382 along with triple insertion product 383 that was isolated in 77% yields by treatment of 378 with 3 equiv of the isocyanide. After the addition of 2 equiv of tert-butyl isocyanide to a solution of 378, the anticipated double insertion product was not formed even AP


Chemical Reviews

Review

Scheme 146. Reaction of Dinuclear Pd−Fe Complexes with Excess Isocyanides

Scheme 147. Reaction of CNXyl with Thienylene Palladium Complexes 386

Scheme 148. Reaction of CNXyl with Thienylene Dipalladium Complexes 390a,b

Scheme 149. Generation of α-Diimines via the Isocyanide Insertion

Canovese and colleagues studied263 the reactivity of several palladium alkyl and aryl substrates, bearing pyridyl-thioethers

and phosphine-quinolines as ancillary ligands, toward the isocyanides CNR (R = Xyl, TsCH2; Scheme 151). Complexes 397a,b in the presence of a stoichiometric amount of an isocyanide give only monoinsertion complex 398a,b (CH2Cl2, RT, 1 h, 81−93%). The authors determined the reaction rates and elucidated the intimate mechanism of the insertion. When 2AQ


Chemical Reviews

Review

Scheme 150. Reactivity of 395 toward CNBut

Scheme 152. Reactivity of Bis(phosphine) Pd−Azido Complexes toward CNXyl

fold stoichiometric excess of CNXyl is added to a solution of the palladium complex bearing more labile ligand (397a), the reaction mixture yields dimeric imidoyl derivative 399 (81%). Reaction of 397a with 3-fold excess CNR in CDCl3 at RT affords 390 (the yields are not reported). Compounds 400 were also synthesized from complexes that are similar to 397, but featuring another ancillary ligand (COD or tmeda; 71−83%). Kim et al.264 prepared bis(phosphine) Pd−azido complexes (L = PPh3) featuring the heterocyclic ligands and studied their reactivity toward isocyanides. Thus, treatment of 2-thienyl complexes 401 and 403 with CNXyl produced imidoyl Pd complex 402 and imidoyl Pd carbodiimide 404, respectively (CH2Cl2, RT, 16 h; Scheme 152), whereas the isocyanide insertion into Pd−CHetaryl bond does not occur for their tetrazolyl or pyrazinyl analogues. Reaction of cationic complex 405 with CNCH2Ts (CH2Cl2, RT, overnight) led to insertion product 406 in excellent yield (Scheme 153).265 The isocyanides CNXyl and CNBut react in CH2Cl2 or CDCl3 with allyl dimers 407a,b (a, R = H, b, R = Me; Scheme 154) giving the insertion products 408a−c (0 °C or RT, from 15 min to 1 h; a, R = H, R′ = Xyl (92%); b, R = Me, R′ = Xyl (94%); c, R = Me, R′ = But (ca. 100%)).266 In particular, the reaction between 407b and CNXyl was studied in detail, and a number of different species involved in the insertion process were identified. A mechanistic network, that takes into account all of the involved derivatives, was proposed on the basis of independently measured equilibrium and rate constants. The products formed from the insertion of CNXyl and CNBut into the Pd−C bond of 409 or 410, respectively (Scheme 155), were studied by 1H NMR (CDCl3, 25 °C).267 The coordinative capabilities of the isocyanides were found to be nearly the same

Scheme 153. Reactivity of 405 toward CNCH2Ts

Scheme 154. Reactivity of Palladium Allyl Complexes toward Isocyanides

despite their different steric and electronic properties. In fact, when equimolar amounts of these two isocyanides are made to compete for the same coordination sites of the Pd−allyl

Scheme 151. Reactivity of 397a,b toward Isocyanides

AR


Chemical Reviews

Review

Scheme 155. Insertion of CNBut and CNXyl into Pd−Allyl Bond

substrate, the statistical mixture of compounds 411−413 is always observed. On the contrary, CNXyl proved to be much more efficient than CNBut in promoting the insertion into the allyl fragment. It means that the overall insertion rate increases with increasing electrophilicity and with reducing steric hindrance on the isocyanide C atom. Pre-coordination of the isocyanide, a preliminary step of the process, is practically insensitive to electronic and steric features of CNR. Therefore, the effect of the nature of CNR on the overall reaction rate can be attributed to its influence on the insertion step. The rate of reactions of the isocyanides CNR (R = Xyl, TsCH2) with palladium allyl complexes 415 and 416 (R′ = H, Me; CH2Cl2, RT, from 15 min to 1.5 h, 70−91%) is governed by the hapticity of the allyl group (Scheme 156), which is, in turn,

Scheme 157. Isocyanide Insertion into Pd−C Bonds of 418a− c

Complex 420 reacts with isocyanides in a CH2Cl2 or CHCl3 solution, giving 423 and 424 derived from coordination or/and insertion of an isocyanide followed by a tautomerization from βketoimine to β-ketoenamine.270 The reaction pathway depends on different molar ratios of the reactants and temperatures as indicated in Scheme 158. When the reaction is performed at a 1:1 molar ratio between 420 and CNBut (reflux, 16 h) or CNXyl (RT, 10 d), compounds 422 derived from the isocyanide insertion are formed (68−89%). Complexes 422 are able to coordinate at 0 °C an additional two CNR affording enamino species 424 (5 min, 68−89%). With a 2-fold excess of CNR (0 °C), complex 420 coordinates two isocyanide species giving 421 (20 min in CH2Cl2 for CNBut or 5 min in CHCl3 for CNXyl, 90− 96%). The reported NMR data indicate that 421 are subject to the isocyanide insertion yielding β-ketoenamine compounds 423 (CDCl3, 25 °C, 2 d). Complex 423a was formed (in a mixture with 424a) from 422a and 1 equiv of CNXyl (CH2Cl2, 0 °C, 10 min), while 423b was also prepared from 420 and 2 equiv of CNBut in one step (CHCl3, RT, 4.5 d, 79%). Isocyanides insert also into a Pd−CrNHC bond of the so-called remote nitrogen heterocyclic carbene ligands (abbreviated as rNHC139,140) (Scheme 159), and treatment of 425 with CNXyl or CNCy led to palladium(II) dimers 426 (CH2Cl2, RT, 24 h).271 Under the same conditions, in the reaction of 425 with 4 equiv of CNXyl, monomeric complex 427 was isolated in 70% yield (CH2Cl2, RT, 24 h). The reaction of eight-membered cationic palladacycles 428 (N∧N = tmeda) with 4 equiv of CNXyl at RT in CH2Cl2 for 15 h or acetone for 24 h afforded dark red solutions containing palladium(0) complex 429 (Scheme 160).272 The other reaction products were (tmedaH)OTf and the acrylamide derivatives 430, 431. These compounds originate from the insertion of CNXyl into the Pd−C bond followed by the subsequent hydrolysis of the resulting iminoacyl complex (RT, CH2Cl2, 15 h or acetone, 24 h, 12−57%). The 1:1 reaction of 428b with CNXyl in refluxing CHCl3 for 48 h gave a precipitate of palladium black and a mixture containing acrylamide derivative 431b that was isolated in 24% yield.

Scheme 156. Reactions of Isocyanides CNR (R = Xyl, TsCH2) with Palladium Allyl Complexes

determined by chelating or monodentate coordination patterns of the two ligands bearing diphenyl(quinolin-8-yl)phosphine skeleton.268 Thus, the monohapto allyl derivatives 415 react slowly following a second-order rate law, whereas the trihapto complex 416 displays a higher rate with a first-order constant. The second-order law implies that the coordination of CNR is the rate-determining step. The facile isocyanide insertion into the Pd−C bonds of palladium complexes featuring a stanna-closo-dodecaborate ligand 418a−c (Scheme 157) was conducted in acetonitrile at RT, and the final products 419a−c (a, P∧P = dppe, R = Xyl (61%); b, P∧P = dppp, R = But (68%); c, P∧P = dppf, R = But (63%)) were isolated as zwitterionic molecules with the protonated N atom.269 AS


Chemical Reviews

Review

Scheme 158. Reactivity of Isocyanides toward 420

Scheme 159. Insertion of Isocyanides into the Pd−C Bond of Remote Nitrogen Heterocyclic Carbene

inserted isocyanides (CH2Cl2, RT, 30 min, 62−81%) or unusual species 435 (Figure 19) with the η3-allyl ligand incorporating the ketenimine moiety (CH2Cl2, 0 °C, 15 min, 35% for R = H; R′ =

Scheme 160. Reaction of 428 with CNXyl

Figure 19. View of the molecular structure of 435 (X = Cl) as a representative example of a product derived from the insertion of isocyanides into the Pd−Cvinyl bond furnishing the η3-allyl ligand incorporating the ketenimine moiety. Thermal ellipsoids are drawn at the 50% probability level.

Reactions of isocyanides with eight-membered palladacycles 432 (R = H, OMe; R′ = H, Me; R″ = Ph, CO2Me; X = Cl, Br) led to mononuclear complexes 434 featuring both ligated and AT


Chemical Reviews

Review

Scheme 161. Reaction of Eight-Membered Palladacycles 432 with Isocyanides

Me; R″ = Ph; R‴ = Xyl, X = Cl; Scheme 161).142 These complexes decompose in toluene (110 °C, 16 h) to afford metallic palladium and the corresponding eight-membered azacycles 436 (69% for R = OMe; R′ = H; R″ = Ph; R‴ = But) generated by the C−N coupling. Vicente and colleagues described 162 the insertion of isocyanides into the Pd−CAryl bond of 437a−c accomplishing iminobenzoyl pincer complexes 438a−c (L = CNBut, MeCN; RT, CH2Cl2 CHCl3, 2−20 h, 53−97%; Scheme 162). The experimental data confirm that CNXyl is more reactive in the insertion than CNBut and the insertion is facilitated by the overall positive charge on the complex. Jordan and Zhou described273 the insertions for several palladium(II) complexes featuring an achiral Hoveydatype141,274 ortho-NHC-arenesulfonate ligand. Complex transC,C-439 (L = 2,6-lutidine, Ar = 2,6-PriC6H3) reacts with CNBut

furnishing intermediate 440 that is generated via stereospecific displacement of ArSO3− by CNBut followed by displacement of L (CD2Cl2, −30 °C, 5 min, 440 formed in essentially quantitative yield; Scheme 163). In 440, the CNBut ligand is cis to the Me ligand, and therefore the complex easily affords insertion product 441 (CD2Cl2, −30 °C up to 20 °C, 5 min, quantitative yield). In contrast, substitution of the ArSO3− ligand of cis-C,C-439 by the isocyanide yields the adduct where L is less labile. In this case, CNBut and the Me group are in the trans position, and therefore insertion is not possible. 3.3.8.1.2. Metal-Mediated Insertions Involving Platinum Centers. Nagashima et al.275 reported the first case of metallacyclopropane ring expansion exemplified by reactions of platinum species 442 to furnish 443 (Figure 20) by insertion of isocyanides (CH2Cl2, RT, 30 min, 68%; Scheme 164). Among the three compounds with the homologous structures (M = Ni, Pd, Pt), only the platinum complex is reactive toward the ring expansion. The solution dynamics of the platinacyclopentane indicated the exchange of the imidoyl CNXyl and the coordinated CNXyl, suggesting that the insertion of CNXyl is reversible. A DFT study of the reaction potential surfaces of 442 (Scheme 164, Ar = Ph) with two CNPh molecules was also conducted for similar nickel, palladium, and platinum species.165 The ring expansion reactivity increases in the order of the metal centers Ni < Pd ≪ Pt. The reason for this can be traced back to the singlet− triplet gap of the 16-electron d10 ML2 species. Thus, the Pt center would prefer to remain in a high-spin state, whereas both the Ni and the Pd centers favor a low-spin state. This suggests that the ring expansion of isocyanides into a metallacyclopropane is easier and more exothermic for the Pt system than for either its Ni or its Pd congeners. 3.3.8.2. Metal-Catalyzed Transformations Involving Isocyanide Insertions. 3.3.8.2.1. Nickel. Gomes and colleagues described149 both stoichiometric and catalytic reactions between isocyanides and dinuclear compound 444 (Scheme 165; L = PPh3, CNR; R = (S)-(−)-PhCH(Me)NC). Treatment of 444 with stoichiometric amounts of an isocyanide in o-dichlorobenzene at room temperature gives exclusively the product of a monosubstitution of PPh3 with CNR at each Ni center, and no

Scheme 162. Insertion of Isocyanides into the Pd−CAryl Bond of 437a−c

AU


Chemical Reviews

Review

Scheme 163. Insertion Reaction of CNBut to the Pd−C Bond of trans-C,C-439

isocyanide insertion was carried out in the presence of nickel complex 447 (formed by interaction of tetrakis(tert-butyl isocyanide)nickel(II) perchlorate 446 (L = CNBut) with nucleophiles XH (XH = RNH2; R = Bun, Bus, But, Ph, PhCH2, 4-MeSC6H4, or diphenylphosphine oxide Ph2(H)PO) as an initiator (CH2Cl2, RT, 30 min) followed by treatment of resulted complex 448 (L = CNBut, CNR′) with MeOH (Scheme 166; Mn Scheme 166. Polymerization of Aryl Isocyanide Catalyzed by Tetrakis(tert-butyl isocyanide)nickel(II) Perchlorate

Figure 20. View of the molecular structure of 443 as a representative example of a isocyanide bis-insertion product. Thermal ellipsoids are drawn at the 50% probability level.

Scheme 164. Ring Expansion of Metallacyclopropane 442 to Metallacyclopentane 443 by Insertion of CNAr = 2180−15 500)).276 The polymerization of aliphatic monomer (R′ = PhCH2) gave a product with a broad polydispersity and a high yield of low molecular weight material. Using the chiral arylisocyanide (R′ = 4-{(−)-menthyl-CO}C6H4) gave the predominantly one-handed helical polyisocyanide with narrow polydispersity. A novel synthetic method for generation of isocoumarins 451 and phthalides 455 from 2-bromophenylethanones 449 and 453, respectively, and tert-butyl isocyanide via Ni-catalyzed insertion of the isocyanide was developed by Fei and colleagues (2.5 mol % NiCl2, 5 mol % dppe, DMF, K2CO3, 135 °C, 12 or 24 h; then HCl, THF, reflux; 48−91%; Scheme 167).277 This is the first example of nickel complex acting as a catalyst in the coupling of an aryl halide and isocyanide. A plausible mechanism for this twocomponent reaction involves the oxidative addition of ArX to the nickel(0) center followed by the isocyanide insertion accomplishing nickel iminoacyl species 452. 3.3.8.2.2. Palladium. As mentioned in the Introduction, in the first half of 2013, two reviews,10,11 devoted to palladiumcatalyzed conversions of isocyanides to various heterocycles and some other metal-free organic compounds, were published almost simultaneously. Therefore, in this section, our coverage is selective and restricted to reports that appeared after publication of the two above-mentioned articles. Orru and colleagues166 reported the palladium-catalyzed synthesis of 4-aminophthalazin-1(2H)-ones that utilizes the insertion of the isocyanides CNR″ (R″ = But, ButCH2C(Me)2) (2 mol % Pd(OAc)2, DMSO, MW irradiation, 150 °C, 5 min, 29−99%; Scheme 168; X = Cl, Br, I, OTs; Y = CH, N; R = H, Me, MeO, CF3, F, Cl, NH2, 4-FC6H4CH2NH, morpholinyl; R′ = H, Me, Ph, 4-CF3C6H4). A plausible mechanism for this threecomponent reaction involves the oxidative addition of ArX to the

Scheme 165. Polymerization of S-(−)-1-Phenylethyl Isocyanide Catalyzed by 444

isocyanide insertion products were observed in the reaction mixture. Addition of an excess of S-(−)-PhCH(Me)NC to 444 leads to the catalytic nonliving polymerization of the isocyanide (CH2Cl2, 25 °C, 16 h) yielding polymers. On the basis of experimental data, the authors proposed that an initiation step involves the insertion of S-(−)-PhCH(Me)NC into the Ni−Cp bonds of labile intermediate 445 bearing two isocyanide ligands at each Ni atom. The fast living polymerization of arylisocyanides CNR′ (R′ = 4-(C6H13)C6H4, 4-{(−)-menthyl-CO}C6H4) including multiple AV


Chemical Reviews

Review

Scheme 167. Ni-Catalyzed Generation of Isocoumarins and Phthalides via Isocyanide Insertion

Scheme 168. Pd-Catalyzed Synthesis of 4-Aminophthalazin-1(2H)-ones

palladium(0) catalyst followed by the CNR″ insertion accomplishing palladium iminoacyl species 456 (Scheme 168). A similar synthetic approach leading to 4-aminoquinazolines and including palladium-catalyzed intramolecular imidoylation of N-(2-bromoaryl)amidines and involving the CNR′ (R′ = nC5H11, PhCH2, Cy, But) insertion was developed by the same group (Scheme 169; R = H, Cl, CF3; Ar′ = Ph, 4-MeC6H4, 2ClC6H4, 3-ClC6H4, 4-ClC6H4, 4-Py, 2-furyl; L = XPhos, SPhos, JohnPhos, DCPB; Pd(OAc)2, DMF, KOAc, 120−160 °C, 7 h, 50−95%).278 Recently they extended this approach to a wide range of 4-aminopyrido[2,3-d]pyrimidines 457 (R = 4-Py, 2furyl; R′ = Cy, But; L = CyJohnPhos; 3 mol % Pd(OAc)2, 6 mol % L, DMF, KOAc, 120 °C, 7 h, 72−97%) and 4-aminopyrido[3,2d]pyrimidines 458 (R = Ph, 2-ClC6H4, 3-ClC6H4, 4-ClC6H4, 4Py, 2-furyl; R′ = Cy, But; L = CyJohnPhos; 5 mol % Pd(OAc)2, 10 mol % L, DMF, KOAc, 160 °C, 7 h, 29−71%) (Scheme 170).279 A palladium-catalyzed reaction of enaminones 459 with isocyanides280 yields 4-aminoquinoline 460 derivatives through a similar isocyanide insertion (Scheme 171; 1 mol %

Scheme 169. Pd-Catalyzed Synthesis of 4-Aminoquinazolines Generated via CNR Insertion

AW


Chemical Reviews

Review

Scheme 170. Pd-Catalyzed Generation of 4-Aminopyrido[2,3-d]pyrimidines and 4-Aminopyrido[3,2-d]pyrimidines by CNR Insertion

Scheme 172. Pd-Catalyzed Synthesis of 4-Aminoquinolines by the Imidoylative Oxidative Cyclization

Scheme 171. Pd-Catalyzed Synthesis of 4-Aminoquinoline Derivatives Scheme 173. Pd-Catalyzed Synthesis of 2-Arylindole Derivatives and Tetracyclic Carbazoles

[PdCl2(dppf)2], 1,4-dioxane, 3 equiv of Cs2CO3, 110 °C, 12 h, 23−98%; X = Br, I; Y = H, Cl; Z = H, 3-Me, 3-Ph, 3-(4-ClC6H4), 3-(4-MeC6H4), 2,2-Me2, 3,3-Me2; R = But, Pri, Cy, Ad). On the other hand, application of 2-(2-bromovinyl)anilines as substrates affords 2-aminoquinolines (5 mol % [PdCl2(dppf)2], 1,4-dioxane, 2 equiv of Cs2CO3, 100 °C, 3 h, 80−87%).281 Another efficient method for the synthesis of nitrogen heterocycles featuring a cyclic amidine moiety, 6-aminophenanthridines, involves palladium-catalyzed C(sp2)−H activation and isocyanide insertion starting with easily accessible 2aminobiphenyl derivatives, and this reaction proceeds under mild conditions (DCE, 120 °C, 12 h, 50−92%).281 It is also established that the reaction is catalyzed by Co complexes.282 A synthesis of 4-aminoquinolines 462283 by palladiumcatalyzed imidoylative oxidative cyclization of N-aryl imines 461 (Scheme 172; Ar = Ph, 4-MeC6H4, 4-ClC6H4, 4-MeOC6H4; R = MeO, Cl, Me; R′ = Pri, But; 10 mol % Pd(OAc)2, 30 mol % PivOH, 1 atm O2, 4 Å molecular sieves, toluene, 100 °C, 20 h, 13−27%) also involves the isocyanide insertion. The characteristic feature of this reaction is an imidoylative coupling of the two C−H fragments using aerobic oxidative palladium catalysis. Palladium-catalyzed isocyanide insertion of (orthoalkynylphenyl)isocyanides 463 (Ar = Ph, 4-MeOC6H4, 4ClC6H4; R = H, 2-Me, 3-Me, 4-MeO, 4-Cl, 4-CF3, 4-CN, 4CO2Me; R′ = H, MeO, Cl) affords 2-arylindole derivatives 465 (5−10 mol % Pd(OAc)2, 10−20 mol % Ad2PBun, 3 equiv of Cs2CO3, DMF, 100 °C, 3 h, 41−93%) or tetracyclic carbazoles 466 (X = NH2, CH2CN; 10 mol % Pd(OAc)2, 20 mol % Ad2PBun, 3 equiv of Cs2CO3, toluene, or DMF, 100 °C, 56−73%; Scheme 173).284 In this process, the making of two C−C bonds via the isocyanide insertion was achieved (Scheme 174; X = H, OH,

NH2, CH2CN), and CNR was effectively used by incorporating both the C and the N atoms as components of the indole skeleton. Scheme 174. Plausible Mechanism of Pd-Catalyzed Generation of 2-Arylindoles

AX


Chemical Reviews

Review

The indole moiety is also formed upon the treatment of 2-(2bromophenyl)-1H-indoles with CNBut in the presence of Pd(OAc)2 (5 mol %), and this reaction affords 6H-isoindolo[2,1-a]indol-6-ones with high efficiency (10% DPEPhos, Cs2CO3, DMSO, 100 °C, 5−8 h, 59−98%).282 Another method for the synthesis of five-membered nitrogen heterocycles is a palladium-catalyzed ortho-C−H activation in benzamides, followed by isocyanide insertion to synthesize isoindolinone derivatives (Pd(OAc)2, 0.05 mmol, O2, Cs2CO3, toluene, 90 °C, 16 h, 31−91%).285 An expedient route to benzo[b][1,4]oxazepines 467 (X = Br, I; Y = H, Cl, Me, Ph; Alk = But, Cy, ButCH2C(Me)2; R, R′ = (CH2)3, (CH2)4, (H, Ph), (H, CH2Ph)) is based upon a palladium-catalyzed tandem reaction of a range of readily accessible N-tosylaziridines, 2-iodophenols (or 2-bromophenol), and isocyanides (10 mol % Pd(OAc)2, 20 mol % Ad2PBun, 3 equiv of Cs2CO3, toluene, or DMF, 100 °C, 56−73%; Scheme 175).286 This process involves the aziridine ring-opening reaction with 2-iodophenol followed by the Pd-catalyzed isocyanide insertion.

Scheme 176. Pd-Catalyzed Carbonylative Sonogashira Coupling of Aryl Bromides via the CNBut Insertion

Insertion of isocyanides into the Pd−N bond is one of the steps in the catalytic generation of 2-amino-1,3,4-oxadiazoles 471 (for R′ = H, Ac) or 2-imino-1,3,4-oxadiazolines 472 (for R′ = 2Naph, 6-Cl-2-pyridyl, But, Ph, 2-EtC6H4, 2-ClC6H4, 2,4Me2C6H3, 3,4-Cl2C6H3, 2-Cl-6-MeC6H3) by Pd-catalyzed oxidative annulation of hydrazides 470 (R = vinyl, 2-C6H4vinyl, 2-furyl, 2-thienyl, 4-pyridyl, 2-Naph, Ph, 2-MeC6H4, 3MeC6H4, 2-ClC6H4, 3-MeOC6H4, 4-MeC6H4, 4-FC6H4, 4ClC6H4, 4-BrC6H4, 4-Me2NC6H4, 3,5-Me2C6H3) with isocyanides CNR″ (R″ = But, Cy) (5 mol % of Pd(OAc)2, O2, toluene, 80 °C, 1−27 h, 45−94%; Scheme 177).289

Scheme 175. Pd-Catalyzed Tandem Reaction of oHalophenols, N-Tosylaziridines, and Alkylisocyanides

Scheme 177. Catalytic Synthesis of 2-Amino-1,3,4oxadiazoles 471 and 2-Imino-1,3,4-oxadiazolines 472

3.4. MetalC Bond

The insertion of CNMe into the MC bond of chromium and tungsten Fischer carbenes 473 leads to N-metalated ketenimine complexes 475 (Scheme 178).290 DFT calculations were used to Scheme 178. Mechanism of the Thermal Generation of Ketenimine Complexes

A simple and efficient palladium-catalyzed carbonylative Sonogashira coupling via the CNBut insertion into a CAr−Pd bond 287 demonstrates the utility of isocyanides in an intermolecular C−C bond construction (Scheme 176; L = DPEPhos; 3 mol % Pd(OAc)2, 6 mol % L, 2 equiv of Cs2CO3, DMSO, 100 °C, 2 h, followed by stirring in CH2Cl2 with SiO2, RT, overnight, 33−97%; Ar = H, 2-Me, 4-Me, 3-MeO, 4-MeO, 4F, 4-Cl, 4-CF3, 4-CO2Me, 4-NO2, 4-Ph, 3,5-Me2, 3,5-F2, 2naphthyl, 3-thienyl, 3-pyridyl, 6-quinolinyl, 5-(N-Me-indolyl; R = Ph, 4-MeC6H4, 4-MeOC6H4, 4-ButC6H4, 4-FC6H4, n-C7H15, nC12H25). This methodology provides a route to the synthesis of alkynyl imines 468, which can undergo simple SiO2-catalyzed hydrolysis to afford alkynones 469. An analogous approach was reported for carbonylative Suzuki coupling.288

disclose the mechanism of this thermal generation of the ketenimine complexes. It includes the insertion to form metallacyclopropanimine species 474 followed by the isomerization and 1,2-metallotropic rearrangement. Barluenga and co-workers employed an isocyanide reaction with a carbene complex for multicomponent organic synthesis.291 Enynylcarbenes 476 undergo consecutive [6 + 2]/[5 + 1] cyclization reactions with diazafulvene and CNBut to yield tetracyclic organic adducts (THF, RT, 2 h; Scheme 179). In these cases, primary [6 + 2] cycloadducts 477 would undergo isocyanide insertion to produce nonisolated metal heterocumuAY


Chemical Reviews

Review

Scheme 179. Isocyanide Reaction with the Fischer Carbene in Polyheterocyclic Synthesis

Scheme 181. Reactivity of Carbene Complex 483 toward CNXyl

into the Cu−B bond of the borylcopper(I) species. The cyclization also proceeds when silylboronate and hydroboronate (or hydrosilane) were employed to generate (silyl)CuI and (hydride)CuI species, respectively.

lene species 478 followed by metal-mediated electrocyclic ringclosure and isomerization to the aromatic ring. The mechanism of the reaction of Fischer-type carbene 479 and methylisocyanide was studied theoretically by DFT method (Scheme 180).290 Similarly to the Cr and W carbenes depicted in

3.6. Metal−Si Bond

The M−Si bonds in silylmetallocenes 486a,b are not less reactive toward the isocyanide insertion than the Zr−Alkyl bond in alkylzirconocenes 170 (see section 3.3.2). Thus, 486 reacted with CNXyl easily yielding insertion products 487a,b under mild conditions (toluene, RT, 16 h, 55− 81%; Scheme 183).294 The resulting iminoacyl ligand exhibits the η2-coordination as verified by X-ray diffraction.

Scheme 180. Reaction of 479 with CNMe

3.7. Metal−N Bond

Better π-bonding properties of metal centers make a metal− amido bond more resistant to insertion reactions than a metal− alkyl bond. However, some rare exceptions when metal−amido bonds undergo preferential insertion of organic isocyanides (governed by kinetic factors) should be mentioned.134 Group 4 metal amides react with isocyanides giving η2formamidinyl species.150,151,295 Thus, titanium complex 488 reacts with 1 equiv of CNXyl to yield 489 (toluene, RT, 24 h, 86%) (Scheme 184).150 Treatment of zirconium complex 490 with 2 equiv of CNXyl (toluene, RT, 18 h, 77%) furnishes bisinsertion compound 491 (Scheme 185). The iminocarbamoyl ligands of 489 and 491 exhibit extensive delocalization of electron density through the N−C−N core. When the same reaction was performed with CNBut, it proceeds slowly on the NMR time scale accomplishing a mixture of mono-formamidinyl species 492 and bis-formamidinyl complex 493 (toluene, 45 °C, 15 h). The latter is the kinetic product, which transforms into thermodynamically stable conformer 494 for 1 month at RT (toluene). The experimental results agree with the insertion reaction mechanism elucidated by DFT calculations. When zirconium complex 496 was heated in a toluene solution with CNXyl for 4 h at 100 °C, insertion product 497 was observed (91%; Scheme 186),151 whereas under the same conditions titanium complex 495 was recovered intact, despite its weaker Ti−N bond. The different reactivity observed for the zirconium and titanium complexes is consistent with the larger size of the zirconium atom that reduces a steric hindrance. In contrast to CNXyl, the more sterically encumbered isocyanide CNBut does not react with both Zr and Ti dimethylamido species 495 and 496 upon keeping the reaction mixtures for several days even at temperatures higher than 100 °C. Zironium tetra-amide 498 was treated in n-hexane with 2 equiv of CNXyl at −90 °C for 2.5 h giving 500 in 77% yield (Scheme 187).295 This new zirconium diamido di(η2-formamidinyl)

Scheme 178, the reaction starts with the nucleophilic attack of CNMe on the electrophilic carbene C atom of 479 leading to 480. Yet, in contrast to the Cr and W species, 480 is the most stable of the possible Fe complexes in this system Thus, the energy of 480 is 5.8 kcal/mol less than that of isomer 481 and 2.6 kcal/mol less than ketenimine 482. According to these results, the isolable compound should be metallacyclopropanimines 480 rather than metal-bound ketenimines 482; this is in full agreement with the obtained experimental data. Cadierno, Gimeno and colleagues described292 the generation of carbene 483 as well as its reactivity toward CNXyl (Scheme 181). Formation of 485 involves the insertion of one CNXyl molecule into the RuC moiety and concomitant coordination of four molecules of the isocyanide to the Ru center via substitution of the arene ligand (THF, RT, 10 min, 75%). The authors confirmed that ketenimine ruthenium derivative 484 is an intermediate in the generation of 485, the latter being cleanly formed by reacting 484 with an excess of the isocyanide (THF, RT, 1 h, 79%). 3.5. Metal−B Bond

The Cu-catalyzed borylative cyclization of 2-alkenylphenyl isocyanides brings about the formation of otherwise inaccessible 2-borylated indoles (THF, 25 °C, 5 h, 57−98%; Scheme 182).293 This cyclization was initiated by the insertion of the isocyanide AZ


Chemical Reviews

Review

Scheme 182. Insertion of 2-Alkenylphenyl Isocyanides into the Cu−B Bond

Scheme 183. Insertion of CNXyl into the Zr−Si and Hf−Si Bonds

Scheme 186. Insertion of CNXyl into the Zr−N Bond of 496

Scheme 184. Insertion of CNR into the Ti−N Bond

the metallacyclopentane complex 286 with an excess of CNXyl (pentane, RT, overnight, 46%). The authors believe that the amide ligand in 287 could be activated toward isocyanide insertion by π-ligand interactions. The interaction between the lone pair electrons in the (TMS)2pda ligand and Mo in 287 was explored by the hybrid DFT method. The competition among πdonor ligands (the imide and the diamide) for empty metal πacceptor orbitals results in the unusual reactivity of these complexes. The weakening of the diamide bonds by the repulsive interaction between the metal and the diamide lone pairs leads to increased reactivity of the diamide ligand (see later). The NCN-bridged dinuclear iridium complex 502 exhibits versatile reactivity patterns including the CNXyl insertion.296 Unfortunately, no synthetic details of the latter reaction were provided, but schematic representation of the reaction is given in Scheme 189. The overall reaction consists of the insertion and the coordination of the isocyanide accompanied by the Ir−Ir bond splitting furnishing 503 that has different coordination

species is derived from the bis-insertion of isocyanides into the Zr−N amide bonds. An outcome of the insertion strongly depends on substituents at the amido group. Thus, in particular, the insertion of 4 equiv of CNXyl into the Zr−N bonds of the homoleptic complex Zr(NMe2)4 (499) was observed in a C6D6 solution at RT, while the treatment of 499 with 2 equiv of the isocyanide even at −90 °C led to a mixture of products (Scheme 187). Treatment of a C7D8 solution of molybdenum complex 287 (see section 3.3.4) with 2 equiv of CNXyl results in a slow insertion (1 d) into the Mo−N bonds followed by a 1,3-silatropic shift (Scheme 188).228 Iminocarbamoyl complex 288 (Figure 21) may also be obtained on a preparative scale by treatment of Scheme 185. Insertion of CNR into the Ti−N and Zr−N Bonds

BA


Chemical Reviews

Review

Scheme 187. Insertion of CNXyl into the Zr−N Bonds of 498

Figure 21. View of the molecular structure of 288 as a representative example of complexes derived from the isocyanide insertion into M−N bonds. Thermal ellipsoids are drawn at the 30% probability level.

modes of the two iridium atoms. One should mention that the authors provided only IR and 1H NMR data supporting the suggested formulation, and neither other physicochemical data for 503 nor its yield were reported. A novel palladium-catalyzed synthesis of heterocycles from isocyanides and bis-nucleophiles (MeTHF, 75 °C) (Scheme 190) was developed by Vlaar et al.297 The proposed mechanism includes the insertion of isocyanides into the Pd−N bonds of 504 (Scheme 191). It is worth mentioning that the reported reaction is applicable to a wide variety of pharmaceutically relevant heterocyclic systems.

Scheme 189. Insertion of CNXyl into the Ir−N Bonds of 502

yield. Addition of 1 more equiv of CNBut to 506 resulted in the formation of 507. The authors reported a plausible energy profile for the reaction of 505 with 1 and 2 equiv of CNBut. The reaction between 508 and CNBut furnishes 509 that contains a five-membered ZrSCPC ring system (toluene, RT, 24 h, 79%; Scheme 193).299 In this case, the driving force of the reaction is apparently the lower stability of the four-membered

3.8. Metal−P Bond

Reaction of bridged phosphido scandium complex 505 with 2 equiv of CNBut furnishes bis-insertion product 507 (RT, 5 h, 69% yield; Scheme 192).298 The 1H NMR monitoring of the reaction indicated that 505 rapidly reacts with 1 equiv of CNBut giving monoinsertion product 506, which was isolated in 81% Scheme 188. Insertion of CNXyl into the Mo−N Bonds of 287

BB


Chemical Reviews

Review

Scheme 194).144,300 This process occurs via the insertion of the isocyanide into the Zr−P bond followed by the rearrangement of

Scheme 190. Palladium-Catalyzed Synthesis of GuanidineContaining and Related Heterocycles from Bis-nucleophiles and Aliphatic Isocyanides

Scheme 194. Insertion of Isocyanides into the Zr−P Bonds of 510 and 513

Scheme 191. Proposed Mechanism of the PalladiumCatalyzed Synthesis of Guanidine-Containing Heterocycles (L = CNR)

Scheme 192. Insertion of CNBut into the Sc−P Bonds of 505 (Ar = 2,6-PriC6H3)

intermediate 511. Reaction of 510 with 1 equiv of CNCH2Ph in a benzene solution at 5 °C afforded insertion product 511a (94%).300 Complex 511a exhibits low thermal stability, and it gradually decomposes even in the solid state when stored in the dark at −30 °C under N2. The conversion of 511a is significantly accelerated in solution giving phosphaalkene 512a. The latter was prepared directly by the reaction of phosphido compound 510 with CNCH2Ph in C6H6 (90 °C, 3 h, 78%). Reaction of 510 with CNMes led to 511d isolated in 67% yield (Et2O, 30 °C).144 Compound 511d also is not stable for extended periods, and its heating in a solution furnishes 512d in quantitative yield. Additional support for the insertion product as an intermediate came from a secondary phosphide complex 513. Reaction of 513 with 1 equiv of CNCH2Ph yields 514 (81%; −30 °C, 1 h; Figure 22). The phosphorus-containing ligands were liberated as the phosphaformamides (57−81%) from the zirconium center by the reaction of 512 with an organic electrophile AlkX (Alk = Me, PhCH2, Ph3C; X = Cl, Br, I; Scheme 195).144 Thus, for example, reaction of 512 with 1 equiv of PhCH 2 Br afforded bromozirconium complex 515 (X = Br) and phosphaformamidine 516 (X = CH2Ph) (benzene, 80 °C, 2 h, 78%).

Scheme 193. Insertion of CNBut into the Zr−P Bond of 508

3.9. Metal−As Bond

Zirconium complexes featuring arsenido ligands react similarly. Treatment of diphenylarsenido complex 517 with CNCH2Ph in a benzene solution gave the expected insertion product 518 in 72% yield (RT, 15 min, toluene; Scheme 196),301 whereas monoarylarsenido species 519 (Ar = Ph, Mes) formed arsaalkene products 520 (Et2O, RT or 40 °C, from 20 min to 5 h, 78−97%; Scheme 197; Figure 23).302

ring as compared to the reaction product, the five-membered ring system. Also, it is interesting to note that this reaction clearly demonstrates the increased reactivity of the Zr−P bond as compared to the Zr−S bond toward the isocyanide insertion. Reaction of isocyanides with terminal zirconium primary phosphido complexes 510 is a mild and general route to phosphaalkene products 512 (R = Ph, Cy; R′ = Cy, But, PhCH2, Ph, 2,6-Cl2−C6H4, Mes; benzene, 25−100 °C, 2−18 h; 50−92%;

3.10. Metal−Sb Bond

Treatment of a benzene solution of bis(stibido) complex 521 with 2 equiv of CNXyl results in the insertion to give 522 in 85% isolated yield (Scheme 198).303 Usually the insertion into both BC


Chemical Reviews

Review

Figure 23. View of the molecular structure of 520 (R = CH2Ph, Ar = Mes) as a representative example of complexes derived from the isocyanide insertion into M−As bonds. Thermal ellipsoids are drawn at the 50% probability level.

Figure 22. View of the molecular structure of 514 as a representative example of complexes derived from the insertion into M−P bonds. Thermal ellipsoids are drawn at the 50% probability level.

Scheme 198. Insertion of CNXyl into the Hf−Sb Bond of 521

Scheme 195. Formation of Phosphaformamidine 516 from Insertion Product 512

insertion of the organic into the metal−oxygen bonds.143 The mechanism of this reaction has not been elucidated; both innerand outer-sphere steps are possible even when preformed metal−oxygen bonds are present in the starting complexes. Probably the reaction includes heterolysis of the Pt−OR bond followed by nucleophilic attack of RO− onto the coordinated isocyanide. Indeed, CNBut inserts exclusively into the Pt−O bond of platinaoxetane 523 (Scheme 199).156 Treatment of 523

Scheme 196. Insertion of CNCH2Ph into the Zr−As Bond of 517

Scheme 199. Insertion of CNBut into the Pt−O Bond of 523

Scheme 197. Insertion of CNR (R = CH2Ph, Mes) into the Zr−As Bond of 519

with 3 equiv of CNBut (benzene, RT, 5 min) leads to the immediate formation of a new product and free COD. After removal of COD, 524 was isolated in 89% yield and characterized as the product of the isocyanide substitution at the metal center and isocyanide insertion into the M−O bond. 3.12. Metal−Metal Bond

M−X bonds of Cp2MX2 is quite rare for group 4 metallocene derivatives.150 Facile reaction in case of 521 reflects a high reactivity for the Hf−Sb bonds.

Treatment of 525 with 4-isocyano[2.2]paracyclophane in an 1:1 ratio (CH2Cl2, 25 °C, 1 d, ca. quantitative yield) affords 526a that derives from the insertion of the isocyanide into the PdI−PtI bond (Scheme 200).304 The reaction of 525 with the isocyanide group of the phosphonium salt [CNCH2PPh3]Cl also affords the structurally characterized A-frame compound 526b (CH2Cl2, 25 °C, 40 min, 93%).137 Surprisingly, the addition of CNXyl (and

3.11. Metal−O Bond

In general, the insertion of nonelectrophilic agents into M−O bond is quite rare.136 Yet it is known that addition of isocyanides to alkyl platinum methoxide complexes results in the overall BD


Chemical Reviews

Review

Scheme 200. Reaction of Isocyanides with Complex 525 Bearing the PdI−PtI Bond

Scheme 202. Schematic Representation of Electrophilic and Nucleophilic Additions to CNR and NCR Ligands

also CNCy) to 525 leads to the substitution of one chloride ligand with the isocyanide giving exclusively cationic complex 527 bearing a terminal isocyanide ligand (CH2Cl2, 25 °C, 40 min, 72−89%), and no insertion was observed. Later, the same group suggested what controls the generation of the A-frame complex versus the terminal coordination mode of a new isocyanide ligand for reaction of the different homo- and heterodinuclear 529 species (Scheme 201) with isocyanides.305 Scheme 201. Insertion of Isocyanides into M−M Bondsa

addition at electron-reach metal centers (for recent works, see refs 306−309) to afford a methyleneamide (also called alkylideneamide or azavinylidene) species or nucleophilic addition at electron-poor metals furnishing imines proceed at the C atom of NCR ligands (Scheme 202).310,311 Coordination of isocyanides to low-valent electron-rich metal centers, for example, ReI, Mo0, or W0, activates CNR species toward β-electrophilic addition that gives aminocarbyne complexes (Scheme 203).

a

Scheme 203. General Scheme of the Electrophilic Addition to CNR Ligand

M, M′ = Pd, Pt; X = Cl, I; R = 4-PriC6H4, 2-MeOC6H4.

Various subtle parameters such as the π-acceptor property of CNR ligand, the nature of the M−X bond, and, finally, the polarity of the solvent determine the coordination mode. In general, the reactivity pattern depends on easy formation of the cationic complex (e.g., 527; Scheme 200). The A-frame ligation is more characteristic for palladium centers in nonpolar solvents, and the terminal coordination is more common for platinum centers under conditions that favor the formation of a cationic complex. The application of these principles allowed the synthesis of new A-frame complexes 529 (CH2Cl2, 25 °C, 1−2 h, 73−93%; Scheme 201).

This type of reactivity of ligated isocyanide along with properties of aminocarbyne species were discussed in detail in a review published in the year 2001.20 Taking into account a relatively small number of the known low-valent metal centers as compared to the massive average, high, and highest oxidation state metal species, it is quite natural that the amount of reports on electrophilic additions to isocyanides is relatively small. Indeed, since 2001 only a few articles devoted to electrophilic addition to isocyanide ligands appeared, and they are considered in the following paragraphs. Protonation with an excess HBF4·Et2O of the bridging isocyanide ligands in heteronuclear complexes 530a and 530b (a, M = W, R = CF3; b, M = Mo, R = CH2Ts; CH2Cl2, 10 min, RT or −20 °C, correspondingly) results in generation of μaminocarbyne complexes 531a and 531b in excellent yields (Scheme 204).312 Rosenblat and Henderson313 reported stopped-flow kinetic studies of the reactions between anhydrous HCl and trans[MoL(CNPh)(dppe)2] (L = CO, N2, or H2) conducted in THF at 25 °C. For all three complexes, the initial site of the protonation is always the isocyanide ligand, but the final

4. ELECTROPHILIC ADDITION TO CNR LIGANDS Depending on the electronic properties of the metal center, coordinated CNR species can exhibit two opposite activation patterns (Scheme 202). The first is activation toward nucleophilic addition at the ligated C atom, to form an aminocarbene, when the binding site behaves as an efficient Lewis acid (section 2), and second is activation toward electrophilic attack, which occurs at the N atom of the CN group to give aminocarbyne species. The latter reactivity mode is usually realized when the coordination site is a low-valent electron-rich metal exhibiting a high π-electron releasing ability to the metal-bound isocyanide. It should be noted that for coordinated nitriles NCR, which are isomeric to isocyanides, these two types of addition are also known. Both electrophilic BE


Chemical Reviews

Review

Scheme 204. Protonation of μ2-CNR at the N Atom

coordinated isocyanide or nitrile with 1,3-dipole (Scheme 206). 1,3-Dipolar cycloaddition to CNR and NCR species in many Scheme 206. 1,3-Dipolar Cycloaddition to Complexed CNR and NCR

products, [MoH(CO)(CNPh)(dppe)2]+ (L = CO) and trans[MoCl(CNHPh)(dppe)2] (L = H2 or N2), are the result of a combination of numerous reactions including protonation, substitution of the trans-ligands, proton migration to the metal (in the case of L = CO), and proton dissociation. It was observed that prolonged reflux of isocyanide complexes 532 (R = But, Ph, CH2CH2NC2H4O, CH2CO2Et) with HCl (toluene/H2O mixture, HCl, 2 h) gave carbonyl complex 533 (37−64%) (Scheme 205a).314 The authors suggested that the reaction proceeds via electrophilic attack of H+ to the isocyanide ligand (b) followed by nucleophilic attack of H2O that serves as a source of OH− (c). Elimination of an amine from the latter product (e) furnishes carbonyl complex 533.314 Several other works report on the generation of aminocarbyne complexes from isocyanides that proceed by other routes (i.e., isocyanide insertion into M−H and/or M−M bonds, see section 3), while in some cases formation of aminocarbyne species through deprotonation/protonation processes could not be excluded.315

instances proceeds as a metal-mediated process, and leads to complexed products of cycloaddition, while for nitriles it also can be realized in a catalytic manner such as reaction of NCR with azides. It should be noticed that metal-mediated 1,3-dipolar cycloaddition to nitriles is much more developed than that for isocyanides. Thus, these reactions for nitriles include interaction with azides,316−319 nitrile oxides,320,321 acyclic320,322−329 and cyclic330,331 nitrones, oxazoline-N-oxides,332,333 imidazoline-Noxides,334 and nitronates334 as dipoles, while the known examples of isocyanide reactivity toward cycloaddition are so far restricted to azides,319,335−339 nitrile imine and ylides,340 and acyclic and cyclic nitrones.341 Starting from the very first report on cycloaddition between isocyanides and azides published by Beck and co-workers in 1971 (ref 336 and references therein), only few studies devoted to this isocyanide reactivity mode were performed.

5. 1,3-DIPOLAR CYCLOADDITION TO LIGATED ISOCYANIDES 5.1. Comparison of Metal-Mediated Cycloaddition to CNR and NCR Species

5.2. Cycloaddition of Propargyl-allenyl Anion-Type Dipoles

Metal-mediated 1,3-dipolar cycloaddition is known for both types of dipolarophiles bearing a CN group, isocyanides and nitriles. This reaction starts either from free dipole and coordinated dipolarophile, or from complexed 1,3-dipole and free dipolarophile, or even from both free dipole and dipolarophile with a metal salt. Despite this diversity, it is assumed that the key step of the reaction involves interaction of

Kim and colleagues disclosed335 the cycloaddition between azides in [M(N3)2(PR13)2] (534, M = Pd or Pt) with 2 equiv of CNR2 (R2 = Bun, But, Cy). The reaction proceeds at RT and brings about the formation of the bis(C-tetrazolato) complexes [M{CN4(R2)}2(PR13)2] (535, 79−86%, Scheme 207, Figure 24).

Scheme 205. Transformation of Isocyanide Complex 532 to Carbonyl Species 533

BF


Chemical Reviews

Review

Scheme 207. Reaction of [M(N3)2(PR13)2] with Isocyanides

anion and subsequent ring closure. Furthermore, the thus generated tetrazolate-type carbene ligands exhibit a limited thermal stability and gradually decomposed to furnish carbodiimide species and N2. In the related study by Lee et al.,319 the reaction of palladium(II)-azides with CNCy afforded corresponding bis(C-tetrazolato)-palladium(II) species. Kim et al.337 and Huynh et al.339 extended the reaction observed for the palladium(II) species to a nickel(II) center by using the complexes [Ni(N3)2(PR13)2] as the starting materials. The cycloaddition and generation of the carbodiimide proceed similarly for palladium(II) and nickel(II) species. The isocyanides CNR1 (R1 = Xyl, But, Cy; 10 equiv) react with the gold(I) azide complex [Au(N3)(PPh3)] (538) at RT to give the corresponding C-tetrazolyl(phosphine) species [Au{CN4(R1)}(PPh3)] (539, 69%, Scheme 208).338 Alkylation of these species with methyl triflate was only successful for R1 = Xyl, and it proceeds exclusively at the N4 center affording the corresponding carbene compound [Au{CN4(R1R2)}(PPh3)] (540, 91%). The authors338 believe that the low solubility of other tetrazolyl(phosphine) complexes (R1 = But, Cy) precludes the alkylation. When a large excess of CNCy (20 equiv) was used, the reaction proceeds with the formation of a mixture of phosphine/ tetrazolyl cycloadduct (541) and the isocyanide/tetrazolyl species [Au{CN4(Cy)}(CNCy)] (542). The latter reacted with H2NCy formed in situ from the excess of CNCy in EtOH solution to afford the mixed tetrazolyl/aminocarbene species [Au(tetrazolyl){C(NHCy)2}] in low yields (543). 5.3. Cycloaddition of Allyl Anion-Type Dipoles

The only known reaction of this type of dipoles involves the addition of aldonitrones.341 Thus, the reaction between cis[PdCl2(CNR1)2] (27, R1 = Cy, But, Xyl) and the acyclic nitrones (Z)-O+N(R2)C(H)R3 (R2 = Me, CH2Ph; R3 = Tol) at 5 °C in benzene provides complexes [PdCl2{C(ONR2CcHR3)NdR1}(CNR1)(Cc−Nd)] bearing the cyclic carbene ligand (544, 54− 70%, route A, Scheme 209). These species are derived from metal-mediated [2 + 3] cycloaddition of nitrones to coordinated isocyanides. The reaction proceeds only at one isocyanide ligand, while the second ligated CNR1 remains intact even when an excess of nitrone was used. When the reaction between cis[PdCl2(CNR1)2] and (Z)-O+N(R2)C(H)R3 is taken at RT in CHCl3, the cycloaddition loses its selectivity, and the reaction proceeds as deoxygenation (route B, see section 7.1 for more details) to furnish the imine species [PdCl2{N(R2)CHR3}(CNR1)] (545, ca. 75%). The cycloaddition of cis-[PdCl2(CNR1)2] with the cyclic nitrone depicted in Scheme 209 at 5 °C in benzene leads to the

Figure 24. View of the molecular structure of [Pt{CN4(Bun)}2(PMe3)2] as a representative example of 535. Thermal ellipsoids are drawn at the 25% probability level.

The reaction of [Pd(N3)2(PR13)2] with 2 equiv of CNXyl at RT affords mixed carbodiimido/tetrazolato complexes 536 (57− 88%). These species are converted into the corresponding bis(carbodiimido) species [Pd{NCN−Xyl}2(PR13)2] (537, 74−89%) upon heating at 60 °C. Complexes 537 can also be prepared directly starting from [Pd(N3)2(PR13)2] and 2 equiv of CNR2 when reaction is performed at 60 °C. Reaction of [Pd(N3)2(dppe)] with CNXyl at 60 °C gave the structurally related bis(carbodiimido) complex [Pd{NCN− Xyl}2(dppe)]. It is believed335 that the cycloaddition between an isocyanide and an azide can occur via the initial replacement of the coordinated azide with an isocyanide followed by the nucleophilic attack to CNR2 ligand by the uncomplexed azide Scheme 208. Reaction of [Au(N3)(PPh3)] with Isocyanides

BG


Chemical Reviews

Review

Scheme 209. Cycloaddition of Nitrones to Palladium-Bound Isocyanides

corresponding carbene species 546 (78−92%, route C).341 With an excess of the nitrone, the reaction affords the mixed iminecarbene complexes 547 (25−30%, Figure 25), where the imine

Scheme 210. Reductive C−C Coupling of Isocyanide (A) and Carbon Monoxide (B) Ligands

Figure 25. View of the molecular structure of [PdCl 2 {C(ONaCMe2CH2CH2CbH)NeBut}(Nf CMe2CH2CH2CgH)(Na−Cb)(Cb−Ne)(Nf−Cg)] as a representative example of 547. Thermal ellipsoids are drawn at the 30% probability level.

catalytic transformation of syngas to any C2+ products347,348 or enzymatic reduction of CO to C2 and C3 hydrocarbons.349−351 Only a few examples of the C−C coupling reactions occurring at di- and multinuclear complexes were published in the past decade. Thus, dinuclear Mo complex 549 reacts with NaSH· xH2O (THF, 3 equiv of CNXyl, reflux, 72 h) to give C−C coupling product 550 (Scheme 211) in 73% isolated yield.352 Interestingly, this coupling is reversible, and when 550 was treated with 1 equiv of HBF4 (−40 °C), the C−C cleavage accompanied by the dihydrogen elimination was observed, and starting 549 was generated in 87% yield.

ligand originates from the deoxygenation of the nitrone.342 When the reaction of cis-[PdCl2(CNR1)2] and the nonaromatic cyclic nitrone was performed in CHCl3 at room temperature, bis-imine complex 548 (ca. 20%) was obtained. The main reason accounting for the instability of the prepared carbenes on the basis of quantum chemistry calculations is the low stability of the N−O bond in the heterocyclic ring, which can in turn be explained by the electrostatic repulsion of two negatively charged atoms that form this bond.343

Scheme 211. Reductive C−C Coupling of Isocyanide Ligands at Mo2 Center

6. REDUCTIVE COUPLING OF ISOCYANIDES AT METAL CENTERS The reductive C−C coupling leading to coordinated diaminoacetylenes is known for isocyanide ligands (Scheme 210A), but almost all examples date back to works of the 1970−1990s (these early data are summarized in Supporting Information Table A1). This process attracted attention insofar as it has relevance with the reductive C−C coupling of isoelectronic carbon monoxide (Scheme 210B).344−346 The latter process is the crucial step of BH


Chemical Reviews

Review

In another example, two adjacent μ3-coordinated isocyanides in Fe4 cluster 551 undergo reductive coupling under treatment with excess LiAlH4 ((i) THF, RT, 3 h; (ii) NaOH, H2O) followed by air oxidation (O2, (NH4)[PF6], CH2Cl2, RT, 3 h) achieving the coordinated acetylene in 552 (isolated yield 29%, Scheme 212).353 The fate of the NPh moieties of 551 was not elucidated.

Scheme 213. Reaction of Isocyanide Ligands with Ketonitrones

Scheme 212. Acetylene Generation at the Fe4 Center

Scheme 214. Reaction of Isocyanide Ligands with Aldonitrones

Some early representative examples of reductive coupling published before the 2000s include reactions involving Nb,354,355 Ta,354 Mo,354,356 and W354,356,357 metal centers. To finalize this section, one should mentioned that no single example of metalmediated oxidative coupling of isocyanides was published until now.

7. OXYGENATION AND SULFURATION OF CNR SPECIES INVOLVING METAL CENTERS The conversion of CNR to OCNR is still incomparably less investigated than similar oxygenations of the isoelectronic CO. The reported examples of such reactions include the oxygenation of an isocyanide by amine (pyridine) N-oxides,358,359 nitrones,342 N2O,360 nitrile oxides,361 DMSO,350,362 ozone,363 Pb(OAc)4,364 HgO,365 and Hg(OAc)2.366 In the vast majority of cases, these processes require an activation of the isocyanide C atom toward attack by an O-nucleophile that can be achieved by (i) application of metal-free electrophiles (sulfur tetrafluoride-,362 halogen-, acid-,362 and trifluoracetic anhydride-catalyzed350 oxidations by DMSO, iodine-catalyzed oxygenation by amine (pyridine) Noxides359) or (ii) a metal-involving route (see sections 7.1−7.3) when metal centers bind the isocyanide C atom and act as electrophilic activators, thus facilitating nucleophilic oxygenations of CNR ligands (e.g., Au0-,367 MoII/MoIV-catalyzed,360 NiII -, 365 and Pd II-,342 or W II/W IV -,360 or CuI -mediated nucleophilic oxygenations368). These reactions will be considered in the following two sections.

they decompose only upon heating (C6H6, 60 °C or CHCl3, RT) to give the corresponding isocyanates OCNR and imineisocyanide complexes 558 (path B, ca. 75%). The theoretical calculations at the DFT level indicate that in the case of aldonitrones, formation of the imine complexes occurs preferably via cycloaddition/splitting pathway including the generation of a cycloadduct, while, in the case of ketonitrones, both cycloaddition/splitting route and the direct oxygen atom transfer pathway are equally plausible from the kinetic viewpoint. With regard to noncatalytic metal-mediated processes, several other examples of oxidation of an isocyanide ligand to furnish isocyanate species were reported. One of them includes the reaction of the CuI(CNR) species with ButCO3−. The work, which describes this reaction, is unavailable, and data are based on Chemical Abstracts. It is believed that this transformation also proceeds via the nucleophilic oxygenation of the isocyanide ligand by ButCO3−.368 Yet another example is presented by the reaction of the oxo complexes 559 (MIV = Mo, W) with excess (1.0−2.1 equiv) CNBut (toluene, −30 °C) furnishing k2-(O,C) ligated OCNBut (Scheme 215A).360 Complexes 560 were characterized by solidstate IR and X-ray diffraction. In the presence of CNBut, a benzene solution of the Mo isocyanate derivative slowly produces the uncomplexed OCNBut (Scheme 215B), while the W complex does not undergo similar transformations and remains intact.

7.1. Metal-Mediated Oxygenations of CNR Species

Metal-mediated oxygenation of CNR is illustrated by the reaction of the isocyanide complexes 27 (R = Xyl, Cy, But, 2Cl-6-MeC6H3 with the ketonitrones 553 (R′ = Me, Cl) followed by generation of imine-isocyanide palladium(II) species 554 (yield 90−94%) and free isocyanate 555 (Scheme 213).342 It should be pointed out that the ketonitrones do not react with the uncomplexed isocyanides even under drastic conditions (125 h, reflux in the CNR media), and this observation means that the oxygenation of the isocyanides by the ketonitrones is palladium(II)-mediated. It has been reported341 (Scheme 214) that the acyclic aldonitrones 556 (R″ = 4-CH3C6H4; R′ = Me, CH2Ph) react with 27 (molar ratio 1:1, at ca. 5 °C in C6H6) to give stable carbene-isocyanide complexes 557 (path A, 60−70%), which are formed via 1,3-dipolar cycloaddition (see also section 5), and BI


Chemical Reviews

Review

Scheme 215. Reaction of the Oxo Complexes with CNBut

Scheme 217. Reaction between Isocyanides and Amines, Catalyzed by Gold Powder

7.2. Metal-Catalyzed Oxygenation of CNR Species

The processes involving metal-catalyzed conversions of isocyanides to give isocyanates (Scheme 216) are represented by

resulting in either carbodiimide or urea (Scheme 217).369 The nucleophilic attack of the coordinated CNR by an amine is the rate-determining stage, and the reaction rate does not depend on O2 concentration. The reaction of the isocyanides CNR (R = Bun, But, CH2Ph) and amines in the presence of R″3NO, taken instead of O2, is also catalyzed by gold powder (MeCN, 60 °C, 24 h, CNR:R′2NH:R″3NO = 1:5:20, gold powder); it proceeds via another mechanism and leads to ureas 561 and 562 for both the primary R′NH2 (R′ = Cy, Hexn, Ph) and the secondary R′2NH (R′2 = Prn2, Bun2, Pri2, C4H8O, C5H10) amines (Scheme 218).369 The rate of the reaction depends on substituents in amine oxide and is faster for more basic amine oxides (Me3NO, (C11H23)Me2NO, (C4H8O)MeNO) rather than for pyridine oxide.

Scheme 216. Metal-Catalyzed Oxygenations

Scheme 218. Reaction between Isocyanides and Amines in the Presence of R″3NO Catalyzed by Gold Powder

the amine N-oxides Au0-catalyzed oxygenation,367 MoIIcatalyzed oxidation by N2O.360 The plausible mechanisms of these transformations include the nucleophilic addition of R3NO367 or N2O360 to metal-activated isocyanides followed by the formation of R3N or N2, respectively, and generation of πcoordinated isocyanate, which is then substituted by CNR. Formation of the oxo complex 560 (M = MoIV; Scheme 215) in the reaction with N2O followed by intramolecular oxygen atom transfer in the presence of excess isocyanide is suggested to be the key step in the Mo-mediated catalytic process. Mironov365 summarized several examples of NiII-catalyzed oxygenation of isocyanides by ozone or oxygen published before 2000. In excess of oxygen, the oxidation of CNBut into OCNBut in the presence of NiII salts was observed, while a catalytic amount of oxygen favored the polymerization of the isocyanide to a polyimine. 7.3. Other Metal-Mediated Oxidations of Isocyanides

Angelici summarized369 the results of his studies on the reaction between an isocyanide and an amine, catalyzed by gold powder, and proceeding under aerobic conditions. The reaction of CNR (R = Bun) with the primary amine NH2Bun (hexane, 60 °C, 90 h, CNBun:NH2Bun = 1:10, 1 atm O2, gold powder) leads to carbodiimide (73%, based on CNBun; Scheme 217A), while the reaction with the secondary amines HNR′R″ (R = Bun, ButCH2C(Me)2; R′R″ = Prn2, C4H8O, C5H10; MeCN, 60 °C, 24 h, CNR:HNR′R″ = 1:40, 1 atm O2, gold powder) results in substituted ureas (19−44%, based on CNR) (Scheme 217B). The study of the mechanism of this processes demonstrates that adsorption (coordination) of CNR on the Au surface takes place in the first stage, followed by the nucleophilic attack of an amine on the coordinated CNR and consequent reaction with O2

One of the primary steps is the nucleophilic attack of the amine oxide to the isocyanide, which leads to the isocyanate (see section 7.2) that desorbs from the Au surface. This isocyanate then reacts with amines furnishing ureas (Scheme 218). Replacement of amine with alcohol in this reaction (MeCN, 60 °C, R = Bun, Me3NO, PrnOH, gold powder) gave carbamate 563 (92%).369 Other examples of metal-mediated oxidative reactions involving isocyanides were considered in ref 11. Palladium(II)catalyzed oxidative isocyanide insertion into a C−H bond allows the synthesis of amidines and azaheterocycles (see also section 3.3.8.2), while Pd-catalyzed oxidative coupling of isocyanides and amines leads to carbodiimides and heterocycles bearing guanidine moiety. BJ


Chemical Reviews

Review

7.4. Sulfuration of Metal-Bound Isocyanides

Scheme 221. Catalytic Intramolecular Sulfuration of Isocyanides at a Rh Center

Several processes of sulfurization of isocyanides involving transition metal derivatives are known. Thus, MoII/MoIVcatalyzed (0.01 mol %) sulfur-atom transfer to isocyanides proceeds under mild reaction conditions (acetone, 56 °C, 72 h, Ar) to afford a variety of isothiocyanates (yields 68−93%) without the need of a base.370 As suggested, the molybdenum oxo disulfur complex 565 operates as an active sulfur-transfering agent (Scheme 219). The authors370 believe that the sulfur atom is transferred upon the direct nucleophilic attack of the isocyanide on the electrophilically activated disulfur functionality. Scheme 219. Catalytic Sulfuration of Isocyanides

Only one example of noncatalytic sulfurization of isocyanides was reported by Karlin et al.,372 who observed sulfur atom transfer from the μ-η2:η2-disulfide dicopper complex [{Cu(MePY)} 2 (S 2 )] 2 + (MePY = N,N-bis{2-[2-(N′,N′-4dimethylamino)pyridyl]ethyl} methylamine) onto CNXyl (CH2Cl2, RT) furnishing the corresponding isothiocyanate in almost quantitative GC−MS yield. Metal-free sulfurization and selenation of CNR are represented by its reaction with S8 in the presence of a catalytic amount of selenium and an amine (e.g., Et3N),373,374 or reaction with selenium powder in the presence of an amine (e.g., Et3N).375,376

However, intramolecular attack of disulfur to coordinated CNR can also proceed by a process that is analogous to the known catalytic oxygen transfer to either CO or CNR (see ref 360 and section 7.2, Scheme 215) and includes formation of fourmembered metallacycle 567 (Scheme 220).

8. CLEAVAGE OF THE CN−R SINGLE BOND AT METAL CENTERS 8.1. Cyanation of Metal Centers via Dealkylation of CNR Species

Scheme 220. Proposed Mechanism of Intramolecular Attack of Disulfur to CNR

The formation of metal cyanides in reactions of transition metal complexes with isocyanides CNR or nitriles NCR (for recent works on the cyanation with CNR ligands, see refs 377−382) is known for various metal centers (Scheme 222). It is anticipated that in both cases the generation of highly thermodynamically stable C-bound or C,N-bridged metal cyanides383 drives the dealkylation. Furthermore, the charge neutralization (when cationic isocyanide complexes yield neutral or lower charged cyanide species) and successful trapping of R• radical or R+ cation formed upon the homo- or heterolytic R−C bond cleavage, respectively, could also enhance the dealkylation. In the past decade, metal-mediated cyanation involving isocyanides was reported for group 3 (Ln and U377,384), group 6 (Mo,385,386 W188,387), group 7 (Mn388), group 8 (Fe,389,390 Ru391), group 9 (Rh392), and group 10 (Ni,393 Pd,393,394 and Pt393) species, and these examples will be considered accordingly below in this section. The actinide complex UCp3 (569) reacts with CNBut (toluene, RT, 30 min) giving trinuclear complex 572 (76%) bearing C,N-bridged cyanide ligands (Scheme 223).377 In case of lanthanide derivatives LnCp3 (Ln = La 570, Pr 571), similar products (Ln = La 573, Pr 574; yields up to 99%) were obtained upon the Me3Si−CN bond cleavage (C6D6, RT). In the latter case, the Me3Si fragment was trapped by cyclopentadienyl producing CpSiMe3. For the UCp3/CNBut system, no other product of the cleavage, apart from 572, was identified in the reaction mixture.377 A similar reaction was observed for the N,N′-dimethyl substituted porphyrinogen samarium(II) compound 575 that

Additionally, it was demonstrated370 that the highly reactive isocyanides CNR, bearing either electron-withdrawing group (R = MesCHCH, EtCO2CH2) or base- or acid-sensitive (R = HOCH2C(Me)2CH2, (C4H8)C(OAc)) functionalities, can be converted into isothiocyanates (yields 81−89%) even under milder conditions (CH2Cl2, 20−25 °C, 70 h, Ar) by using 2methylthiirane, (MeCHCH2)S, as a sulfur source and [Mo(O)(S2CNEt2)2] as a catalyst (0.05 mol %). Yamaguchi and colleagues371 reported on the rhodium(I)catalyzed generation of isothiocyanates from an isocyanide and sulfur (Scheme 221). The reaction of CNR (R = Cy, n-C8H17, ButCH2CMe2, PhCH2, HOCH2CMe2CH2, Xyl, p-ClC6H4, Tol, p-MeOC6H4) with S8 proceeds under rather mild conditions (1 mol % [Rh], acetone, reflux, 1.5−8 h) producing SCNR in 83− 96% yields. The authors371 suggest that likely the mechanism involves the initial formation of low-valent rhodium complexes 568 (Ln = (H)(PPh3)4 or (acac)(C2H4)), followed by oxidative addition of sulfur and further transfer of a sulfur atom to the isocyanide. BK


Chemical Reviews

Review

Scheme 222. Cyanation of Metal Centers with Isocyanides and Nitriles

formation does not involve the {Sm(But)} intermediate due to steric restrictions at the Sm center.384 GC−MS monitoring of the reaction mixture indicated excess CNBut along with NCBut, as well as a small amount of the imine But(H)CNBut and both isobutane and isobutene, derived from the But substituent, as the dominant byproducts.384 Several works report base-385,386 or alkali metal-mediated387 dealkylation of isocyanide ligands at Mo2 or W2 centers. Thus, [Mo2Cp2(μ-SMe)3(CNBut)2]+ reacts with excess BunLi/NaOH (THF, reflux for 14 h385) or NaSH·10H2O (10 equiv, THF, reflux for 24 h386) yielding the monodealkylated product [Mo2Cp2(μ-SMe)3(CNBut)(CN)] (95% and 69%, correspondingly); formation of ButSH was observed in the latter reaction.386 The dinuclear complex [W2Cp2(μ-COMe)(μPPh2)2(CNBut)2]+ was reduced by a sodium amalgam (THF, RT, 2 h) giving the neutral cyanide derivative [W2Cp2(μCOMe)(μ-PPh2)2(CN)(CNBut)] (69%) and But• radical as the result of the reductive C−N bond cleavage in one of the isocyanide ligands.387 Wolczanski and colleagues188 reported on a rapid insertion of CNBut into the W−H bond in 578 achieving 579 (benzene, RT, 1.5 h; 62%), which can be converted (hexane, 100 °C, 3 d) to the cyanide complex 580 (48%) and ButH (Scheme 225). The reaction of Mn2(CO)10 with CNBut in the presence of CO (10 bar) leads to the isomeric mixture cis/trans-[Mn(CN)(CNBut)4(CO)] (toluene, 140 °C, sealed tube, overnight, yield

Scheme 223. Formation of C,N-Bridged Cyanide Ligands from Isocyanide and Trimethylsilylcyanide

produces trimeric samarium(III) complex 576 (87%) in the reaction with excess CNBut (benzene, 77 °C, 18 h; Scheme 224).384 Iminoacyl complex 577 (19%) was isolated along with 576 when the reaction was performed at RT. The former complex originates from trapping of the tert-butyl fragment, which is generated as a result of the SmII-mediated reductive cleavage of CNBut. The authors384 suggest that the C−C bond Scheme 224. SmII-Mediated Cleavage of CNBut

BL


Chemical Reviews

Review

Scheme 225. Cyanation at the WIV Center via Isocyanide Insertion into the W−H Bond

Scheme 226. Thermally Induced Dealkylation of CNBut at the Fe0 Center

not given), along with [Mn(CNBut)6](CN) as a minor product.388 The fate of the tert-butyl group after the cyanation was not verified. Interestingly, a similar reaction of Fe(CO)5 with CNBut (10 bar CO, toluene, 135 °C) leads to the substitution product [Fe(CNBut)2(CO)3] (88%), while when the same reaction is carried out without additional carbon monoxide, a 1:1 mixture cis/trans-[Fe(CN)2(CNBut)4] (overall yield 93%) is produced via the reductive cleavage of the isocyanide.389 The cluster Ru 3 (CO) 12 was converted into [Ru(CN)2(CNBut)4] (83%) by treatment with excess CNBut in toluene (sealed tube, 145 °C, overnight) under CO pressure (10 bar).391 The reaction results in the formation of the cis and trans isomers in ca. 1:1 molar ratio. Tennent and Jones studied a mechanism of the thermally induced dealkylation of the isocyanide in 581 (Scheme 226).390 On the basis of experimental data, they postulate a radical mechanism for this transformation. Thus, addition of 1,4-cyclohexadiene as hydrogen atom donor allows trapping the •But radical (as isobutene) and the 17electron Fe intermediate (as 582a). The small amount of isobutene still observed in the presence of neat 1,4-cyclohexadiene suggests the possibility that some reaction of the radical pairs occurs within the solvent cage (Scheme 226). The appearance of an intense ESR signal, when a benzene solution of 581 was treated with excess N-tert-butyl-α-phenylnitrone, also supports the radical mechanism of the dealkylation.390 Rhodium(II) complex 583 (tmp = tetra-mesitylporphyrin) reacts with the isocyanides CNR (R = Bun, But) under N2 (benzene, RT, 0.5 h) giving 587 (R = But, 57%; Bun, 47%) and 588 (45%, only for R = Bun) as a result of the C−N bond cleavage (Scheme 227).392 The same reaction in the presence of Py (2 equiv) leads to [Rh(CN)(tmp)(Py)] (R = But, 35%; Bun 17%) and a small amount of 588 (6%, only for R = Bun).392 The kinetic study of the reaction between 583 and CNBun in benzene verified the kobsd[583]2[CNBun]2 rate law, which gives an insight into the mechanism of the reaction (Scheme 227).392 Complex 585 (R = Bun), which is formed in a solution, loses the isocyanide ligand upon isolation accomplishing 588.

Scheme 227. RhII-Mediated C−N Bond Cleavage in CNBut

The complexes [MCl(PONOP)]Cl (M = Ni 589, Pd 590, Pt 591; PONOP = 2,6-bis(di-tert-butylphosphinito)pyridine) promote the C−N cleavage in CNBut (Scheme 228). The Scheme 228. C−N Bond Cleavage in CNBut Mediated by [MCl(PONOP)]Cl

reaction proceeds via coordination of the isocyanide and yields the cyano complexes [M(CN)(PONOP)]Cl (M = Ni 592, Pd 593, Pt 594; 93−95%) along with ButCl and ButOMe (Scheme 228). The same reaction of 589 and CNBut in CD2Cl2 proceeds much slower (RT, 7 d) furnishing 592 (40%) and ButCl. The other isocyanides, CNR (R = Xyl, PhCH2), do not yield 592 in the reaction with 589 (MeOH, RT, 1 d). The authors393 confirmed a two-step mechanism of the reaction by identification of the isocyanide complexes [M(CNBut)(PONOP)](Cl)2 by 1H and 31P{1H} NMR monitoring BM


Chemical Reviews

Review

of the reaction mixtures.393 The second step proceeds via the C− N bond heterolysis (rather than homolysis), and loss of But+ is followed by a rapid capture by a chloride anion or methanol to give ButCl and ButOMe along with final products 592−594. The complex [NiCl2(dippe)] undergoes similar transformations when reacted with CNBut (MeOH, 100 °C, 10 min), giving [Ni(CN)2(dippe)], ButCl, and ButOMe.393 The complex [Pd2(CN) 2(dpppen) 2(CNBut) 2](TCNQ) 2 (dpppen = bis(diphenylphosphino) pentane, TCNQ − = tetracyanoquinodimethane anion) was formed (65%) upon the treatment of [PdCl2(PhCN)2] with CNBut (2 equiv) and dpppen (CH2Cl2, RT, 30 min) followed by addition of LiTCNQ (H2O, RT, overnight).394 Typically the cyanation of metal centers requires end-on Ccoordination of an isocyanide followed by the cleavage of the C− N bond. The cleavage proceeds via either homolysis or heterolysis of the C−N bond (Scheme 229). The homolytic

Scheme 230. Plausible Mechanism of Cyanation of Aromatic Species

palladium(0) center in the last stage. The use of CNBut as the “CN” source is important because But easily gives stable carbocation. Cyanation of the indole 596 with the isocyanide 4FC6H4CH2C(Me2)NC bearing a tertiary substituent leads to the cyanated product.396 The 2:1 mixture of 1-(4-fluorophenyl)2-methyl-propene and 3-(4-fluorophenyl)-2-methyl-propene was obtained as byproducts, indicating a tertiary carbon cation might be an intermediate (indole abbreviated as Ar−H and the source of CN is CNBut, see Scheme 230). In contrast, secondary amine and aniline derived isocyanides, CNPri, CNCy, and CNTol, under similar conditions do not accomplish cyanation products.396 Substrates, that undergo the cyanation, are displayed in Figure 26. The regioselectivity of the reaction for 595 and 596, bearing

Scheme 229. Different Mechanisms of the Cyanation

mechanism is more common for low oxidation state metal centers (electron-reach centers) and leads to oxidation of the metal center and generation of an alkyl radical.390 The heterolytic cleavage is more abundant for transition metals in higher oxidation states, and, in this case, the reaction gives a carbocation, which can be easily trapped by anions in polar protic solvents.386,393 Interestingly, similar cyanation of metal centers can be realized by using nitriles NCR as a “CN” source.378,379,382 In this case, the reactions proceed via a different mechanism that includes an oxidative addition of NCR to a metal center. Furthermore, the metal-mediated cyanation by nitriles requires the cleavage of the R−C bond that is more endoergic than the R−N bond in isocyanides; therefore, the cyanation with isocyanides proceeds easier. Thus, the cyanation with CNR could proceed even in the presence of a nitrile, which remains intact in the reaction.394

Figure 26. Substrates for the metal-catalyzed cyanation involving CNBut; the C−H bonds, which undergoes activation, are marked in bold.

pyridyl or pyrimidyl substituents, is governed by the bidentate N,C-coordination at PdII center at the initial stage of the reaction. In the case of 597, this bidentate ligation is not possible, and, consequently, another C−H bond is subject to activation. Palladium-catalyzed reaction of N,N-dimethyl-2-alkynylaniline 598 with isocyanide397 (Scheme 231) leading to 3cyanoindoles 601 (70 °C, DCE, overnight, 5 mol % Pd(OTf)2, 2 equiv of AgOTf) has a closely related mechanism as for the reactions discussed above (see Scheme 230 and refs 395 and 396). In this reaction, 2 equiv of the AgI salt was used as oxidant (Scheme 231d) instead of the CuII salt, and the first step includes cyclization of 2-alkynylaniline to indolyl-Pd species 599 (a). The second key step is the isocyanide insertion (b), and its product 600 can be converted into cyanation product 601 in an anhydrous solvent (c). In the presence of water, the insertion product could be transformed into 3-amidated indole 602 (e). Vicente et al.272 report on the reaction of eight-membered palladacycle 603 with CNBut (CHCl3, reflux, 1 d) leading to acrylonitrile derivatives 604 (yields 29−55%) with concomitant

8.2. Metal-Catalyzed Cyanation of Aromatics and Olefins

Metal-catalyzed cyanation of organic species could involve, at least formally, the CN−R bond cleavage. However, the detailed mechanism is complicated and, as believed, includes C−H activation, isocyanide insertion into M−C bond, and formation of cyano derivatives accompanied by carbocation elimination. Two works395,396 report on palladium-catalyzed cyanation of arenes and heteroarenes through functionalization of the C−H bond using CNBut as a “CN” source. The plausible mechanism include C−H activation of aromatic substrates followed by insertion of the isocyanide into the M−C bond (for various insertions into M−C bonds, see section 3) (Scheme 230). The reaction requires 5 mol % of Pd(OAc)2 as catalyst and the presence of 1 or 3 equiv of CuII(CO2CF3)2 as the oxidant of BN


Chemical Reviews

Review

groups, such as α-C−H of coordinated CNCH2R species. The acidity of the C−H proton can be increased by coordination of the isocyanides to high- and average-oxidation-state metal centers. In addition, the coordination could stabilize α-C−H deprotonated isocyanides. In this section, metal-mediated and metal-catalyzed reactions of CNCH2R species will be discussed. Reactions of isocyanoacetates, a class of isocyanides having an acidic α-H atom, in the presence of metal centers were briefly and selectively reviewed in 2013 (see Chapter 4 in ref 9) and substantially more comprehensively in 2010.18 The latter article surveys various aspects of isocyanoacetate chemistry, including metal-mediated and metal-catalyzed conversions; it covers reports published between 1960 and early 2010. These two reviews are mainly focused on the synthetic aspects of conversions of isocyanoacetates useful for organic chemistry. Insofar as this Review is devoted to metal involving processes, here we consider from a different angle some works on metalmediated reactions published between 2000 and 2010, putting particular emphasis on how isocyanide coordination to metal centers enhances the overall reaction. In addition, we thoroughly inspect new reports that have appeared in the past four years. Metal-catalyzed reactions of isocyanoacetates are substantially more abundant than metal-mediated. In the overwhelming majority of cases, the main goal of these works is synthesis, while steps where metal center is involved are only postulated. Hence, in these instances, we discuss only recent reports that had not been analyzed earlier.

Scheme 231. Plausible Mechanism of Generation of Cyanoindole and Amidated Indole

formation of isobutene and palladium(0) (Scheme 232). The authors272 suggest that compounds 604 apparently resulted from Scheme 232. Route to Acrylonitrile Derivative 604

9.1. Deprotonation of α-C−H of Coordinated Isocyanides and Metal-Mediated Reactions

Mono-α-deprotonation of isocyanoacetate ligands of complexes 607 ([M] = Cr(CO)5, W(CO)5, PtCl(PPh3)2(BF4); R = Me, Et) by treatment with strong bases (BunLi or ButOK) led to metal nitrile ylides 608, which were stabilized by coordination to a second transition metal complex fragment [M′] ([M′] = Cr(CO)5, [Mn(CO)5]+, [Re(CO)5]+, [FeCp(CO)2]+, [PtCl(PEt3)2]+, [PtCl(PEt3)2]+) (Scheme 233, compound 609, Figure 27).414 Scheme 233. Synthesis of Stable Metal Nitrile Ylides

the C−C reductive coupling of cyano(vinyl) palladium complex 606 that could have formed after the dealkylation of the coordinated CNBut ligand in the corresponding complexes 605 (Scheme 232). To support this reaction path, cyano complex 606 was obtained from 603 and KCN and refluxed in CHCl3 solution for 15 h, and this reaction leads to a precipitate of palladium black and 604 (61%). Before the year 2000, the dealkylation of isocyanides was reported for Sm,398 Ti,399 Zr,399 V,400 Mo,401−403 Tc,404 Re,404 Ru,405−407 Os,407 Co,408 Rh,409 Pt,410−412 and Cu413 metal centers.

Lin et al.415,416 reported the cyclization (Scheme 234) of ruthenium complexes 610 (R = CHCH2, CN, Ph) into azirinyl species 611 (88−95%); this conversion was conducted in CH2Cl2 under basic conditions ([Bun4N]OH in MeOH or [Bun4N]F in THF) at 0 °C for 10 min. In contrast, treatment of 610 with [Bun4N]OH/MeOH (R = CN) or NaOH/MeOH (R = CHCH2, Ph) in acetone afforded oxazolinyl species 612 (82− 91%) derived from the carbonyl 1,2-insertion into the C−C bond of the initially formed azirinyl complexes. Similarly, 610 (R = CN, Ph) reacted with different ketones, aldehydes, amides, and esters, R′R″CO (R′ = H, R″ = Ph, But, Fp; R′ = Me, R″ = Et, NMe2; R′ = Ph, R″ = OMe), affording metalated oxazolines 612 (54−87%).

9. REACTIONS OF ISOCYANIDES WITH ACIDIC α-H ATOM INVOLVING METAL CENTERS Coordination to a metal center often changes the properties of metal-bound species (e.g., electrophilic or nucleophilic character, acidity, susceptibility to oxidation or reduction), and ligand reactivity can thus be enhanced or inhibited. The end-on coordination of isocyanide not only affects the reactivity of the CN functionality, but also has an effect on other neighboring BO


Chemical Reviews

Review

Scheme 236. RhIII-Mediated Reaction of Isocyanide Ligands with Aldehydes

9.2. Metal-Catalyzed Conversions of Isocyanides with Acidic α-H

A substantial number of examples of metal-catalyzed processes involving isocyanoacetate and its derivatives were reported in recent years. It is proposed that isocyanoacetates coordinate to metal centers, which enhance the acidity of α-CH and facilitate deprotonation; thus generated anion 618 reacts further (Scheme 237). Alternatively, deprotonation proceeds under action of a

Figure 27. View of the molecular structure of [(OC)5W{μ2-CNCH(CO2Et)}Pt(Cl)(PEt3)2] as a representative example of 609. Thermal ellipsoids are drawn at the 75% probability level.

Scheme 234. Reaction of Ru Isocyanide Complexes with Bases and Carbonyl Species

Scheme 237. Activation of Isocyanoacetics in Catalytic Reactions

Treatment of the complex 613 (Scheme 235) with [Bun4N]OH/acetone (RT, 10 min) gave oxazolinyl complex 614 (60%),

base, and the deprotonated isocyanide species coordinates to a metal, which then activates the CN group in the resulting complex 619 toward further transformations. 9.2.1. Formal [2 + 3] Dipolar Cycloaddition Accompanied by C−O Bond Formation. Among metal-catalyzed transformations of isocyanides with acidic α-H, the most studied is the reaction of isocyanoacetate derivatives 620 with aldehydes 621 producing oxazolines 622 (Scheme 238). This kind of reactivity was recently analyzed in the review18 that covers publications until early 2010. Therefore, in this Review, we consider only reports that were published in recent years and were not covered in ref 18. These reactions, that are usually catalyzed by late transition metals (e.g., Cu, Ag, Au, and Pd), lead to diastereomeric oxazolines 622, and the diastereoselectivity can

Scheme 235. Reaction of Isocyanide Ligand with Acetone under Basic Conditions

Scheme 238. Catalytic Formation of Oxazolines while treatment of 613 with NaOMe in the presence of KPF6 in an acetone solution (RT, 2 d) produced 614 (38%).415 Nishiyama417 observed a similar reactivity mode for the rhodium(III) complexes 616 (R = CO2Me, Ts), where isocyanide ligand bearing the electron-withdrawing groups undergoes asymmetric aldol-type condensation (ButOK, THF, 0 °C, 22−90%) with the aldehydes R′CHO (R′ = Ph, But) with preferentially trans diastereoselectivity (Scheme 236). On the basis of low-temperature NMR studies performed for 616 (R = Ts) in the presence of ButOK, the authors suggested a plausible mechanism of this reaction, which involves generation of the isocyano enolate complexes [RhCl 2 (Phebox)(CNCH(−)R)] followed by their reaction with the aldehydes. BP


Chemical Reviews

Review

heteroaryl)-methylene]-5-oxazolones 625 (R = Ph, thienyl; X = Ar, Het) with activated methylene isocyanides CNCH2EWG (EWG = CO2Et, Ts, C(O)NC4H8O, p-ClC6H4, 4-C5H4N; Scheme 239).420 The domino process involves initial catalytic

be enhanced by applying properly designed catalyst. In addition, the enantioselective reaction is feasible when enantioselective transition metal catalysts are employed. Oh and Kim418 reported asymmetric cooperative catalytic reaction between isocyanide 620 (R = Me) and aldehydes 621 (R′ = Ph, 4-FC6H4, 4-MeOC6H4, 2-C4H3X (X = O, S), Cy, Pri, Bui, But). Applying a chiral transition-metal catalyst (CoI2/L, 10 mol %; for L see Figure 28, 623) and an achiral organocatalyst

Scheme 239. Catalytic Generation of Bisoxazoles

Figure 28. Chiral ligand (623) and intermediate (624).

(the thiourea (3,5-(CF3)2C6H3NH)2CS (20 mol %) or DBU (10 mol %)) allows the performance of the aldol reaction with high diastereo- and enantioselectivities (THF, RT, 18 h, isolated yields 48−78%; trans/cis ratio varies from 10/1 to 20/1; 74−97% ee). Proposed intermediate of the reaction anticipates the cooperative action of the organic catalyst and the metal center as it is depicted in Figure 28 (624). In the reaction, organocatalysts activate the isocyano moiety, whereas the metal center bearing the chiral ligand coordinates carbonyl group and provides enantioselective coupling with the aldehyde. Albrecht et al.419 studied the aldol condensation of isocyanoacetate and the aldehydes RCHO (R = Ph, 4NO2C6H4, 4-MeOC6H4, 4-ClC6H4, But) giving oxazolines (CH2Cl2, 20 °C, 18 h, conversion 90−95% and 46% for R = But) in the presence of gold triazolylidene complexes (1 mol %) (Figure 29) as precatalyst and AgBF4 (1 mol %) and Pri2EtN (10 mol %) as cocatalysts; high TONs (105) and TOFs (104 h−1) were achieved for these catalytic systems.

nucleophilic ring opening of oxazolones by methylene isocyanides followed by sequential construction of two oxazole rings in the presence of the copper catalyst. 9.2.2. Formal [2 + 3] Dipolar Cycloaddition Accompanied by C−N Bond Formation. Other processes involving isocyanoacetates are catalytic reactions with imines leading to imidazolines, and they will be considered below in this section. Szabó and coauthors421 reported palladium(II)-catalyzed condensation of sulfonimines (Figure 30B) with isocyanoacetate using Pd(OAc)2 and various PCP, SCS, SeCSe, and NCN pincer complexes (1 mol %) as catalysts (Figure 30A). This reaction produces 2-imidazoline derivatives (THF, 20 °C, 2 h, 82−99%; Scheme 240). The first stage of the catalytic cycle is coordination of the isocyanide (Scheme 240a), as confirmed by mechanistic studies and also by isolation of one PCP-type pincer complex bearing η1bound isocyanoacetate. The next step (b) is deprotonation of the coordinated CNCH2CO2Me followed by an attack (c) of the electron-rich enolate moiety by the sulfonimine substrate, and further cyclization (d) by nucleophilic attack on the carbon atom of the isocyanide moiety. The stereoselectivity of the reaction strongly depends on the applied pincer ligand, with highest syn selectivity (syn/anti is 10:1) for the trifluoroacetate PCP pincer complex, and anti selectivity (syn/anti is 1:3) for the SeCSe complex. Substituted imidazoles were obtained from isocyanoacetates and other cyanides or carbodiimides by catalytic processes. Thus, Yamamoto et al.422 reported the copper-catalyzed (Cu2O/1,10phenantroline, 20/20 mol %) cross-cycloaddition between the arylisocyanides CNAr (Ar = Ph, 2-, 3-, and 4-MeOC6H4, 4MeCO2C6H4, 4-NCC6H4, 4-ClC6H4, 4-(TMSCC)C6H4, Xyl, and 1-naphthyl) and isocyanoacetate producing 1,4-disubstituted imidazoles in high yields (THF, 80 °C, 3 h, 88−98%; Scheme 241). Isocyanobenzene and the isocyanides CNCH2R (R = CO2But, PO(OEt)2, CONEt2) under the same conditions gave the corresponding imidazoles in good to excellent yields (62−97%). The reaction starts with activation of a C−H bond of the isocyanides by the Cu catalyst (Scheme 241a) followed by

Figure 29. Precatalysts for the aldol reaction.

The catalytic activity strongly depends on the presence of Ag+ ions that abstracts carbenes providing active gold species. Dynamic light scattering data indicated the presence of nanoparticles as potentially catalytically active species. Isocyanoacetates similarly react with other carbonyl reagents achieving heterocycles. Thus, 2,5,4′-trisubstituted 4,5′-bisoxazoles 626 were synthesized (DMF, 90 °C, 4−6 h, N2, 67−94%) by copper(I)-catalyzed (CuI 10 mol %, 1 equiv of Cs2CO3) domino-reactions of 2-phenyl- and 2-(2-thienyl)-4-[(aryl/ BQ


Chemical Reviews

Review

Scheme 241. CuI-Catalyzed Generation of N-Arylimidazoles

N-formylglycine esters EWGCH2N(H)CHO. This catalytic system has a mechanism very similar to that described above (Scheme 241). The first stage includes formation of a crude mixture of isocyanides from formamides (under action of POCl3, Et3N), which was then treated with Cu2O/proline catalyst (10/ 20 mol %) at RT. It was demonstrated that this is a direct route to N-arylimidazoles. Importantly, different functionalities at different positions on Ar survived the reaction conditions. The developed methodology was applied toward the synthesis of imidazole-bearing glycomimetics.423 Qui and Wu424 described tandem reactions of carbodiimides 627 (X = H, I; R1 = H, Me, Cl; R2 = H, Me, Cl) with the isocyanides 628 (R3 = CO2Me, CO2Et, CO2But, Ts) catalyzed by a system comprised of copper(I) iodide (5 mol %) and DMEDA (10 mol %), leading to benzoimidazo[1,5-a]imidazoles 629 in moderate to excellent yields (40−92%; K3PO4, toluene, reflux; Scheme 242). The initial activation of 628 proceeds through its coordination to the CuI center followed by deprotonation (Scheme 243) as in the previously described catalytic cycles.

Figure 30. Palladium pincer complexes (A) and sulfonimines (B) applied in the condensation.

Scheme 240. Pd-Catalyzed Condensation of Isocyanoacetate with Sulfonimines

Scheme 242. CuI-Catalyzed Synthesis of Benzoimidazo[1,5a]imidazoles

9.2.3. Formal [2 + 3] Dipolar Cycloaddition Accompanied by C−C Bond Formation. Metal-catalyzed reactions of isocyanoacetates with substrates bearing double or triple CC bonds lead to pyrroles or pyrrolines.425 Thus, a catalytic cascade reaction of the isocyanoacetates 630 (R = H, PhCH2; R″ = Me, Et, But) and the α,β-unsaturated ketones 631 (R″ = Me, Et) produces enantioselectively 2,3-dihydropyrroles 632 (CH2Cl2, RT, 14 h, yields 20−85%, ee 16−89%; Scheme 244). The reaction is catalyzed by a combination of cinchona alkaloid derived organocatalysts (10 mol %; 633) and silver nitrate (5 mol %). The α-deprotonation of isocyanoacetate by chiral base 633 and electrophilic activation of the isocyano functionality via coordination allowed two bond formations in a cascade sequence. Organocatalyst 633 might engage with the vinyl

the insertion (c). Intramolecular attack of the nitrogen atom derived from arylisocyanide to the carbon atom of the CN group and subsequent 1,3-hydrogen shift would produce the cyclized intermediate (d). The C−Cu bond in this intermediate is protonated to yield N-arylimidazole (e). Roy and colleagues423 reported a catalytic synthesis of Narylimidazoles that starts from the corresponding N-arylformamides ArN(H)CHO (Ar = 2-, 3-, and 4-MeOC6H4, 2-, 3-, and 4MeC6H4, 2-, 3-, and 4-NO2C6H4, 2-, 3-, and 4-ClC6H4) and the BR


Chemical Reviews

Review

isocyanide CNCH2CO2Et with a variety of alkynes 638 (R = H, R′ = Ar, Het, Alk, CO2Et, OAlk; R = CO2Et, COPh, R′ = Ar, Het, Alk, CO2Et; Scheme 246). On the basis of the mechanistic

Scheme 243. Mechanism for Catalytic Generation of Benzoimidazo[1,5-a]imidazoles

Scheme 246. Ag2CO3-Catalyzed Cycloaddition of Isocyanide with Alkynes

Scheme 244. Catalytic Reaction of the Isocyanoacetates and the α,β-Unsaturated Ketones

investigation of reaction and reported data, it is proposed that the silver-catalyzed reaction of terminal alkynes 638 involves the generation of a silver-acetylene intermediate 639 with subsequent insertion (see section 3) of the isocyanide into the metal−carbon bond, followed by cyclization. The copper-catalyzed (CuI 10 mol %, 1 mol Cs2CO3, DMF, 90−130 °C, 10 min) synthesis of pyrrolo[3,2-c]quinolin-4-ones 643, reported by Cai et al.,427 proceeds as a tandem formal [3 + 2] cycloaddtion/coupling reaction of isocyanides 641 (R″ = CO2Et, CO2But, Ph, SO2C6H4Me, PO(OEt)2) with N-(2haloaryl)propiolamides 642 (R = Alk; R′ = Alk, Ar; X = I, Br; Scheme 247), and it includes an isocyanide activation step involving CNCH2R″ coordination to the Cu center.

ketone through hydrogen-bonding interactions that promote the reaction in a stereoselective manner. Highly diastereo- and enantioselective formal [2 + 3] cycloaddition of the aryl isocyanoacetates 634 (R = Ar; R′ = Me, Et, But, CH2Ph) with N-aryl maleimides 635, cooperatively catalyzed by a cinchona alkaloid-derived squaramide (5 mol %) and AgSbF6 (10 mol %), was recently reported (Scheme 245).426 Scheme 245. Catalytic Reaction of Isocyanoacetates and NSubstituted Maleimides

Scheme 247. Tandem Copper-Catalyzed Formal [3 + 2] Cycloaddition/Coupling Reaction of Isocyanides

9.2.4. Other Cyclization Reactions. Some recent examples of cyclizations include generation of tetrahydro-3H-indeno[2,1d]pyrimidines 646 (isolated yields 50−74%) by the basepromoted (2 equiv of Cs2CO3, MeCN, 80 °C, 2−3 h) tandem reaction of 2-(2-alkynylphenyl)-1-tosylaziridines 644 (R1 = H, Hal, OAlk, Alk; R2 = Ar, Alk; R3 = H, Alk) with 2isocyanoacetates 645 (R4 = Et, But) in the presence of Cu(OTf)2 (10 mol %; Scheme 248).428 The mechanism was not discussed. Silver triflate-catalyzed (10 mol %) reaction of 2-alkynylbenzaldehydes 647 (R1 = H, Hal, OAlk, Alk; R2 = Ar, Alk; R3 = H, Me) with 2-isocyanoacetates 648 (R4 = Me, Et, But) occurs in air under mild conditions (DBU, MeCN, 80 °C, 5 h) leading to

This catalytic enantioselective reaction leads to optically active 1,3a,4,5,6,6a-hexahydropyrrolo[3,4-c]pyrrole derivatives 636 in high yield (CH2Cl2, RT; 67−98%) along with good to excellent diastereo- (dr > 20:1) and enantioselectivities (ee up to 90%). 2,3-Disubstituted and 2,3,4-trisubstituted pyrroles 640 were obtained regioselectively in good (71−94%) yields by Ag2CO3catalyzed cycloaddition (1,4-dioxane, 80 °C, 30−90 min) of the BS


Chemical Reviews

Review

10. MISCELLANEOUS In this section, we have compiled material that does not belong to the categories described above. The nickel(0) isocyanide complex [Ni(CNXyl)(triphos)] (654) reacts with 2 equiv of HBF4 affording the dicationic nickel carbene complex [Ni{C(H)N(H)Xyl}(triphos)](BF4)2 (657) (THF, RT, 3 h, 85%; Scheme 251a−c).430 The authors of ref 430

Scheme 248. Synthesis of Tetrahydro-3H-indeno[2,1d]pyrimidines

Scheme 251. Electrophilic Addition to CNXyl Ligand at Ni Center

isoquinolines 649 in good yields (50−90%; Scheme 249).429 The authors of ref 429 believe that isocyanoacetate is activated by DBU, and, in addition, silver triflate is required for activation of the alkyne moiety. Scheme 249. Catalyzed Reaction of 2-Alkynylbenzaldehyde with 2-Isocyanoacetate

3′,5′-Dihydro-1H-spiro[benzo[d]oxepine-2,4′-imidazoles] 653 were obtained through a copper(I)-catalyzed (CuCl, 10 mol %) reaction (1.5 equiv of Pri2EtN, 1,4-dioxane, RT, 40−82%) between 2-(2-ethynylphenyl)oxiranes 650 (R1 = H, Hal, OAlk, Alk; R2 = H, Ar, Alk; R3 = H, Me), sulfonyl azides, and 2isocyanoacetates 651 (R4 = Me, Et; Scheme 250).367 To Scheme 250. Catalyzed Reaction between 2-(2Ethynylphenyl)oxiranes, Sulfonyl Azides, and 2Isocyanoacetates

argue that the mechanism is based on initial metal protonation (a) furnishing nickel hydride complex depicted in Scheme 251. Subsequent insertion of the isocyanide ligand gives the nickel imino formyl complex 656 (b) followed by its N-protonation (c) providing 657. Interestingly, the isocyanide ligand can be regenerated by treatment with excess acetone (acetone, 45 °C, 1 d) that leads to conversion of 657 to [Ni(triphos)(CNXyl)](BF4)2 (658, 80%) and 2-propanol (d). Alkylation of 654 with MeI (toluene, RT, 12 h) results in the iminoacyl complex [Ni{C(Me)NXyl}(triphos)]I (659, 83%) (e), and it is believed that this reaction supports the mechanism for formation of 657 from 654 (see structures 659 and intermediate of path a, Scheme 251). Complex 660 reacts with 1 equiv of CNBut (THF, 16 h, reflux) producing compound 661 featuring an η3(4e)-vinylcarbene (Scheme 252a).431 Adams et al.431 suggested that the overall reaction includes coordination of the fourth isocyanide, insertion of the diphenylacetylene into two of the metal−isocyanide bonds, the gain of one proton, and the loss of [But]+. In the neutral media, protons can come from rearrangement of the eliminated [But]+ moiety to Me2CCH2 and H+, and the reaction takes 3−4 d at RT; the addition of acid facilitates the conversion (HBF4, 30 s, RT). When 660 reacts with HBF4 in the absence of isocyanide (THF, 1 min, RT), it gives 662 (Scheme 252b). Noticeably,

elucidate a plausible mechanism, the authors performed the copper-catalyzed reaction of 2-(2-ethynylphenyl)oxirane 650 (R1 = H; R2 = Pri; R3 = H) with tosyl azide. Compound 652 was isolated in 64% yield. Compound 652 reacted with ethyl 2isocyanoacetate 651 (R4 = Et) leading to the corresponding product 653 (R1 = H; R2 = Pri; R3 = H; R4 = Et; Ar = 4-MeC6H4) in 85% yield. The authors do not discuss whether the latter step requires the Cu catalyst. BT


Chemical Reviews

Review

Scheme 252. Intramolecular Isocyanide−Alkyne Coupling at the Mo Center

Figure 31. View of the molecular structure of 664. Thermal ellipsoids are drawn at the 30% probability level.

Scheme 254. Reaction of Titanium Imido Complex with CNXyl

protonation of 660 is reversible and treatment of 662 with NEt3 produces 660 (d). Reductive coupling of the isocyanide and alkyne ligands was observed when a THF solution of 660 was treated with sodium amalgam (0.5% Na/Hg, RT, THF, 5 min) with subsequent addition of HBF4 in Et2O (Scheme 253a).431 When protonation Scheme 253. Reductive Coupling of the Isocyanide and Alkyne Ligands

was carried out in Et2O instead THF, product 664 (Figure 31) was obtained (b), and its generation is rationalized by twoelectron reduction and tris-protonation. Complex 665 reacts with CNXyl furnishing 668 (Et2O, RT, 16 h, 85%; Scheme 254).432 NMR monitoring of the reaction (C6D6, RT) demonstrates that reaction proceeds via immediate formation of isocyanide complex 666 that slowly converts to 668 (19 h, RT). The authors432 suggested that initially formed 666 undergoes the isocyanide insertion into the TiN bond giving intermediate 667, which then transforms to 668 (Figure 32) as result of nucleophilic attack of the CNXyl moiety on the oposition of C6F5.

Figure 32. View of the molecular structure of 668. Thermal ellipsoids are drawn at the 30% probability level.

11. FINAL REMARKS AND OUTLOOK This Review highlights advances reported in metal-involved isocyanide chemistry since 2000. In these years, an impressive amount of metal-mediated and metal-catalyzed synthetic applications have been found for CNR species with types of reactions that span from classical procedures such as [2 + 3] cycloaddition to CNR ligands, transition metal-catalyzed cascade

reactions involving isocyanides to afford heterocycles, metalmediated and metal-catalyzed oxidation of CNRs, metalcatalyzed cyanation of organic species by CNRs, and conversions of isocyanides with acidic α-H. The types of CNR reactions are great in number, and the improvements already achieved are inspiring in many cases, although others are still in their early stages. Most importantly, absolutely new reactions of isocyanides BU


Chemical Reviews

Review

that involve metal centers have been reported in the past decade, and they were considered in this Review. Despite the substantial number of contributions and results obtained, many challenges remain. A better understanding of various processes, as well as the role of metal species, is required, and there is always room for improvement in both the scope and the mildness of the reaction conditions for many of the described methods. Achieving higher turnover numbers of the catalytic cycles for metal-catalyzed systems can also be expected to be an area of rapt attention. Finally, one can anticipate that future studies will provide new applications, as well as a finer tuning of the reactions, with the opportunities for pursuing new protocols that could lay the foundation for possible innovations. Last, it should be noted again that many researchers are reluctant to get involved in isocyanide chemistry in part due to the unpleasant smell characteristic of CNRs. As coordination to metal centers completely eliminates the foul odors, we hope that this issue should additionally stimulate interest in the area of organometallic and metal-involving organic CNR chemistry!

complexes and their catalytic activity in aryl halide carbonylation. He was also involved in phenol tar utilization and PCBs remediation. His interests later spanned all aspects of aryl halides activation by Co, Cu, and Pd complexes. Prof. Boyarskiy’s current work is focused on the synthesis of Pd−ADC complexes that act as efficient cross-coupling catalysts.

ASSOCIATED CONTENT S Supporting Information *

Nadezhda Arsenievna Bokach was born in Vologda, Russian Federation (1976). She studied biology and chemistry at Vologda State Pedagogical University and graduated with distinction in 1998. She received her Ph.D. in inorganic chemistry from Saint Petersburg Technological Institute (2002), followed by postdoctoral work at Instituto Superior Técnico in Lisbon, Portugal (2003−2004). Prof. Bokach simultaneously held a researcher position at Saint Petersburg University starting from 2002 and was appointed associate professor in 2007. She received her posthabilitation D.Sc. degree in organometallic chemistry in 2012 and was awarded full professorship in 2014. She is a recipient of Academia Europea’s award for young Russian scientists (2002), National L’Oreal Award for Woman in Science (2007), Leonard Euler Prize from the Government of Saint Petersburg (2010), and the Presidential Award for Young Scientists (2012), the highest official honor for young Russian researchers. Prof. Bokach is an author and coauthor of more than 70 original papers and 5 reviews. Her research interests include transition metals coordination chemistry, ligand reactivity, metal-mediated synthesis, and metal-involving reactions of carbon−heteroatom multiple bonds.

Table of additional reviews and textbook considerations. This material is available free of charge via the Internet at http://pubs. acs.org.

AUTHOR INFORMATION Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. *E-mail: [email protected]. *E-mail: [email protected]. Notes

The authors declare no competing financial interest. Biographies

Vadim Pavlovich Boyarskiy was born in Saint Petersburg, Russia (former Leningrad, USSR). He graduated from Leningrad State University with an M.S. degree in chemistry (1986) and received his Ph.D. in industrial organic chemistry from Leningrad Technological Institute (1990). After four years at the oil refining and oil chemistry-oriented VNIINEFTECHIM Institute (Saint Petersburg), he began his career at Saint Petersburg State University as a senior researcher (1994), followed by assistant professorship in 1997. He received his posthabilitation D.Sc. degree and was appointed full professor in 2010. Prof. Boyarskiy is deputy editor-in-chief of Russian Journal of General Chemistry. While in VNIINEFTECHIM, he conducted research on cobalt carbonyl

Konstantin Vladimirovich Luzyanin was born in 1980 in Leningrad (now Saint Petersburg), Russian Federation. He studied chemistry at Saint Petersburg State University, graduating with distinction in 2002. He received his Ph.D. in chemistry from Lisbon Technical University, where he was also a postdoctoral researcher (2007−2008) and a senior research associate (2009−2012). For his Ph.D. studies, he was awarded Bruker’s António Xavier Prize for application of modern NMR techniques in organometallic chemistry. Dr. Luzyanin later worked for BV


Chemical Reviews

Review

DEDICATION Dedicated to Vladimir Isaakovich Minkin, Full Member of the Russian Academy of Sciences, on the occasion of his 80th birthday as a sign of appreciation for his contribution to chemistry.

one year at the University of Liverpool (2012−2013) before returning to his alma mater in Saint Petersburg in 2013, where he is currently preparing his habilitation. His research interests include organometallic chemistry of late transition metals, activation of small molecules, metalmediated and metal-catalyzed reactions, and application of modern techniques of NMR spectroscopy. Dr. Luzyanin is an author of more than 50 original papers, patents, reviews, as well as four book chapters. In his spare time, Konstantin enjoys opera, playing chess, and working out.

ABBREVIATIONS Radicals in Alphabetical Order

Ac Ad Alk Ar Boc Bu Cy Et Fp Hept Het Hex Me Mes Naph Oct Ph Piv Pr Tol Ts Xyl

Vadim Yurievich Kukushkin was born in 1956 in Leningrad (now Saint Petersburg), Russian Federation. He studied chemistry at Lensovet Technological Institute (Technical University), where he obtained his Diploma in 1979 and doctoral degree in 1982. Following two years at the industrially oriented Mekhanobr Institute (Leningrad), he joined the faculty at Saint Petersburg State University (1984). He obtained his posthabilitation D.Sc. degree in 1992, was appointed full Professor in 1996, and became head of the Department of Physical Organic Chemistry in 2007. He is a corresponding member of the Russian Academy of Sciences (elected 2006), foreign member of the Academy of Sciences of Lisbon (Portugal; elected 2011), and invited chair professor at the National Taiwan University of Science and Technology (since 2007). He is the chairman of the Saint Petersburg branch of the Russian Chemical Society (since 2012), titular member of IUPAC (since 2012), and a member of the Councils of the Russian Foundation for Basic Research (since 2008), Grant Commission of the Government of the Russian Federation, and the Russian Science Foundation (since 2014). Prof. Kukushkin is a recipient of numerous prizes for his achievements in science and teaching. His research interests include platinum group metal chemistry, ligand reactivity, organic synthesis involving metal complexes, and catalysis. He is an author of ca. 300 original papers, patents, reviews, as well as two books and a number of book chapters.

acetyl adamantyl alkyl aryl tert-butoxycarbonyl butyl cyclohexyl ethyl ferrocenyl heptyl hetaryl hexyl methyl 2,4,6-Me3C6H2 naphthyl octyl phenyl trimethylacetyl propyl 4-MeC6H4 4-MeC6H4SO2 2,6-Me2C6H3

Other Abbreviations in Alphabetical Order

acac ADC bpy COD Cp Cp* dba DBU DCA DCE DCPB dippe DMEDA DMF DMSO DPEphos phen dppe dppf dppp dpppen EWG Hal JohnPhos NHC Py OTf RT SPhos THF

ACKNOWLEDGMENTS We are indebted to our former and current co-workers, postdoctoral fellows, and students who shared with us the fascination of this area of chemistry and whose contributions are acknowledged through their coauthorship of the papers cited. We express our deepest gratitude to Professors M. Y. Krasavin, R. A. Michelin, V. G. Nenajdenko, and J. Vicente for valuable discussions and comments on different parts of this Review. We acknowledge the current grants from the Russian Science Foundation (14-13-00060 and 14-43-00017). In addition, K.V.L., who wrote sections 2 and 5, thanks the Russian Fund of Basic Research for support of his studies (grants 14-03-01005 and 15-33-20536). BW

acetylacetonate acyclic diaminocarbene 2,2′-bipyridyl cycloocta-1,4-diene cyclopentadienyl pentamethylcyclopentadienyl dibenzilydeneacetone 1,8-diazabicyclo[5.4.0]undec-7-ene 1,3-dipolar cycloaddition dichloroethane 2-(dicyclohexylphosphino)biphenyl bis(diisopropylphospino)ethane 1,2-dimethylethylendiamine dimethylformamide dimethyl sulfoxide bis(2-diphenylphosphinophenyl)ether 1,10-phenanthroline 1,2-bis(diphenylphosphine)ethane 1,1′-bis(diphenylphosphino)ferrocene 1,3-bis(diphenylphosphine)propane bis(diphenylphosphino)pentane electron-withdrawing group halide 2-(biphenyl)di-tert-butylphosphine N-heterocyclic carbene pyridine triflate (CF3SO3−) room temperature 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl tetrahydrofuran DOI: 10.1021/cr500380d Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

(34) Ito, Y.; Murakami, M. Yuki Gosei Kagaku Kyokaishi 2010, 68, 1239. (35) Lauzon, J. M. P.; Schafer, L. L. Dalton Trans. 2012, 11539. (36) Pombeiro, A. J. L. Inorg. Chem. Commun. 2001, 4, 585. (37) Harvey, P. D. Coord. Chem. Rev. 2001, 219, 17. (38) Kuznetsov, M. L. Russ. Chem. Bull. 2002, 71, 307. (39) Basato, M.; Michelin, R. A.; Mozzon, M.; Sgarbossa, P.; Tassan, A. J. Organomet. Chem. 2005, 690, 5414. (40) Angelici, R. J.; Lazar, M. Inorg. Chem. 2008, 20, 9155. (41) Lazar, M.; Angelici, R. J. Isocyanide Binding Modes on Metal Surfaces and in Metal Complexes. In Modern Surface Organometallic Chemistry; Basset, J.-M., Psaro, R., Roberto, D., Ugo, R., Eds.; WileyVCH Verlag GMBH & Co.: Weinheim, 2009; Chapter 13, pp 513−556. (42) Moderhack, D. Tetrahedron 2012, 68, 5949. (43) Boyarskiy, V. P.; Luzyanin, K. V.; Kukushkin, V. Y. Palladium(acyclic diaminocarbene) species as alternative to palladium-(nitrogen heterocyclic carbenes) in cross-coupling catalysis. In Advances in Organometallic Chemistry and Catalysis: The Silver/Gold Jubilee International Conference on Organometallic Chemistry Celebratory Book; Pombeiro, A. J. L., Ed.; John Wiley & Sons, Inc.: New York, 2014; pp 145−156. (44) Ruiz, J.; Perandones, B. F. Organometallics 2009, 28, 830. (45) Ruiz, J.; García, L.; Mejuto, C.; Perandones, B. F.; Vivanco, M. Organometallics 2012, 31, 6420. (46) Ruiz, J.; García, L.; Mejuto, C.; Vivanco, M.; Díaz, M. R.; GarcíaGranda, S. Chem. Commun. 2014, 2129. (47) Yu, I.; Wallis, C. J.; Patrick, B. O.; Diaconescu, P. L.; Mehrkhodavandi, P. Organometallics 2010, 29, 6065. (48) Anding, B. J.; Ellern, A.; Woo, L. K. Organometallics 2014, 33, 2219. (49) Vicente, J.; Chicote, M. T.; Huertas, S.; Jones, P. G. Inorg. Chem. 2003, 42, 4268. (50) Han, Y.; Huynh, H. V. Dalton Trans. 2009, 2201. (51) Moncada, A. I.; Tanski, J. M.; Slaughter, L. M. J. Organomet. Chem. 2005, 690, 6247. (52) Moncada, A. I.; Manne, S.; Tanski, J. M.; Slaughter, L. M. Organometallics 2006, 25, 491. (53) Martínez-Martínez, A.-J.; Chicote, M.-T.; Bautista, D.; Vicente, J. Organometallics 2012, 31, 3711. (54) Hashmi, A. S. K.; Böhling, C.; Lothschütz, C.; Rominger, F. Organometallics 2011, 30, 2411. (55) Vicente, J.; Chicote, M. T.; Alvarez-Falcón, M. M.; Abrisqueta, M.-A.; Hernández, F. J.; Jones, P. G. Inorg. Chim. Acta 2003, 347, 67. (56) Vicente, J.; Chicote, M. T.; Abrisqueta, M. D.; Ramírez de Arellano, M. C. Organometallics 2000, 19, 2968. (57) Vicente, J.; Chicote, M.-T.; Abrisqueta, M.-D. Organometallics 1997, 16, 5628. (58) Heathcote, R.; Howell, J. A. S.; Jennings, N.; Cartlidge, D.; Cobden, L.; Coles, S.; Hursthouse, M. Dalton Trans. 2007, 1309. (59) Bartolomé, C.; Carrasco-Rando, M.; Coco, S.; Cordovilla, C.; Espinet, P.; Martín-Alvarez, J. M. Dalton Trans. 2007, 5339. (60) Bartolomé, C.; Carrasco-Rando, M.; Coco, S.; Cordovilla, C.; Martín-Alvarez, J. M.; Espinet, P. Inorg. Chem. 2008, 47, 1616. (61) Arias, J.; Bardají, M.; Espinet, P. Inorg. Chem. 2008, 47, 3559. (62) Bartolomé, C.; Ramiro, Z.; García-Cuadrado, D.; Pérez-Galán, P.; Raducan, M.; Bour, C.; Echavarren, A. M.; Espinet, P. Organometallics 2010, 29, 951. (63) Hashmi, A. S. K.; Hengst, T.; Lothschütz, C.; Rominger, F. Adv. Synth. Catal. 2010, 352, 1315. (64) Bartolomé, C.; García-Cuadrado, D.; Ramiro, Z.; Espinet, P. Inorg. Chem. 2010, 49, 9758. (65) Handa, S.; Slaughter, L. M. Angew. Chem., Int. Ed. 2012, 51, 2912. (66) Anisimova, T. B.; Guedes da Silva, M. F. C.; Kukushkin, V. Y.; Pombeiro, A. J. L.; Luzyanin, K. V. Dalton Trans. 2014, 15861. (67) Crespo, O.; Gimeno, M. C.; Laguna, A.; Montanel-Pérez, S.; Villacampa, M. D. Organometallics 2012, 31, 5520. (68) Luzyanin, K. V.; Guedes da Silva, M. F. C.; Kukushkin, V. Y.; Pombeiro, A. J. L. Inorg. Chim. Acta 2009, 362, 833.

thiphos tmeda TMS XPhos

Ph2PCH2CH2P(Ph)CH2CH2PPh2 N,N,N′,N′-tetramethyl-1,2-ethylenediamine trimethylsilyl 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl XantPhos 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene

REFERENCES (1) Slaughter, L. M. ACS Catal. 2012, 2, 1802. (2) Vignolle, J.; Catton, X.; Bourissou, D. Chem. Rev. 2009, 109, 3333. (3) Boyarskiy, V. P.; Luzyanin, K. V.; Kukushkin, V. Y. Coord. Chem. Rev. 2012, 256, 2029. (4) Díez-González, S.; Nolan, S. P. Coord. Chem. Rev. 2007, 251, 874. (5) Hahn, F. E.; Jahnke, M. C. Angew. Chem., Int. Ed. 2008, 47, 3122. (6) Slaughter, L. M. Comments Inorg. Chem. 2008, 29, 46. (7) Glorius, F. Top. Organomet. Chem. 2007, 21, 1. (8) Díez-González, S. N-Heterocyclic Carbenes: From Laboratory Curiosities to Efficient Synthetic Tools; RSC Publishing: Cambridge, UK, 2011. (9) Isocyanide Chemistry. Applications in Synthesis and Material Science; Nenajdenko, V., Ed.; Wiley-VCH: New York, 2012. (10) Lang, S. Chem. Soc. Rev. 2013, 42, 4867. (11) Vlaar, T.; Ruijter, E.; Maes, B. U. W.; Orru, R. V. A. Angew. Chem., Int. Ed. 2013, 52, 7084. (12) Qiu, G.; Ding, Q.; Wu, J. Chem. Soc. Rev. 2013, 42, 5257. (13) Suginome, M.; Ito, Y. Adv. Polym. Sci. 2004, 171, 77. (14) Ito, Y.; Suginome, M. Synthesis of oligomeric and polymeric materials via palladium-catalyzed successive migratory insertion of isonitriles. In Handbook of Organopalladium Chemistry for Organic Synthesis; Negishi, E.-i., Ed.; John Wiley & Sons, Inc.: New York, 2003; pp 2705−2712. (15) Yamamoto, Y.; Miyachi, M.; Yamanoi, Y.; Minoda, A.; Maekawa, S.; Oshima, S.; Kobori, Y.; Nishihara, H. J. Nanopart. Res. 2011, 13, 6333. (16) Yamamoto, Y.; Miyachi, M.; Yamanoi, Y.; Minoda, A.; Maekawa, S.; Oshima, S.; Kobori, Y.; Nishihara, H. J. Inorg. Organomet. Polym. Mater. 2014, 24, 208. (17) Tuchscherer, A.; Schaarschmidt, D.; Schulze, S.; Hietschold, M.; Lang, H. Eur. J. Inorg. Chem. 2011, 4421. (18) Gulevich, A. V.; Zhdanko, A. G.; Orru, R. V. A.; Nenajdenko, V. G. Chem. Rev. 2010, 110, 5235. (19) Michelin, R. A.; Pombeiro, A. J. L.; Guedes da Silva, M. F. C. Coord. Chem. Rev. 2001, 218, 75. (20) Pombeiro, A. J. L.; Guedes da Silva, M. F. C.; Michelin, R. A. Coord. Chem. Rev. 2001, 218, 43. (21) Zhu, J. P. Eur. J. Org. Chem. 2003, 1133. (22) Dömling, A. Chem. Rev. 2006, 106, 17. (23) Hulme, C.; Lee, Y.-S. Mol. Diversity 2008, 12, 1. (24) El Kaim, L.; Grimaud, L. Tetrahedron 2009, 65, 2153. (25) Sadjadi, S.; Heravi, M. M. Tetrahedron 2011, 67, 2707. (26) Heravi, M. M.; Moghimi, S. J. Iran. Chem. Soc. 2011, 8, 306. (27) van Berkel, S. S.; Bogels, B. G. M.; Wijdeven, M. A.; Westermann, B.; Rutjes, F. P. J. T. Eur. J. Org. Chem. 2012, 3543. (28) Ramon, R.; Kielland, N.; Lavilla, R. Recent Progress in Nonclassical Isocyanide-Based MCRs; Wiley-VCH Verlag GmbH & Co. KGaA.: New York, 2012. (29) Dixon, S.; Whitby, R. J. Elaboration of organozirconium species by insertion of carbenoids. In Titanium and Zirconium in Organic Synthesis; Marek, I., Ed.; Wiley-VCH Verlag GmbH & Co. KGaA: New York, 2002; pp 88−109. (30) Gómez, M. Eur. J. Inorg. Chem. 2003, 20, 3681. (31) Cummings, S. A.; Tunge, J. A.; Norton, J. R. Top. Organomet. Chem. 2005, 10, 1. (32) Jeong, N. Rhodium(I)-catalyzed [2 + 2 + 1] and [4 + 1] carbocyclization reactions. In Modern Rhodium-Catalyzed Organic Reactions; Evans, P. A., Ed.; Wiley-VCH Verlag GmbH & Co. KGaA: New York, 2005; pp 215−240. (33) Antiñolo, A.; Garcı ́a-Yuste, S.; Otero, A.; Villaseñor, E. J. Organomet. Chem. 2007, 692, 4436. BX


Chemical Reviews

Review

(69) Luzyanin, K. V.; Guedes da Silva, M. F. C.; Kukushkin, V. Y.; Pombeiro, A. J. L. Organometallics 2008, 27, 833. (70) Chay, R. S.; Luzyanin, K. V. Inorg. Chim. Acta 2012, 380, 322. (71) Chay, R. S.; Luzyanin, K. V.; Kukushkin, V. Y.; Guedes da Silva, M. F. C.; Pombeiro, A. J. L. Organometallics 2012, 31, 2379. (72) Kinzhalov, M. A.; Boyarskiy, V. P.; Luzyanin, K. V.; Dolgushin, F. M.; Kukushkin, V. Y. Dalton Trans. 2013, 10394. (73) Khripun, A. V.; Kukushkin, V. Y.; Selivanov, S. I.; Haukka, M.; Pombeiro, A. J. L. Inorg. Chem. 2006, 45, 5066. (74) Arroyo, M.; Lopez-Sanvicente, A.; Miguel, D.; Villafane, F. Eur. J. Inorg. Chem. 2005, 4430. (75) Reisner, E.; Arion, V. B.; Rufińska, A.; Chiorescu, I.; Schmid, W. F.; Keppler, B. K. J. Chem. Soc., Dalton Trans. 2005, 2355. (76) Hsieh, C.-C.; Lee, C.-J.; Horng, Y.-C. Organometallics 2009, 28, 4923. (77) Liu, X. L.; Chen, W. Z. Dalton Trans. 2012, 599. (78) Luzyanin, K. V.; Tskhovrebov, A. G.; Carias, M. C.; Guedes da Silva, M. F. C.; Pombeiro, A. J. L.; Kukushkin, V. Y. Organometallics 2009, 28, 6559. (79) Yakimanskiy, A.; Boyarskaya, I.; Boyarskiy, V. J. Coord. Chem. 2013, 66, 3592. (80) Rocha, B. G. M.; Valishina, E. A.; Chay, R. S.; Guedes da Silva, M. F. C.; Buslaeva, T. M.; Pombeiro, A. J. L.; Kukushkin, V. Y.; Luzyanin, K. V. J. Catal. 2014, 309, 79. (81) Valishina, E. A.; Buslaeva, T. M.; Luzyanin, K. V. Russ. Chem. Bull. 2013, 62, 1361. (82) Kinzhalov, M. A.; Boyarskiy, V. P.; Luzyanin, K. V.; Dolgushin, F. M.; Kukushkin, V. Y. Organometallics 2013, 32, 5212. (83) Fehlhammer, W. P.; Bartel, K.; Metzner, R.; Beck, W. Z. Anorg. Allg. Chem. 2008, 634, 1002. (84) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290. (85) Hubbert, C.; Breunig, M.; Carroll, K. J.; Rominger, F.; Hashmi, A. S. K. Aust. J. Chem. 2014, 67, 469. (86) Hashmi, A. S. K.; Lothschütz, C.; Böhling, C.; Hengst, T.; Hubbert, C.; Rominger, F. Adv. Synth. Catal. 2010, 352, 3001. (87) Spallek, M. J.; Riedel, D.; Rominger, F. A.; Hashmi, A. S. K.; Trapp, O. Organometallics 2012, 31, 1127. (88) Ruiz, J.; Perandones, B. F.; García, G.; Mosquera, M. E. G. Organometallics 2007, 26, 5687. (89) Hashmi, A. S. K.; Lothschütz, C.; Graf, K.; Häffner, T.; Schuster, A.; Rominger, F. Adv. Synth. Catal. 2011, 353, 1407. (90) Hahn, F. E.; Tamm, M. J. Chem. Soc., Chem. Commun. 1995, 569. (91) Hahn, F. E. Angew. Chem., Int. Ed. Engl. 1993, 32, 650. (92) Hahn, F. E.; Tamm, M. Coord. Chem. Rev. 1999, 182, 175. (93) Hahn, F. E.; Tamm, M.; Lügger, T. Angew. Chem., Int. Ed. Engl. 1994, 33, 1356. (94) Hahn, F. E.; Tamm, M. Organometallics 1995, 14, 2597. (95) Hahn, F. E.; Tamm, M. Organometallics 1997, 16, 763. (96) Edwards, P. G.; Hahn, F. E. Dalton Trans. 2011, 40, 10278. (97) Hahn, F. E. ChemCatChem 2013, 5, 419. (98) Hahn, F. E.; Langenhahn, V.; Meier, N.; Lügger, T.; Fehlhammer, W. P. Chem.Eur. J. 2003, 9, 704. (99) Hahn, F. E.; Langenhahn, V.; Pape, T. Chem. Commun. 2005, 5390. (100) Hahn, F. E.; García Plumed, C.; Münder, M.; Lügger, T. Chem.Eur. J. 2004, 10, 6285. (101) Dumke, A. C.; Pape, T.; Kösters, J.; Feldmann, K.-O.; Schulte to Brinke, C.; Hahn, F. E. Organometallics 2013, 32, 289. (102) Basato, M.; Facchin, G.; Michelin, R. A.; Mozzon, M.; Pugliese, S.; Sgarbossa, P.; Tassan, A. Inorg. Chim. Acta 2003, 356, 349. (103) Ng, C.-O.; Yiu, S.-M.; Ko, C.-C. Inorg. Chem. 2014, 53, 3022. (104) Ko, C.-C.; Ng, C.-O.; Yiu, S.-M. Organometallics 2012, 31, 7074. (105) Flores-Figueroa, A.; Kaufhold, O.; Feldmann, K.-O.; Hahn, F. E. Dalton Trans. 2009, 9334. (106) Flores-Figueroa, A.; Pape, T.; Weigand, J. J.; Hahn, F. E. Eur. J. Inorg. Chem. 2010, 2907. (107) Kaufhold, O.; Stasch, A.; Edwards, P. G.; Hahn, F. E. Chem. Commun. 2007, 1822.

(108) Kaufhold, O.; Stasch, A.; Pape, T.; Hepp, A.; Edwards, P. G.; Newman, P. D.; Hahn, F. E. J. Am. Chem. Soc. 2009, 131, 306. (109) Basato, M.; Benetollo, F.; Facchin, G.; Michelin, R. A.; Mozzon, M.; Pugliese, S.; Sgarbossa, P.; Sbovata, S. M.; Tassan, A. J. Organomet. Chem. 2004, 689, 454. (110) Facchin, G.; Michelin, R.; Mozzon, M.; Pugliese, S.; Sgarbossa, P.; Tassan, A. Inorg. Chem. Commun. 2002, 5, 915. (111) Facchin, G.; Michelin, R.; Mozzon, M.; Sgarbossa, P.; Tassan, A. Inorg. Chim. Acta 2004, 357, 3385. (112) Flores-Figueroa, A.; Pape, T.; Feldmann, K.-O.; Hahn, F. E. Chem. Commun. 2010, 324. (113) Hahn, F. E.; Langenhahn, V.; Lügger, T.; Pape, T.; Le Van, D. Angew. Chem., Int. Ed. 2005, 44, 3759. (114) Blase, V.; Flores-Figueroa, A.; Schulte to Brinke, C.; Hahn, F. E. Organometallics 2014, 33, 4471. (115) Facchin, G.; Michelin, R. A.; Mozzon, M.; Tassan, A. J. Organomet. Chem. 2002, 662, 70. (116) Hahn, F. E.; Klusmann, D.; Pape, T. Eur. J. Inorg. Chem. 2008, 4420. (117) Conrady, F. M.; Fröhlich, R.; Schulte to Brinke, C.; Pape, T.; Hahn, F. E. J. Am. Chem. Soc. 2011, 133, 11496. (118) Schmidtendorf, M.; Pape, T.; Hahn, F. E. Dalton Trans. 2013, 42, 16128. (119) Schmidtendorf, M.; Pape, T.; Hahn, F. E. Angew. Chem., Int. Ed. 2012, 51, 2195. (120) Vicente, J.; Abad, J.-A.; Lopez-Serrano, J.; Jones, P. G.; Najera, C.; Botella-Segura, L. Organometallics 2005, 24, 5044. (121) Wanniarachchi, Y. A.; Slaughter, L. M. Chem. Commun. 2007, 3294. (122) Wanniarachchi, Y. A.; Subramanium, S. S.; Slaughter, L. M. J. Organomet. Chem. 2009, 694, 3297. (123) Wanniarachchi, Y. A.; Slaughter, L. M. Organometallics 2008, 27, 1055. (124) Owusu, M. O.; Handa, S.; Slaughter, L. M. Appl. Organomet. Chem. 2012, 26, 712. (125) Savicheva, E. A.; Kurandina, D. V.; Nikiforov, V. A.; Boyarskiy, V. P. Tetrahedron Lett. 2014, 55, 2101. (126) Miltsov, S.; Karavan, V.; Boyarsky, V.; Gómez-de Pedro; AlonsoChamarro, S. J.; Puyol, M. Tetrahedron Lett. 2013, 54, 1202. (127) Ryabukhin, D. S.; Sorokoumov, V. N.; Savicheva, E. A.; Boyarskiy, V. P.; Balova, I. A.; Vasilyev, A. V. Tetrahedron Lett. 2013, 54, 2369. (128) Khaibulova, T. S.; Boyarskaya, I. A.; Boyarskii, V. P. Russ. J. Org. Chem. 2013, 49, 360. (129) Tskhovrebov, A. G.; Luzyanin, K. V.; Kuznetsov, M. L.; Sorokoumov, V. N.; Balova, I. A.; Haukka, M.; Kukushkin, V. Y. Organometallics 2011, 30, 863. (130) Tskhovrebov, A. G.; Luzyanin, K. V.; Dolgushin, F. M.; Guedes da Silva, M. F. C.; Pombeiro, A. J. L.; Kukushkin, V. Y. Organometallics 2011, 30, 3362. (131) Kinzhalov, M. A.; Luzyanin, K. V.; Boyarskiy, V. P.; Haukka, M.; Kukushkin, V. Y. Russ. Chem. Bull. 2013, 62, 758. (132) Gonzalez-Fernandez, E.; Rust, J.; Alcarazo, M. Angew. Chem., Int. Ed. 2013, 52, 11392. (133) Viguri, M. E.; Huertos, M. A.; Perez, J.; Riera, L. Chem.Eur. J. 2013, 19, 12974. (134) Amor, F.; Sanchez-Nieves, J.; Royo, P.; Jacobsen, H.; Blacque, O.; Berke, H.; Lanfranchi, M.; Pellinghelli, M. A.; Tiripicchio, A. Eur. J. Inorg. Chem. 2002, 2810. (135) Alvarez, M. A.; Alvarez, B.; Garcı ́a, M. E.; Garcı ́a-Vivó, D.; Ruiz, M. A. Dalton Trans. 2013, 11039. (136) Fulton, J. R.; Holland, A. W.; Fox, D. J.; Bergman, R. G. Acc. Chem. Res. 2002, 35, 44. (137) Evrard, D.; Clement, S.; Lucas, D.; Hanquet, B.; Knorr, M.; Strohmann, C.; Decken, A.; Mugnier, Y.; Harvey, P. D. Inorg. Chem. 2006, 45, 1305. (138) Ma, J.-F.; Kojima, Y.; Yamamoto, Y. J. Organomet. Chem. 2000, 616, 149. BY


Chemical Reviews

Review

(139) Schuster, O.; Yang, L.; Raubenheimer, H. G.; Albrecht, M. Chem. Rev. 2009, 109, 3445. (140) Crabtree, R. H. Coord. Chem. Rev. 2013, 257, 755. (141) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 8168. (142) Oliva-Madrid, M.-J.; Garcı ́a-Loṕ ez, J.-A.; Saura-Llamas, I.; Bautista, D.; Vicente, J. Organometallics 2014, 33, 19. (143) Bryndza, H. E.; Tam, W. Chem. Rev. 1988, 88, 1163. (144) Roering, A. J.; Elrod, L. T.; Pagano, J. K.; Guillot, S. L.; Chan, S. M.; Tanski, J. M.; Waterman, R. Dalton Trans. 2013, 1159. (145) Vicente, J.; Abad, J. A.; Lopez-Saez, M.-J.; Jones, P. G. Angew. Chem., Int. Ed. 2005, 44, 6001. (146) Vicente, J.; Abad, J.-A.; Lopez-Saez, M.-J.; Jones, P. G.; Bautista, D. Chem.Eur. J. 2010, 16, 661. (147) De Angelis, F.; Fantacci, S.; Sgamellotti, A.; Re, N. Theor. Chem. Acc. 2003, 110, 196. (148) Semproni, S. P.; Graham, P. M.; Buschhaus, M. S. A.; Patrick, B. O.; Legzdins, P. Organometallics 2009, 28, 4480. (149) Ribeiro, A. F. G.; Gomes, P. T.; Dias, A. R.; Ferreira da Silva, J. L.; Duarte, M. T.; Henriques, R. T.; Freire, C. Polyhedron 2004, 23, 2715. (150) Martins, A. M.; Ascenso, J. R.; de Azevedo, C. G.; Dias, A. R.; Duarte, M. T.; da Silva, J. F.; Veiros, L. F.; Rodrigues, S. S. Organometallics 2003, 22, 4218. (151) Cano, J.; Sudupe, M.; Royo, P.; Mosquera, M. E. G. Organometallics 2005, 24, 2424. (152) Cano, J.; Sudupe, M.; Royo, P. J. Organomet. Chem. 2007, 692, 4448. (153) CRC Handbook of Chemistry and Physics, 81st ed.; Lide, D. R., Ed.; CRC Press: New York, 2000. (154) Fandos, R.; Gallego, B.; Otero, A.; Rodriguez, A.; Ruiz, M. J.; Terreros, P.; Pastor, C. Dalton Trans. 2006, 2683. (155) Bo, C.; Fandos, R.; Feliz, M.; Hernandez, C.; Otero, A.; Rodriguez, A.; Ruiz, M. J.; Pastor, C. Organometallics 2006, 25, 3336. (156) Wu, J.; Sharp, P. R. Organometallics 2008, 27, 4810. (157) Barnea, E.; Andrea, T.; Berthet, J.-C.; Ephritikhine, M.; Eisen, M. S. Organometallics 2008, 27, 3103. (158) Cook, K. S.; Piers, W. E.; Patrick, B. O.; McDonald, R. Can. J. Chem. 2003, 81, 1137. (159) Zhang, Y.; Keaton, R. J.; Sita, L. R. J. Am. Chem. Soc. 2003, 125, 8746. (160) Sebastı ́an, A.; Royo, P.; Gómez-Sal, P.; Ramı ́rez de Arellano, C. Eur. J. Inorg. Chem. 2004, 3814. (161) Fernández-Galán, R.; Antiñolo, A.; Carrillo-Hermosilla, F.; López-Solera, I.; Otero, A.; Serrano-Laguna, A.; Villaseñ or, E. Organometallics 2012, 31, 8360. (162) Abellán-López, A.; Chicote, M.-T.; Bautista, D.; Vicente, J. Organometallics 2012, 31, 7434. (163) Kofod, P.; Harris, P.; Larsen, S. Inorg. Chem. 2003, 42, 244. (164) Fernández-Gallardo, J.; Bellarosa, L.; Ujaque, G.; Lledós, A.; Ruiz, M. J.; Fandos, R.; Otero, A. Organometallics 2012, 31, 7052. (165) Hsiao, J.; Su, M.-D. Organometallics 2008, 27, 4139. (166) Vlaar, T.; Mampuys, P.; Helliwell, M.; Maes, B. U. W.; Orru, R. V. A.; Ruijter, E. J. Org. Chem. 2013, 78, 6735. (167) Thomson, R. K.; Schafer, L. L. Organometallics 2010, 29, 3546. (168) Durfee, L. D.; Rothwell, I. P. Chem. Rev. 1988, 88, 1059. (169) Vicente, J.; Abad, J.-A.; Hernandez-Mata, F. S.; Rink, B.; Jones, P. G.; Ramirez de Arellano, M. C. Organometallics 2004, 23, 1292. (170) Khripun, A. V.; Kukushkin, V. Y.; Selivanov, S. I.; Haukka, M.; Pombeiro, A. J. L. Inorg. Chem. 2006, 45, 5073. (171) Chernyshev, A. N.; Bokach, N. A.; Gushchin, P. V.; Haukka, M.; Kukushkin, V. Y. Dalton Trans. 2012, 12857. (172) Lee, J. P.; Pittard, K. A.; DeYonker, N. J.; Cundari, T. R.; Gunnoe, T. B.; Petersen, J. L. Organometallics 2006, 25, 1500. (173) Tsurugi, H.; Ohno, T.; Yamagata, T.; Mashima, K. Organometallics 2006, 25, 3179. (174) Vicente, J.; Abad, J.-A.; Martinez-Viviente, E.; Jones, P. G. Organometallics 2002, 21, 4454. (175) Knorr, M.; Jourdain, I.; Braunstein, P.; Strohmann, C.; Tiripicchio, A.; Ugozzoli, F. Dalton Trans. 2006, 5248.

(176) Elgazwy, A.-S. S. H. Appl. Organomet. Chem. 2007, 21, 1041. (177) Lu, E.; Chen, Y.; Leng, X. Organometallics 2011, 30, 5433. (178) Zhang, J.; Yi, W.; Zhang, Z.; Chen, Z.; Zhou, X. Organometallics 2011, 30, 4320. (179) Podiyanachari, S. K.; Fröhlich, R.; Daniliuc, C. G.; Petersen, J. L.; Kehr, G.; Erker, G.; Suzuki, N.; Yuasa, S.; Hagimori, K.; Inoue, S.; Asada, T.; Takemoto, T.; Masuyama, Y. Dalton Trans. 2012, 10811. (180) McGovern, G. P.; Hung-Low, F.; Tye, J. W.; Bradley, C. A. Organometallics 2012, 31, 3865. (181) Weinert, C. S.; Fanwick, P. E.; Rothwell, I. P. Organometallics 2005, 24, 5759. (182) Fandos, R.; Fernández-Gallardo, J.; Otero, A.; Rodrı ́guez, A.; Ruiz, M. J. Organometallics 2011, 30, 1551. (183) Fernández-Gallardo, J.; Bajo, A.; Fandos, R.; Otero, A.; Rodrı ́guez, A.; Ruiz, M. J. Organometallics 2013, 32, 1752. (184) Watanabe, T.; Kurogi, T.; Ishida, Y.; Kawaguchi, H. Dalton Trans. 2011, 7701. (185) Cabon, N.; Pétillon, F. Y.; Schollhammer, P.; Talarmin, J.; Muir, K. W. Dalton Trans. 2004, 2708. (186) Alvarez, C. M.; Alvarez, M. A.; Garcia, M. E.; Ramos, A.; Ruiz, M. A.; Lanfranchi, M.; Tiripicchio, A. Organometallics 2005, 24, 7. (187) Alvarez, M. A.; Garcı ́a, M. E.; Garcı ́a-Vivo,́ D.; Ruiz, M. A.; Vega, M. F. Organometallics 2013, 32, 4543. (188) Schafer, D. F.; Wolczanski, P. T.; Lobkovsky, E. B. Organometallics 2011, 30, 6539. (189) Duckett, S. B.; Lowe, J. P.; Mawby, R. J. Dalton Trans. 2006, 2661. (190) Hirai, T.; Han, L.-B. J. Am. Chem. Soc. 2006, 128, 7422. (191) Zalesskiy, S. S.; Ananikov, V. P. Organometallics 2012, 31, 2302. (192) Wicker, B. F.; Pink, M.; Mindiola, D. J. Dalton Trans. 2011, 9020. (193) Komeyama, K.; Sasayama, D.; Kawabata, T.; Takehira, K.; Takaki, K. Chem. Commun. 2005, 634. (194) Wiley, W. N. O.; Kang, X.; Luo, Y.; Hou, Z. Organometallics 2014, 33, 1030. (195) Barnea, E.; Andrea, T.; Kapon, M.; Berthet, J.-C.; Ephritikhine, M.; Eisen, M. S. J. Am. Chem. Soc. 2004, 126, 10860. (196) Evans, W. J.; Takase, M. K.; Ziller, J. W.; Rheingold, A. L. Organometallics 2009, 28, 5802. (197) Evans, W. J.; Walensky, J. R.; Ziller, J. W. Organometallics 2010, 29, 945. (198) Siladke, N. A.; Ziller, J. W.; Evans, W. J. J. Am. Chem. Soc. 2011, 133, 3507. (199) Takase, M. K.; Siladke, N. A.; Ziller, J. W.; Evans, W. J. Organometallics 2011, 30, 458. (200) Ferreira, M. J.; Matos, I.; Ascenso, J. R.; Duarte, M. T.; Marques, M. M.; Wilson, C.; Martins, A. M. Organometallics 2007, 26, 119. (201) Trunkely, E. F.; Epshteyn, A.; Zavalij, P. Y.; Sita, L. R. Organometallics 2010, 29, 6587. (202) Vujkovic, N.; Fillol, J. L.; Ward, B. D.; Wadepohl, H.; Mountford, P.; Gade, L. H. Organometallics 2008, 27, 2518. (203) Antiñolo, A.; Fernández-Galán, R.; Gallego, B.; Otero, A.; Prashar, S.; Rodrı ́guez, A. M. Eur. J. Inorg. Chem. 2003, 2626. (204) Antiñolo, A.; Fernández-Galán, R.; Otero, A.; Prashar, S.; Rivilla, I.; Rodrı ́guez, A. M. J. Organomet. Chem. 2006, 691, 2924. (205) Parfenova, L. V.; Berestova, T. V.; Molchankina, I. V.; Khalilov, L. M.; Whitby, R. J.; Dzhemilev, U. M. J. Organomet. Chem. 2013, 726, 37. (206) Ramos, C.; Royo, P.; Lanfranchi, M.; Pellinghelli, M. A.; Tiripicchio, A. Eur. J. Inorg. Chem. 2005, 3962. (207) Leshinski, S.; Shalumova, T.; Tanski, J. M.; Waterman, R. Dalton Trans. 2010, 9073. (208) Chen, L.; Nie, W.-L.; Paradies, J.; Kehr, G.; Froehlich, R.; Wedeking, K.; Erker, G. Organometallics 2006, 25, 5333. (209) Beweries, T.; Burlakov, V. V.; Peitz, S.; Bach, M. A.; Arndt, P.; Baumann, W.; Spannenberg, A.; Rosenthal, U. Organometallics 2007, 26, 6827. (210) Thomas, E.; Kasatkin, A. N.; Whitby, R. J. Tetrahedron Lett. 2006, 47, 9181. BZ


Chemical Reviews

Review

(211) Thomas, E.; Dixon, S.; Whitby, R. J. Tetrahedron 2007, 63, 11686. (212) Zhang, S.; Zhang, W. X.; Xi, Z. Chem.Eur. J. 2010, 16, 8419. (213) Spencer, L. P.; Fryzuk, M. D. J. Organomet. Chem. 2005, 690, 5788. (214) Waterman, R.; Tilley, T. D. Chem. Sci. 2011, 2, 1320. (215) Prashar, S.; Fajardo, M.; Garcés, A.; Dorado, I.; Antiñolo, A.; Otero, A.; López-Solera, I.; López-Mardomingo, C. J. Organomet. Chem. 2004, 689, 1304. (216) Galajov, M.; Garcı ́a, C.; Gómez, M.; Gómez-Sal, P. Dalton Trans. 2011, 2797. (217) Del Hierro, I.; Fernández-Galán, R.; Prashar, S.; Antiñolo, A.; Fajardo, M.; Rodrı ́guez, A. M.; Otero, A. Eur. J. Inorg. Chem. 2003, 2438. (218) Garcı ́a, C.; Gómez, M.; Gómez-Sal, P.; Hernández, J. M. Eur. J. Inorg. Chem. 2009, 4401. (219) Antiñolo, A.; García-Yuste, S.; Lopez-Solera, M. I.; Otero, A.; Pérez-Flores, J. C.; Reguillo-Carmona, R.; Villaseñor, E. Dalton Trans. 2006, 1495. (220) Antiñolo, A.; Garcı ́a-Yuste, S.; López Solera, I.; Otero, A.; PérezFlores, J. C.; Reguillo-Carmona, R.; Villaseñor, E.; Santos, E.; Zuidema, E.; Bo, C. Dalton Trans. 2010, 1962. (221) Elorriaga, D.; Carrillo-Hermosilla, F.; Antiñolo, A.; LópezSolera, I.; Menot, B.; Fernández-Galán, R.; Villaseñor, E.; Otero, A. Organometallics 2012, 31, 1840. (222) Galakhov, M. V.; Gómez, M.; Gómez-Sal, P.; Velasco, P. Organometallics 2005, 24, 3552. (223) Sanchez-Nieves, J.; Royo, P.; Mosquera, M. E. G. Eur. J. Inorg. Chem. 2006, 127. (224) Anderson, L. L.; Schmidt, J. A. R.; Arnold, J.; Bergman, R. G. Organometallics 2006, 25, 3394. (225) Fandos, R.; Fernandez-Gallardo, J.; Lopez-Solera, M. I.; Otero, A.; Rodriguez, A.; Ruiz, M. J.; Terreros, P. Organometallics 2008, 27, 4803. (226) Fandos, R.; Fernandez-Gallardo, J.; Otero, A.; Rodriguez, A.; Ruiz, M. J. Organometallics 2010, 29, 5834. (227) Galajov, M.; Garcı ́a, C.; Gómez, M. Dalton Trans. 2011, 40, 413. (228) Ison, E. A.; Ortiz, C. O.; Abboud, K.; Boncella, J. M. Organometallics 2005, 24, 6310. (229) Semproni, S. P.; Legzdins, P. Organometallics 2009, 28, 6139. (230) Liu, L.-J.; Bi, S.-W.; Yuan, X.-A.; Ling, B.-P.; Sun, H.-T.; Li, P. Wuji Huaxue Xuebao 2012, 28, 551. (231) Becker, T. M.; Alexander, J. J.; Bauer, J. A. K.; Nauss, J. L.; Wireko, F. C. Organometallics 1999, 18, 5594. (232) Alexander, J. J.; Padolik, L. L.; Ho, D. M. Inorg. Chim. Acta 1995, 240, 495. (233) Albano, V. G.; Busetto, L.; Marchetti, F.; Monari, M.; Zacchini, S.; Zanotti, V. Organometallics 2007, 26, 3448. (234) Zhu, C.; Xie, W.; Falck, J. R. Chem.Eur. J. 2011, 17, 12591. (235) Vicente, J.; Chicote, M. T.; Vicente-Hernandez, I.; Bautista, D. Inorg. Chem. 2007, 46, 8939. (236) Vicente, J.; Abad, J.-A.; Martinez-Viviente, E.; Jones, P. G. Organometallics 2003, 22, 1967. (237) Vicente, J.; Saura-Llamas, I.; Garcı ́a-López, J.-A.; CalmuschiCula, B.; Bautista, D. Organometallics 2007, 26, 2768. (238) Vicente, J.; Saura-Llamas, I.; Garcı ́a-López, J.-A.; Bautista, D. Organometallics 2009, 28, 448. (239) Vicente, J.; Chicote, M. T.; Martinez-Martinez, A. J.; AbellanLopez, A.; Bautista, D. Organometallics 2010, 29, 5693. (240) Vicente, J.; González-Herrero, P.; Frutos-Pedreño, R.; Chicote, M.-T.; Jones, P. G.; Bautista, D. Organometallics 2011, 30, 1079. (241) Vicente, J.; Saura-Llamas, I.; Gruenwald, C.; Alcaraz, C.; Jones, P. G.; Bautista, D. Organometallics 2002, 21, 3587. (242) Vicente, J.; Abad, J.-A.; Clemente, R.; Lopez-Serrano, J.; Ramirez de Arellano, M. C.; Jones, P. G.; Bautista, D. Organometallics 2003, 22, 4248. (243) Vicente, J.; Abad, J.-A.; Lopez-Serrano, J.; Jones, P. G. Organometallics 2004, 23, 4711. (244) Vicente, J.; Saura-Llamas, I. Comments Inorg. Chem. 2007, 28, 39.

(245) Vicente, J.; Chicote, M. T.; Martinez-Martinez, A. J.; Jones, P. G.; Bautista, D. Organometallics 2008, 27, 3254. (246) Vicente, J.; Chicote, M. T.; Martinez-Martinez, A. J.; Bautista, D. Organometallics 2009, 28, 5915. (247) Vicente, J.; Abad, J. A.; Lopez-Nicolas, R.-M.; Jones, P. G. Organometallics 2011, 30, 4983. (248) Chicote, M.-T.; Vicente-Hernandez, I.; Jones, P. G.; Vicente, J. Organometallics 2012, 31, 6252. (249) Oliva-Madrid, M.-J.; Garcı ́a-López, J.-A.; Saura-Llamas, I.; Bautista, D.; Vicente, J. Organometallics 2012, 31, 3647. (250) Abellan-Lopez, A.; Chicote, M.-T.; Bautista, D.; Vicente, J. Dalton Trans. 2014, 43, 592. (251) Vicente, J.; Abad, J. A.; Förtsch, W.; López-Sáez, M. J.; Jones, P. G. Organometallics 2004, 23, 4414. (252) (a) Frutos-Pedreño, R.; González-Herrero, P.; Vicente, J.; Jones, P. G. Organometallics 2013, 32, 4664. (b) Frutos-Pedreño, R.; GonzálezHerrero, P.; Vicente, J.; Jones, P. G. Organometallics 2013, 32, 1892. (253) Abellan-Lopez, A.; Chicote, M.-T.; Bautista, D.; Vicente, J. Organometallics 2013, 32, 7612. (254) Vicente, J.; Abad, J.-A.; Frankland, A. D.; Lopez-Serrano, J.; Ramirez de Arellano, M. C.; Jones, P. G. Organometallics 2002, 21, 272. (255) Vicente, J.; Abad, J.-A.; Foertsch, W.; Jones, P. G.; Fischer, A. K. Organometallics 2001, 20, 2704. (256) Oliva-Madrid, M.-J.; Garcı ́a-Loṕ ez, J.-A.; Saura-Llamas, I.; Bautista, D.; Vicente, J. Organometallics 2014, 33, 6420. (257) Vicente, J.; Saura-Llamas, I.; Turpin, J.; Bautista, D.; Ramirez de Arellano, C.; Jones, P. G. Organometallics 2009, 28, 4175. (258) Garcı ́a-López, J.-A.; Oliva-Madrid, M.-J.; Saura-Llamas, I.; Bautista, D.; Vicente, J. Organometallics 2012, 31, 6351. (259) Vicente, J.; Saura-Llamas, I.; Garcı ́a-Loṕ ez, J.-A.; Bautista, D. Organometallics 2010, 29, 4320. (260) Vicente, J.; Arcas, A.; Fernandez-Hernandez, J. M.; Bautista, D.; Jones, P. G. Organometallics 2005, 24, 2516. (261) Morishita, M.; Amii, H. J. Organomet. Chem. 2007, 692, 620. (262) Albert, J.; D’Andrea, L.; Granell, J.; Zafrilla, J.; Font-Bardia, M.; Solans, X. J. Organomet. Chem. 2007, 692, 4895. (263) Canovese, L.; Visentin, F.; Santo, C.; Levi, C.; Dolmella, A. Organometallics 2007, 26, 5590. (264) Kim, Y.-J.; Lee, K.-E.; Jeon, H.-T.; Huh, H. S.; Lee, S. W. Inorg. Chim. Acta 2008, 361, 2159. (265) Bortoluzzi, M.; Paolucci, G.; Pitteri, B.; Vavasori, A.; Bertolasi, V. Organometallics 2009, 28, 3247. (266) Canovese, L.; Visentin, F.; Santo, C.; Levi, C. Organometallics 2009, 28, 6762. (267) Canovese, L.; Chessa, G.; Visentin, F. Inorg. Chim. Acta 2010, 363, 3426. (268) Canovese, L.; Visentin, F.; Santo, C.; Bertolasi, V. Organometallics 2014, 33, 1700. (269) Hornung, M.; Wesemann, L. Eur. J. Inorg. Chem. 2010, 2949. (270) Vicente, J.; Arcas, A.; Julia-Hernandez, F.; Bautista, D.; Jones, P. G. Organometallics 2010, 29, 3066. (271) Han, Y.; Yuan, D.; Teng, Q.; Huynh, H. V. Organometallics 2011, 30, 1224. (272) Frutos-Pedreño, R.; González-Herrero, P.; Vicente, J.; Jones, P. G. Organometallics 2012, 31, 3361. (273) Zhou, X.; Jordan, R. F. Organometallics 2011, 30, 4632. (274) Vidavsky, Y.; Anaby, A.; Lemcoff, N. G. Dalton Trans. 2012, 32. (275) Tsuchiya, K.; Kondo, H.; Nagashima, H. Organometallics 2007, 26, 1044. (276) Asaoka, S.; Joza, A.; Minagawa, S.; Song, L.; Suzuki, Y.; Iyoda, T. ACS Macro Lett. 2013, 2, 906. (277) Fei, X.-D.; Tang, T.; Ge, Z.-Y.; Zhu, Y.-M. Synth. Commun. 2013, 43, 3262. (278) Van, B. G.; Kuijer, S.; Rýcě k, L.; Sergeyev, S.; Janssen, E.; de Kanter, F. J. J.; Maes, B. U. W.; Ruijter, E.; Orru, R. V. A. Chem.Eur. J. 2011, 17, 15039. (279) Estévez, V.; Van Baelen, G.; Lentferink, B. H.; Vlaar, T.; Janssen, E.; Maes, B. U. W.; Orru, R. V. A.; Ruijter, E. ACS Catal. 2014, 4, 40. CA


Chemical Reviews

Review

(280) Gu, Z.-Y.; Zhu, T.-H.; Cao, J.-J.; Xu, X.-P.; Wang, S.-Y.; Ji, S.-J. ACS Catal. 2014, 4, 49. (281) Jiang, B.; Hu, L.; Gui, W. RSC Adv. 2014, 4, 13850. (282) Tang, T.; Jiang, X.; Wang, J.-M.; Sun, Y.-X.; Zhu, Y.-M. Tetrahedron 2014, 70, 2999. (283) Vlaar, T.; Maes, B. U. W.; Ruijter, E.; Orru, R. V. A. Chem. Heterocycl. Compd. 2013, 49, 902. (284) Nanjo, T.; Yamamoto, S.; Tsukano, C.; Takemoto, Y. Org. Lett. 2013, 15, 3754. (285) Wang, D.; Cai, S.; Ben, R.; Zhou, Y.; Li, X.; Zhao, J.; Wei, W.; Qian, Y. Synthesis 2014, 46, 2045. (286) Ji, F.; Lv, M.-f.; Yi, W.-b.; Cai, C. Adv. Synth. Catal. 2013, 355, 3401. (287) Tang, T.; Fei, X.-D.; Ge, Z.-Y.; Chen, Z.; Zhu, Y.-M.; Ji, S.-J. J. Org. Chem. 2013, 78, 3170. (288) Chen, Z.; Duan, H.; Jiang, X.; Wang, J.; Zhu, Y.; Yang, S. Synlett 2014, 25, 1425. (289) Fang, T.; Tan, Q.; Ding, Z.; Liu, B.; Xu, B. Org. Lett. 2014, 16, 2342. (290) Fernandez, I.; Cossio, F. P.; Sierra, M. A. Organometallics 2007, 26, 3010. (291) Barluenga, J.; Garcia-Rodriguez, J.; Martinez, S.; Suarez-Sobrino, A. L.; Tomas, M. Chem.Eur. J. 2006, 12, 3201. (292) Cadierno, V.; Diez, J.; Garcia-Alvarez, J.; Gimeno, J. Organometallics 2008, 27, 1809. (293) Tobisu, M.; Fujihara, H.; Koh, K.; Chatani, N. J. Org. Chem. 2010, 75, 4841. (294) Zirngast, M.; Baumgartner, J.; Marschner, C. Eur. J. Inorg. Chem. 2008, 1078. (295) Benetollo, F.; Carta, G.; Cavinato, G.; Crociani, L.; Paolucci, G.; Rossetto, G.; Veronese, F.; Zanella, P. Organometallics 2003, 22, 3985. (296) Kajitani, H.; Tanabe, Y.; Kuwata, S.; Iwasaki, M.; Ishii, Y. Organometallics 2005, 24, 2251. (297) Vlaar, T.; Cioc, R. C.; Mampuys, P.; Maes, B. U. W.; Orru, R. V. A.; Ruijter, E. Angew. Chem., Int. Ed. 2012, 51, 13058. (298) Lv, Y.; Kefalidis, C. E.; Zhou, J.; Maron, L.; Leng, X.; Chen, Y. J. Am. Chem. Soc. 2013, 135, 14784. (299) d’Arbeloff-Wilson, S. E.; Hitchcock, P. B.; Nixon, J. F.; Kawaguchi, H.; Tatsumi, K. J. Organomet. Chem. 2003, 672, 1. (300) MacMillan, S. N.; Tanski, J. M.; Waterman, R. Chem. Commun. 2007, 4172. (301) Roering, A. J.; Davidson, J. J.; MacMillan, S. N.; Tanski, J. M.; Waterman, R. Dalton Trans. 2008, 4488. (302) Maddox, A. F.; Davidson, J. J.; Shalumova, T.; Tanski, J. M.; Waterman, R. Inorg. Chem. 2013, 52, 7811. (303) Waterman, R.; Tilley, T. D. Inorg. Chem. 2006, 45, 9625. (304) Clement, S.; Guyard, L.; Knorr, M.; Dilsky, S.; Strohmann, C.; Arroyo, M. J. Organomet. Chem. 2007, 692, 839. (305) Clement, S.; Aly, S. M.; Bellows, D.; Fortin, D.; Strohmann, C.; Guyard, L.; Abd-El-Aziz, A. S.; Knorr, M.; Harvey, P. D. Inorg. Chem. 2009, 48, 4118. (306) Lis, E. C., Jr.; Delafuente, D. A.; Lin, Y.; Mocella, C. J.; Todd, M. A.; Liu, W.; Sabat, M.; Myers, W. H.; Harman, W. D. Organometallics 2006, 25, 5051. (307) Sivasankar, C.; Tuczek, F. Dalton Trans. 2006, 3396. (308) Sivasankar, C.; Boeres, N.; Peters, G.; Habeck, C. M.; Studt, F.; Tuczek, F. Organometallics 2005, 24, 5393. (309) Cunha, S. M. P. R. M.; Guedes da Silva, M. F. C.; Pombeiro, A. J. L. Inorg. Chem. 2003, 42, 2157. (310) Kukushkin, V. Y.; Pombeiro, A. J. L. Chem. Rev. 2002, 102, 1771. (311) Pombeiro, A. J. L.; Kukushkin, V. Y. Reactivity of coordinated nitriles. In Comprehensive Coordination Chemistry II; McCleverty, J. A., Meyer, T. J., Eds.; Elsevier Pergamon: New York, 2004; Chapter 1.34, pp 639−660. (312) Knorr, M.; Jourdain, I.; Lentz, D.; Willemsen, S.; Strohmann, C. J. Organomet. Chem. 2003, 684, 216. (313) Rosenblat, M. C.; Henderson, R. A. Inorg. Chim. Acta 2002, 331, 270.

(314) Spies, H.; Glaser, M.; Pietzsch, H.-J.; Hahn, F. E.; Lügger, T. Inorg. Chim. Acta 1995, 240, 465. (315) Cimadevilla, F.; García, M. E.; García-Vivo, D.; Ruiz, M. A.; Graiff, C.; Tiripicchio, A. Organometallics 2013, 32, 4624. (316) Demko, Z. P.; Sharpless, K. B. J. Org. Chem. 2001, 66, 7945. (317) Habibi, D.; Nasrollahzadeh, M.; Faraji, A. R.; Bayat, Y. Tetrahedron 2010, 66, 3866. (318) Huang, X.; Li, P.; Li, X.-S.; Xu, D.-C.; Xie, J.-W. Org. Biomol. Chem. 2010, 8, 4527. (319) Huh, H. S.; Lee, Y. K.; Lee, S. W. J. Mol. Struct. 2006, 789, 209. (320) Bokach, N. A.; Krokhin, A. A.; Nazarov, A. A.; Kukushkin, V. Y.; Haukka, M.; Fraústo da Silva, J. J. R.; Pombeiro, A. J. L. Eur. J. Inorg. Chem. 2005, 3042. (321) Bokach, N. A.; Khripoun, A. V.; Kukushkin, V. Y.; Haukka, M.; Pombeiro, A. J. L. Inorg. Chem. 2003, 42, 896. (322) Kritchenkov, A. S.; Bokach, N. A.; Haukka, M.; Kukushkin, V. Y. Dalton Trans. 2011, 40, 4175. (323) Kritchenkov, A. S.; Bokach, N. A.; Starova, G. L.; Kukushkin, V. Y. Inorg. Chem. 2012, 51, 11971. (324) Wagner, G.; Haukka, M. J. Chem. Soc., Dalton Trans. 2001, 2690. (325) Coley, H. M.; Sarju, J.; Wagner, G. J. Med. Chem. 2008, 51, 135. (326) Desai, B.; Danks, T. N.; Wagner, G. Dalton Trans. 2003, 2544. (327) Desai, B.; Danks, T. N.; Wagner, G. Dalton Trans. 2004, 166. (328) Wagner, G.; Marchant, A.; Sayer, J. Dalton Trans. 2010, 39, 7747. (329) Wagner, G.; Pombeiro, A. J. L.; Kukushkin, V. Y. J. Am. Chem. Soc. 2000, 122, 3106. (330) Charmier, M. A. J.; Haukka, M.; Pombeiro, A. J. L. Dalton Trans. 2004, 2741. (331) Lasri, J.; Guedes da Silva, M. F. C.; Kopylovich, M. N.; Mukhopadhyay, S.; Charmier, M. A. J.; Pombeiro, A. J. L. Dalton Trans. 2009, 2210. (332) Bokach, N. A.; Balova, I. A.; Haukka, M.; Kukushkin, V. Y. Organometallics 2011, 30, 595. (333) Makarycheva-Mikhailova, A. V.; Golenetskaya, J. A.; Bokach, N. A.; Balova, I. A.; Haukka, M.; Kukushkin, V. Y. Inorg. Chem. 2007, 46, 8323. (334) Bokach, N. A.; Kuznetsov, M. L.; Haukka, M.; Ovcharenko, V. I.; Tretyakov, E. V.; Kukushkin, V. Y. Organometallics 2009, 28, 1406. (335) Kim, Y.-J.; Kwak, Y.-S.; Joo, Y.-S.; Lee, S.-W. J. Chem. Soc., Dalton Trans. 2002, 144. (336) Wehlan, M.; Thiel, R.; Fuchs, J.; Beck, W.; Fehlhammer, W. P. J. Organomet. Chem. 2000, 613, 159. (337) Kim, Y.-J.; Joo, Y.-S.; Han, J.-T.; Han, W. S.; Lee, S.-W. J. Chem. Soc., Dalton Trans. 2002, 3611. (338) Gabrielli, W. F.; Nogai, S. D.; McKenzie, J. M.; Cronje, S.; Raubenheimer, H. G. New J. Chem. 2009, 33, 2208. (339) Jothibasu, R.; Huynh, H. V. Organometallics 2009, 28, 2505. (340) Fuchita, Y.; Hidaka, K.; Morinaga, S.; Hiraki, K. Bull. Chem. Soc. Jpn. 1981, 54, 800. (341) Luzyanin, K. V.; Tskhovrebov, A. G.; Guedes da Silva, M. F. C.; Haukka, M.; Pombeiro, A. J. L.; Kukushkin, V. Y. Chem.Eur. J. 2009, 15, 5969. (342) Kritchenkov, A. S.; Luzyanin, K. V.; Bokach, N. A.; Kuznetsov, M. L.; Gurzhiy, V. V.; Kukushkin, V. Y. Organometallics 2013, 32, 1979. (343) Novikov, A. S.; Kuznetsov, M. L.; Pombeiro, A. J. L. Chem.Eur. J. 2013, 19, 2874. (344) Carnahan, E. M.; Protasiewicz, J. D.; Lippard, S. J. Acc. Chem. Res. 1993, 26, 90. (345) Miller, A. J. M.; Labinger, J. A.; Bercaw, J. E. J. Am. Chem. Soc. 2008, 130, 11874. (346) Watanabe, T.; Ishida, Y.; Matsuo, T.; Kawaguchi, H. J. Am. Chem. Soc. 2009, 131, 3474. (347) Elowe, P. R.; West, N. M.; Labinger, J. A.; Bercaw, J. E. Organometallics 2009, 28, 6218. (348) West, N. M.; Miller, A. J. M.; Labinger, J. A.; Bercaw, J. E. Coord. Chem. Rev. 2011, 255, 881. (349) Dance, I. Dalton Trans. 2011, 40, 5516. (350) Hu, Y. L.; Lee, C. C.; Ribbe, M. W. Science 2011, 333, 753. (351) Hu, Y. L.; Lee, C. C.; Ribbe, M. W. Dalton Trans. 2012, 41, 1118. CB


Chemical Reviews

Review

(388) Halbauer, K.; Goerls, H.; Fidler, T.; Imhof, W. J. Organomet. Chem. 2007, 692, 1898. (389) Halbauer, K.; Dönnecke, D.; Görls, H.; Imhof, W. Z. Anorg. Allg. Chem. 2006, 632, 1477. (390) Tennent, C. L.; Jones, W. L. Can. J. Chem. 2005, 83, 626. (391) Dönnecke, D.; Imhof, W. Dalton Trans. 2003, 2737. (392) Zhang, L.; Fung, C. W.; Chan, K. S. Organometallics 2006, 25, 5381. (393) Kundu, S.; Brennessel, W. W.; Jones, W. D. Inorg. Chim. Acta 2011, 379, 109. (394) Samar, D.; Fortin, J.-F.; Fortin, D.; Decken, A.; Harvey, P. D. J. Inorg. Organomet. Polym. Mater. 2006, 15, 411. (395) Xu, S.; Huang, X.; Hong, X.; Xu, B. Org. Lett. 2012, 14, 4614. (396) Peng, J.; Zhao, J.; Hu, Z.; Liang, D.; Huang, J.; Zhu, Q. Org. Lett. 2012, 14, 4966. (397) Qiu, G.; Qiu, X.; Liu, J.; Wu, J. Adv. Synth. Catal. 2013, 355, 2441. (398) Evans, W. J.; Forrestal, K. J.; Ziller, J. W. J. Am. Chem. Soc. 1998, 120, 9273. (399) Lukens, W. W., Jr.; Andersen, R. A. Organometallics 1995, 14, 3435. (400) Gambarotta, S.; Floriani, C.; Chiesi-Villa, A.; Cuastini, C. Inorg. Chem. 1984, 23, 1739. (401) Greco, G. E.; O’Donoghue, M. B.; Seidel, S. W.; Davis, W. M.; Schrock, R. R. Organometallics 2000, 19, 1132. (402) Adachi, T.; Sasaki, N.; Ueda, T.; Kaminaka, M.; Yoshida, T. J. Chem. Soc., Chem. Commun. 1989, 1320. (403) Bell, A.; Lippard, S. J.; Roberts, M.; Walton, R. A. Organometallics 1983, 2, 1562. (404) Farr, J. P.; Abrams, M. J.; Costello, C. E.; Davison, A.; Lippard, S. J. Organometallics 1985, 4, 139. (405) Rodriguez, V.; Donnadieu, B.; Sabo-Etienne, S.; Chaudret, B. Organometallics 1998, 17, 3809. (406) Jones, W. D.; Kosar, W. P. Organometallics 1986, 5, 1823. (407) Tetrick, S. M.; Walton, R. A. Inorg. Chem. 1985, 24, 3363. (408) Werner, H.; Strecker, B. J. Organomet. Chem. 1989, 413, 379. (409) Poszmik, G.; Carroll, P. J.; Wayland, B. B. Organometallics 1993, 12, 3410. (410) Treichel, P. M.; Hess, R. W. J. Chem. Soc., Chem. Commun. 1970, 1626. (411) Tschugaeff, L.; Teearu, P. Chem. Ber. 1914, 47, 2643. (412) Crociani, B.; Nicolini, M.; Richards, R. L. Inorg. Chim. Acta 1975, 12, 53. (413) Otsuka, S.; Mori, K.; Yanagami, K. J. Org. Chem. 1966, 31, 4170. (414) Voelkl, A.; Achatz, D.; Schoder, F.; Zinner, G.; Stolzenberg, H.; Beck, W.; Fehlhammer, W. P. Z. Anorg. Allg. Chem. 2010, 636, 1339. (415) Lo, Y.-H.; Hsu, S.-C.; Huang, S.-L.; Lin, Y.-C.; Liu, Y.-H.; Wang, Y. Organometallics 2004, 23, 5924. (416) Yang, J.-Y.; Lo, Y.-H.; Huang, S.-L.; Lin, Y.-C. Organometallics 2001, 20, 3621. (417) Motoyama, Y.; Shimozono, K.; Aoki, K.; Nishiyama, H. Organometallics 2002, 21, 1684. (418) Kim, H. Y.; Oh, K. Org. Lett. 2011, 13, 1306. (419) Canseco-Gonzalez, D.; Petronilho, A.; Mueller-Bunz, H.; Ohmatsu, K.; Ooi, T.; Albrecht, M. J. Am. Chem. Soc. 2013, 135, 13193. (420) Yugandar, S.; Acharya, A.; la, H. J. Org. Chem. 2013, 78, 3948. (421) Aydin, J.; Kumar, K. S.; Eriksson, L.; Szabo, K. J. Adv. Synth. Catal. 2007, 349, 2585. (422) Kanazawa, C.; Kamijo, S.; Yamamoto, Y. J. Am. Chem. Soc. 2006, 128, 10662. (423) Bonin, M. A.; Giguere, D.; Roy, R. Tetrahedron 2007, 63, 4912. (424) Qiu, G. Y. S.; Wu, J. Chem. Commun. 2012, 6046. (425) Arróniz, C.; Gil-González, A.; Semak, V.; Escolano, C.; Bosch, J.; Amat, M. Eur. J. Org. Chem. 2011, 3755. (426) Zhao, M.-X.; Wei, D.-K.; Ji, F.-H.; Zhao, X.-L.; Shi, M. Chem. Asian J. 2012, 7, 2777. (427) Zhou, F. T.; Liu, J. G.; Ding, K.; Liu, J. S.; Cai, Q. J. Org. Chem. 2011, 76, 5346. (428) Zheng, D.; Wu, J. Eur. J. Org. Chem. 2014, 767. (429) Zheng, D.; Li, S.; Wu, J. Org. Lett. 2012, 14, 2655.

(352) Ojo, W.-S.; Petillon, F. Y.; Schollhammer, P.; Talarmin, J. Organometallics 2008, 27, 4207. (353) Okazaki, M.; Suto, K.; Kudo, N.; Takano, M.; Ozawa, F. Organometallics 2012, 31, 4110. (354) Carnahan, E. M.; Protasiewicz, J. D.; Lippard, S. J. Acc. Chem. Res. 1993, 26. (355) Collazo, C.; Rodewald, D.; H, S.; Rehder, D. Organometallics 1996, 15, 4884. (356) Wang, Y.; Fraústo da Silva, J. J. R.; Pombeiro, A. J. L.; Pellinghelli, M. A.; Tiripicchio, A.; Henderson, R. A.; Richards, R. L. J. Chem. Soc., Dalton Trans. 1995, 1183. (357) Acho, J. A.; Lippard, S. J. Organometallics 1994, 13, 1294. (358) Ichikawa, Y.; Ohara, F.; Kotsuki, H.; Nakano, K. Org. Lett. 2006, 8, 5009. (359) Ichikawa, Y.; Nishiyama, T.; Isobe, M. J. Org. Chem. 2001, 66, 4200. (360) Yonke, B. L.; Reeds, J. P.; Zavalij, P. Y.; Sita, L. R. Angew. Chem., Int. Ed. 2011, 50, 12342. (361) Alpoim, C. M.; Barrett, A. G. M.; Barton, D. H. R.; Hiberty, P. C. Nouv. J. Chim. 1980, 4, 127. (362) Martin, D. G. Ann. N. Y. Acad. Sci. 1967, 145, 161. (363) Feuer, H.; Rubinstein, H.; Nielsen, A. T. J. Org. Chem. 1958, 23, 1107. (364) Hiebl, J.; Zbiral, E. Liebigs Ann. Chem. 1988, 765. (365) Mironov, M. A. General aspects of isocyanide reactivity. In Isocyanide Chemistry; Nenajdenko, V. G., Ed.; Wiley-VCH Verlag: Weinheim, Germany, Germany, 2012; 2 pp. (366) Herdeis, C.; Syvari, J. Arch. Pharm. (Weinheim, Ger.) 1988, 321, 491. (367) Klobukowski, E. R.; Angelici, R. J.; Woo, L. K. Organometallics 2012, 31, 2785. (368) Tsuda, T. e-EROS Encyclopedia of Reagents for Organic Synthesis, DOI:10.1002/047084289X.rc212. (369) Angelici, R. J. Catal. Sci. Technol. 2013, 3, 279. (370) Adam, W.; Bargon, R. M.; Bosio, S. G.; Schenk, W. A.; Stalke, D. J. Org. Chem. 2002, 67, 7037. (371) Arisawa, M.; Ashikawa, M.; Suwa, A.; Yamaguchi, M. Tetrahedron Lett. 2005, 46, 1727. (372) Helton, M. E.; Maiti, D.; Zakharov, L. N.; Rheingold, A. L.; Porco, J. A.; Karlin, K. D. Angew. Chem., Int. Ed. 2006, 45, 1138. (373) Fukamachi, S.; Fujita, S.; Murahashi, K.; Konishi, H.; Kobayashi, K. Synthesis 2010, 2985. (374) Fujiwara, S.; Shin-Ike, T. Tetrahedron Lett. 1991, 32, 3503. (375) Moellendal, H.; Samdal, S.; Bunkan, A. J. C.; Guillemin, J.-C. J. Phys. Chem. A 2012, 116, 4074. (376) Chennakrishnareddy, G.; Nagendra, G.; Hemantha, H. P.; Das, U.; Guru, R. T. N.; Sureshbabu, V. V. Tetrahedron 2010, 66, 6718. (377) Evans, M. E.; Li, T.; Jones, W. D. J. Am. Chem. Soc. 2010, 132, 16278. (378) Garcia, J. J.; Arevalo, A.; Brunkan, N. M.; Jones, W. D. Organometallics 2004, 23, 3997. (379) Garcia, J. J.; Brunkan, N. M.; Jones, W. D. J. Am. Chem. Soc. 2002, 124, 9547. (380) Garcia, J. J.; Jones, W. D. Organometallics 2000, 19, 5544. (381) Li, X.; Sun, H.; Yu, F.; Floerke, U.; Klein, H.-F. Organometallics 2006, 25, 4695. (382) Xu, H.; Williard, P. G.; Bernskoetter, W. H. Organometallics 2012, 31, 1588. (383) Sharpe, A. G. Cyanides and Fulminates. In Comprehensive Coordination Chemistry; Wilkinson, G., Ed.; Pergamon Press: New York, 1987; pp. (384) Gardiner, M. G.; James, A. N.; Jones, C.; Schulten, C. Dalton Trans. 2010, 39, 6864. (385) Cabon, N.; Paugam, E.; Petillon, F. Y.; Schollhammer, P.; Talarmin, J.; Muir, K. W. Organometallics 2003, 22, 4178. (386) Ojo, W.-S.; Petillon, F. Y.; Schollhammer, P.; Talarmin, J. Organometallics 2008, 27, 4207. (387) Garcia, M. E.; Garcia-Vivo, D.; Ruiz, M. A.; Herson, P. Organometallics 2008, 27, 3879. CC


Chemical Reviews

Review

(430) Hou, H.; Gantzel, P. K.; Kubiak, C. P. Organometallics 2003, 22, 2817. (431) Adams, C. J.; Anderson, K. M.; Bartlett, I. M.; Connelly, N. G.; Orpen, A. G.; Paget, T. J. Organometallics 2002, 21, 3454. (432) Groom, L. R.; Russell, A. F.; Schwarz, A. D.; Mountford, P. Organometallics 2014, 33, 1002.

CD


Metal-Mediated and Metal-Catalyzed Reactions of Isocyanides

Recommend Documents