Complexes Bearing Protic N-Heterocyclic Carbene Ligands

Review pubs.acs.org/CR

Cite This: Chem. Rev. XXXX, XXX, XXX−XXX

Complexes Bearing Protic N‑Heterocyclic Carbene Ligands Shigeki Kuwata*,† and F. Ekkehardt Hahn*,‡ †

Chem. Rev. Downloaded from pubs.acs.org by NAGOYA UNIV on 06/25/18. For personal use only.

School of Materials and Chemical Technology, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan ‡ Institut für Anorganische und Analytische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstraße 30, D-48149 Münster, Germany ABSTRACT: Complexes bearing protic N-heterocyclic carbenes (protic NHCs, pNHCs), defined as cyclic carbenes stabilized by two heteroatoms including at least one NH group, have been less explored in comparison to the conventional N,N′disubstituted NHCs. The small and reactive NH group of the pNHCs differentiates this class of compounds from the classical NR,NR-NHCs with regard to their properties and reactivity. While the free pNHCs have so far eluded isolation due to isomerization to the azole tautomer, a significant number of transition-metal pNHC complexes have by now been prepared by a variety of methods. This article reviews the coordination chemistry of the pNHCs. Synthetic approaches toward complexes of pNHCs are first described, followed by a discussion of the properties and reactivity of pNHC complexes with emphasis on the Brønsted-acidic nature of the NH wingtip. Involvement of the pNHC ligands in catalytically active intermediates and in cooperative catalysis is also discussed.

CONTENTS 1. Introduction 2. Synthesis 2.1. Formal Tautomerization of Azoles 2.1.1. Acid/Base-Induced Reactions 2.1.2. Chelation-Assisted Reactions 2.1.3. Mechanistic Aspects 2.2. Protonation of C-Azolyl Complexes 2.2.1. Transmetalation of C-Lithiated Azoles and Subsequent Protonation 2.2.2. Oxidative Addition of 2-Haloazoles Followed by Protonation 2.3. Oxidative Addition of Imidazolium Cations 2.4. Annulation or Cyclization at a Metal Template 2.4.1. Annulation of Isocyanide and Carbonyl Complexes 2.4.2. Template-Controlled Cyclization of Functionalized Isocyanides 2.4.3. Annulation of Carbene Complexes 2.4.4. Synthesis of Protic Cyclic Alkylaminocarbene Complexes 2.5. Deprotection of N-Masked NHC Complexes 3. BrØnsted Acidity and Related Properties 3.1. Deprotonation of pNHC Ligands 3.2. Deprotonation-Induced Reactions 3.2.1. N-Functionalization Reactions 3.2.2. Metal−Ligand Cooperative Reactivity 3.2.3. Metalation and Carbene Transfer Reactions 4. Complexes Bearing pNHC in Catalysis

© XXXX American Chemical Society

4.1. Intermediary pNHC Complexes Originating from Catalytic Substrates 4.2. Catalysts with Built-in pNHC Ligands 5. Summary and Outlook Author Information Corresponding Authors ORCID Notes Biographies Acknowledgments Abbreviations References

A C C C D G I I I J

X Z AA AB AB AB AB AB AB AB AB

1. INTRODUCTION N-Heterocyclic carbenes (NHCs) continue to develop into a class of effective and versatile ligands1−4 in coordination chemistry and related research fields ranging from homogeneous5 and immobilized heterogeneous6 catalysis to supramolecular chemistry,7,8 materials sciences,9 and biomedical applications.10,11 In most scenarios, the NHCs act as excellent spectator ligands owing to their chemical robustness. The electronic and steric tunability is an additional attractive feature of NHCs.12,13 The strong σ-donor properties of NHCs can be modified by the substituents at the nitrogen atoms as well as at the carbon backbone of the heterocyclic skeleton. Bulky groups on the ring-nitrogen atoms do exert an additional impact on the

K K N O P Q Q R T T U

Special Issue: Carbene Chemistry

W X

Received: March 19, 2018

A

DOI: 10.1021/acs.chemrev.8b00176 Chem. Rev. XXXX, XXX, XXX−XXX

Chemical Reviews

Review

2-ylidene form would be favored in the coordination sphere by a large substituent at the C5 position and a small one at the N3 position of the heterocycle.23 Furthermore, suitably located Brønsted-basic coligands significantly contribute to stabilization of the pNHC ligands through intramolecular hydrogen bonding,23 highlighting once more the Brønsted-acidic character of the pNHC ligand. The importance of intramolecular hydrogen bonding in the stabilization of protic carbene ligands has also been described for related dihydropyridin-2-ylidene24 complexes featuring an NH group.25 As they lack the isolable metal-free form, the coordination chemistry of pNHCs has been much less explored than that of their nonprotic analogues. The first synthesis of a complex bearing a pNHC ligand was achieved by Sundberg and Taube through acid-induced tautomerization of imidazole, a synthetic method unique to the preparation of pNHC complexes, in 1972 (Figure 2 and Scheme 2a).26,27 The Brønsted-acidic nature of the wingtip NH group in these complexes was soon demonstrated by the reversible deprotonation and formation of hydrogenbonding contacts with counterions in selected crystal structures.27 The acidic character of the NH group also led to the development of base-induced N-functionalization of pNHC complexes by Angelici and co-workers.28 As expected from the acid−base chemistry, protonation of azolyl complexes provides rational access to pNHC complexes (Scheme 2b). On the other hand, isocyanide ligands have been recognized as useful building blocks for the construction of pNHCs on metal templates, starting with the pioneering work on the cyclization of functionalized isocyanides by Fehlhammer group in 1974 (Scheme 2c).29 Nucleophilic substitution of Fischer carbene complexes also offers an annulative route to the pNHC complexes, as first demonstrated by Angelici in 1979 (Scheme 2d).30 Some significant breakthroughs in pNHC chemistry were realized in the late 2000s. A decade after the initial report by Houlton in 1997,31 chelation-assisted formal tautomerization of imidazoles has been found to be a general and powerful methodology for the synthesis of pNHC−chelate complexes. This synthetic protocol was later termed redox tautomerization by Hahn on the basis of mechanistic considerations.32 Baseinduced tautomerizations (Scheme 2a),33 as well as detachment of the protecting group from masked pNHC ligands (Scheme 2e),34,35 have emerged as additional synthetic routes to pNHC complexes. Parallel to these synthetic advances, new functions and reactivity patterns of the pNHC complexes have been uncovered. Ellman and Bergman extensively studied the C−H functionalization of N-heterocylic compounds using rhodium catalysts and revealed the involvement of pNHC complexes in these catalytic reactions (see section 4.1). In 2007, Hahn and Waldvogel established substrate recognition by the NH wingtip, which allowed the chemoselective catalytic hydrogenation of an esterfunctionalized olefin over an unfunctionalized one (Scheme 3a).36 Such a proton-responsive, smart nature37 of the pNHC further led to the development of bond activation and catalysis through metal−pNHC cooperation. In 2008, Kuwata and Ikariya reported C−O bond cleavage in allyl alcohol under neutral and mild conditions utilizing such a bifunctional approach (Scheme 3b) and applied it to the catalytic dehydrogenative coupling of an allyl alcohol and an imidazole.14 In the same year, Grotjahn demonstrated heterolytic cleavage of dihydrogen by the Lewis acid/Brønsted base cooperation of an (imidazolyl)iridium complex (Scheme 3c).38 Application of

steric demand of NHCs in the coordination sphere of a metal atom, which influences the properties of NHC complexes such as the catalytic activity and selectivity. Replacement of one N-substituent at an NHC by a sterically less demanding hydrogen atom brings about some new features regarding the properties and coordination chemistry of the resulting ligand. The NHCs featuring one or two NH wingtips have been termed as NH-NHCs, NR,NH-stabilized carbenes, NH-functionalized NHCs, and so on. In this review, we refer to this subclass of NHCs as protic N-heterocyclic carbenes (pNHCs). The name first appeared in the literature in 200814 to emphasize the potential Brønsted-acidic character of the wingtip. The NH group in close proximity to the nucleophilic carbene carbon atom actually renders the free pNHC less stable than the corresponding azole isomer,15−20 thereby differing from the nonprotic (N-alkylated) classical NHCs (Scheme 1). Scheme 1. Comparison between Nonprotic and Protic NHeterocyclic Carbenes

Coordination to a metal center, however, may shift the relative stability of the tautomers. In 2002, Sini, Eisenstein, and Crabtree performed density functional theory (DFT) calculations on the energies of imidazolin-2-ylidene and imidazoles with and without ligation.21 Representative results are depicted in Figure 1. The

Figure 1. Relative energies ΔE of the pNHC and azole forms estimated for some hypothetical complexes by DFT calculations. Positive ΔE indicates that the azole form is favored.

free protic imidazolin-2-ylidene is so unstable that is is not significant in the equilibrium, as shown in Scheme 1. However, coordination to second- and third-row transition metal complex fragments with strong π-basicity makes the carbene form more accessible. A trans ligand (designated as L in Figure 1) with lower trans influence also favors the pNHC form with stronger σdonating ability,22 probably owing to reduced electronic repulsion. From the steric point of view, the protic imidazolinB


Chemical Reviews

Review

Figure 2. Timeline of significant advances in the chemisty of pNHC complexes.

protic dihydropyridin-2-ylidene45 and cyclic alkylaminocarbene (CAAC) complexes are mentioned if appropriate. Protic acyclic diaminocarbene (ADC) complexes53 along with metallacyclic exo-NH carbene complexes exemplified by Tschugajeff’s red salt,55,56 depicted in Chart 1, will not be covered in this review, although they are closely related to pNHC complexes.

Scheme 2. Representative Synthetic Strategies To Access pNHC Complexesa

Chart 1

a

PG represents a protecting group

2. SYNTHESIS The NH group of a pNHC significantly affects the synthetic methods available for synthesis of its metal complexes. While direct ligation of free or in situ generated cyclic aminocarbenes has provided the most straightforward synthetic route to complexes bearing nonprotic, classical NHC ligands, such reactions conducted under basic conditions are generally incompatible with the pNHC ligands featuring a Brønsted-acidic NH group. Silver pNHC complexes suitable for carbene transfer reactions57 are also currently not known. Nevertheless, an increasing number of pNHC complexes have been synthesized in recent years. This section summarizes the preparative methods leading to complexes with pNHC ligands.

Scheme 3. Pioneering Examples of Metal−Ligand Cooperation Involving pNHC Complexes

2.1. Formal Tautomerization of Azoles

Since azoles constitute formal tautomers of unsaturated pNHCs, they should be potential precursors for the preparation of pNHC complexes. Throughout this review, we refer to such azole-topNHC conversion as formal tautomerization when we only intend to describe the outcome of the reaction without a discussion of mechanistic details. 2.1.1. Acid/Base-Induced Reactions. The kinetic barrier between imidazole and pNHC complexes is often reduced in the presence of Brønsted acids and bases, which can promote the isomerization of imidazole complexes to the corresponding pNHC complexes. Sundberg and Taube reported the first pNHC complexes 2−4, which were obtained by acid-promoted formal tautomerization of the imidazole ligand in complex 1 (Scheme

pNHC complexes to metal−ligand bifunctional catalysis39−45 has continued to grow in recent years. This review provides an overview of the synthesis, properties, and reactions of pNHC complexes, including latest results up to 2017. This topic has previously been reviewed by Hahn46−49 and by Kuwata and Ikariya,45,50 and more specific reviews for selected families of pNHC complexes are also available.51−54 Related C


Chemical Reviews

Review

4).26,27 The carbonyl derivative 4 represents the first crystallographically characterized pNHC complex.27 The molecular

been observed for bipyridine-coordinated molybdenum(II) complexes bearing N-coordinated imidazole ligands.64 Pérez and Riera described the reaction of tris(imidazole)rhenium complexes 9 with a base (Scheme 6).65,66 X-ray

Scheme 4. Acid-Mediated Formal Tautomerization of Coordinated Imidazoles

Scheme 6. Base-Induced Formal Tautomerization of Azoles Coordinated to Rhenium

structure clearly reveals the hydrogen-bonding interactions between NH groups of the pNHC ligand and the hexafluorophosphate counteranion (vide infra). The acid-catalyzed tautomerization of azoles has been applied to various functionalized imidazole (xanthine) derivatives such as caffeine to give pNHC ruthenium(III) complexes 558,59 and the osmium(III) congener.60 In some cases, C-deprotonation of N-coordinated azoles induces rearrangement to the C-bound azolyl ligands, which can subsequently undergo N-protonation to afford pNHC complexes. The overall transformation may be described as a baseinduced formal tautomerization of N-coordinated azoles to Ccoordinated pNHCs. In 2007, for example, Ruiz demonstrated that deprotonation of imidazoles N-bound to manganese (complexes 6, E = NR) resulted in the formation of complexes 7 with a C-bound imidazolyl (or anionic NHC ligand; see below and section 3.1), which react with an ammonium salt to afford the pNHC complexes 8 (Scheme 5).33 DFT calculations indicated that the deprotonation of 6 first gives an N-metalated NHC, which rearranges to the azolyl complex 7 via an acyl intermediate involving one carbonyl coligand.61 The reaction scope was soon expanded to oxazoles and thiazoles.62,63 Similar conversions have

diffraction analysis of 10 revealed a small N−C−N angle [(106.9(6)°] for the C-bound heterocyclic ligand, indicative of increased σ-bond character of this coordinative bond.67,68 The 13 C NMR resonance recorded at δ 182.4 for the coordinated carbon atom in 10 indicates that this ligand is best described as an anionic carbene ligand (see section 3.1). Protonation of 10 leads to formation of pNHC complex 11. Deprotonation of bis(imidazole) complex 12 in the presence of an external imidazole also leads to formation of an anionic NHC ligand, concurrent with formal tautomerization of the second imidazole to the pNHC, giving bis(carbene) complex 13 with an intramolecular hydrogen bond between two diaminoheterocycles.69 As expected, subsequent protonation of 13 afforded the bis(pNHC) complex 14. 2.1.2. Chelation-Assisted Reactions. In 1997, Houlton demonstrated that an adenine derivative functionalized with an ethylenediamine donor unit, 15, undergoes metalation at the C-8 position of the adenine to afford the pNHC ruthenium(II) complex 16 as illustrated in Scheme 7.31 The guanine-derived complex 1770 as well as the palladium complex 1871 were obtained in a similar manner.72 The N-tethered diamine unit in the ligand precursor 15 appears to trigger C-metalation of the neighboring imidazole and its isomerization to the pNHC. Ellman and Bergman subsequently reported in 2002 the synthesis of complex 19 bearing an olefin-tethered pNHC ligand through formal tautomerization (Scheme 8).73 Apart from this notable exception, however, the synthetic importance of this operationally simple, cyclometalative construction of pNHC complexes shown in Scheme 7 had apparently been overlooked for a decade.

Scheme 5. Base-Induced Formal Tautomerization of Azoles Coordinated to Manganese

D


Chemical Reviews

Review

Scheme 7. Synthesis of pNHC Complexes through ChelationAssisted Formal Tautomerization of Nucleobases

Scheme 10. Synthesis of a Phosphine-Tethered pNHC Complex

Chart 2

Scheme 8. Synthesis of an Olefin-Tethered pNHC Complex

The chelation-assisted formal tautomerization methodology has burst into bloom with the use of simpler yet strongly coordinating N-tethered donor groups such as pyridine or phosphines. These functional groups not only promote the metalation of the imidazole but also stabilize the resulting pNHC complexes, for example, against retautomerization to the parent imidazole. In 2008, Kuwata and Ikariya demonstrated that a pyridine-tethered benzimidazole reacts with [Cp*RuCl]4 to afford the C,N-chelate pNHC ruthenium(II) complex 20 (Scheme 9).14

N-Tethered Schiff bases can also serve as assisting groups for the formal tautomerization of imidazoles to pNHCs. Danopoulos and Braunstein described the reaction of imine-tethered imidazoles with the iridium(I) complex [IrCl(cod)]2 (Scheme 11).78,79 After initial formation of the N-imidazole complex 26, chloride abstraction with a thallium salt leads to formal tautomerization of the imidazole to afford the C,N-chelate pNHC iridium(I) complex 27. Synthesis of the rhodium analogue of 27 requires heating at 110 °C.79 The reaction of 26 with an additional amount of the iridium complex yields the

Scheme 9. Synthesis of a Pyridine-Tethered pNHC Complex

Scheme 11. Synthesis of Imine-Tethered pNHC Complexes

Shortly thereafter, Grotjahn described the synthesis of the phosphine-tethered pNHC iridium(III) complex 21, obtained by reaction of an N-(2-phosphinoethyl)imidazole with [Cp*IrCl2]2 as shown in Scheme 10.38 Grotjahn74 and Hahn75−77 applied this strategy for the synthesis of a series of half-sandwich-type ruthenium(II) and iridium(III) complexes bearing C,P-chelate pNHC ligands such as 22−24 (Chart 2). The square planar rhodium(I) complex 25 was obtained in a similar manner.32 It should be noted that the imidazoles used are normally substituted at the 4- and 5-positions to disfavor metalation at these positions and to suppress formation of N-imidazole complexes.23,50 E


Chemical Reviews

Review

dinuclear iridium(III) complex 28a, suggesting an oxidative addition pathway for the azole-to-pNHC tautomerization (see section 2.1.3). As exemplified by the reaction shown in Scheme 7, use of a bidentate N-tether in the chelation-assisted approach leads to the formation of complexes bearing a tridentate pNHC−donor− donor ligand. Kuwata and Ikariya prepared the protic pincer-type ruthenium(II) complex 29 from a pyrazolylpyridine-tethered imidazole (Scheme 12).80 A related pincer-type complex with a five-membered chelate ring involving a pNHC has been obtained in a similar fashion.81

Scheme 14. Synthesis and Reactions of C,C-Chelate Bis(pNHC) Complexes

Scheme 12. Synthesis of Protic CNN Pincer-Type Complex

Esteruelas, Oliván, and Yus reported the formation of the osmium(IV) complex 30, bearing a C,O-chelate pNHC ligand, from hydroxyalkyl-tethered imidazoles, concurrent with acceptorless dehydrogenation of the tethering chain (Scheme 13).82 Scheme 15. Synthesis of CPC-Chelate Bis(pNHC) Complexes

Scheme 13. Synthesis of Enolate-Tethered pNHC Complex

The hydroxyl group appears to anchor the imidazole to the metal for the formal tautomerization, since N-alkyl- and arylimidazoles without a hydroxy group do not afford the corresponding pNHC complexes. Recently, Grotjahn demonstrated that the bis(imidazole) 31 reacts with the acetato complex [Cp*Ir(OAc)2] to afford the bis(pNHC) iridium(III) complexes 32 and 33, which can be converted quantitatively to the chlorido complex 34 upon treatment with hydrochloric acid (Scheme 14).83 Since the positions of the nitrogen atoms in the ligand precursor are inappropriate for a cyclometalation, the bis(pNHC) complexes 32 and 33 are most likely formed via an initial acetate-promoted C−H metalation,84−86 followed by chelation-assisted formal tautomerization. Derivatization of the chlorido complex 34 to give hydrido, nitrile, or amine complexes has also been achieved. Bis(pNHC) complexes are also accessible from donor ligands flanked by two imidazole units, which can undergo double tautomerization to give two pNHCs. In 2014, Cossairt described the reaction of a tertiary phosphine substituted with two benzimidazoles, 35 (Scheme 15).87 The initial reaction product is the macrocyclic, dinuclear complex 36, in which the ligand bridges the two metal atoms through coordination of the phosphine and one of the benzimidazoles. Heating of 36 yields the facial, tridentate bis(pNHC) ruthenium(II) complex 37 through formal tautomerization of both benzimidazole groups. Upon deprotonation of the benzimidazole groups in 37 and subsequent reaction with metal halides, the heterodinuclear complexes 38 and 39 were obtained.

Grotjahn explored the formal tautomerization of bis(imidazolyl)carbazole 40 as illustrated in Scheme 16.88 Although the reactions are rather slow, the resulting bis(pNHC) complexes 41 represent the first examples of group 10 metal− pNHC complexes obtained by the chelation-assisted formal tautomerization methodology. Chelation-assisted formal tautomerization has so far only been applied to a rather limited number of transition metals. Protic F


Chemical Reviews

Review

mechanism. As depicted in Scheme 18, oxidative addition of the C2−H bond to platinum(0) proceeds even with O- and S-

Scheme 16. Synthesis of Bis(pNHC) Pincer-Type Complexes

Scheme 18. Oxidative Addition of the C−H Bond of Oxazole and Thiazole

heteroaromatic compounds without a tethered donor group present (see section 2.2.2), although the analogous reaction of imidazoles and benzimidazoles results, in selected cases, in oxidative addition of the N−H bond instead of the C−H bond.90 Formal tautomerization of benzimidazole without a tethering group in a rhodium(I) complex, shown in Scheme 19, is thus likely to proceed through redox tautomerization.91

aminooxycarbene and aminothiocarbene complexes are also out of the scope of the reaction because a donor group cannot be installed at the oxygen or sulfur atoms of the oxazole and thiazole precursors. However, chelation-assisted formal tautomerization provides convenient access to complexes with unsaturated protic imidazolin-2-ylidene and dihydropyridin-2-ylidene (see section 2.1.3) ligands incorporated into a robust chelate framework (functionalized NHC),89 which benefits the development of pNHC complexes. 2.1.3. Mechanistic Aspects. The mechanism of the formal tautomerization of imidazoles to pNHCs has not been unambiguously established. The two mechanistic postulations, redox tautomerization and redox-neutral mechanism, are summarized in Scheme 17. In 2011, Hahn proposed a redox tautomerization sequence, which is composed of a tether-assisted oxidative addition of the C−H bond at the 2-position of the azoles followed by reductive elimination (1,3-H shift), as illustrated in Scheme 17a.32 This mechanism appears very probable when a low-valent metal is involved in the reaction. Some experimental and calculation results actually support this

Scheme 19. Synthesis of a pNHC Rhodium(I) Complex by Formal Tautomerization of N-Methylbenzimidazole

In fact, an exquisite double-labeling experiment with closely related six-membered dihydroquinazoline compounds of type 44 excluded an intermolecular H-transfer associated with the redoxneutral mechanism (vide infra) as mostly compounds of type 45 (and not 45cross) were obtained (Scheme 20)92 in spite of the Scheme 20. Double-Labeling Crossover Experiment with Dihydroquinazoline

Scheme 17. Proposed Mechanisms for Chelation-Assisted Formal Tautomerization of Azoles to pNHCsa

a

reasonable Brønsted acidity of the NH proton (vide infra). Kinetic analysis revealed that a complex with an N-bound ligand is an intermediate in the formation of 45. The analogous conversion of the seven-membered cyclic imine 46 to the protic carbene complex 47 was also reported (Scheme 21).93 Ellman and Bergman92 and Yates94 performed theoretical calculations on the formal tautomerization of an olefin-tethered imidazole and a related six-membered N-heterocycle, dihydroquinazoline. Both concluded that the C−H cleavage step takes place via oxidative addition of the C−H bond to the rhodium(I) center in 48 to give the intermediate 49, as illustrated in Scheme 22.94 In their effort to obtain imine-tethered pNHC complexes (Scheme 11), Danopoulos and Braunstein isolated the dinuclear

D represents a tethered donor group. G


Chemical Reviews

Review

state of the metal through deprotonative metalation, referred to as concerted metalation−deprotonation (CMD)98 or σ-complex-assisted metathesis (σ-CAM).99 Subsequent N-protonation would ultimately give the pNHC complexes. In 2016, Hahn demonstrated that monoalkylated imidazolium−imidazole salts 52 react with [Cp*MCl2]2 (M = Rh, Ir) in the presence of sodium acetate to afford C,C-chelate NHCimidazolyl complexes 53 (Scheme 24).100,101 The reaction of di-

Scheme 21. Synthesis of a Protic Carbene Complex by Formal Tautomerization of a Cyclic Imine

Scheme 24. Cyclometalation of a Nonprotic NHC-Tethered Imidazole and Subsequent Protonation To Give pNHC Complexes

Scheme 22. Proposed Mechanism for C−H Cleavage of Olefin-Tethered Imidazole at Rhodium(I)

hydrido-imidazolyl IrIII/IrI complex 28a and found that 28a is easily converted (by reductive elimination) to the pNHC iridium(I) complex 27 upon chloride abstraction with a thallium salt.78,79 This observation suggests that the formal tautomerization of 26 to 27 involves the Lewis acid-aided formation of complexes like 28a and 28b by an oxidative addition reaction, in accordance with the redox tautomerization mechanism. Han, Zhang, and Li obtained an equilibrium mixture of the hydrido-pyridyl complex 50 and the protic dihydropyridin-2ylidene complex 51 by reaction of an iridium(I) precursor with 1,9-phenanthroline (Scheme 23).95 The facile 1,3-H shift Scheme 23. Chelation-Assisted C−H Cleavage in 1,9Phenanthroline To Give a Mixture of Dihydropyridin-2ylidene and Hydrido-Pyridyl Complexes

NHC precursors 52 with [Cp*RhCl2]2 in the absence of NaOAc proceeds via carbene transfer (Ag2O method) to give the monometalated derivative 54, confirming the intermediacy of 54 in the formation of 53. During the direct formation of 53 from 52, the acetate appears to promote the deprotonative C−H bond cleavage according to the CMD mechanism as well as to neutralize the acid that forms. Related acetate-assisted C−H metalation reactions are well-documented.84−86 Protonation to the imidazolyl ligand in rhodium(III) complex 53a yields the pNHC complexes 55,100 which follows the σ-bond metathesis pathway shown in Scheme 17b. Recent reports described a mercury(II)-promoted C−H bond activation in imidazoles102 and triazoles103 followed by N-protonation or electrophilic Nmethylation to give protic/aprotic mercury(II) NHC complexes. The initial mercury-promoted C−H cleavage step involving mercury(II) most likely follows the CMD mechanism. López-Serrano, Poveda, and Carmona investigated the formal tautomerization of 2-substituted pyridines to give protic dihydropyridin-2-ylidene complexes 56. They concluded that the reaction proceeds via the σ-CAM mechanism (Scheme 25, top).104 Furthermore, Esteruelas studied the formal tautomerization reaction in a polyhydrido osmium(IV) complex, shown at the bottom of Scheme 25.105 A different mechanism involving an initial hydrogen shift from the metal to the nitrogen atom has been proposed for the formation of 57. In addition, some examples of formal tautomerization of tether-free pyridines to protic dihydropyridin-2-ylidenes have been described.106−115

between the product of the oxidative addition, 50, and the complex bearing the protic carbene, 51, which can be accelerated in the presence of water,96 appears to be involved in the redox tautomerization reaction sequence. Theoretical studies also support the initial oxidative addition of the C10−H bond of phenanthroline.96 Analogous chelation-assisted tautomerization of related pyridine derivatives has been described.97 As an alternative pathway, the redox-neutral mechanism illustrated in Scheme 17b may be operative for mid- to highvalent metal complexes, because the higher valent hydridoimidazolyl intermediate postulated in the redox tautomerization would be inaccessible for these complexes. Instead, C−H cleavage may be achieved without a change in the oxidation H


Chemical Reviews

Review

Scheme 25. Formal Tautomerization of Pyridines To Give Dihydropyridin-2-ylidene Complexes

protonation step of the isolated and structurally characterized azolyl-pNHC intermediate 60, which affords the bis(pNHC) complex 61. Most of the gold pNHC complexes, including the mono(pNHC) complex 62, have been prepared by the transmetalation−protonation methodology.116,119,120 This protocol has also been applied for the preparation of pNHC complexes of other metals such as palladium (63),121 tungsten,36 and iron,122 and even the bis(protic dihydropyridin-2-ylidene)gold complex 64.123 Occasionally, the protonation step causes conversion of the C-bound azolyl ligand to the N-bound azole.124 2.2.2. Oxidative Addition of 2-Haloazoles Followed by Protonation. As early as 1973, Roper described the oxidative addition of 2-chlorothiazoles as well as 2-chlorobenzoxazole to an iridium(I) complex.125 The resulting iridium(III) azolyl complexes 65 undergo N-protonation to afford the thiazolin-2ylidene and oxazolin-2-ylidene complexes 66 (Scheme 28; see

2.2. Protonation of C-Azolyl Complexes

Scheme 28. Synthesis of pNHC Complexes by Oxidative Addition of Chloroazoles and Subsequent Protonation

N-Protonation of C-metalated azolyl ligands provides rational and reliable access to pNHC complexes. In fact, the azolyl complexes generated by deprotonation of N-bound azoles (section 2.1.1) as well as those obtained by cyclometalation of an NHC-tethered imidazole (53 in Scheme 24) undergo protonation to give pNHC complexes. The azolyl complexes subjected to protonation can be obtained by general and reliable methods such as the transmetalation of C-lithiated azoles116 or the oxidative addition of 2-haloazoles, as described in sections 2.2.1 and 2.2.2. 2.2.1. Transmetalation of C-Lithiated Azoles and Subsequent Protonation. In 1989, Burini demonstrated that reaction of a gold(I) complex with the imidazolyllithium derivative 58, generated from C2 lithiation of N-benzylimidazole, followed by N-protonation resulted in formation of the pNHC complex 59a (Scheme 26).117 The reaction most likely proceeds via an (imidazolyl)gold intermediate.

also Scheme 18). Facile deprotonation of the pNHC ligands in complexes 66 regenerates the azolyl complexes 65, corroborating the Brønsted-acidic nature of the pNHC ligands (see section 3). This type of oxidative addition has been extended to platinum(0) and nickel(0) phosphine complexes, giving the corresponding pNHC complexes.126 In 1983, Crociani revealed that protonation of the 2-pyridylbridged dinuclear palladium(II) complexes 67, synthesized by oxidative addition of 2-halopyridines to [Pd(PPh3)4],127 yields the mononuclear complex 68 bearing a dihydropyridin-2-ylidene ligand (Scheme 29).128 Some protic dihydropyridin-2-ylidene complexes of group 10 metals,129−132 as well as a rhodium complex,133 have also been synthesized by utilizing this protocol.

Scheme 26. Synthesis of pNHC Complexes from C-Lithiated Imidazole

Scheme 29. Synthesis of pNHC Complexes by Oxidative Addition of Halopyridines and Subsequent Protonation Raubenheimer reported a related reaction using thiazoles instead of imidazoles.118 Scheme 27 illustrates the final Scheme 27. Protonation of a Thiazolyl Complex To Give a pNHC Complex and Related pNHC Complexes In spite of the important precedents mentioned above, it is surprising to note that oxidative addition of haloimidazoles has been only recently been applied systematically for the synthesis of pNHC complexes. In 2011, Hahn disclosed that the oxidative addition of chloroimidazole 69, obtained by N-methylation of commercially available 2-chlorobenzimidazole, to palladium(0) and platinum(0) complexes followed by N-protonation yields the MII pNHC complexes 70 and 71 (Scheme 30).134 Isolation of the anionic NHC (or imidazolyl; see section 3.1) platinum(II) complex 72135 as well as the N,C-metalated NHC (or imidazolylI


Chemical Reviews

Review

limited, partly due to the facile deprotonation of the NH group in the azole starting material. In 2015, Danopoulos and Braunstein reported the oxidative addition of imidazolium salt 78a to an iridium(I) complex to afford the pNHC iridium(III) complex 79 as shown in Scheme 32.78 It should be noted that the reaction

Scheme 30. Synthesis of pNHC Complexes by Oxidative Addition of 2-Haloazoles and Subsequent Protonation

Scheme 32. Oxidative Addition of an Imidazolium Cation

product strongly depends on the counteranion present in the imidazolium salt. Use of the chloride salt 78b resulted in oxidative addition of the N−H bond (instead of the C−H bond) and formation of dichloride−imidazole complex 80 in high yield. During their studies on the chelate-assisted tautomerization of imidazole 81 bearing an imine−pyridine anchor, Danopoulos and Braunstein found that reaction of 81 with the iridium(I) complex [IrCl(cod)]2 yields either the N-metalated iridium(I)− imidazole complex 82 or the cyclometalated iridium(III) complex 83, depending on the ratio of metal precursor to 81 (Scheme 33).146 If the imidazole moiety in 81 is protonated to give 84, N-coordination of this group is suppressed, and oxidative addition to give the pincer-type pNHC iridium(III) complex 85 was observed. In addition to oxidative addition of the C−H bond, some reactions involving carbon−heteroelement bond-cleavage reactions at the 2-position of azolium salts and azoles have been

bridged) dinuclear palladium(II) complex 73136 from the reaction in the absence of a proton source strongly indicates that the complexes with pNHC ligands are formed via an initial oxidative addition of the haloimidazole to the transition metal. Extensive studies by Hahn and co-workers,137−139 with some relevance to the elucidation of the redox tautomerization mechanism,48,49 revealed the generality and utility of the oxidative addition−protonation methodology. Apart from palladium and platinum complexes, the synthesis of some nickel(II) complexes with pNHC ligands,140 as well as the purine-base-derived complexes 74 and 75 (Scheme 30), has been described.141 Even abnormal NHC ligands can exist in metal complexes as pNHCs. The imidazol-4-yl precursor complex 76 has been obtained by oxidative addition of 4iodoimidazole to a platinum(0) complex. N-Protonation of 76 gives the abnormal pNHC complex 77 (Scheme 31).142 The protonation is reversible, and reaction of 77 with a base regenerates 76.

Scheme 33. Reactions of an Imine−Pyridine-Tethered Imidazole

2.3. Oxidative Addition of Imidazolium Cations

Although oxidative addition to the C−H bond of imidazolium cations to transition metals has been known for a long time as a potent synthetic method for preparation of NHC complexes,143−145 its application to pNHC complexes remains very Scheme 31. Synthesis of a Complex Bearing an Abnormal pNHC Ligand by Oxidative Addition of 4-Iodoimidazole Followed by N-Protonation

J


Chemical Reviews

Review

controlled syntheses, since the construction of the heterocycle is achieved in the coordination sphere of a template metal. This methodology is particularly effective for the preparation of complexes bearing saturated pNHCs or more than one pNHC ligands, which are generally difficult to access through other synthetic routes. Some early reviews on this synthetic route are available.151−155 2.4.1. Annulation of Isocyanide and Carbonyl Complexes. Various patterns of annulation for the synthesis of pNHC complexes have been developed, and the most important ones are summarized in Scheme 37.

reported. Cabeza described the oxidative addition of levamisolium chloride 86 to carbonyl clusters of ruthenium and osmium to afford a diastereomeric mixture of trinuclear clusters 87 featuring a pNHC−thiolato chelate ligand (Scheme 34).147 The Scheme 34. Formation of pNHC−Thiolato Clusters by C−S Bond Cleavage in the Levamisolium Cation

Scheme 37. Annulation Reactions of Isocyanide and Carbonyl Complexes To Give pNHC Complexes

C−S bond-cleavage products of type 87 represent rare examples of pNHC metal cluster complexes. The related oxidative addition of the C−S bond of a 2-thiomethylimidazole has also been described.148 No oxidation of the metal is apparent during the formation of pNHC complex 90 from the secondary imidazolylphosphine oxide 88 (Scheme 35).149 The reaction is believed to proceed via a P−C bond cleavage of the zwitterionic imidazolium− phosphinite ligand in intermediate 89. Scheme 35. Formation of a pNHC Complex from Imidazolylphosphine Oxide

Finally, Scheme 36 illustrates another example of protonationtriggered P−C bond fission leading to the formation of pNHC complexes 59b,c.150 Scheme 36. Formation of pNHC Complexes by Methanolysis of Imidazolylphosphine Complexes

In 1978, Ito and Saegusa demonstrated that annulation of the palladium isocyanide complex 91 with an α-aminoacetal affords the pNHC complexes 93 as illustrated in Scheme 38.156 The reaction can be categorized as a variant of the reaction shown in Scheme 37a (where E = NR).121,157 Angelici showed in 1982 that reaction of iron and manganese carbonyl complexes 94 with 2bromoethylamine in the presence of a base yields the saturated pNHC complexes 95 (Scheme 39).158 Related reactions of palladium, platinum,159,160 and rhenium157 isocyanide complexes to give protic diaminocarbene complexes are also known.

2.4. Annulation or Cyclization at a Metal Template

Reactions of protic nucleophiles with a coordinated isocyanide result in the formation of aminocarbene complexes.53 Use of appropriately designed substrates thus allows the synthesis of cyclic carbenes through annulation or cyclization. The isoelectronic carbonyl complexes may undergo analogous transformation. Such reactions are often referred as templateK


Chemical Reviews

Review

Scheme 38. Synthesis of pNHC Complexes from Isocyanide Complexes and α-Aminoacetal

Scheme 41. Synthesis of pNHC Complexes from Isocyanide Complex and Propargylamine

Scheme 39. Synthesis of pNHC Complexes from Carbonyl Complexes and Propargylamine

Scheme 42. Synthesis of pNHC Complexes from Carbonyl Complex and Aziridine

Even chelate complexes 98, featuring a pNHC donor, have been synthesized by annulation of C,P-chelate isocyanide complexes 96 with ω-chloroalkylamines (Scheme 40).161 Scheme 40. Synthesis of C,P-Chelate Complexes by Annulation of Isocyanide Complexes

Scheme 37d illustrates another type of annulation utilizing strained three-membered heterocyclic compounds and hydrogen isocyanide complexes. The reaction is believed to proceed via an initial protonation of the heteroelement in the strained threemembered ring by the hydrogen isocyanide complex. Fehlhammer et al.171 described the reactions of hydrogen isocyanide complexes 102 with aziridines (Scheme 43). Nucleophilic attack Scheme 43. Synthesis of pNHC Complexes from Hydrogen Isocyanide Complexes and Aziridine

Nucleophilic addition to an unsaturated C−C bond instead of substitution also constitutes a strategy for ring closure in annulation reactions (Scheme 37b). In 2005, for example, Ruiz described such an annulation reaction with manganese isocyanide complexes 99.162,163 The reaction ultimately yielded complex 100, bearing an unsaturated pNHC ligand, via an initial nucleophilic attack at the isocyanide followed by nucleophilic addition of the isocyanide-derived amino group to the CC bond and subsequent 1,3-H shift from the endocyclic methylene group to the exocyclic one (Scheme 41). More recently, iron164 and gold165 pNHC complexes have been synthesized by this strategy. Aziridine can also serve as a building block in the annulation involving an initial nucleophilic attack of the aziridine nitrogen atom at the isocyanide carbon atom, followed by halide-aided cyclization (Scheme 37c). As early as 1983, Angelici166 demonstrated that a wide range of carbonyl complexes, as well as a thiocarbonyl complex, react with a protic aziridine to afford pNHC complexes of type 101 (Scheme 42).160,167−170 Similarly, the reaction of isocyanide complexes proceeds to give the protic imidazoliden-2-ylidene complexes.171−173 In contrast, a less strained, four-membered cyclic amine, azetidine, does not appear reactive enough to undergo the ring opening and to give the pNHC complex with a six-membered heterocycle.174

of the anionic cyanido complex 103 at the aziridinium cation results in ring opening to give complex 104 bearing a βfunctionalized isocyanide ligand. Subsequent cyclization of the functionalized isocyanide affords complexes 105 with pNHC ligands. Epoxides also undergo this type of annulation. When the epoxide bears a cyano substituent, concurrent elimination of hydrogen cyanide occurs to give unsaturated, protic aminooxycarbene complexes.175,176 Beck reported a closely related L


Chemical Reviews

Review

transformation, the reaction of hydrogen cyanometalates and expoxides, to give protic oxazolidin-2-ylidene complexes.177,178 Intermediary complexes bearing donor-functionalized isocyanides such as 104 can also be accessed by condensation of a carbonyl complex and a suitable phosphine imine (Scheme 37e). Liu investigated the reaction of group 6 metals and rhenium carbonyl complexes with amino-substituted iminophosphoranes (Scheme 44).179,180 The reactions afford the saturated protic

In the same year, Roper reported an analogous reaction of the p-toluenesulfonylmethyl isocyanide (TosMIC) complex of osmium, 110 (Scheme 45, bottom).188 Both reactions appear to involve nucleophilic addition of the α-deprotonated isocyanide ligand at the aldehyde, leading to complexes 108 and 111 bearing alkoxide-substituted isocyanide ligands. Subsequent cyclization yields the saturated oxazolidin-2-ylidene complexes 109 and 112. In the case of TosMIC, concurrent elimination of a sulfinic acid takes place to afford the unsaturated oxazolin-2-ylidene complex 113 for benzaldehyde, while for acetoaldehyde, the tosyl group in 112 is replaced by the methoxide base to give the saturated alkoxyoxazoliden-2-ylidene complex 114. Fehlhammer showed that, in addition to aldehydes, nitriles,189 isocyanates,189,190 thioisocyanates,190 keteneimines,191 and carbon disulfide192 can be used as dipolarophiles to obtain a variety of pNHC complexes such as those depicted in Chart 3. Even a 1,2,4-triazolin-5-ylidene complex 117 has been synthesized by this type of reaction employing a diazonium salt.193

Scheme 44. Synthesis of pNHC Complexes from Metal Carbonyl Complexes and Amino-Substituted Iminophosphoranes

Chart 3 diaminocarbene complexes 106 efficiently, although the final cyclization step requires addition of diethylamine for M = W, R = H, n = 3. This method is applicable to the synthesis of other pNHC complexes,181−184 including a bis(pNHC)-bridged dinuclear tungsten complex185 and an unsaturated benzimidazolin-2-ylidene rhenium complex.186 Coordinated isocyanides bearing an electron-withdrawing group can also undergo template-controlled cyclization reactions (Scheme 37f). As early as 1975, Fehlhammer demonstrated that the isocyanoacetate platinum complex 107 reacts with aldehydes in the presence of a base to afford the protic oxazolidin-2-ylidene complex 109 (Scheme 45, top).187

Nishiyama reported that annulation of the optically active pincer-type rhodium complex 118, bearing a TosMIC ligand, leads to formation of the chiral protic oxazolidin-2-ylidene complexes 119 with trans stereoselectivity (Scheme 46).194 The Scheme 46. Synthesis of Chiral pNHC Complexes and Conversion to Optically Pure Oxazolines

Scheme 45. Synthesis of pNHC Complexes from Isocyanide Complexes and Aldehydes

diastereoselectivity in the reactions of related isocyanoacetate complexes reached up to 82%. Diastereomers 119 can be separated by column chromatography, and converted into optically pure 2-oxazolines (4S,5S)-120 and (4R,5R)-120 upon treatment with a silver salt. As an extension of the annulation strategy, Fehlhammer demonstrated that Ugi-type four-component condensation reactions afford a series of amino-substituted pNHC complexes of type 121 (Scheme 47).195 M


Chemical Reviews

Review

Scheme 47. Synthesis of pNHC Complexes by the Metalla-Ugi Reaction

Scheme 49. Synthesis of O-Silylated 2-Hydroxyphenyl Isocyanide 128

2.4.2. Template-Controlled Cyclization of Functionalized Isocyanides. Given that functionalized isocyanides generated at metal templates are the key intermediates in a number of annulation reactions (Scheme 37), suitably functionalized isocyanides themselves should also serve as useful precursors for the generation of pNHC complexes. In fact, prior to discovery of the annulation reactions discussed in section 2.4.1, Fehlhammer demonstrated as early as 1974 that coordination of the isolable 2-hydroxyethyl isocyanide (122) to palladium(II) leads to rapid cyclization of the isocyanides to give the homoleptic, poly(protic oxazolidin-2-ylidene) palladium complex 123 (Scheme 48).29 Related platinum,29,196 nick-

Scheme 50. Template-Controlled Deprotection−Cyclization of 2-Siloxyphenyl Isocyanide To Give pNHC Complexes

Scheme 48. Synthesis of pNHC Complexes by Cyclization of a Functionalized Isocyanide at the Palladium Template

complex fragment employed. While coordination to electronpoor Fe(CO)4 exclusively gives the pNHC complex 131a,205 complexes of group 6 metals react to form an equilibrium between the isocyanide complexes 130b,c and the pNHC complexes 131b,c.206−208 Formation of the equilibrium is based on enhanced metal-to-ligand backbonding from electron-rich metal complex fragments, thereby deactivating the isocyanide carbon atom for an intramolecular nucleophilic attack. Substitution of one carbonyl ligand in the tungsten complexes 130c and 131c for a stonger-donating phosphine completely shifts the equilibrium to the isocyanide side.209,210 A variety of benzoxazolin-2-ylidene complexes of palladium,211−214a platinum,212,214b,215 cobalt,211 iridium,216 rhenium,157,217,218 gold,214a and boron219 have been synthesized from the masked ligand 128. Direct reaction of the isomeric mixture of lithium salts 126 and 127 with triphenylborane, followed by hydration, also yields a borane−pNHC adduct.220 Interestingly, deprotection of the tris(isocyanide) iron(II) complex 132 leads to formation of an iron complex 133 bearing three different types of ligands derived from the masked isocyanide: 2-hydroxyphenyl isocyanide, oxazolyl, and protic oxazolin-2-ylidene (Scheme 51).221 Cyclization of two isocyanide ligands in 132 led to increased electron density at the metal center, which in turn resulted in deactivation of the remaining isocyanide ligand toward cyclization by enhanced backbonding. Cyclization of the remaining isocyanide ligand in 133 required oxidation of the iron center, which decreased the electron density at the metal center, leading to the tris(pNHC) iron(III) complex 134. Amino-functionalized isocyanides bearing a protection group at the amine similarly provide synthetic access to protic diaminocarbene complexes. In 2003, Hahn disclosed the reactions of 2-azidophenyl isocyanide (135) with group 6 carbonyl complexes (Scheme 52).222 Liberation of the amino group in the isocyanide complexes 136 was achieved by a Staudinger reaction,223 followed by hydrolysis of the resulting

el,196,197 gold,29 and manganese197 complexes, and even hexakis(pNHC) cobalt and rhodium complexes198 as well as borane adducts,199,200 have been synthesized by this method involving initial coordination of the isocyanide to electron-poor template centers. In contrast to this, electron-rich chromium(0) and molybdenum(0) complexes only yield simple isocyanide complexes such as fac-[M(CO)3(CNCH2CH2OH)3] (M = Cr, Mo) without cyclization, due to the reduced electrophilic nature of the isocyanide carbon atom on the less Lewis-acidic metal centers.196 The siloxy derivative CNCH2CH2OSiMe3 behaves as the synthetic equivalent of 122 upon O−SiMe3 bond cleavage with fluoride anion.201,202 Comprehensive contributions by Hahn’s group in the 1990s significantly expanded the scope of the cyclization of functionalized isocyanides at metal templates.48,152,203 The key compounds are properly functionalized isocyanides such as 124, featuring a planar o-phenylene linker instead of an aliphatic chain to promote the cyclization geometrically (Scheme 49). This class of bifunctional isocyanides is generally unstable and they normally cyclize to give azoles of type 125, due to the coplanarity of the two functional groups and the rigid linker connecting them. The problem has been solved elegantly by use of an O-protection group. The masked isocyanide 128 is prepared by lithiation of oxazole 125 followed by electrophilic silylation as illustrated in Scheme 49.204 Coordination of the O-silylated phenyl isocyanide and subsequent O-deprotection with a catalytic amount of potassium fluoride afford a variety of unsaturated, protic benzoxazolin-2ylidene complexes as exemplified in Scheme 50. The stability of the pNHC complexes significantly depends on the metal N


Chemical Reviews

Review

Scheme 51. Triple Cyclization of 2-Siloxyphenyl Isocyanide to a Tris(pNHC) Complex

Scheme 53. Nitro Reduction−Cyclization of 2-Nitrophenyl Isocyanide

tion−electrophilic alkylation sequence. In addition, reduction of the nitro group in 140 with Sn/HCl236 results in formation of the imidazolin-2-ylidene complexes 139, similarly to the reaction of azidophenyl isocyanide complexes 136 (Scheme 52). Double cyclization of properly functionalized bis(isocyano)benzene affords dicarbene-bridged polynuclear complexes. Hahn described a molecular square 144 containing rigid dicarbene linkers obtained by this approach (Scheme 54)216 next to dicarbene-bridged digold(I) and tetraplatinum(II) complexes.214 2.4.3. Annulation of Carbene Complexes. Electrophilic Fischer-type carbene ligands undergo annulative coupling with bifunctional primary amines to afford pNHC complexes. Angelici demonstrated that the dithiocarbene complex 145 reacts with 1,2-diaminobenzene to afford the pNHC complex 146 along with liberation of two equiv of MeSH (Scheme 55).30

Scheme 52. Template-Controlled Deprotection−Cyclization of 2-Azidophenyl Isocyanide

Scheme 54. Synthesis of a Dicarbene-Bridged Molecular Square by Multiple Cyclizations of Difunctionalized Isocyanides

iminophosphorane in 137. Complexes 138 generated by deprotection immediately undergo cyclization to give the benzimidazolin-2-ylidene complexes 139. The application of this protocol to ruthenium224,225 and platinum226 complexes, along with investigations on deprotection conditions,224 have been explored. Hahn also described the azide-to-amine deprotection−cyclization sequence of ω-azidoalkyl isocyanides CN(CH2)nN3 (n = 2, 3), which provides saturated, protic diaminocarbene complexes of tungsten,227 manganese,183 rhenium,224 iron,228 ruthenium,224,225,229 and platinum.230,231 Ligation of an electron-donating phosphine again suppresses the cyclization.210 Reactions of the homologues of 128 and 135, 2CNC6H4CH2X (X = OSiMe3232,233 or N3234,235), have been described by Michelin.155 Furthermore, 2-nitrophenyl isocyanide can also be used as a synthon for the preparation of aminocarbene complexes. Reduction of the nitro group in group 6 metal carbonyl complexes 140 with hydrazine yields hydroxyimidazolin-2ylidene complexes 142, most likely through the hydroxylamine intermediate 141 (Scheme 53).236 Complex 142 (M = W) undergoes further O- and N-functionalization in a deprotonaO


Chemical Reviews

Review

Scheme 55. Nucleophilic Substitution at a Dithiocarbene Ligand To Give the pNHC Complex

Scheme 58. Synthesis of a Protic CAAC Complex by Cyclization of a Phosphonium−Isocyanide Ligand

The analogous reactions with aliphatic diamines including 1,3diaminopropane and N-methylethylenediamine, as well as with 2-aminoethanol and 2-aminoethanethiol, similarly lead to formation of the complexes bearing five- and six-membered, saturated pNHC ligands with NH,NH-, NH,O-, and NH,Swingtip sets, respectively. On the other hand, 3-aminopropanol behaves as a simple primary amine and its reaction with 145 yields only the cationic hydroxyalkyl isocyanide complex [CpFe(CO)2{CN(CH2)3OH}]+ without cyclization. Dihalocarbene complexes237 can also serve as precursors for pNHC complexes. As illustrated in Scheme 56, treatment of the

position α to the carbene carbon atom to give the protic CAAC complex 153, but facile loss of this proton has been observed. Synthesis of related group 6 metal carbonyl complexes has been attempted.250 Recently, Wong demonstrated that cyclization of an aminofunctionalized alkyne takes place on a thiamacrocycle-ligated ruthenium(II) complex to afford complex 154, most likely through a vinylidene intermediate (Scheme 59).251

Scheme 56. Nucleophilic Substitution at a Dichlorocarbene Ligand

Scheme 59. Synthesis of a Protic CAAC Complex by Template-Controlled Cyclization of an Aminoalkyne dichlorocarbene complex 147 with functionalized primary amines results in the formation of complexes 148 bearing a saturated pNHC ligand.238 The related iridium complex [Ir( CCl2)Cl3(PPh3)2] exhibits an analogous reactivity.239 In addition, the trichloromethyl isocyanide complex [Cr(CO)5(CNCCl3)] 149, which is known as a dichlorocarbene equivalent,240 can be converted into the pNHC complexes 150 (Scheme 57).241,242 This protocol is also applicable to the synthesis of a saturated protic thiazolylidin-2-ylidene complex.243 Scheme 57. Reactions of a Trichloromethyl Isocyanide Complex with Diamines

Much earlier, Dötz had described the synthesis of the protic CAAC chromium and tungsten complexes 157, obtained by ringopening aminolysis followed by Mitsunobu cyclization of the Fischer-type carbene complexes 155,252 which are derived from an alkynol (Scheme 60).253 A sugar-derived protic CAAC chromium(0) complex has also been obtained by this aminationrecyclization strategy.254 Annulation of allenylidene complexes with amidines, guanidines, and diamines also affords protic dihydropyrimidin-

2.4.4. Synthesis of Protic Cyclic Alkylaminocarbene Complexes. Cyclic alkylaminocarbene (CAAC) complexes can be considered as a new class of NR-stabilized heterocyclic carbenes with structural and electronic characteristics different from those of the conventional N,N′-disubstituted cyclic diaminocarbenes.3,244−247 Some complexes bearing protic CAACs can be accessed by template-controlled syntheses. Michelin reported the deprotonation-induced cyclization of phosphonium−isocyanide platinum complex 151, which results in formation of the protic mono(amino)carbene complex 152 (Scheme 58).248 The arsine analogues of 152 can be prepared in a similar manner.249 Complex 152 undergoes protonation at the

Scheme 60. Synthesis of Protic CAAC Complexes by Aminolysis of Fischer Carbene Complexes and Subsequent Intramolecular Mitsunobu Reaction

P


Chemical Reviews

Review

4-ylidene complexes,255,256 as exemplified by the reaction shown in Scheme 61.255

Scheme 63. Synthesis of a pNHC Complex by N−C Bond Cleavage at the Coordinated NHC Ligand

Scheme 61. Synthesis of Protic CAAC Complexes by Annulation of an Allenylidene Complex

2.5. Deprotection of N-Masked NHC Complexes

Some types of functional groups at the ring-nitrogen atoms of coordinated NHCs can be substituted with hydrogen atoms to give pNHC complexes. Such deprotective transformations start with the preparation of classical, nonprotic NHC complexes, followed by N-deprotection. In 2006, Whittlesey reported the thermolysis of cyclometalated imidazolin-2-ylidene ruthenium complex 159 to give, via C−N bond cleavage at the wingtip and elimination of propene, the protic imidazolin-2-ylidene complex 160 along with the imidazole complex 161 (Scheme 62, top).34 A

Scheme 64. Synthesis of pNHC Complex by Alcoholysis of an N-Silyl NHC Ligand

Scheme 62. Synthesis of pNHC Complex by C−N Bond Cleavage in a Nonprotic NHC Ligand

separate experiment confirmed that the imidazole complex 161 originates from pNHC-to-azole tautomerization in the coordination sphere of 160 without involvement of a free NHC (Scheme 62, bottom). Related alkene elimination from an NHC ligand was also observed for an iron257 and a platinum258 complex. Meanwhile, Li revealed that the N-acetonyl-substituted NHC iridium complex 163 converts to the pNHC complex 164 during silica gel chromatography (Scheme 63).35 Interconversion of 164 and the isomeric imidazole complex 165 has not been observed even at an elevated temperature, highlighting the synthetic significance of the deprotection approach. Chloride abstraction from the imidazole complex 165 is also ineffective for a formal azole-to-pNHC tautomerization (compare to the conversion of 26 to 27 in Scheme 11). Wagler described the ethanolysis of N-silylated NHC platinum complex 167, derived from (methimazolyl)chlorosilane 166, which gives rise to the formation of pNHC complex 168 as shown in Scheme 64.259 These early findings prompted the development of generally applicable protection groups for the synthesis of pNHC complexes from nonprotic (N,N′-disubstituted) NHC complexes. In 2010, Crabtree demonstrated that N-benzoylbenzimi-

dazolium salt 169, constituting a stoichiometric acylation agent,260 forms the iridium complexes 170 and 171, each featuring a masked pNHC ligand. Complex 171 is easily Ndeprotected with methanol to give the protic imidazolin-2ylidene complex 172 (Scheme 65).261 In 2011, a synthetic route to the bis(imidazolin-2-ylidene) gold complex 175, as illustrated in Scheme 66, was developed.262 The parent imidazole 173 was first protected with triethyl orthoformate for the subsequent C-lithiation. The 2-lithioimidazole thus obtained was subjected to a transmetalation− protonation sequence (see section 2.2.1), which leads to formation of the N-protected imidazolin-2-ylidene complex 174. Finally, N-deprotection of 174 with hydrochloric acid yields the bis-pNHC complex 175.

3. BRØNSTED ACIDITY AND RELATED PROPERTIES As indicated by their name, the pNHC complexes generally exhibit Brønsted acidity.50 The 1H NMR spectrum of pNHC complexes thus shows a characteristic low-field (usually more Q


Chemical Reviews

Review

Scheme 65. Synthesis of pNHC Complexes by Alcoholysis of an N-Benzoyl NHC Ligand

Figure 3. Hydrogen bonding between the pNHC complex 176 and a urea derivative in solution.

On the other hand, quantification of the Brønsted acidity of pNHC complexes remains difficult and thus rare. Taube evaluated the pKa values of some pNHC complexes they have synthesized.58 For example, the pKa value of the imidazolin-2ylidene ruthenium(III) complex cation [Ru(CNHCH CHNH)(NH3)5]3+ was determined to be 11.0, which is smaller than that of the free imidazole (14.2).263 Kuwata and Ikariya reported reversible deprotonation of the pincer-type ruthenium complex 177 bearing a protic pyrazole and a pNHC (Scheme 67).81 Selective formation of the pNHC−pyrazolato complex Scheme 67. Site-Selective Deprotonation of a pNHC− Pyrazole Pincer-Type Complex Scheme 66. Synthesis of a pNHC Complex by Protonation of a C-Imidazolyl Complex Followed by N-Deprotection

178 has been confirmed by 15N labeling of the pyrazole ring, indicating that the pNHC donor is less acidic than the isoelectronic pyrazole donor. The presence of the NH group in pNHC complexes is also inferred by IR spectroscopy. IR data are available for some pNHC complexes and the N−H stretching frequencies have been reported to fall generally in the range of 3500−3100 cm−1. In the 13C NMR spectra, the pNHC complexes are apparently not much different from conventional nonprotic NHC complexes. For example, the NHC-tethered pNHC complex 55 (Scheme 24; R = Me, X = I) exhibits carbene resonances at δ 168.5 (pNHC) and δ 172.7 (nonprotic NHC).100 3.1. Deprotonation of pNHC Ligands

than 8 ppm) resonance for the NH proton, which often disappears upon H−D exchange with an external deuterated reagent such as D2O. In most of the crystallographic studies with pNHC complexes, including the first structurally characterized compound 4 (Scheme 4), electronegative atoms present in counterions or solvent molecules are often found in close proximity to the NH group. This arrangement often provides definitive evidence for the presence of the NH hydrogen atom, which can engage in hydrogen bonding even when the refinement of its positional paramters is difficult. Hydrogen bonding of the NH group in pNHC complexes has been established even in solution. In 2007, Hahn demonstrated that addition of N,N′-dimethylpropyleneurea to a solution of the pNHC tungsten complex 176 in CDCl3 causes a significant downfield shift of the NH resonance of 176 in the 1H NMR spectrum, confirming the hydrogen bonding in solution for the first time (Figure 3).36 As mentioned in section 1, hydrogen bonding often affects the stability of the pNHC complex relative to its tautomeric N-bound azole form.21,23

The inherent Brønsted acidity of the pNHC ligand is the reverse of the protonation of C-azolyl complexes (section 2.2). In their studies of pNHC complexes, Roper found as early as 1973 that deprotonation of the cationic thiazolin-2-ylidene complex 66 regenerates the starting thiazolyl complex 65 (Scheme 28).125 The nucleophilic species generated by deprotonation of a pNHC complexes can be described as an azolyl complex or an anionic Ndeprotonated NHC complex (Scheme 68), although the Scheme 68. N-Deprotonation of pNHC Complexes

R


Chemical Reviews

Review

Table 1. Structural and Spectral Comparison of Selected Pairs of pNHC and Azolyl (Anionic NHC) Complexes

distances (Å) entry

complex

type

M−C

13

angles (deg)

C−N:/NH

C−E

α

β

C NMR

δc

Δδa

ref

2

179 180

NH N:

2.060(5) 2.048(4)

Oxazolidin-2-ylidene (E = O) 1.368(11) 1.393(9) 104.1(7) 1.327(10) 1.399(9) 110.0(8) Imidazolin-2-ylidene (E = NR) 1.332(7) 1.396(6) 106.5(4) 1.297(6) 1.417(4) 111.4(3)

3

181a 182a

NH N:

2.061(4) 2.0715(17)

1.360(5) 1.342(2)

1.351(5) 1.383(2)

103.7(3) 108.31(14)

112.8(3) 107.05(13)

166.7d 156.4e

10.3

74 74

183 184

NH N:

2.224(3) 2.236(8)

1.358(4) 1.299(9)

1.368(3) 1.497(9)

102.9(2) 108.0(7)

112.8(2) 103.2(7)

188.2d 184.5d

3.7

64 64

trans-71 72

NH N:

1.972(4) 1.987(2)

1.349(6) 1.319(3)

1.350(6) 1.389(2)

107.1(4) 111.37(17)

110.6(5) 105.81(18)

157.8d 149.4d

8.4

134 135

6

74 185

NH N:

1.967(3) 1.980(3)

1.373(3) 1.352(3)

1.343(3) 1.360(3)

106.0(2) 110.6(2)

109.9(2) 104.8(2)

na 150.3d

7

75f

NH

1.327(7) 1.345(8) 1.323(3)

1.359(7) 1.352(8) 1.385(3)

107.0(5) 107.1(5) 111.70(19)

110.4(5) 109.8(5) 105.32(19)

155.2g 149.9d

5.3

−3.7

1

4

5

8

9

10

11

133

NH N:

1.843(9) 1.931(9)

112.4(8) 106.6(8)

nab na

221

110.5(4) 106.4(3)

182.2c na

14 14

186

N:

1.979(6) 1.976(6) 1.996(2)

11 10

NH N:

2.191(5) 2.190(7)

1.353(7) 1.359(8)

1.358(6) 1.387(9)

103.6(4) 106.9(6)

112.0(4) 107.6(6)

178.7d 182.4d

13′ (NR = NMes)

NH N:

2.216(10) 2.205(9)

1.346(13) 1.345(13)

1.354(13) 1.401(13)

104.9(9) 105.5(8)

112.1(9) 111.0(9)

180.7d,h

22 187

NH NLi

2.047(2) 2.0659(17)

1.360(3) 1.351(2)

1.361(3) 1.376(2)

103.25(19) 107.72(15)

112.79(19) 107.53(15)

184.1e 175.0e

37f

NH

38i

NLi

2.029(10) 2.029(8) 2.059(9) 2.066(10) 2.073(9) 2.024(9)

1.357(12) 1.378(12) 1.324(11) 1.365(12) 1.339(11) 1.381(10)

1.374(11) 1.328(11) 1.337(11) 1.368(12) 1.348(10) 1.376(11)

105.1(8) 103.6(7) 105.7(8) 106.9(8) 111.7(8) 107.5(8)

111.6(7) 113.4(8) 111.6(7) 110.2(8) 104.5(8) 109.0(9)

na na

141 141

141 141 65 65

69

9.1

74 74

87 . 87

Δδ = δc(pNHC) − δc(deprotonated pNHC). Not available or assigned. In CD3CN. In CD2Cl2. In THF-d8. fValues are given for two crystallographically independent molecules. gIn (CD3)2SO. hAppear equivalent due to fluctional behavior. iN−Li 1.925(17)/1.916(18).

a

b

c

d

e

ligands are also included. These complexes are useful to establish the carbenic character of the deprotonated ligand. In 1995, Hahn disclosed the crystal structure of the iron complex 133 ligated by both a protic benzoxazolin-2-ylidene and

contribution of the two canonical forms remains debatable. Table 1 summarizes the crystallographic and 13C NMR spectroscopic data of selected pairs of pNHC complexes and their Ndeprotonated derivatives. Complexes bearing both types of S


Chemical Reviews

Review

its deprotonated form (Scheme 51).221 While the N−C−O angle (α) of the pNHC ligand is as small as 104.1(7)°, the equivalent angle opens up to 110.0(8)° in the deprotonated ligand (Table 1, entry 1). The increased s-character of the lone pair at the deprotonated nitrogen atom reduces the C−N−C angle (β) to 106.6(8)° [from 112.4(8)° in the protonated ligand], keeping the sum of the five interior angles in the planar ring to 540°. These structural characteristics indicate that the protic benzoxazolin-2-ylidene in 133 is a typical carbene while the oxazolyl form is dominant in the deprotonated ligand.2,67,68 The Fe−C distance involving the pNHC ligand [1.843(9) Å] is much shorter than that of the oxazolyl ligand [1.931(9) Å], in accord with the observations for most imidazolin-2-ylidene complexes, where the differences in M−C bond lengths are generally less significant (Table 1, entries 2−11). Following that, Kuwata and Ikariya discussed the structural differences between the protic imidazolin-2-ylidene ruthenium complex 179 and the N-deprotonated derivative 180 (Table 1, entry 2).14 As was observed in the benzoxazolidin-2-ylidene complex 133, the N−C−N angle α increases and the C−N−C angle β decreases upon N-deprotonation (Table 1). It should be noted that the Ccarbene−N bond distances in the deprotonated ligand [1.297(6) and 1.417(4) Å] differ significantly, in agreement with the canonical structure of the imidazolyl form. Similar trends for bond distances and angles have been observed for other ruthenium (Table 1, entry 3)74 and molybdenum (Table 1, entry 4)64 complexes. In the examples mentioned above, the 13C NMR resonance for the pNHC carbon atom was observed approximately 10 ppm or less shifted to lower field than the equivalent resonance for the azolyl carbon atom.38,77,100 Later, Hahn explored in detail the molecular structures of deprotonated pNHC complexes obtained by oxidative addition of haloimidazoles to low-valent transition metals (Table 1, entries 5−7; Scheme 30).134,135 The calculated natural bond orbital (NBO) charges in complex 72 (Table 1, entry 5) indicates a sizable contribution of an anionic (deprotonated) carbene structure, and the short C−N− bond distance is ascribed to an electrostatic interactions between the negatively charged ringnitrogen atom and the carbene carbon atom.135 In complex 185 (Table 1, entry 6), the two C−N distances involving the carbene carbon are equally long within experimental error, suggesting reduced electron density at the deprotonated ring-nitrogen atom, most likely caused by the attachment of an electron-poor sixmembered ring to the azolyl ring.141 On the other hand, Pérez and Riera reported the molecular structure of complex 10 (Scheme 6), derived by C-deprotonation of an N-bound imidazole ligand followed by rearrangement (Table 1, entry 8).65 The small N−C−N angle α in the C-bound ligand [106.9(6)°], as well as the almost equally long Ccarbene−N bond distances in 10, is consistent with a dominant contribution of the anionic carbene form. In addition, the 13C NMR resonance for the metal-bound heterocycle carbon atom in 10 (δ 182.4) appears at lower field than that of the protonated derivative 11 (δ 178.7), in contrast to the examples previously mentioned. The low-field-shifted resonance may support the anionic carbene character of the deprotonated pNHC complex 10. Complex 13′ (Scheme 6, N−Me groups in 13 substituted by N−Mes groups in 13′; Table 1, entry 9) also features both pNHC and anionic carbene ligands, although the 13C NMR resonances for the two carbene carbon resonances are averaged in solution, probably due to fast proton shift between the two ligands.69 Cossairt synthesized the bis(pNHC) complex 37 and its lithiated derivative 38 (Scheme 15; Table 1, entry 11).87 The bond

angles suggest that one of the two chelate arms in 38 would be best described as a benzimidazolyl ligand and the other as an anionic NHC ligand. Grotjahn have systematically studied the 15N NMR shifts of protic imidazolin-2-ylidene complexes and their deprotonated derivatives.74,88,264 While the 15N chemical shifts of the two nitrogen atoms in the protic imidazolin-2-ylidene ligand are quite similar regardless of the N-substituents (H versus alkyl, for example), the deprotonation results in a large high-field shift for the deprotonated nitrogen atom. The resonance is also shifted to higher field, but slightly less so, upon deprotonative lithiation of an NH group. 3.2. Deprotonation-Induced Reactions

Deprotonation of a pNHC ligand leads to formation of a nucleophilic species regardless of the dominant electron distribution within the heterocycle. A variety of functionalizations and transformations of the pNHC complexes have been developed by use of the deprotonated intermediate. 3.2.1. N-Functionalization Reactions. In 1987, Angelici demonstrated that deprotonation of the protic oxazolidin-2ylidene iron complex 188, followed by addition of electrophiles, results in N-functionalization of 188 (Scheme 69).28 Scheme 69. Deprotonation-Induced Functionalization of a pNHC Complex

This method is quite general and has been employed for the functionalzation of other pNHC complexes. Hahn applied this approach to the synthesis of macrocyclic carbene complexes from multifunctional ligands including pNHC ligands with two NH wingtips at a metal template.48,51 Connection of the four pNHC ligands in the platinum complex 194 was achieved by multiple electrophilic attack of N,N-dimethylformamide at the ring-nitrogen atoms in the presence of phosgene as a dehydrating agent, yielding the macrocyclic complex 195 in over 60% yield (Scheme 70).226 Intramolecular nucleophilic substitution at the 2-fluorophenylphosphine ligand in rhenium,182,183,265 manganese,183 ruthenium,229 and iron228 complexes of type 196 results in formation of the facially coordinated, macrocyclic mixed-donor NHC complexes 197 (Scheme 71). T


Chemical Reviews

Review

Scheme 70. Template Synthesis of a Macrocyclic Tetra-NHC Complex through Multiple Addition−Elimination

Scheme 73. Metal−Ligand Cooperation in Protic Amine and pNHC Complexes

Scheme 71. Template Synthesis of Facially Coordinated Macrocyclic NHC Ligand through Intramolecular Nucleophilic Substitution by a pNHC

similarly to the reactivity observed for frustrated Lewis pairs.267−269 In 2008, Grotjahn uncovered the metal−ligand bifunctional reactivity of pNHC iridium(III) complex 21 (Scheme 74).38 Scheme 74. Metal−Ligand Cooperative Reactivity of a pNHC Iridium Complex

Finally, Scheme 72 illustrates multiple intramolecular nucleophilic addition of the NH groups of 198 to the olefin Scheme 72. Template Synthesis of a Macrocyclic P2C2 NHC Ligand through Intramolecular Nucleophilic Addition

bonds of a divinylphosphine ligand, which leads to the macrocyclic P2C2 ligand in complex 199.230 3.2.2. Metal−Ligand Cooperative Reactivity. Direct participation of ligands in substrate recognition, activation, and transformation, through various secondary interactions such as hydrogen bonding and proton transfer in the coordination sphere, has attracted much attention in order to shed light on the action of metalloenzymes and to develop novel transition-metal catalysts. The non-innocent properties of selected ligands have been investigated with an initial special focus placed on complexes bearing protic amine ligands.39−42 As illustrated in Scheme 73a, dehydrohalogenation of the protic amine complex provides an amido complex containing a coordinatively unsaturated Lewis-acidic metal center and a Brønsted-basic amido ligand. This amido complex can react with a variety of substrates H−X and even dihydrogen in a concerted or stepwise manner. The resulting complex with the protic amine ligand can subsequently transfer the nucleophilic ligand X to unsaturated substrates with the aid of, for example, hydrogen bonding to the amine ligand.266 An analogous type of interconversion can be envisioned for complexes bearing protic NHC ligands. Such complexes can also be dehydrohalogenated to the coordinatively unsaturated azolyl complexes, which can add polar molecules for a subsequent transfer to selected substrates (Scheme 73b),45,50

Imidazolyl complex 200, obtained by N-deprotonation of the cationic pNHC complex 21, undergoes chloride abstraction with KB(C6F5)4, leading to transient formation of the unsaturated imidazolyl complex 201. This species reacts in a cooperative fashion with acetylene to give the pNHC−acetylido complex 202 in the manner illustrated in Scheme 73b. Even heterolytic cleavage of H2 by 201 takes place to afford the pNHC-hydrido complexes of type 203 without any change in the formal oxidation state of the metal center.38 The hydrido complexes of type 203 are also accessible by treatment of chlorido complex 21 with a base in ethanol. Stepwise U


Chemical Reviews

Review

deprotonation of the pNHC ligand and removal of the hydrido ligand from 203b with a strong base results in formation of a highly moisture-sensitive iridium(I) complex 205 bearing an Nlithiated NHC, which undergoes electrophilic alkylation to give an alkyl−imidazolyl iridium(III) complex such as 206 instead of the complex bearing an N-alkylated NHC ligand. Cleavage of dihydrogen has also been demonstrated with additional iridium complexes bearing phosphine-tethered pNHC ligands.77 Similar reactivity was observed with isoelectronic ruthenium complexes such as 22 (Chart 2), as summarized in Scheme 75.74

Scheme 76. Nucleophilic Addition of a pNHC Ligand at a Coordinated Nitrile

Scheme 77. Bifunctional Addition of Carbon Dioxide to a Deprotonated pNHC Complex

Scheme 75. Metal−Ligand Cooperative Reactivity of a pNHC Ruthenium Complex

azolyl ligand and a labile aqua ligand. This complex can then undergo bifunctional addition of carbon dioxide to afford the cycloaddition product 210. Analogous metal−ligand bifunctional additions of H2, CO2, alkenes, and acetylenes272,273 are known for some protic dihydropyridin-2-ylidene complexes.45 Cooperation of a Brønsted-acidic pNHC ligand and a Lewisacidic metal center is also possible. In 2008, Kuwata and Ikariya demonstrated that the reaction of pNHC ruthenium(II) complex 20 with allyl alcohol results in the formation of 2-allylimidazole complex 213 (Scheme 78).14 The mechanism proposed for this transformation involves hydrogen-bond formation between the Scheme 78. Metal−pNHC Cooperative Reactions Triggered by Proton Transfer

Deprotonation of the pNHC ligand of 22 with lithium bases results in formation of the anionic imidazolyl (or lithiated NHC) complex 187, which has been characterized by X-ray diffraction. Recently a sodium−NHC−ruthenium complex closely related to 187 but bearing a hydrido ligand instead of the chlorido ligand has been isolated and structurally characterized.270 Complex 187 can be considered as a LiCl adduct of a coordinatively unsaturated imidazolyl complex similar to the iridium complex 201 (Scheme 74). The LiCl is easily removed from 187 even by ethylene to afford the ethylene complex 182a (L = C2H4) (Scheme 75). Complexes of type 182 can also be obtained by coordination of ligands of type L to 22, followed by N-deprotonation of the pNHC. Complexes of type 182b, bearing labile amine ligands, as well as the LiCl adduct 187, smoothly react with H2 and 2-propanol to give the hydridopNHC complex 207, most probably via a coordinatively unsaturated imidazolyl complex as was postulated for the related iridium complexes.38 Bifunctional activation of acetonitrile has been achieved by chloride abstraction from the pNHC complex 164 in acetonitrile, which leads to a subsequent intramolecular nucleophilic attack of the pNHC ligand at the coordinated acetonitrile to give the imine chelate complex 208 (Scheme 76).35 Recently Cossairt reported the reaction of bis(pNHC) ruthenium complex 209, prepared by chelation-assisted oxidative addition of a bis(imidazolium) salt to ruthenium, with carbon dioxide (Scheme 77).271 Initial deprotonation of 209 with a strong base probably yields the complex with the nucleophilic V


Chemical Reviews

Review

pNHC ligand and the hydroxy group of the allyl alcohol, which promotes C−O bond cleavage under mild and neutral conditions. Reductive elimination from the resulting π-allyl(azolyl)ruthenium(IV) complex 212 occurs easily in spite of the presence of the anchoring pyridyl group to afford the 2allylimidazole complex 213. Such metal−ligand cooperation apparently also operates in dehydrative conversion of the nitrite ion in 214 to the nitrosyl ligand in 180. The significance of the NH group in this transformation is evident, since similar treatment of an aprotic 2,2′-bipyridine complex gives only a nitrito complex without N−O bond cleavage.274 The imidazolyl complex 180 thus formed undergoes reversible protonation to regenerate the pNHC ligand in complex 179.14,77 Very recently, the first examples for complexes bearing protic abnormal carbene complexes [carbene coordinated to a platinum(II) center via the imidazole C4 ring-carbon atom with protons at the C2 and N3 imidazole ring atoms] appeared (Scheme 31).142 The N3 ring-nitrogen atom in 77 can be reversibly deprotonated, thereby generating a nucleophilic ringnitrogen atom in the presence of the Lewis-acidic platinum(II) center. Complexes bearing such deprotonated abnormal NHCs can activate molecular hydrogen and also react in a coopertive fashion with carbon disulfide, where the nucleophilic ringnitrogen attacks first the CS2 carbon atom, followed by attack of the generated thiolate at the platinum center.275 3.2.3. Metalation and Carbene Transfer Reactions. In the absence of electrophilic reagents, the nucleophilic azolyl (or anionic NHC) complexes generated by deprotonation of pNHC ligands often dimerize to complexes of type 216 by replacement of one coligand,136,146 as exemplified in Scheme 79.173

Scheme 81. N-Metalation of a Bis(NHC) Complex

novel conventional NHC complexes, direct pNHC transfer between two metal centers is currently unknown. In 2007, however, Ruiz found that deprotonation of the pNHC ligand in manganese complex 100 promotes pNHC transfer as illustrated in Scheme 82.33,62 The (azolyl)manganese complex 221, Scheme 82. Base-Induced Formal pNHC Transfer Reaction

Scheme 79. Deprotonation-Induced Dimerization of pNHC Complexes

Selected pNHCs can even serve as chelate ligands and afford heterobimetallic complexes such as 39 (Scheme 15)87 and 217 (Scheme 80).276 Scheme 80. N-Deprotonation−Metalation of a pNHC Complex generated by N-deprotonation of the pNHC ligand in complex 100, reacts with a gold complex to give, most likely (but not detected), an N-metalated NHC (or imidazolyl-bridged) complex 222. Subsequent metal exchange occurs rapidly, probably owing to the preference of the carbene carbon atom for the softer gold(I) center, to give complex 223. Protonation leads to the pNHC ligand with loss of manganese to yield complex 224. DFT calculations revealed that the overall metal exchange involves an intermediate wherein the azolyl carbon atom bridges the two metal atoms.277 Although the metals suitable for such a carbene transfer reaction are limited to manganese and gold at this time, a thiazolin-2-ylidene complex has been synthesized in a similar manner.63

Recently, Ruiz demonstrated that the stepwise deprotonation of bis(pNHC) complex 218 in the presence of copper(I) chloride results in formation of the Au/Cu mixed-metal complex 220, forming a one-dimensional, infinite chain structure (Scheme 81).165 While the transmetalation of NHC ligands, particularly from silver complexes,57 offers a well-established synthetic route to W


Chemical Reviews

Review

4. COMPLEXES BEARING PNHC IN CATALYSIS The utility of pNHC complexes in catalysis has first been demonstrated in metal-catalyzed C−C bond formation with Nheterocyclic compounds such as imidazoles. In these reactions, the substrate-derived pNHC ligand is generated in each turnover and subsequently liberated from the coordination sphere as the reaction product. Later developments in the synthesis of pNHC complexes, as described in section 2, enabled pNHC-based metal−ligand bifunctional catalysis, in which a pNHC moiety tightly bound to the metal center promotes the catalytic transformation in a cooperative manner.

Scheme 84. Proposed Mechanisms for Catalytic Intramolecular Alkylation of an Olefin-Tethered Imidazole

4.1. Intermediary pNHC Complexes Originating from Catalytic Substrates

In their groundbreaking work on rhodium-catalyzed C−H bond functionalization of N-heterocycles,278,279 Ellman and Bergman revealed the intermediacy of pNHC complexes in these reactions. Scheme 83 illustrates the catalytic intramolecular alkylation of benzimidazoles reported in 2001.280 Scheme 83. Catalytic Intramolecular Alkylation of Benzimidazole complex 49 is followed by reductive elimination to give the cyclization product 229.94 In this scenario, formation of the pNHC complex 226 is a nonproductive (and probably reversible) side reaction. Yates also proposed yet another mechanism for catalytic cyclization in the presence of an acid, featuring the C−H oxidative addition of an imidazolium cation derived from protonation of the substrate (Scheme 85).

A wide range of polycyclic 2-alkylimidazole derivatives, including the highly functionalized, chiral bioactive compound 225 (Chart 4),281 has been obtained by this reaction.282 Enantioselective cyclization has further been achieved by using chiral phosphine ligands.283 Chart 4

Scheme 85. Proposed Mechanism for Catalytic Intramolecular Alkylation of Imidazole with Brønsted Acid Cocatalyst

A stoichiometric reaction between the olefin-tethered azole and [RhCl(coe)2]2 in the presence of a phosphine, at a temperature below that required for catalysis, leads to the isolation of the catalytically active olefin-tethered pNHC complex 19 (Scheme 8).73 The pNHC catalyst 19 catalyzes cyclization at the same rate as the binary RhI/PCy3 catalyst. In addition to detailed experimental investigations including the double-labeling crossover experiment shown in Scheme 20, DFT calculations have been performed on the catalytic cyclization.92,94 As mentioned in section 2.1.3 (Scheme 22), the initial coordination of the ring-nitrogen atom of the substituted azole and the subsequent C−H oxidative addition, which gives the azolyl intermediate 49, have been established. Isolation of the pNHC complex 19 supports route 1 shown in Scheme 84, involving an initial 1,3-H shift in 49 and subsequent olefin insertion into the metal−carbene bond of 226, followed by reductive elimination with formation of 229. Meanwhile, Yates explored a competitive mechanism (route 2 shown in Scheme 84), in which an initial olefin insertion in azolyl

Indeed, addition of weak Brønsted acids such as lutidinium chloride accelerates the intermolecular version of the C−H alkylation of azoles, as illustrated in Scheme 86.284,285 Various heterocycles with different functional groups are compatible with the catalyst. Application of the catalyst to intra- and intermolecular C−H alkylation of related heterocycles led to formation of various compounds depicted in Chart 4 (right).286,287 Even ortho-substituted pyridines and quinolines bearing only one heteroatom adjacent to the reactive C−H bond undergo intermolecular alkylation.288 Although the detailed mechanism has not been elucidated, involvement of a protic dihydropyridin-2-ylidene complex is likely. C−H functionalization guided by the pNHC mechanism has further been extended to arylation of N-heterocycles featuring no X


Chemical Reviews

Review

proposed mechanism for arylation of azoles shown in Scheme 89 involves formal tautomerization of the azole substrate to the pNHC complex 237.

Scheme 86. Catalytic Alkylation of Imidazoles

Scheme 89. Proposed Mechanism for Catalytic Arylation of Azoles

N-tethered donor. In 2004, Ellman and Bergman described arylation of imidazoles with a RhI/PCy3 binary catalyst (Scheme 87).91 In contrast to the previously described alkylation, a base Scheme 90 illustrate a closely related C−H arylation of orthosubstituted pyridine and quinoline catalyzed by a rhodium(I)

Scheme 87. Early Example of Catalytic Arylation of Imidazoles

Scheme 90. Catalytic Arylation of Pyridine

additive is required, presumably to neutralize the acid that is generated. The reaction is also applicable to other heterocycles, including benzoxazole and a substituted oxazoline. However, the yields generally remain moderate due to concurrent hydrodehalogenation of iodobenzene. The efficiency, in addition to the substrate scope, of arylation of N-substituted azoles has been improved significantly by using the bicyclophosphine ligand 234 (Scheme 88) as well as by using a bulky amine base.287,289 Detailed mechanistic studies finally led to development of the hemilabile bidentate phosphine−olefin ligand 235, which allows the use of inexpensive and broadly available aryl bromides without concurrent hydrodehalogenation as well as expansion of the substrate scope (Scheme 88).290 The

complex.291 A hypothetical mechanism presented by the authors involves a dihydropyridin-2-ylidene intermediate. In 2008, Kuwata and Ikariya demonstrated that the pyridinetethered pNHC ruthenium complex 20, synthesized by chelation-assisted formal tautomerization (Scheme 9), quantitatively catalyzes the dehydrative coupling of N-(2-pyridyl)benzimidazole 240 and allyl alcohol to give the 2-alkenylimidazoles 241 (Scheme 91).14 The proposed mechanism for Scheme 91. Catalytic Dehydrative Coupling of Pyridylbenzimidazole and Allyl Alcohol

Scheme 88. Catalytic Arylation of Azoles

formation of 241 from 240 shown in Scheme 92 features an initial two-point interaction between the pNHC complex and allyl alcohol as discussed in section 3.2.2. The allylimidazole ligand in complex 213, generated as explained in Scheme 78, is replaced by the pyridylimidazole substrate, and concurrent chelation-assisted formal tautomerization would regenerate the pNHC complex 20. The high reaction temperature required in Y


Chemical Reviews

Review

74). Donor-substituted, chelating pNHC ligands are often effective to prevent catalyst decomposition through dissociation of the pNHC ligand. In 2011, Grotjahn demonstrated that the (hydrido)ruthenium complex 207 (see also Scheme 75) bearing a P,C-chelate pNHC ligand catalyzes the transfer hydrogenation of acetophenone with 2-propanol in the absence of a base (Scheme 94).74 As expected, the parent chlorido complex 22 also

Scheme 92. Proposed Mechanism for Dehydrative Coupling of Pyridylbenzimidazole and Allyl Alcohol Catalyzed by a pNHC Complex

Scheme 94. Transfer Hydrogenation of Acetophenone Catalyzed by pNHC Complex 22 or 207

exhibits catalytic activity with the aid of a base. Metal−pNHC cooperation in the hydrogen-transfer step has been proposed as established for related protic amine complexes.39−42 The cationic bis(pNHC)iridium chlorido complex 34, as well as the hydrido complex 242, catalyzes the transfer hydrogenation of unsaturated ketones (Scheme 95).83 While alkenones 243 are

this step causes double-bond migration, giving the 2alkenylimidazoles 241 as the final reaction products.

Scheme 95. Transfer Hydrogenation of Unsaturated Ketones Catalyzed by pNHC Complex 34 or 242

4.2. Catalysts with Built-in pNHC Ligands

Coordination of a Brønsted-acidic pNHC ligand offers a site for hydrogen bonding and acid−base catalysis in the secondary coordination sphere. This renders the pNHC as an attractive cooperating ligand, besides being a catalytic intermediate in the transformations of N-heterocycles. In 2007, Hahn and Waldvogel demonstrated the chemoselective catalytic hydrogenation of alkenes with the pNHC complex 43b (Scheme 93).36 Scheme 93. Competitive Hydrogenation of Alkenes with and without Carbonyl Group, Catalyzed by a pNHC Complex

reduced to unsaturated alcohols 244, an α,β-unsaturated ketone 245 undergoes much faster reduction of the olefin bond to give the saturated ketone 246 selectively. Substrate recognition of the bis(pNHC) catalysts through hydrogen bonding is proposed to explain this notable chemoselectivity. Song applied the hydrogen-transfer ability of the P,C-chelate pNHC ruthenium complex 23′ (see Chart 2 for complex 23) to the acceptorless dehydrogenation of alcohols as well as to dehydrogenative coupling of primary and secondary alcohols (Scheme 96).270 Hahn reported hydrogenation of imines catalyzed by pNHC complexes (Scheme 97).101 In the presence of H2, Nbenzylideneamines are smoothly reduced in methanol to the

The alkene with an ester group is reduced more than two times faster than that without the functional group, suggesting possible substrate recognition through a hydrogen bond between the pNHC ligand and the substrate. In addition to substrate recognition, the pNHC ligand can participate in bond activation directly, as demonstrated by Kuwata and Ikariya14 (Scheme 78) and by Grotjahn38 (Scheme Z


Chemical Reviews

Review

the hydration of 1-hexyne to give a 4:1 mixture of the aldehyde and ketone (Scheme 99).88 Greater selectivity was observed in

Scheme 96. Dehydrogenative Oxidation Reactions of Alcohols Catalyzed by pNHC Complex 23′

Scheme 99. Hydration of Alkynes Catalyzed by pNHC Complex 249

Scheme 97. Hydrogenation of Imines Catalyzed by Imidazolyl Complex 53b-Ia

the reaction of phenylacetylene, which yields the antiMarkovnikov product, 2-phenylacetoaldehyde, exclusively. The mechanism involving a vinylidene intermediate is suggested by the stoichiometric reactions, including that with a 13C-labeled alkyne (Scheme 99, bottom). The role of the NH group in this class of catalysis, however, remains poorly understood.

a

5. SUMMARY AND OUTLOOK This review article focused on progress in the synthesis, properties, and reactivities of protic N-heterocyclic carbene complexes since 1972. It becomes apparent that pNHC ligands do not constitute a simple subclass of the conventional Nheterocyclic carbenes. The characteristic NH wingtip requires special methods for synthesis of the pNHC complexes. However, this restriction has now been overcome by the development of various elegant methods including formal tautomerization of azoles, oxidative addition of haloazoles and azolium cations, annulation or cyclization of isocyanides at a metal template, and deprotection of masked NHCs. These methods have been optimized for an efficient synthesis of the ambiphilic pNHC complexes featuring a Brønsted-acidic NH group and an electron-donating carbene donor. Formation of pNHC complexes from azoles is also implicated in some catalytic C−H functionalization reactions of azoles.278,279 Once installed within the NHC ring, the Brønsted-acidic NH group enables new reactivity patterns. Hydrogen bonding of the NH wingtip in the secondary coordination sphere provides a method for substrate recognition. In some cases, proton transfer between the pNHC ligand and the substrate coupled with a metal-centered reaction occurs, realizing metal−ligand cooperative reactions. On the other hand, deprotonation of the NH group results in formation of the conjugate base. This nucleophilic species is apparently best described as a resonance hybrid between an anionic NHC and an azolyl complex, but further experimental and theoretical investigations are needed for better understanding of the electronic situation in these derivatives. The N-deprotonation of the pNHC ligand also allows N-functionalization of the pNHC complexes and even bond activation with the cooperation of Lewis-acidic metal centers. Owing to the non-innocent character of the pNHC ligand, metal−ligand bifunctional cooperating catalysis with pNHC complexes is currently emerging. Although this type of catalysis is

Entry 2, without H2.

corresponding amines. No catalytic transformation occurs in the absence of H2 (entry 2), suggesting that the reaction involves dihydrogen activation. N-Benzylidene-t-butylamine is also hydrogenated, although the reaction is much slower. An iridium complex without any proton-responsive ligand (entry 6) is not effective in the reaction, which implicates the role of the imidazolyl ligand in 53b-I in catalytic transformation (for the preparation of complexes of type 53b, see Scheme 24). Catalysis other than hydrogenation and hydrogen-transfer reactions by pNHC complexes have also been explored recently. Liu evaluated the catalytic activity of selected pNHC rhenium complexes toward the insertion of phenylacetylene into a β-keto ester (Scheme 98).292 pNHC complexes 247 and 248 catalyze the reaction, but the efficiency is less than that of conventionally used complexes such as [ReBr(CO)5]. In 2015, Grotjahn reported that the bis(pNHC) pincer-type platinum complex 249, derived from 41c (Scheme 16), catalyzes Scheme 98. Insertion of Phenylacetylene into a β-Keto Ester Catalyzed by pNHC Complexes 247 and 248

AA


Chemical Reviews

Review

coe Cp* DEAD Dipp DMF DMSO EWG LutHCl Mes NBO NHC pNHC PPN σ-CAM Tf THF THT TIPS Tol TosMIC Ts

still in its infancy, modulation of the pNHC ligands, as well as mechanistic investigations to elucidate the role of the pNHC ligands in chemical transformations, will lead to the development of more sophisticated catalytic applications for pNHC complexes. There is no doubt that the preparation of new pNHC complexes, particularly those of silver and group 3−5 metals for which pNHC complexes are currently unknown, will continue to be explored in order to obtain new complexes for various applications such as catalysis and supramolecular chemistry. Analogous developments should be expected for the closely related other proton-responsive N-heterocyclic ligands such as protic dihydropyridin-2-ylidenes,45 protic cyclic alkylaminocarbenes, and pyrazoles.45,50

AUTHOR INFORMATION Corresponding Authors

*(S.K.) E-mail [email protected]. *(F.E.H.) E-mail [email protected]. ORCID

Shigeki Kuwata: 0000-0002-3165-9882 F. Ekkehardt Hahn: 0000-0002-2807-7232

cyclooctene 1,2,3,4,5-pentamethylcyclopentadienyl diethyl azodicarboxylate 2,6-diisopropylphenyl N,N-dimethylformamide dimethyl sulfoxide electron-withdrawing group 2,6-dimethylpyridinium chloride 2,4,6-trimethylphenyl natural bond orbital N-heterocyclic carbene protic N-heterocyclic carbene bis(triphenylphosphine)iminium, (Ph3P)2N+ σ-complex-assisted metathesis triflyl, CF3SO2 tetrahydrofuran tetrahydrothiophene triisopropylsilyl p-tolyl p-toluenesulfonylmethyl isocyanide tosyl

Notes

REFERENCES

The authors declare no competing financial interest.

(1) Hopkinson, M. N.; Richter, C.; Schedler, M.; Glorius, F. An Overview of N-Heterocyclic Carbenes. Nature 2014, 510, 485−496. (2) Melaimi, M.; Soleilhavoup, M.; Bertrand, G. Stable Cyclic Carbenes and Related Species beyond Diaminocarbenes. Angew. Chem., Int. Ed. 2010, 49, 8810−8849. (3) Schuster, O.; Yang, L.; Raubenheimer, H. G.; Albrecht, M. Beyond Conventional N-Heterocyclic Carbenes: Abnormal, Remote, and Other Classes of NHC Ligands with Reduced Heteroatom Stabilization. Chem. Rev. 2009, 109, 3445−3478. (4) Hahn, F. E.; Jahnke, M. C. Heterocyclic Carbenes: Synthesis and Coordination Chemistry. Angew. Chem., Int. Ed. 2008, 47, 3122−3172. (5) N-Heterocyclic Carbenes: Effective Tools for Organometallic Synthesis; Nolan, S. P., Ed.; Wiley−VCH: Weinheim, Germany, 2014. (6) Zhong, R.; Lindhorst, A. C.; Groche, F. J.; Kühn, F. E. Immobilization of N-Heterocyclic Carbene Compounds: A Synthetic Perspective. Chem. Rev. 2017, 117, 1970−2058. (7) Sinha, N.; Hahn, F. E. Metallosupramolecular Architectures Obtained from Poly-N-heterocyclic Carbene Ligands. Acc. Chem. Res. 2017, 50, 2167−2184. (8) Peris, E. Polyaromatic N-Heterocyclic Carbene Ligands and πStacking. Catalytic Consequences. Chem. Commun. 2016, 52, 5777− 5787. (9) Strassner, T. Phosphorescent Platinum(II) Complexes with C∧C* Cyclometalated NHC Ligands. Acc. Chem. Res. 2016, 49, 2680−2689. (10) Karaca, Ö .; Meier-Menches, S. M.; Casini, A.; Kühn, F. E. On the Binding Modes of Metal NHC Complexes with DNA Secondary Structures: Implications for Therapy and Imaging. Chem. Commun. 2017, 53, 8249−8260. (11) Liu, W.; Gust, R. Update on Metal N-Heterocyclic Carbene Complexes as Potential Anti-Tumor Metallodrugs. Coord. Chem. Rev. 2016, 329, 191−213. (12) Nelson, D. J.; Nolan, S. P. Quantifying and Understanding the Electronic Properties of N-Heterocyclic Carbenes. Chem. Soc. Rev. 2013, 42, 6723−6753. (13) Hillier, A. C.; Sommer, W. J.; Yong, B. S.; Petersen, J. L.; Cavallo, L.; Nolan, S. P. A Combined Experimental and Theoretical Study Examining the Binding of N-Heterocyclic Carbenes (NHC) to the Cp*RuCl (Cp* = η5-C5Me5) Moiety: Insight into Stereoelectronic Differences Between Unsaturated and Saturated NHC Ligands. Organometallics 2003, 22, 4322−4326. (14) Araki, K.; Kuwata, S.; Ikariya, T. Isolation and Interconversion of Protic N-Heterocyclic Carbene and Imidazolyl Complexes: Application to Catalytic Dehydrative Condensation of N-(2-Pyridyl)benzimidazole and Allyl Alcohol. Organometallics 2008, 27, 2176−2178.

Biographies Shigeki Kuwata was born in 1969 in Osaka, Japan. He received his Dr.Eng. degree from the Department of Chemistry and Biotechnology at the University of Tokyo in 1997 under the supervision of Professors Masanobu Hidai and Yasushi Mizobe. Just after that, he was appointed as an assistant professor in the department. In 2002, he moved to Tokyo Institute of Technology as an associate professor in the group of Professor Takao Ikariya. He was also a PRESTO researcher in Japan Science and Technology Agency (JST) in 2014−2018. He obtained an Award for Young Scientists in Coordination Chemistry, Japan, in 2002. His current research interests focus on the chemistry of azametallics featuring reactive metal−nitrogen units. F. Ekkehardt Hahn was born in 1955 in Jena, Germany. He studied chemistry at the Technische Universität Berlin and the University of Oklahoma (M.S. 1982). He graduated with a Dr.rer.nat. degree from the Technische Universität Berlin in 1985. After a postdoctoral stay with Professor Raymond at UC Berkeley (1985−1988), he completed the Habilitation in 1990 and became an associate professor at Freie Universität Berlin (1992−1998) before moving in 1998 to a position as Chair of Inorganic Chemistry at the University of Münster. His research is centered on the chemistry of N-heterocyclic carbenes and isocyanide ligands. He has been appointed Senior Editor of Chemistry Letters in 2014. Since 2004 he has acted as Permanent Secretary of the International Conference of Organometallic Chemistry (ICOMC).

ACKNOWLEDGMENTS The PRESTO program on “Molecular Technology and Creation of New Functions” from JST (Grant JPMJPR14K6) is acknowledged (S.K.). F.E.H. thanks the Deutsche Forschungsgemeinschaft (IRTG 2027 and SFB 858). ABBREVIATIONS ADC acyclic diaminocarbene BArF4 tetrakis(3,5-bis(trifluoromethyl)phenyl)borate anion CAAC cyclic alkyl amino carbene CMD concerted metalation−deprotonation cod 1,5-cyclooctadiene AB


Chemical Reviews

Review

(15) Karmakar, S.; Datta, A. Tunneling Assists the 1,2-Hydrogen Shift in N-Heterocyclic Carbenes. Angew. Chem., Int. Ed. 2014, 53, 9587− 9591. (16) Amyes, T. L.; Diver, S. T.; Richard, J. P.; Rivas, F. M.; Toth, K. Formation and Stability of N-Heterocyclic Carbenes in Water: the Carbon Acid pKa of Imidazolium Cations in Aqueous Solution. J. Am. Chem. Soc. 2004, 126, 4366−4374. (17) Maier, G.; Endres, J.; Reisenauer, H. P. 2,3-Dihydrothiazol-2ylidene. Angew. Chem., Int. Ed. Engl. 1997, 36, 1709−1712. (18) McGibbon, G. A.; Hrušaḱ , J.; Lavorato, D. J.; Schwarz, H.; Terlouw, J. K. The Thiazole Ylide: A Frequently Invoked Intermediate Is a Stable Species in the Gas Phase. Chem. - Eur. J. 1997, 3, 232−236. (19) McGibbon, G. A.; Heinemann, C.; Lavorato, D. J.; Schwarz, H. Imidazol-2-ylidene: Generation of a Missing Carbene and Its Dication by Neutralization−Reionization and Charge-Stripping Mass Spectrometry. Angew. Chem., Int. Ed. Engl. 1997, 36, 1478−1481. (20) Heinemann, C.; Thiel, W. Ab initio Study on the Stability of Diaminocarbene. Chem. Phys. Lett. 1994, 217, 11−16. (21) Sini, G.; Eisenstein, O.; Crabtree, R. Preferential C-Binding versus N-Binding in Imidazole Depends on the Metal Fragment Involved. Inorg. Chem. 2002, 41, 602−604. (22) Tonner, R.; Heydenrych, G.; Frenking, G. Bonding Analysis of NHeterocyclic Carbene Tautomers and Phosphine Ligands in TransitionMetal Complexes: A Theoretical Study. Chem. - Asian J. 2007, 2, 1555− 1567. (23) Häller, L. J. L.; Macgregor, S. A. Computational Study of the Cand N-Bound Tautomers of [Ru(Cl)(H)(CO)(PPh3)2(IiPrMe2)] (IiPrMe2 = 3-Isopropyl-4,5-Dimethylimidazol-2-Ylidene). Eur. J. Inorg. Chem. 2009, 2009, 2000−2006. (24) Most of the literature refers to this class of compounds as 2pyridylidene, which, however, appears inappropriate. See Herrmann, W. A.; Köcher, C. N-Heterocyclic Carbenes. Angew. Chem., Int. Ed. Engl. 1997, 36, 2162−2187. (25) Esteruelas, M. A.; Fernández-Alvarez, F. J.; Oñate, E. Stabilization of NH Tautomers of Quinolines by Osmium and Ruthenium. J. Am. Chem. Soc. 2006, 128, 13044−13045. (26) Sundberg, R. J.; Shepherd, R. E.; Taube, H. Carbon-Bound Imidazolium Ylides as Ligands in Ruthenum(II) and Ruthenium(III) Complexes. J. Am. Chem. Soc. 1972, 94, 6558−6559. (27) Sundberg, R. J.; Bryan, R. F.; Taylor, I. F.; Taube, H. NitrogenBound and Carbon-Bound Imidazole Complexes of Ruthenium Ammines. J. Am. Chem. Soc. 1974, 96, 381−392. (28) Johnson, L. K.; Angelici, R. J. Synthesis of Aminooxycarbene Complexes of Iron with N-Alkyl, -Allyl, and -Carbamoyl Groups. Inorg. Chem. 1987, 26, 973−976. (29) Bartel, K.; Fehlhammer, W. P. Modes of Reaction of 2- and 3Hydroxyalkyl Isocyanides with Metal Compounds; Oxazolidinylidene and Perhydrooxazinylidene Complexes of Palladium, Platinum, and Gold. Angew. Chem., Int. Ed. Engl. 1974, 13, 599−600. (30) McCormick, F. B.; Angelici, R. J. Synthesis of Cyclopentadienyldicarbonyl(dithiocarbene)iron Cations and Their Reactions with Amines. Inorg. Chem. 1979, 18, 1231−1235. (31) Price, C.; Elsegood, M. R. J.; Clegg, M.; Rees, N. H.; Houlton, A. Evidence for Directed Metalation: A Structural Intermediate in the Formation of a Novel C-Bound Adenine Complex of Ruthenium. Angew. Chem., Int. Ed. Engl. 1997, 36, 1762−1764. (32) Naziruddin, A. R.; Hepp, A.; Pape, T.; Hahn, F. E. Synthesis of Rhodium(I) Complexes Bearing Bidentate NH,NR-NHC/Phosphine Ligands. Organometallics 2011, 30, 5859−5866. (33) Ruiz, J.; Perandones, B. F. Base-Promoted Tautomerization of Imidazole Ligands to N-Heterocyclic Carbenes and Subsequent Transmetalation Reaction. J. Am. Chem. Soc. 2007, 129, 9298−9299. (34) Burling, S.; Mahon, M. F.; Powell, R. E.; Whittlesey, M. K.; Williams, J. M. J. Ruthenium Induced C−N Bond Activation of an NHeterocyclic Carbene: Isolation of C- and N-Bound Tautomers. J. Am. Chem. Soc. 2006, 128, 13702−13703. (35) Wang, X.; Chen, H.; Li, X. Ir(III)-Induced C-Bound to N-Bound Tautomerization of a N-Heterocyclic Carbene. Organometallics 2007, 26, 4684−4687.

(36) Meier, N.; Hahn, F. E.; Pape, T.; Siering, C.; Waldvogel, S. R. Molecular Recognition Utilizing Complexes with NH,NR-Stabilized Carbene Ligands. Eur. J. Inorg. Chem. 2007, 2007, 1210−1214. (37) Peris, E. Smart N-Heterocyclic Carbene Ligands in Catalysis. Chem. Rev. 2017 (in press); DOI: 10.1021/acs.chemrev.6b00695). (38) Miranda-Soto, V.; Grotjahn, D. B.; DiPasquale, A. G.; Rheingold, A. L. Imidazol-2-yl Complexes of Cp*Ir as Bifunctional Ambident Reactants. J. Am. Chem. Soc. 2008, 130, 13200−13201. (39) Khusnutdinova, J. R.; Milstein, D. Metal−Ligand Cooperation. Angew. Chem., Int. Ed. 2015, 54, 12236−12273. (40) Eisenstein, O.; Crabtree, R. H. Outer Sphere Hydrogenation Catalysis. New J. Chem. 2013, 37, 21−27. (41) Zhao, B.; Han, Z.; Ding, K. The N−H Functional Group in Organometallic Catalysis. Angew. Chem., Int. Ed. 2013, 52, 4744−4788. (42) Ikariya, T. Chemistry of Concerto Molecular Catalysis Based on the Metal/NH Bifunctionality. Bull. Chem. Soc. Jpn. 2011, 84, 1−16. (43) Moore, C. M.; Dahl, E. W.; Szymczak, N. K. Beyond H2: Exploiting 2-Hydroxypyridine as a Design Element from [Fe]Hydrogenase for Energy-Relevant Catalysis. Curr. Opin. Chem. Biol. 2015, 25, 9−17. (44) Grotjahn, D. B. Bifunctional Organometallic Catalysis and Reactivity Using Heterocyclic Phosphines and Metallated Heterocycles. Chem. Lett. 2010, 39, 908−914. (45) Kuwata, S.; Ikariya, T. Metal−Ligand Bifunctional Reactivity and Catalysis of Protic N-Heterocyclic Carbene and Pyrazole Complexes Featuring β-NH Units. Chem. Commun. 2014, 50, 14290−14300. (46) Jahnke, M. C.; Hahn, F. E. Chemistry of N-Heterocyclic Carbene Ligands. Top. Organomet. Chem. 2010, 30, 95−129. (47) Hahn, F. E. Substrate Recognition and Regioselective Catalysis with Complexes Bearing NR,NH-NHC Ligands. ChemCatChem 2013, 5, 419−430. (48) Jahnke, M. C.; Hahn, F. E. Complexes with Protic (NH,NH and NH,NR) N-Heterocyclic Carbene Ligands. Coord. Chem. Rev. 2015, 293−294, 95−115. (49) Jahnke, M. C.; Hahn, F. E. Complexes Bearing Protic NHeterocyclic Carbenes: Synthesis and Applications. Chem. Lett. 2015, 44, 226−237. (50) Kuwata, S.; Ikariya, T. β-Protic Pyrazole and N-Heterocyclic Carbene Complexes: Synthesis, Properties, and Metal−Ligand Cooperative Bifunctional Catalysis. Chem. - Eur. J. 2011, 17, 3542− 3556. (51) Edwards, P. G.; Hahn, F. E. Synthesis and Coordination Chemistry of Macrocyclic Ligands Featuring NHC Donor Groups. Dalton Trans. 2011, 40, 10278−10288. (52) Hock, S. J.; Schaper, L.-A.; Herrmann, W. A.; Kühn, F. E. Group 7 Transition Metal Complexes with N-Heterocyclic Carbenes. Chem. Soc. Rev. 2013, 42, 5073−5089. (53) Boyarskiy, V. P.; Bokach, N. A.; Luzyanin, K. V.; Kukushkin, V. Y. Metal-Mediated and Metal-Catalyzed Reactions of Isocyanides. Chem. Rev. 2015, 115, 2698−2779. (54) Hille, C.; Kühn, F. E. Cationic Rhenium Complexes Ligated with N-Heterocyclic Carbenes  an Overview. Dalton Trans. 2016, 45, 15− 31. (55) Tschugajeff, L.; Skanawy-Grigorjewa, M.; Posnjak, A. Ü ber die Hydrazin-Carbylamin-Komplexe des Platins. Z. Anorg. Allg. Chem. 1925, 148, 37−42. (56) Butler, W. M.; Enemark, J. H.; Parks, J.; Balch, A. L. Chelative Addition of Hydrazines to Coordinated Isocyanides. The Structure of Chugaev’s Red Salt. Inorg. Chem. 1973, 12, 451−457. (57) Lin, J. C. Y.; Huang, R. T. W.; Lee, C. S.; Bhattacharyya, A.; Hwang, W. S.; Lin, I. J. B. Coinage Metal−N-Heterocyclic Carbene Complexes. Chem. Rev. 2009, 109, 3561−3598. (58) Clarke, M. J.; Taube, H. Nitrogen-Bound and Carbon-Bound Xanthine Complexes of Ruthenium Ammines. J. Am. Chem. Soc. 1975, 97, 1397−1403. (59) Krentzien, H. J.; Clarke, M. J.; Taube, H. Crystal Structure of a Compound Featuring Caffeine Bound at C8 to Ruthenium(III). Bioinorg. Chem. 1975, 4, 143−151. AC


Chemical Reviews

Review

(60) Johnson, A.; O’Connell, L. A.; Clarke, M. J. N7 and C8 Coordinated Purine Complexes of [(NH3)5OsIII]. Crystal Structures of 7-[9MeHyp(NH3)5Os]Cl3·H2O and 8-[1,3,7Me3Xan(NH3)5Os]Cl3· 2H2O. Inorg. Chim. Acta 1993, 210, 151−157. (61) Ruiz, J.; Perandones, B. F.; Van der Maelen, J. F.; Garcia-Granda, S. On the Existence of an N-Metalated N-Heterocyclic Carbene: A Theoretical Study. Organometallics 2010, 29, 4639−4642. (62) Ruiz, J.; Berros, A.; Perandones, B. F.; Vivanco, M. NHC− Manganese(I) Complexes as Carbene Transfer Agents. Dalton Trans. 2009, 6999−7007. (63) Ruiz, J.; Perandones, B. F. Metal-induced Tautomerization of Oxazole and Thiazole Molecules to Heterocyclic Carbenes. Chem. Commun. 2009, 2741−2743. (64) Brill, M.; Díaz, J.; Huertos, M. A.; López, R.; Pérez, J.; Riera, L. Imidazole to NHC Rearrangements at Molybdenum Centers: An Experimental and Theoretical Study. Chem. - Eur. J. 2011, 17, 8584− 8595. (65) Huertos, M. A.; Pérez, J.; Riera, L.; Menéndez-Velázquez, A. From N-Alkylimidazole Ligands at a Rhenium Center: Ring Opening or Formation of NHC Complexes. J. Am. Chem. Soc. 2008, 130, 13530− 13531. (66) Huertos, M. A.; Pérez, J.; Riera, L.; Díaz, J.; López, R. Effect of the Nature of the Substituent in N-Alkylimidazole Ligands on the Outcome of Deprotonation: Ring Opening versus the Formation of NHeterocyclic Carbene Complexes. Chem. - Eur. J. 2010, 16, 8495−8507. (67) Kirmse, W. Stable Singlet Carbenes−Plentiful and Versatile. Angew. Chem., Int. Ed. 2004, 43, 1767−1769. (68) Glorius, F. N-Heterocyclic Carbenes in Catalysis  An Introduction. Top. Organomet. Chem. 2007, 21, 1−21. (69) Huertos, M. A.; Pérez, J.; Riera, L.; Díaz, J.; López, R. From Bis(NAlkylimidazole) to Bis(NH-NHC) in Rhenium Carbonyl Complexes. Angew. Chem., Int. Ed. 2010, 49, 6409−6412. (70) Price, C.; Shipman, M.; Gummerson, S.; Houlton, A.; Clegg, W.; Elsegood, M. R. J. Ruthenium−Carbon Bond Formation via Cyclometallation of a Nucleobase. J. Chem. Soc., Dalton Trans. 2001, 353−354. (71) Price, C.; Shipman, M. A.; Rees, N. H.; Elsegood, M. R. J.; Edwards, A. J.; Clegg, W.; Houlton, A. Macrochelation, Cyclometallation and G-Quartet Formation: N3- And C8-Bound PdII Complexes of Adenine and Guanine. Chem. - Eur. J. 2001, 7, 1194− 1201. (72) Galindo, M.; Houlton, A. Chelate-tethered Nucleobases: New Architectures and Insights in Metal Ion−Nucleobase Chemistry. Inorg. Chim. Acta 2009, 362, 625−633. (73) Tan, K. L.; Bergman, R. G.; Ellman, J. A. Intermediacy of an NHeterocyclic Carbene Complex in the Catalytic C−H Activation of a Substituted Benzimidazole. J. Am. Chem. Soc. 2002, 124, 3202−3203. (74) Miranda-Soto, V.; Grotjahn, D. B.; Cooksy, A. L.; Golen, J. A.; Moore, C. E.; Rheingold, A. L. A Labile and Catalytically Active Imidazol-2-yl Fragment System. Angew. Chem., Int. Ed. 2011, 50, 631− 635. (75) Hahn, F. E.; Naziruddin, A. R.; Hepp, A.; Pape, T. Synthesis, Characterization, and H-Bonding Abilities of Ruthenium(II) Complexes Bearing Bidentate NR,NH-Carbene/Phosphine Ligands. Organometallics 2010, 29, 5283−5288. (76) Brackemeyer, D.; Schulte to Brinke, C.; Roelfes, F.; Hahn, F. E. Regioselective C8-Metalation of N-Phosphine Tethered Adenine Derivatives via C8−H Activation. Dalton Trans. 2017, 46, 4510−4513. (77) Cepa, S.; Schulte to Brinke, C.; Roelfes, F.; Hahn, F. E. Hydrogen Activation by an Iridium(III) Complex Bearing a Bidentate Protic NH,NR-NHC∧Phosphine Ligand. Organometallics 2015, 34, 5454− 5460. (78) He, F.; Braunstein, P.; Wesolek, M.; Danopoulos, A. A. ImineFunctionalised Protic NHC Complexes of Ir: Direct Formation by C−H Activation. Chem. Commun. 2015, 51, 2814−2817. (79) He, F.; Wesolek, M.; Danopoulos, A. A.; Braunstein, P. Homoand Heterodinuclear Ir and Rh Imine-functionalized Protic NHC Complexes: Synthetic, Structural Studies, and Tautomerization/Metallotropism Insights. Chem. - Eur. J. 2016, 22, 2658−2671.

(80) Toda, T.; Kuwata, S.; Ikariya, T. Unsymmetrical Pincer-Type Ruthenium Complex Containing β-Protic Pyrazole and N-Heterocyclic Carbene Arms: Comparison of Brønsted Acidity of NH Groups in Second Coordination Sphere. Chem. - Eur. J. 2014, 20, 9539−9542. (81) Toda, T.; Yoshinari, A.; Ikariya, T.; Kuwata, S. Protic NHeterocyclic Carbene Versus Pyrazole: Rigorous Comparison of Proton- and Electron-Donating Abilities in a Pincer-Type Framework. Chem. - Eur. J. 2016, 22, 16675−16683. (82) Eguillor, B.; Esteruelas, M. A.; García-Raboso, J.; Oliván, M.; Oñate, E.; Pastor, I. M.; Peñafiel, I.; Yus, M. Osmium NHC Complexes from Alcohol-Functionalized Imidazoles and Imidazolium Salts. Organometallics 2011, 30, 1658−1667. (83) Gomez-Lopez, J. L.; Chávez, D.; Parra-Hake, M.; Royappa, A. T.; Rheingold, A. L.; Grotjahn, D. B.; Miranda-Soto, V. Synthesis and Reactivity of Bis(protic N-heterocyclic carbene)iridium(III) Complexes. Organometallics 2016, 35, 3148−3153. (84) Djukic, J.-P.; Sortais, J.-B.; Barloy, L.; Pfeffer, M. Cycloruthenated Compounds  Synthesis and Applications. Eur. J. Inorg. Chem. 2009, 2009, 817−853. (85) Albrecht, M. Cyclometalation Using d-Block Transition Metals: Fundamental Aspects and Recent Trends. Chem. Rev. 2010, 110, 576− 623. (86) Han, Y.-F.; Jin, G.-X. Cyclometalated [Cp*M(C∧X)] (M = Ir, Rh; X = N, C, O, P) Complexes. Chem. Soc. Rev. 2014, 43, 2799−2823. (87) Flowers, S. E.; Cossairt, B. M. Mono- and Dimetalation of a Tridentate Bisimidazole-Phosphine Ligand. Organometallics 2014, 33, 4341−4344. (88) Marelius, D. C.; Darrow, E. H.; Moore, C. E.; Golen, J. A.; Rheingold, A. L.; Grotjahn, D. B. Hydrogen-Bonding Pincer Complexes with Two Protic N-Heterocyclic Carbenes from Direct Metalation of a 1,8-Bis(Imidazol-1-yl)carbazole by Platinum, Palladium, and Nickel. Chem. - Eur. J. 2015, 21, 10988−10992. (89) Kühl, O. The Chemistry of Functionalised N-Heterocyclic Carbenes. Chem. Soc. Rev. 2007, 36, 592−607. (90) Chantson, J. T.; Lotz, S. C−H and N−H Activation by Pt(0) in Nand O-Heteroaromatic Compounds. J. Organomet. Chem. 2004, 689, 1315−1324. (91) Lewis, J. C.; Wiedemann, S. H.; Bergman, R. G.; Ellman, J. A. Arylation of Heterocycles via Rhodium-Catalyzed C−H Bond Functionalization. Org. Lett. 2004, 6, 35−38. (92) Wiedemann, S. H.; Lewis, J. C.; Ellman, J. A.; Bergman, R. G. Experimental and Computational Studies on the Mechanism of NHeterocycle C−H Activation by Rh(I). J. Am. Chem. Soc. 2006, 128, 2452−2462. (93) Gribble, M. W.; Ellman, J. A.; Bergman, R. G. Synthesis of a Benzodiazepine-Derived Rhodium NHC Complex by C−H Bond Activation. Organometallics 2008, 27, 2152−2155. (94) Hawkes, K. J.; Cavell, K. J.; Yates, B. F. Rhodium-Catalyzed C−C Coupling Reactions: Mechanistic Considerations. Organometallics 2008, 27, 4758−4771. (95) Song, G.; Su, Y.; Periana, R. A.; Crabtree, R. H.; Han, K.; Zhang, H.; Li, X. Anion-Exchange-Triggered 1,3-Shift of an NH Proton to Iridium in Protic N-Heterocyclic Carbenes: Hydrogen-Bonding and Ion-Pairing Effects. Angew. Chem., Int. Ed. 2010, 49, 912−917. (96) Su, Y.; Song, G.; Han, K.; Li, X. Theoretical Studies of IridiumMediated Tautomerization of Substituted Pyridines. J. Organomet. Chem. 2011, 696, 1640−1646. (97) Song, G.; Li, Y.; Chen, S.; Li, X. Hydrogen Bonding-Assisted Tautomerization of Pyridine Moieties in the Coordination Sphere of an Ir(I) Complex. Chem. Commun. 2008, 3558−3560. (98) Lapointe, D.; Fagnou, K. Overview of the Mechanistic Work on the Concerted Metallation−Deprotonation Pathway. Chem. Lett. 2010, 39, 1118−1126. (99) Perutz, R. N.; Sabo-Etienne, S. The σ-CAM Mechanism: σ Complexes as the Basis of σ-Bond Metathesis at Late-Transition-Metal Centers. Angew. Chem., Int. Ed. 2007, 46, 2578−2592. (100) Aznarez, F.; Sanz Miguel, P. J.; Tan, T. T. Y.; Hahn, F. E. Preparation of Rhodium(III) Di-NHC Chelate Complexes Featuring AD


Chemical Reviews

Review

alkylimidazolato-N3,C2)]tri-Gold(I) and -Silver(I). Crystal Structure of Bis(1-benzylimidazolin-2-yliden)gold(I) Chloride. J. Organomet. Chem. 1989, 375, 147−160. (118) Raubenheimer, H. G.; Scott, F.; Kruger, G. J.; Toerien, J. G.; Otte, R.; van Zyl, W.; Taljaard, I.; Olivier, P.; Linford, L. Formation and Characterization of Neutral and Cationic Amino(thio)carbene Complexes of Gold(I) from Thiazolyl Precursors. J. Chem. Soc., Dalton Trans. 1994, 2091−2097. (119) Raubenheimer, H.; Lindeque, L.; Cronje, S. Synthesis and Characterization of Neutral and Cationic Diamino Carbene Complexes of Gold(I). J. Organomet. Chem. 1996, 511, 177−184. (120) Kruger, G.; Olivier, P. J.; Lindeque, L.; Raubenheimer, H. G. (1,3-Dimethylimidazolinylidene)(1-methyl-imidazolinylidene)gold(I) Trifluoromethanesulfonate. Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 1995, C51, 1814−1816. (121) Fehlhammer, W. P.; Bliß, T.; Fuchs, J.; Holzmann, G. Homoleptic Carbene Complexes, IV. Tetrakis(N-alkylimidazolin-2ylidene)palladium and -platinum. Z. Naturforsch., B: J. Chem. Sci. 1992, 47, 79−89. (122) Raubenheimer, H. G.; Scott, F.; Cronje, S.; van Rooyen, P. H.; Psotta, K. Synthesis and Crystallographic Characterization of Thiazolyl and Thiazolinylidene Complexes of Cyclopentadienyliron(II). J. Chem. Soc., Dalton Trans. 1992, 1009−1014. (123) Raubenheimer, H. G.; Toerien, J. G.; Kruger, G. J.; Otte, R.; van Zyl, W.; Olivier, P. Characterization of Mono(carbene) and Bis(carbene) Complexes of Gold(I) Derived from Lithiated Pyridine. J. Organomet. Chem. 1994, 466, 291−295. (124) Raubenheimer, H. G.; Stander, Y.; Marais, E. K.; Thompson, C.; Kruger, G. J.; Cronje, S.; Deetlefs, M. Group 6 Carbene Complexes Derived from Lithiated Azoles and the Crystal Structure of a Molybdenum Thiazolinylidene Complex. J. Organomet. Chem. 1999, 590, 158−168. (125) Fraser, P. J.; Roper, W. R.; Stone, F. Cationic Cyclic Carbene or Carbon-Bonded Ylide Complexes of Iridium(III) and Platinum(II). J. Organomet. Chem. 1973, 50, C54−C56. (126) Fraser, P. J.; Roper, W. R.; Stone, F. G. A. Cationic Cyclic Carbene Complexes of Iridium(III), Nickel(II), Palladium(II), and Platinum(II). J. Chem. Soc., Dalton Trans. 1974, 102−105. (127) Isobe, K.; Kawaguchi, S. Organopalladium(II) Complexes Containing Carbon-Bonded Pyridine and Picoline as a Ligand: Preparation, Structures, and Reactions. Heterocycles 1981, 16, 1603− 1612. (128) Crociani, B.; di Bianca, F.; Giovenco, A.; Scrivanti, A. Protonation and Methylation Reactions of 2-Pyridyl-Palladium(II) and -Platinum(II) Complexes. J. Organomet. Chem. 1983, 251, 393−411. (129) Isobe, K.; Nakamura, Y.; Miwa, T.; Kawaguchi, S. Comparative Studies of 2-, 3-, and 4-Pyridylpalladium(II) Complexes: Syntheis and Properties. Bull. Chem. Soc. Jpn. 1987, 60, 149−157. (130) Crociani, B.; di Bianca, F.; Giovenco, A.; Berton, A. NProtonated 2-Pyridylnickel(II) Complexes. Insertion of Isocyanides into the Nickel−2-Pyridyl Bond. J. Organomet. Chem. 1987, 323, 123− 134. (131) Crociani, B.; Di Blanca, F.; Giovenco, A.; Berton, A.; Bertani, R. Preparation and Reactions of 2-Pyridylplatinum(II) Complexes [PtCl(C5H4N-C2)(L)2] (L = Tertiary Phosphine). Compounds with a Markedly Nucleophilic Pyridine Nitrogen Atom. J. Organomet. Chem. 1989, 361, 255−267. (132) Poulain, A.; Neels, A.; Albrecht, M. Palladium Complexes Containing Potentially Chelating Pyridylidene-Type Carbene Ligands. Eur. J. Inorg. Chem. 2009, 2009, 1871−1881. (133) Ito, J.-i.; Miyakawa, T.; Nishiyama, H. Amine-Assisted C−Cl Bond Activation of Aryl Chlorides by a (Phebox)Rh-Chloro Complex. Organometallics 2008, 27, 3312−3315. (134) Kösterke, T.; Pape, T.; Hahn, F. E. Synthesis of NHC Complexes by Oxidative Addition of 2-Chloro-N-methylbenzimidazole. J. Am. Chem. Soc. 2011, 133, 2112−2115. (135) Kösterke, T.; Kösters, J.; Würthwein, E.-U.; Mück-Lichtenfeld, C.; Schulte to Brinke, C.; Lahoz, F.; Hahn, F. E. Synthesis of Complexes

Two Different NHC Donors via a Mild NaOAc-Assisted C−H Activation. Organometallics 2016, 35, 410−419. (101) Aznarez, F.; Iglesias, M.; Hepp, A.; Veit, B.; Sanz Miguel, P. J.; Oro, L. A.; Jin, G.-X.; Hahn, F. E. Iridium(III) Complexes Bearing Chelating Bis-NHC Ligands and Their Application in the Catalytic Reduction of Imines. Eur. J. Inorg. Chem. 2016, 2016, 4598−4603. (102) Yu, M.-H.; Yang, H.-H.; Naziruddin, A. R.; Kanne, S.; Wang, B.H.; Liu, F.-C.; Lin, I. J. B.; Lee, G.-H. Formation of NH,NR NHeterocyclic Carbene Complexes through Mercuration of Mono-Nsubstituted Benzimidazoles. Eur. J. Inorg. Chem. 2016, 2016, 4829− 4834. (103) Lin, N.-C.; Syu, H. J. H.; Naziruddin, A. R.; Liu, F.-C.; Lin, I. J. B. Direct C-Metallation of N-Substituted Triazoles Promoted by Mercury Acetate. An Alternative Route to N-Heterocyclic Carbene Complexes. RSC Adv. 2017, 7, 11652−11656. (104) Conejero, S.; López-Serrano, J.; Paneque, M.; Petronilho, A.; Poveda, M. L.; Vattier, F.; Alvarez, E.; Carmona, E. Tautomerisation of 2-Substituted Pyridines to N-Heterocyclic Carbene Ligands Induced by the 16e− Unsaturated [TpMe2IrIII(C6H5)2] Moiety. Chem. - Eur. J. 2012, 18, 4644−4664. (105) Esteruelas, M. A.; Fernández-Alvarez, F. J.; Oñate, E. NHTautomerization of 2-Substituted Pyridines and Quinolines on Qsmium and Ruthemium: Determining Factors and Mechanism. Organometallics 2008, 27, 6236−6244. (106) Kunz, D. Synthetic Routes to N-Heterocyclic Carbene Complexes: Pyridine−Carbene Tautomerizations. Angew. Chem., Int. Ed. 2007, 46, 3405−3408. (107) Esteruelas, M. A.; Fernández-Alvarez, F. J.; Oñate, E. Osmium and Ruthenium Complexes Containing an N-Heterocyclic Carbene Ligand Derived from Benzo[h]Quinoline. Organometallics 2007, 26, 5239−5245. (108) Buil, M. L.; Esteruelas, M. A.; Garcés, K.; Oliván, M.; Oñate, E. Understanding the Formation of N−H Tautomers from α-Substituted Pyridines: Tautomerization of 2-Ethylpyridine Promoted by Osmium. J. Am. Chem. Soc. 2007, 129, 10998−10999. (109) Buil, M. L.; Esteruelas, M. A.; Garcés, K.; Oliván, M.; Oñate, E. Cβ(sp2)−H Bond Activation of α,β-Unsaturated Ketones Promoted by a Hydride-Elongated Dihydrogen Complex: Formation of Osmafuran Derivatives with Carbene, Carbyne, and NH-Tautomerized αSubstituted Pyridine Ligands. Organometallics 2008, 27, 4680−4690. (110) Esteruelas, M. A.; Fernández-Alvarez, F. J.; Oliván, M.; Oñate, E. NH-Tautomerization of Quinolines and 2-Methylpyridine Promoted by a Hydride-Iridium(III) Complex: Importance of the Hydride Ligand. Organometallics 2009, 28, 2276−2284. (111) Paneque, M.; Poveda, M. L.; Vattier, F.; Alvarez, E.; Carmona, E. Synthesis and Structural Characterization of a Binuclear Iridium Complex with Bridging, Bidentate N-Heterocyclic Carbene Coordination of 2,2′:6′,2″-Terpyridine. Chem. Commun. 2009, 5561−5563. (112) Conejero, S.; Maya, C.; Paneque, M.; Petronilho, A.; Poveda, M. L.; Vattier, F.; Á lvarez, E.; Carmona, E.; Laguna, A.; Crespo, O. Iridium(III) Complexes with Polypyridine Ligands Coordinated as NHeterocyclic Carbenes. Synthesis, Structure and Photophysical Properties. Dalton Trans. 2012, 41, 14126−14136. (113) Bajo, S.; Esteruelas, M. A.; López, A. M.; Oñate, E. Alkenylation of 2-Methylpyridine via Pyridylidene−Osmium Complexes. Organometallics 2012, 31, 8618−8626. (114) Cristóbal, C.; Á lvarez, E.; Paneque, M.; Poveda, M. L. Facile Oxygen Atom Insertion into Unactivated C(sp3)−C(sp2) Single Bonds in Reactions of Iridium(III) Complexes with O2. Organometallics 2013, 32, 714−717. (115) Vattier, F.; Salazar, V.; Paneque, M.; Poveda, M. L.; Á lvarez, E. Tautomerization of Pyridine and 2-Substituted Pyridines to Pyridylidene Ligands by the Iridium(I)−Diene Complex TpMe2Ir(η4-CH2 C(Me)C(Me)CH2). Organometallics 2014, 33, 498−510. (116) Raubenheimer, H.; Cronje, S. Carbene Complexes Derived from Lithiated Heterocycles, Mainly Azoles, by Transmetallation. J. Organomet. Chem. 2001, 617−618, 170−181. (117) Bonati, F.; Burini, A.; Pietroni, B. R.; Bovio, B. Reactions of CImidazolyllithium Derivatives with Group Ib Compounds: Tris[μ-(1AE


Chemical Reviews

Review

Containing an Anionic NHC Ligand with an Unsubstituted RingNitrogen Atom. Chem. - Eur. J. 2012, 18, 14594−14598. (136) Jin, H.; Kluth, P.; Hahn, F. E. Synthesis of Complexes with Protic NH,NR-NHC Ligands by Oxidative Addition of N-Alkyl-2-iodoimidazoles to [M(PPh3)4] (M = Pd, Pt) Complexes. Eur. J. Inorg. Chem. 2017, 2017, 2774−2781. (137) Hervé, A.; Jahnke, M. C.; Pape, T.; Hahn, F. E. Synthesis of Palladium and Platinum Complexes with an NH,NEt-substituted Benzimidazolin-2-ylidene Ligand. Z. Anorg. Allg. Chem. 2013, 639, 2450−2454. (138) Das, R.; Hepp, A.; Daniliuc, C. G.; Hahn, F. E. Synthesis of Complexes with Protic NH,NH-NHC Ligands via Oxidative Addition of 2-Halogenoazoles to Zero-Valent Transition Metals. Organometallics 2014, 33, 6975−6987. (139) Das, R.; Daniliuc, C. G.; Hahn, F. E. Oxidative Addition of 2Halogenoazoles−Direct Synthesis of Palladium(II) Complexes Bearing Protic NH,NH-Functionalized NHC Ligands. Angew. Chem., Int. Ed. 2014, 53, 1163−1166. (140) Kösterke, T.; Pape, T.; Hahn, F. E. Synthesis of Complexes Bearing NH,NMe-Substituted NHCs by Oxidative Addition of 2Halogenato-N-methylbenzimidazoles to Ni(0). Chem. Commun. 2011, 47, 10773−10775. (141) Brackemeyer, D.; Hervé, A.; Schulte to Brinke, C.; Jahnke, M. C.; Hahn, F. E. A Versatile Methodology for the Regioselective C8Metalation of Purine Bases. J. Am. Chem. Soc. 2014, 136, 7841−7844. (142) Jin, H.; Tan, T. T. Y.; Hahn, F. E. Synthesis of Complexes with Abnormal “Protic” N-Heterocyclic Carbenes. Angew. Chem., Int. Ed. 2015, 54, 13811−13815. (143) Cavell, K. J.; McGuinness, D. S. Redox Processes Involving Hydrocarbylmetal (N-Heterocyclic Carbene) Complexes and Associated Imidazolium Salts: Ramifications for Catalysis. Coord. Chem. Rev. 2004, 248, 671−681. (144) Crudden, C. M.; Allen, D. P. Stability and Reactivity of NHeterocyclic Carbene Complexes. Coord. Chem. Rev. 2004, 248, 2247− 2273. (145) Cavell, K. N-Heterocyclic Carbenes/imidazolium Salts as Substrates in Catalysis: the Catalytic 2-Substitution and Annulation of Heterocyclic Compounds. Daton Trans. 2008, 6676−6685. (146) He, F.; Danopoulos, A. A.; Braunstein, P. Trifunctional pNHC, Imine, Pyridine Pincer-Type Iridium(III) Complexes: Synthetic, Structural, and Reactivity Studies. Organometallics 2016, 35, 198−206. (147) Cabeza, J. A.; da Silva, I.; del Rio, I.; Sánchez-Vega, M. G. Triruthenium and Triosmium Carbonyl Clusters Containing Chiral Bidentate NHC-Thiolate Ligands Derived from Levamisole. Dalton Trans. 2006, 3966−3971. (148) Romerosa, A.; Suarez-Varela, J.; Hidalgo, M. A.; Avila-Rosón, J. C.; Colacio, E. Synthesis and Molecular Structure of the First Metal Complex of an Analogue of Guanine with PdII−C(8) Binding. Inorg. Chem. 1997, 36, 3784−3786. (149) Chang, Y.-C.; Chang, C.-H.; Wang, L.-W.; Liang, Y.-H.; Hu, D.F.; Weng, C.-M.; Mao, K.-C.; Hong, F.-E. Imidazolio-Substituted Secondary Phosphine Oxides as Potential Carbene Reagents. Polyhedron 2015, 100, 382−391. (150) Wetzel, C.; Kunz, P. C.; Thiel, I.; Spingler, B. Gold(I) Catalysts with Bifunctional P,N Ligands. Inorg. Chem. 2011, 50, 7863−7870. (151) Belluco, U.; Michelin, R. A.; Ros, R.; Bertani, R.; Facchin, G.; Mozzon, M.; Zanotto, L. Synthesis of Heterocyclic Systems by Activation of Isocyanide, Carbonyl, Trifluoromethyl and Nitrile Ligands in Platinum(II) and Palladium(II) Complexes. Inorg. Chim. Acta 1992, 198−200, 883−897. (152) Tamm, M.; Hahn, F. E. Reactions of β-Functional Phenyl Isocyanides. Coord. Chem. Rev. 1999, 182, 175−209. (153) Weskamp, T.; Böhm, V. P. W.; Herrmann, W. A. N-Heterocyclic Carbenes: State of the Art in Transition-Metal-Complex Synthesis. J. Organomet. Chem. 2000, 600, 12−22. (154) Michelin, R. A.; Pombeiro, A. J. L.; Guedes da Silva, M. F. C. Aminocarbene Complexes Derived from Nucleophilic Addition to Isocyanide Ligands. Coord. Chem. Rev. 2001, 218, 75−112.

(155) Basato, M.; Michelin, R. A.; Mozzon, M.; Sgarbossa, P.; Tassan, A. N-Heterocyclic Carbenes from Transition Metal Coordinated Functional Isocyanides of the Type o-(CH2Y)C6H4NC (Y = OSiMe3, OH; N3; AsR3+). J. Organomet. Chem. 2005, 690, 5414−5420. (156) Ito, Y.; Hirao, T.; Tsubata, K.; Saegusa, T. A New Preparation of Imidazolidinylidene Palladium(II) Complexes. Tetrahedron Lett. 1978, 19, 1535−1538. (157) Ng, C.-O.; Yiu, S.-M.; Ko, C.-C. Synthesis, Characterization, and Photophysical Study of Luminescent Rhenium(I) Diimine Complexes with Various Types of N-Heterocyclic Carbene Ligands. Inorg. Chem. 2014, 53, 3022−3031. (158) Motschi, H.; Angelici, R. J. Synthesis of Cyclic Aminooxo- and Dioxocarbenes from Carbonyl Ligands in Complexes of Iron and Manganese. Organometallics 1982, 1, 343−349. (159) Michelin, R. A.; Zanotto, L.; Braga, D.; Sabatino, P.; Angelici, R. J. Transition-Metal-Promoted Cyclization Reactions of Isocyanide Ligand. Synthesis of Cyclic Diaminocarbenes from Isocyanide Complexes of Palladium(II) and Platium(II) and X-Ray Structure of cis-Br2Pt[CN(C6H4-p-Me)CH2CH2N(H)](PPh3). Inorg. Chem. 1988, 27, 93−99. (160) Zanotto, L.; Bertani, R.; Michelin, R. A. Synthesis and Deprotonation Reactions of Neutral and Cationic Cyclic (Aminooxy)Carbenes Derived from Platinum(II) Carbonyls. Inorg. Chem. 1990, 29, 3265−3268. (161) Yu, I.; Wallis, C. J.; Patrick, B. O.; Diaconescu, P. L.; Mehrkhodavandi, P. Phosphine-Tethered Carbene Ligands: Template Synthesis and Reactivity of Cyclic and Acyclic Functionalized Carbenes. Organometallics 2010, 29, 6065−6076. (162) Ruiz, J.; Garcia, G.; Mosquera, M. E. G.; Perandones, B. F.; Gonzalo, M. P.; Vivanco, M. Generation of N-Heterocyclic Carbenes by Metal-Mediated Coupling of Propargylamine and Isocyanides. J. Am. Chem. Soc. 2005, 127, 8584−8585. (163) Ruiz, J.; Perandones, B. F.; García, G.; Mosquera, M. E. G. Synthesis of N-Heterocyclic Carbene Complexes of Manganese(I) by Coupling Isocyanide Ligands with Propargylamines and Propargylic Alcohols. Organometallics 2007, 26, 5687−5695. (164) Ruiz, J.; García, L.; Mejuto, C.; Vivanco, M.; Díaz, M. R.; GarcíaGranda, S. Strong Electron-Donating Metalla-N-heterocyclic Carbenes. Chem. Commun. 2014, 50, 2129−2132. (165) Ruiz, J.; García, L.; Sol, D.; Vivanco, M. Template Synthesis, Metalation, and Self-Assembly of Protic Gold(I)/(NHC)2 Tectons Driven by Metallophilic Interactions. Angew. Chem., Int. Ed. 2016, 55, 8386−8390. (166) Singh, M. M.; Angelici, R. J. Expansion of Three-Membered Heterocycles to Five-Membered Cyclic Carbenes  Novel Reactions of Aziridine, Oxirane, and Thiirane with CO and CS Ligands in Iron, Ruthenium, and Manganese Complexes. Angew. Chem., Int. Ed. Engl. 1983, 22, 163−164. (167) Singh, M. M.; Angelici, R. J. Reactions of Aziridine, Oxirane, and Thiirane with Carbonyl and Thiocarbonyl Ligands in Complexes of Iron, Manganese, and Ruthenium: Syntheses of Cyclic Carbene Compounds. Inorg. Chem. 1984, 23, 2691−2698. (168) Singh, M. M.; Angelici, R. J. Reactions of Aziridine and Oxirane with Manganese and Rhenium Carbonyl Complexes. Syntheses of Neutral 5-Membered Cyclic Aminooxy- and Dioxycarbene Compounds. Inorg. Chem. 1984, 23, 2699−2705. (169) Singh, M. M.; Angelici, R. J. Dioxy Carbene Complexes From Reactions of Fe(CO)5, Mn2(CO)10, Re2(CO)10, and Ru3(CO)12 with Oxirane. Inorg. Chim. Acta 1985, 100, 57−63. (170) Wang, S.-J.; Angelici, R. J. Synthesis and Reactions of Aminooxy Carbene Complexes of Rhenium. J. Organomet. Chem. 1988, 352, 157− 167. (171) Fehlhammer, W. P.; Bär, E.; Boyadjiev, B. Chemistry of Hydrogen Isocyanide, II Reactions of [M(CO)5CNH] (M = Cr, Mo, W) with Aziridines: Cyclic Diaminocarbene Complexes. Z. Naturforsch., B: J. Chem. Sci. 1986, 41, 1023−1027. (172) Bertani, R.; Mozzon, M.; Michelin, R. Reactions of Aziridine, Thiirane, and Oxirane with Isocyanide Ligands in Complexes of Palladium(II) and Platinum(II): Syntheses of Neutral 5-Membered AF


Chemical Reviews

Review

Cyclic Diamino-, Aminothio-, and Aminooxycarbene Compounds. Inorg. Chem. 1988, 27, 2809−2815. (173) Bertani, R.; Mozzon, M.; Michelin, R.; Benetollo, F.; Bombieri, G.; Castilho, T. J.; Pombeiro, A. J. L. Synthesis, Chemical and Electrochemical Deprotonation Reactions of Aminocarbene Complexes of Palladium(II) and Platinum(II). X-ray Structure of {(PPh3)ClPt[μCOCH2CH2N-C,N]}2. Inorg. Chim. Acta 1991, 189, 175−187. (174) Bertani, R.; Mozzon, M.; Benetollo, F.; Bombieri, G.; Michelin, R. A. Reactions of Isocyanide Complexes of Palladium(II) and Platinum(II) with Azetidine: Synthesis of Acyclic Diaminocarbene D e r i v a ti v e s a n d X - R a y S t r u c tu r e o f [ P d C l ( P M e 2 P h ) (CH2CH2CH2NH){C(NCH2CH2CH2)NHC6H4OMe-p}]Cl·CH2Cl2. J. Chem. Soc., Dalton Trans. 1990, 1197−1205. (175) Bär, E.; Völkl, A.; Beck, F.; Fehlhammer, W. P.; Robert, A. Chemistry of Hydrogen Isocyanide. Part 1. Reactions of [M(CO)5(CNH)] (M = Cr or W) with Epoxides. J. Chem. Soc., Dalton Trans. 1986, 863−868. (176) Kunz, R.; Le Grel, P.; Fehlhammer, W. P. Reactions of CyanoIron and -Ruthenium Compounds with gem-Dicyanoepoxides. A New Pathway to Vinyl Isocyanide Complexes of Iron and Ruthenium. J. Chem. Soc., Dalton Trans. 1996, 3231−3236. (177) Beck, W.; Weigand, W.; Nagel, U.; Schaal, M. Reactions of the Cyanometal Acids H4M(CN)6 (M = Fe, Ru, Os), H2Pt(CN)4, and HAu(CN)2 with Epoxides: β-Hydroxyalkyl Isocyanide- and Oxazolidine-2-ylide-Metal Complexes. Angew. Chem., Int. Ed. Engl. 1984, 23, 377−378. (178) Weigand, W.; Nagel, U.; Beck, W. Pseudohalgeno Metal Compounds, LXVIII. Reactions of Cyano Metal Acids NCAuCNH, (NC)4Pt(CNH)2, (NC)2M(CHN)4 (M = Fe, Ru, Os) and Co[bis(dimethylglyoximato)](CN)CNH with Epoxides: 2-Hydroxyalkylisocyanide- and Oxazolidine-2-ylidene Metal Complexes. Z. Naturforsch. B 1988, 43, 328−338. (179) Liu, C.-Y.; Chen, D.-Y.; Lee, G.-H.; Peng, S.-M.; Liu, S.-T. Synthesis of Cyclic Diamino-Substituted Metal Carbene Complexes. Organometallics 1996, 15, 1055−1061. (180) Xue, W.-M.; Chan, M. C.-W.; Su, Z.-M.; Cheung, K.-K.; Liu, S.T.; Che, C.-M. Spectroscopic and Excited-State Properties of Luminescent Rhenium(I) N-Heterocyclic Carbene Complexes Containing Aromatic Diimine Ligands. Organometallics 1998, 17, 1622− 1630. (181) Ku, R.-Z.; Chen, D.-Y.; Lee, G.-H.; Peng, S.-M.; Liu, S.-T. Novel Alkyne Carbene Tungsten Complexes. Angew. Chem., Int. Ed. Engl. 1997, 36, 2631−2632. (182) Kaufhold, O.; Stasch, A.; Edwards, P. G.; Hahn, F. E. Template Controlled Synthesis of a Coordinated [11]ane-P2CNHC Macrocycle. Chem. Commun. 2007, 1822−1824. (183) Kaufhold, O.; Stasch, A.; Pape, T.; Hepp, A.; Edwards, P. G.; Newman, P. D.; Hahn, F. E. Metal Template Controlled Formation of [11]ane-P2CNHC Macrocycles. J. Am. Chem. Soc. 2009, 131, 306−317. (184) Chen, C.-H.; Liu, Y.-H.; Peng, S.-M.; Chen, J.-T.; Liu, S.-T. Synthesis of N-Heterocyclic Carbene Rhenium(I) Carbonyl Complexes. Dalton Trans. 2012, 41, 2747−2754. (185) Kuo, H.-Y.; Liu, Y.-H.; Peng, S.-M.; Liu, S.-T. N,N′-Dialkylation Catalyzed by Bimetallic Iridium Complexes Containing a Saturated BisN-Heterocyclic Carbene (NHC) Ligand. Organometallics 2012, 31, 7248−7255. (186) Siegmund, D.; Lorenz, N.; Gothe, Y.; Spies, C.; Geissler, B.; Prochnow, P.; Nuernberger, P.; Bandow, J. E.; Metzler-Nolte, N. Benzannulated Re(I)−NHC Complexes: Synthesis, Photophysical Properties and Antimicrobial Activity. Dalton Trans. 2017, 46, 15269−15279. (187) Fehlhammer, W. P.; Bartel, K.; Petri, W. Metallkomplexe mit Mehrfunktionellen Isocyaniden II. Ein Metallorganisches Nitrilylid: [3 + 2]-Cycloadditionen an [{(C6H5)3P}2Pt(Cl)CNCH2CO2C2H5]BF4. J. Organomet. Chem. 1975, 87, C34−C36. (188) Grundy, K. R.; Roper, W. R. Synthesis of Transition Metal− Heterocyclic Carbene Complexes. Oxazol-2-ylidene and Oxazolidin-2ylidene Complexes of Osmium(II) Derived from Coordinated Tosylmethylisocyanide. J. Organomet. Chem. 1975, 91, C61−C64.

(189) Fehlhammer, W. P.; Bartel, K.; Völkl, A.; Achatz, D. Metal Complexes of Functional Isocyanides, VI. Tosylmethyl-, Benzyl- and Benzhydrylisocyanide Metal Complexes and Their Reactivity with Nucleophiles and 1,3-Dipolarophiles. Z. Naturforsch., B: J. Chem. Sci. 1982, 37, 1044−1053. (190) Fehlhammer, W. P.; Völkl, A.; Plaia, U.; Beck, G. 1,3-Dipolare Cycloadditionen von Heteroallenen an die metallorganischen Nitrilylide [(OC)5M−CN−CHR]− (M = Cr, W; R = CO2Et). Chem. Ber. 1987, 120, 2031−2040. (191) Fehlhammer, W. P.; Zinner, G.; Beck, G.; Fuchs, J. Metallkomplexe funktioneller Isocyanide XX. Unerwartetes Resultat einer Cycloaddition zwischen Metallonitrilylid und Ketenimin. J. Organomet. Chem. 1989, 379, 277−288. (192) Fehlhammer, W. P.; Zinner, G.; Bakola-Christianopoulou, M. Metallkomplexe funktioneller Isocyanide. XV. [3 + 2]-Cycloadditionen von freiem und komplexgebundenem Isocyanmethylenphosphoran mit Heteroallenen. J. Organomet. Chem. 1987, 331, 193−205. (193) Eckert, U.; Robl, C.; Fehlhammer, W. P. Reactions of Chromio, Tungstenio, and Platinio Nitrile Ylides with Aryldiazonium Salts. Triazolin-5-ylidene Complexes vs Cleavage of the NN(Ar) Bond and Formation of N-Cyanamidines. Organometallics 1993, 12, 3241−3248. (194) Motoyama, Y.; Shimozono, K.; Aoki, K.; Nishiyama, H. Formation of Fischer Carbene Complexes in Asymmetric Aldol-Type Condensation of an Isocyanide Component on Bis(oxazolinyl)phenylrhodium(III) Complexes with Aldehydes: Stereochemistry, Structural Characterization, and Mechanistic Studies. Organometallics 2002, 21, 1684−1696. (195) Rieger, D.; Lotz, S. D.; Kernbach, U.; André, C.; Bertran-Nadal, J.; Fehlhammer, W. P. Synthesis of Organic Heterocycles via Multicomponent Reactions with Cyano Transition-Metal Complexes. J. Organomet. Chem. 1995, 491, 135−152. (196) Fehlhammer, W. P.; Bartel, K.; Plaia, U.; Völkl, A.; Liu, A. T. Tetrakis(oxazolidin-2-ylidene)- und Tetrakis(perhydrooxazin-2yliden)nickel, -palladium und -platin. Chem. Ber. 1985, 118, 2235−2254. (197) Fehlhammer, W. P.; Plaia, U. Metal Complexes of Functional Isocyanides, XIII. Bis(oxazolidin-2-ylidene) Complexes of Manganese(I) and Nickel(II). Z. Naturforsch., B: J. Chem. Sci. 1986, 41, 1005−1010. (198) Plaia, U.; Stolzenberg, H.; Fehlhammer, W. P. Homoleptic Carbene Complexes. 3. Hexakis(oxazolidin-2-ylidene)cobalt(III) and -rhodium(III). J. Am. Chem. Soc. 1985, 107, 2171−2172. (199) Fehlhammer, W. P.; Hoffmeister, H.; Stolzenberg, H.; Boyadjiev, B. Boron-Stabilized N,O-Carbenes, I. Triphenylboron Adducts of Siloxy- and Hydroxyalkyl Isocyanides and Spontaneous Formation of Ate-Ylids. Z. Naturforsch., B: J. Chem. Sci. 1989, 44, 419−428. (200) Fehlhammer, W. P.; Hoffmeister, H.; Boyadjiev, B.; Kolrep, T. Boron Stabilized N,O-Carbenes, II. X-Ray Structure of (trans-4,5Dimethyloxazolidin-2-ylidene)triphenylboron and N-Alkylations. Z. Naturforsch., B: J. Chem. Sci. 1989, 44, 917−922. (201) Dussel, R.; Pilette, D.; Dixneuf, P. H.; Fehlhammer, W. P. Isocyanide Arene−Ruthenium(II) Complexes and Activation of Alkenylacetylenes: Synthesis and Characterization of Isocyanide Carbene− and Mixed Carbene−Ruthenium Compounds. Organometallics 1991, 10, 3287−3291. (202) Kernbach, U.; Fehlhammer, W. P. Syntheses and Structures of Dicyanobis(oxazolidin-2-ylidene)palladium(II) and Platinum(II) Complexes. Inorg. Chim. Acta 1995, 235, 299−305. (203) Hahn, F. E.; Langenhahn, V.; Le Van, D.; Tamm, M.; Wittenbecher, L.; Lügger, T. Cyclic Polycarbene Ligands with Crown Ether Structure. Heteroat. Chem. 2002, 13, 540−549. (204) Jutzi, P.; Gilge, U. Synthese von Benzoxazol-2-yltrimethylsilan und -stannan. J. Organomet. Chem. 1983, 246, 159−162. (205) Hahn, F. E.; Tamm, M. Facile Synthesis of (1,2-Dihydrobenzoxazol-2-ylidene)tetracarbonyliron Complexes from 2-Trimethylsiloxyphenyl Isocyanide. J. Chem. Soc., Chem. Commun. 1993, 842−843. (206) Hahn, F. E.; Tamm, M. Carbenkomplexe aus koordinierten 2Siloxyphenylisocyaniden. J. Organomet. Chem. 1993, 456, C11−C14. (207) Hahn, F. E.; Tamm, M.; Lügger, T. Equilibrium between Isocyanide and Carbene Complexes in Coordination Compounds of AG


Chemical Reviews

Review

2,6-Dihydroxyphenyl Isocyanide. Angew. Chem., Int. Ed. Engl. 1994, 33, 1356−1359. (208) Tamm, M.; Hahn, F. E. Synthesis of N-Allyl-2,3-dihydrobenzoxazol-2-ylidene Complexes of Chromium(0) and Tungsten(0). Inorg. Chim. Acta 1999, 288, 47−52. (209) Hahn, F. E.; Tamm, M. Equilibrium Between Ylidene and Isocyanide Complexes: Synthesis and Crystal Structure of cis-(NMethyl-1,2-dihydrobenzoxazol-2-ylidene)(triphenylphosphine)tetracarbonyltungsten. Organometallics 1995, 14, 2597−2600. (210) Dumke, A. C.; Pape, T.; Kösters, J.; Feldmann, K.-O.; Schulte to Brinke, C.; Hahn, F. E. Metal-Template-Controlled Stabilization of βFunctionalized Isocyanides. Organometallics 2013, 32, 289−299. (211) Hahn, F. E.; Lügger, T. Komplexe des 2-(Trimethylsiloxy)phenylisocyanids als Vorstufen fü r die Darstellung von N,OHeterocarben-Komplexen. J. Organomet. Chem. 1994, 481, 189−193. (212) Kernbach, U.; Lügger, T.; Hahn, F. E.; Fehlhammer, W. P. Platinum(II) and Palladium(II) Complexes with 1,2-Dihydrobenzoxazol-2-ylidene Ligands and Molecular Structure of trans-Bis(1,2dihydrobenzoxazol-2-ylidene)diiodo Palladium. J. Organomet. Chem. 1997, 541, 51−55. (213) Hahn, F. E.; Lügger, T.; Beinhoff, M. Palladium(II) Complexes with Benzoxazol-2-ylidene Ligands: Crystal Structures of trans-Chloro(benzoxazol-2-ylidene)bis(triphenylphosphine)-palladium(II) Chloride and cis-Diiodo(benzoxazol-2-ylidene)(triphenylphosphine)palladium(II). Z. Naturforsch. B 2004, 59, 196−201. (214) (a) Meier, M.; Tan, T. T. Y.; Hahn, F. E.; Huynh, H. V. Donor Strength Determination of Benzoxazolin-2-ylidene, Benzobisoxazolin2-ylidene, and Their Isocyanide Precursors by 13C NMR Spectroscopy of Their PdII and AuI Complexes. Organometallics 2017, 36, 275−284. (b) Schmidtendorf, M.; Pape, T.; Hahn, F. E. Stepwise Preparation of a Molecular Square from NR,NR- and NH,O-Substituted Dicarbene Building Blocks. Angew. Chem., Int. Ed. 2012, 51, 2195−2198. (215) Hahn, F. E.; Klusmann, D.; Pape, T. Template Synthesis of Platinum Complexes with Benzoxazolin-2-ylidene Ligands. Eur. J. Inorg. Chem. 2008, 2008, 4420−4424. (216) Conrady, F. M.; Frohlich, R.; Schulte to Brinke, C.; Pape, T.; Hahn, F. E. Stepwise Formation of a Molecular Square with Bridging NH,O-Substituted Dicarbene Building Blocks. J. Am. Chem. Soc. 2011, 133, 11496−11499. (217) Hahn, F. E.; Imhof, L. Reactions of 2-(Trimethylsiloxy)phenyl Isocyanide with Complexes of Rhenium in the + 1, + 3, and + 5 Oxidation States. Organometallics 1997, 16, 763−769. (218) Ko, C.-C.; Ng, C.-O.; Yiu, S.-M. Luminescent Rhenium(I) Phenanthroline Complexes with a Benzoxazol-2-ylidene Ligand: Synthesis, Characterization, and Photophysical Study. Organometallics 2012, 31, 7074−7084. (219) Tamm, M.; Lügger, T.; Hahn, F. E. Isocyanide and Ylidene Complexes of Boron: Synthesis and Crystal Structures of (2(Trimethylsiloxy)phenyl isocyanide)−Triphenylborane and (1,2-Dihydrobenzoxazol-2-ylidene)−Triphenylborane. Organometallics 1996, 15, 1251−1256. (220) Lambert, C.; Lopez-Solera, I.; Raithby, P. R. Solid-State and Electronic Structure of Benzoxazol-2-ylidene−Triphenylborane Complex. Organometallics 1996, 15, 452−455. (221) Hahn, F. E.; Tamm, M. Synthesis and Molecular Structure of a Complex Containing All Three Intermediates of the Carbene Synthesis from Coordinated Isocyanides. J. Chem. Soc., Chem. Commun. 1995, 569−570. (222) Hahn, F. E.; Langenhahn, V.; Meier, N.; Lü gger, T.; Fehlhammer, W. P. Template Synthesis of Benzannulated NHeterocyclic Carbene Ligands. Chem. - Eur. J. 2003, 9, 704−712. (223) Köhn, M.; Breinbauer, R. The Staudinger Ligation  A Gift to Chemical Biology. Angew. Chem., Int. Ed. 2004, 43, 3106−3116. (224) Flores-Figueroa, A.; Kaufhold, O.; Feldmann, K.-O.; Hahn, F. E. Synthesis of NHC Complexes by Template Controlled Cyclization of βFunctionalized Isocyanides. Dalton Trans. 2009, 9334−9342. (225) Kaufhold, O.; Flores-Figueroa, A.; Pape, T.; Hahn, F. E. Template Synthesis of Ruthenium Complexes with Saturated and

Benzannulated NH,NH-Stabilized N-Heterocyclic Carbene Ligands. Organometallics 2009, 28, 896−901. (226) Hahn, F. E.; Langenhahn, V.; Lügger, T.; Pape, T.; Le Van, D. Template Synthesis of a Coordinated Tetracarbene Ligand with Crown Ether Topology. Angew. Chem., Int. Ed. 2005, 44, 3759−3763. (227) Hahn, F. E.; Langenhahn, V.; Pape, T. Template Synthesis of Tungsten Complexes with Saturated N-Heterocyclic Carbene Ligands. Chem. Commun. 2005, 5390−5392. (228) Flores-Figueroa, A.; Pape, T.; Weigand, J. J.; Hahn, F. E. Template-Controlled Formation of an [11]ane-P2CNHC Macrocyclic Ligand at an Iron(II) Template. Eur. J. Inorg. Chem. 2010, 2010, 2907− 2910. (229) Flores-Figueroa, A.; Kaufhold, O.; Hepp, A.; Fröhlich, R.; Hahn, F. E. Synthesis of a Ruthenium(II) Complex Containing an [11]aneP2CNHC (NHC = Imidazolidin-2-ylidene) Macrocycle. Organometallics 2009, 28, 6362−6369. (230) Flores-Figueroa, A.; Pape, T.; Feldmann, K.-O.; Hahn, F. E. Template-Controlled Synthesis of a Planar [16]ane-P2CNHC2 Macrocycle. Chem. Commun. 2010, 46, 324−326. (231) Blase, V.; Flores-Figueroa, A.; Schulte to Brinke, C.; Hahn, F. E. Template Synthesis of Tetracarbene Platinum(II) Complexes with Fiveand Six-Membered-Ring N-Heterocyclic Carbenes. Organometallics 2014, 33, 4471−4478. (232) Facchin, G.; Michelin, R. A.; Mozzon, M.; Tassan, A. Synthesis, Coordination and Reactivity of 2-(Trimethylsiloxymethyl)phenyl- and 2-(Hydroxymethyl)phenyl Isocyanides. J. Organomet. Chem. 2002, 662, 70−76. (233) Basato, M.; Biffis, A.; Martinati, G.; Polo, M.; Ronconi, L.; Tubaro, C.; Michelin, R. A.; Sgarbossa, P.; Sbovata, S. M. Formation of N-Coordinated 4H-Benzo[d][1,3]oxazine from 2-(Trimethylsiloxymethyl)- and 2-(Hydroxymethyl)-phenyl Isocyanides Promoted by Dirhodium(II) Acetate. Inorg. Chem. Commun. 2007, 10, 407−409. (234) Basato, M.; Facchin, G.; Michelin, R. A.; Mozzon, M.; Pugliese, S.; Sgarbossa, P.; Tassan, A. Transition Metal Coordination and Reactivity of 2-(Azidomethyl)-, 2-(Chloromethyl)- and 2(Iodomethyl)phenyl Isocyanides. Inorg. Chim. Acta 2003, 356, 349− 356. (235) Basato, M.; Benetollo, F.; Facchin, G.; Michelin, R. A.; Mozzon, M.; Pugliese, S.; Sgarbossa, P.; Sbovata, S. M.; Tassan, A. The Staudinger Reaction of Platinum(II)- and Palladium(II)-Coordinated 2(Azidomethyl)phenyl Isocyanide. X-ray Structure of trans-[PtCl{CN(H)C6H4-2-CH2N(H)}(PPh3)2][BF4]·CDCl3·H2O. J. Organomet. Chem. 2004, 689, 454−462. (236) Hahn, F. E.; García Plumed, C.; Münder, M.; Lügger, T. Synthesis of Benzannulated N-Heterocyclic Carbene Ligands by a Template Synthesis from 2-Nitrophenyl Isocyanide. Chem. - Eur. J. 2004, 10, 6285−6293. (237) Brothers, P. J.; Roper, W. R. Transition-Metal Dihalocarbene Complexes. Chem. Rev. 1988, 88, 1293−1326. (238) Roper, W. R.; Wright, A. H. Reactions of a DichlorocarbeneRuthenium Complex, RuCl2(CCl2)(CO)(PPh3)2. J. Organomet. Chem. 1982, 233, C59−C63. (239) Clark, G. R.; Roper, W. R.; Wright, A. H. Synthesis, Structure, and Reactions of IrCl3(CCl2)(PPh3)2, A Compound with an Iridium− Carbon Double Bond (LnIr = CCl2). J. Organomet. Chem. 1982, 236, C7−C10. (240) Fehlhammer, W. P.; Fritz, M. Emergence of a CNH and Cyano Complex Based Organometallic Chemistry. Chem. Rev. 1993, 93, 1243− 1280. (241) Beck, G.; Fehlhammer, W. P. Reactions of Pentacarbonyl(trichloromethyl isocyanide)chromium. Angew. Chem., Int. Ed. Engl. 1988, 27, 1344−1347. (242) Fehlhammer, W. P.; Beck, G. Reaktionen am koordinierten Trichlormethylisocyanid: II. Cyclische Dithio- und Diaminocarbene. J. Organomet. Chem. 1989, 369, 105−116. (243) Fehlhammer, W. P.; Ahn, S.; Beck, G. Isocyanidsynthesen am Komplex: XI. Reaktionen von Cr(CO)5CNCCl3 mit primären Aminen: Aliphatische, aromatische, funktionelle und chirale Isocyanide. J. Organomet. Chem. 1991, 411, 181−191. AH


Chemical Reviews

Review

(244) Lavallo, V.; Canac, Y.; Präsang, C.; Donnadieu, B.; Bertrand, G. Stable Cyclic (Alkyl)(Amino)Carbenes as Rigid or Flexible, Bulky, Electron-Rich Ligands for Transition-Metal Catalysts: A Quaternary Carbon Atom Makes the Difference. Angew. Chem., Int. Ed. 2005, 44, 5705−5709. (245) Paul, U. S. D.; Radius, U. What Wanzlick Did Not Dare To Dream: Cyclic (Alkyl)(amino)carbenes (cAACs) as New Key Players in Transition-Metal Chemistry. Eur. J. Inorg. Chem. 2017, 2017, 3362− 3375. (246) Soleilhavoup, M.; Bertrand, G. Cyclic (Alkyl)(Amino)Carbenes (CAACs): Stable Carbenes on the Rise. Acc. Chem. Res. 2015, 48, 256− 266. (247) Melaimi, M.; Jazzar, R.; Soleilhavoup, M.; Bertrand, G. Cyclic (Alkyl)(amino)carbenes (CAACs): Recent Developments. Angew. Chem., Int. Ed. 2017, 56, 10046−10068. (248) Michelin, R. A.; Facchin, G.; Braga, D.; Sabatino, P. Functionalized Isocyanides as Ligands. 4. Base-Promoted Cyclization Reactions of Free and Platinum(II)-Coordinated o(Phosphoniomethyl)phenyl Isocyanide Tetrafluoroborates, o(BF4−R3P+−CH2)C6H4NC. Synthesis and Spectroscopic Characterization of 1- and 2-Platinum(II)-Substituted Indole Derivatives and XRay Structure of trans-{(PPh3)2Pt[CN(H)-o-C6H4C(PMe3)]Cl}BF4- · C2H4Cl2. Organometallics 1986, 5, 2265−2274. (249) Facchin, G.; Michelin, R. A.; Mozzon, M.; Sgarbossa, P.; Tassan, A. Synthesis and Cyclization Reactions of Platinum(Il)-Coordinated Arsonium-Substituted Phenyl Isocyanides, o-(I−R3As+−CH2)C6H4N C. Inorg. Chim. Acta 2004, 357, 3385−3389. (250) Facchin, G.; Mozzon, M.; Michelin, R. A.; Ribeiro, M. T. A.; Pombeiro, A. J. L. Chemistry and Electrochemistry of PhosphoniumFunctionalized Isocyanide and Derived Carbene and Indole Complexes of Group 6 Transition-Metal Carbonyls. J. Chem. Soc., Dalton Trans. 1992, 2827−2835. (251) Yeung, C.-F.; Chung, L.-H.; Lo, H.-S.; Chiu, C.-H.; Cai, J.; Wong, C.-Y. Isolation of Ruthenium−Indoline and − Indole Zwitterion Complexes: Insight into the Metal-Induced Cyclization of AnilineTethered Alkynes and Strategy to Lower the Activation Barrier of Metal−Vinylidene Formation. Organometallics 2015, 34, 1963−1968. (252) Haase, W.-C.; Dötz, K. H. One-Pot Synthesis of N-Unprotected Azacyclopentylidene Complexes from Their Oxa Analogues. Tetrahedron Lett. 1999, 40, 2919−2920. (253) Dötz, K. H.; Sturm, W.; Alt, H. G. Metal-Assisted Cyclization of Alkynols at a d 6 Metal Template: One-Pot Synthesis of 2Oxacycloalkylidene Complexes of Chromium, Tungsten, and Manganese. Organometallics 1987, 6, 1424−1427. (254) Dötz, K. H.; Haase, W.-C.; Klumpe, M.; Nieger, M. Metal Modified Carbohydrates: Syntheses of Furanosylidene Complexes and Their Aza Analogues. Chem. Commun. 1997, 1217−1218. (255) Szesni, N.; Drexler, M.; Weibert, B.; Fischer, H. A Convenient Route to Six-Membered Heterocyclic Carbene Complexes: Reactions of Aminoallenylidene Complexes with 1,3-Bidentate Nucleophiles. J. Organomet. Chem. 2005, 690, 5597−5608. (256) Szesni, N.; Hohberger, C.; Mohamed, G. G.; Burzlaff, N.; Weibert, B.; Fischer, H. Synthesis of Heterocyclic Carbene Ligands via 1,2,3-Diheterocyclization of Allenylidene Complexes with Dinucleophiles. J. Organomet. Chem. 2006, 691, 5753−5766. (257) Day, B. M.; Pugh, T.; Hendriks, D.; Guerra, C. F.; Evans, D. J.; Bickelhaupt, F. M.; Layfield, R. A. Normal-to-Abnormal Rearrangement and NHC Activation in Three-Coordinate Iron(II) Carbene Complexes. J. Am. Chem. Soc. 2013, 135, 13338−13341. (258) Hering, F.; Radius, U. From NHC to Imidazolyl Ligand: Synthesis of Platinum and Palladium Complexes d10-[M(NHC)2] (M = Pd, Pt) of the NHC 1,3-Diisopropylimidazolin-2-ylidene. Organometallics 2015, 34, 3236−3245. (259) Brendler, E.; Hill, A. F.; Wagler, J. A Donor-Stabilized Silanethione or a Si-Substituted N-Heterocyclic Platinum Carbene? Chem. - Eur. J. 2008, 14, 11300−11304. (260) Watkins, B. E.; Rapoport, H. Synthesis of Benzyl and Benzyloxycarbonyl Base-Blocked 2′-Deoxyribonucleosides. J. Org. Chem. 1982, 47, 4471−4477.

(261) Dobereiner, G. E.; Chamberlin, C. A.; Schley, N. D.; Crabtree, R. H. Acyl Protection Strategy for Synthesis of a Protic NHC Complex via N-Acyl Methanolysis. Organometallics 2010, 29, 5728−5731. (262) Kunz, P. C.; Wetzel, C.; Kögel, S.; Kassack, M. U.; Spingler, B. [(C3H4N2)2Au]Cl  a Bis Protic Gold(I)-NHC. Dalton Trans. 2011, 40, 35−37. (263) Tweedle, M. F.; Taube, H. Reactivity of Imidazoliumruthenium Ammine Complexes: Nitrogen- to Carbon-Bound Rearrangement, Trans Labilization, and Redox Behavior. Inorg. Chem. 1982, 21, 3361− 3371. (264) Marelius, D. C.; Moore, C. E.; Rheingold, A. L.; Grotjahn, D. B. Reactivity Studies of Pincer Bis-Protic N-Heterocyclic Carbene Complexes of Platinum and Palladium under Basic Conditions. Beilstein J. Org. Chem. 2016, 12, 1334−1339. (265) Blase, V.; Pape, T.; Hahn, F. E. Template Synthesis of a Macrocycle with a Mixed NHC/phosphine Donor Set. J. Organomet. Chem. 2011, 696, 3337−3342. (266) Dub, P. A.; Gordon, J. C. Metal−Ligand Bifunctional Catalysis: the “Accepted” Mechanism, the Issue of Concertedness, and the Function of the Ligand in Catalytic Cycles Involving Hydrogen Atoms. ACS Catal. 2017, 7, 6635−6655. (267) Scott, D. J.; Fuchter, M. J.; Ashley, A. E. Designing Effective ’Frustrated Lewis Pair’ Hydrogenation Catalysts. Chem. Soc. Rev. 2017, 46, 5689−5700. (268) Kehr, G.; Erker, G. Frustrated Lewis Pair Chemistry: Searching for New Reactions. Chem. Rec. 2017, 17, 803−815. (269) Stephan, D. W. The Broadening Reach of Frustrated Lewis Pair Chemistry. Science 2016, 354, aaf7229. (270) Chang, W.; Gong, X.; Wang, S.; Xiao, L.-P.; Song, G. Acceptorless Dehydrogenation and Dehydrogenative Coupling of Alcohols Catalysed by Protic NHC Ruthenium Complexes. Org. Biomol. Chem. 2017, 15, 3466−3471. (271) Norris, M. R.; Flowers, S. E.; Mathews, A. M.; Cossairt, B. M. H2 Production Mediated by CO2 via Initial Reduction to Formate. Organometallics 2016, 35, 2778−2781. (272) Á lvarez, E.; Hernández, Y. A.; López-Serrano, J.; Maya, C.; Paneque, M.; Petronilho, A.; Poveda, M. L.; Salazar, V.; Vattier, F.; Carmona, E. Metallacyclic Pyridylidene Structures from Reactions of Terminal Pyridylidenes with Alkenes and Acetylene. Angew. Chem., Int. Ed. 2010, 49, 3496−3499. (273) Cristóbal, C.; Hernández, Y. A.; López-Serrano, J.; Paneque, M.; Petronilho, A.; Poveda, M. L.; Salazar, V.; Vattier, F.; Á lvarez, E.; Maya, C.; CArmona, E. Reactivity Studies of Iridium Pyridylidenes [TpMe2Ir(C6H5)2(C(CH)3C(R)NH] (R = H, Me, Ph). Chem. - Eur. J. 2013, 19, 4003−4020. (274) Kashiwame, Y.; Watanabe, M.; Araki, K.; Kuwata, S.; Ikariya, T. Synthesis, Structure, and Proton-Transfer Reactions of Brønsted Acidic Pyridylpyrazole Complexes of Ruthenium. Bull. Chem. Soc. Jpn. 2011, 84, 251−258. (275) Jin, H.; Mück-Lichtenfeld, C.; Hepp, A.; Stephan, D. W.; Hahn, F. E. Small Molecule Activation with N,NR-MIC Platinum Complexes. Chem. - Eur. J. 2017, 23, 5943−5747. (276) Hahn, F. E.; Hein, P.; Lügger, T. Synthesis of Heterobimetallic Metal Derivatives: a Carbene Complex as Chelate Ligand. Z. Anorg. Allg. Chem. 2003, 629, 1316−1321. (277) Ruiz, J.; Sol, D.; Van der Maelen, J. F.; Vivanco, M. BasePromoted Transmetalation Reactions of Protic N-Heterocyclic Carbenes and Acyclic Diamino Carbenes from MnI to AuI: A Mechanistic Study. Organometallics 2017, 36, 1035−1041. (278) Lewis, J. C.; Bergman, R. G.; Ellman, J. A. Direct Functionalization of Nitrogen Heterocycles via Rh-Catalyzed C−H Bond Activation. Acc. Chem. Res. 2008, 41, 1013−1025. (279) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Rhodium-Catalyzed C−C Bond Formation via Heteroatom-Directed C−H Bond Activation. Chem. Rev. 2010, 110, 624−655. (280) Tan, K. L.; Bergman, R. G.; Ellman, J. A. Annulation of AlkenylSubstituted Heterocycles via Rhodium-Catalyzed Intramolecular C−H Activated Coupling Reactions. J. Am. Chem. Soc. 2001, 123, 2685−2686. AI


Chemical Reviews

Review

(281) Rech, J. C.; Yato, M.; Duckett, D.; Ember, B.; LoGrasso, P. V.; Bergman, R. G.; Ellman, J. A. Synthesis of Potent Bicyclic Bisarylimidazole c-Jun N-Terminal Kinase Inhibitors by Catalytic C− H Bond Activation. J. Am. Chem. Soc. 2007, 129, 490−491. (282) Tan, K. L.; Vasudevan, A.; Bergman, R. G.; Ellman, J. A.; Souers, A. J. Microwave-Assisted C−H Bond Activation: A Rapid Entry into Functionalized Heterocycles. Org. Lett. 2003, 5, 2131−2134. (283) Tsai, A. S.; Wilson, R. M.; Harada, H.; Bergman, R. G.; Ellman, J. A. Rhodium Catalyzed Enantioselective Cyclization of Substituted Imidazoles via C−H Bond Activation. Chem. Commun. 2009, 3910− 3912. (284) Tan, K. L.; Bergman, R. G.; Ellman, J. A. Intermolecular Coupling of Isomerizable Alkenes to Heterocycles via RhodiumCatalyzed C−H Bond Activation. J. Am. Chem. Soc. 2002, 124, 13964− 13965. (285) Tan, K. L.; Park, S.; Ellman, J. A.; Bergman, R. G. Intermolecular Coupling of Alkenes to Heterocycles via C−H Bond Activation. J. Org. Chem. 2004, 69, 7329−7335. (286) Wiedemann, S. H.; Bergman, R. G.; Ellman, J. A. RhodiumCatalyzed Direct C−H Addition of 4,4-Dimethyl-2-oxazoline to Alkenes. Org. Lett. 2004, 6, 1685−1687. (287) Wiedemann, S. H.; Ellman, J. A.; Bergman, R. G. RhodiumCatalyzed Direct C−H Addition of 3,4-Dihydroquinazolines to Alkenes and Their Use in the Total Synthesis of Vasicoline. J. Org. Chem. 2006, 71, 1969−1976. (288) Lewis, J. C.; Bergman, R. G.; Ellman, J. A. Rh(I)-Catalyzed Alkylation of Quinolines and Pyridines via C−H Bond Activation. J. Am. Chem. Soc. 2007, 129, 5332−5333. (289) Lewis, J. C.; Wu, J. Y.; Bergman, R. G.; Ellman, J. A. MicrowavePromoted Rhodium-Catalyzed Arylation of Heterocycles through C−H Bond Activation. Angew. Chem., Int. Ed. 2006, 45, 1589−1591. (290) Lewis, J. C.; Berman, A. M.; Bergman, R. G.; Ellman, J. A. Rh(I)Catalyzed Arylation of Heterocycles via C−H Bond Activation: Expanded Scope through Mechanistic Insight. J. Am. Chem. Soc. 2008, 130, 2493−2500. (291) Berman, A. M.; Lewis, J. C.; Bergman, R. G.; Ellman, J. A. Rh(I)Catalyzed Direct Arylation of Pyridines and Quinolines. J. Am. Chem. Soc. 2008, 130, 14926−14927. (292) Su, T.-C.; Liu, Y.-H.; Peng, S.-M.; Liu, S.-T. Rhenium Complexes with a Pyridinyl-Naphthyridine Ligand: Synthesis, Characterization, and Catalytic Activity. Eur. J. Inorg. Chem. 2013, 2013, 2362−2367.

AJ


Complexes Bearing Protic N-Heterocyclic Carbene Ligands

Recommend Documents