Recent Developments in Palladium-Catalyzed Oxidative Cascade

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Perspective

Recent Developments in PalladiumCatalyzed Oxidative Cascade Carbocyclization Di Zhang, Jianguo Liu, Armando Cordova, and Wei-Wei Liao ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.7b02438 • Publication Date (Web): 08 Sep 2017 Downloaded from http://pubs.acs.org on September 8, 2017

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Recent Developments in Palladium-Catalyzed Oxidative Cascade Carbocyclization Di Zhang§, Jianguo Liu†, Armando Córdova*†, Wei-Wei Liao*§ Dedicated to Prof. Jan-E. Bäckvall on the occasion of his 70th Birthday §Di Zhang, Wei-Wei Liao, [email protected] Department of Organic Chemistry, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China †Jianguo Liu, Armando Córdova* [email protected] [email protected] Department of Natural Sciences, Holmgatan 10, Mid Sweden University, 851 70 Sundsvall, Sweden Berzelii Center EXSELENT, The Arrhenius Laboratory, Stockholm University, 106 91 Stockholm, Sweden

ABSTRACT In this Perspective, we describe recent advances on Pd-catalyzed oxidative cascade carbocyclizations. These cascade processes enable efficient construction of the molecular complexity and structural diversity of carbocyclic compounds via introducing diverse functionalities concomitant with multiple C-C bond-formations in one-pot operations. In many cases, these processes are facilitated by Pd-catalysts alone, while co-catalysis by combination of Pd catalyst and other catalysts are also discussed, since they represent a new entry to address the preparation of functionalized cyclic compounds with high efficiency and selectivity. KEYWORDS: catalysis, palladium, carbocyclization, oxidation, cascade reaction

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1. INTRODUCTION The construction of carbocyclic frameworks holds a vital position in modern organic chemistry due to their ubiquity in natural products and synthetic compounds with impressive biological and medicinal properties.1 Although various methods have been demonstrated, 2 the development of efficient and selective approaches to construct these cyclic scaffolds are still highly demanded because of the structural diversity of cyclic compounds (e.g. monocyclic, polycyclic and spiro-compounds with various ring-size) and the related chemical selectivity issues. Among them, Pd-catalyzed oxidative cyclizations, which are facilitated by a catalytic cycle of Pd0/PdII (few examples involved PdII/PdIV) by the aid of stoichiometric oxidant concomitant with C-C bond formation, proved to be efficient protocols for the preparation of carbocyclic compounds, and have received increasing attention. 3 Cascade reactions in which multiple bond-forming events occur in one pot, thereby gaining several merits including high atom and step economy to build complicated molecule skeletons, constitute a topic of great interest. 4 As a versatile transition metal, Palladium is widely used for catalytic C-C and C-X bond-forming reactions due to its intriguing reactivity with various functional groups. 5 Therefore, there is a great potential for palladium-catalyzed cascade transformations, and a range of impressive palladium-catalyzed cascade reactions have been reported. 4a, 6 With this context, the development of Pd-catalyzed cascade oxidative carbocyclizations with external reagents are highly attractive, due to their efficiencies on the construction of the molecular complexity and structural diversity of carbocyclic compounds via introducing diverse functionalities concomitant with mutli-C-C bond formations. Despite their promising prospect, Pd-catalyzed cascade oxidative carbocyclizations, which require a combination of highly selective transformations compatible with different functional groups under the oxidative reaction conditions, are challenging to engineer and even more challenging to scale up.

Figure 1. Pd(II)-Catalyzed Cascade Carbocyclizations with External Reagents The aim of this perspective is to emphasize the recent advances on Pd-catalyzed cascade carbocyclizations in the presence of oxidants. The perspective will focuse on the tandem transformations in which external reagents are involved concomitant with mutli-C-C bond formations, while intramolecular transformations are not covered since they have been addressed previously (Figure 1). 3d As electrophilic species, palladium(II) salts tend to activate unsaturated carbon-carbon bonds such as olefins, allenes and alkynes by coordinating to such unsaturated bond, which makes these bonds susceptible to addition reactions. Much effort has been devoted to construct a variety of carbocycles by utilizing different kinds of 2


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nucleophiles such as acetate, alkene and aromatic compounds. In particular, increasing efforts have been focused on the triggering, quenching and interrupting these carbocyclic processes with external reagents, which eventually provided various functionalized carbocycles. Thus, we will begin to discuss the cascade processes including acetoxylation, chlorination, arylation, borylation and carbonylation so on. In addition, the cascade carbocyclizations promoted by combination of Pd catalysis and organocatalysis or other transition-metal catalysis are also discussed, since they represent a new entry to address the preparation of functionalized cyclic compounds with high efficiency and selectivity. 7

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1. CARBOCYCLIZATION STARTING OR ENDING WITH “EXTERNAL REAGENTS” The nucleopalladation of alkenes, allenes and alkynes via a Pd-catalyzed acetoxylation has proven to be efficient protocol in constructing multiple new chemical bonds, thus leading to cyclic structures. Moberg and co-workers reported that the acetoxy-carbocyclization of 1,5-dienes could be achieved via a Pd-catalyzed oxidative oxypalladation–insertion sequence that ends with a β-elimination to provide acetoxylated carbocycle with BQ (1,4-Benzoquinone) and MnO2 as oxidants (Scheme 1, eq-1 and eq-2).8 Later, this oxidative carbocyclization methodology was applicable for the construction of 4-acetoxy-1-(5’-hydroxy-3’-pentenyl)-2-methylenecyclopentane, a key intermediate in the synthesis of sativene (Scheme 1, eq-3). 9 Scheme 1. Pd(II)-Catalyzed Acetoxy or Alkoxy/Carbocyclization of Dienes H

5 mol% Pd(OAc)2 20 mol% BQ 1 equiv. MnO2 HOAc, RT, 42 h

H

H

5 mol% Pd(OAc)2 20 mol% BQ 1 equiv. MnO2 HOAc, RT, 42 h

H

H

OAc eq-1

H 70% yield, > 99/1 d.r. H

OAc

H

OAc

+ H 87%

eq-2 13%

54% yield OAc

sativene

5 mol% Pd(OAc)2 0.25 equiv. BQ 0.75 equiv. MnO2 HOAc, RT OH

eq-3

OH 63% yield, E/Z = 55/45

Meanwhile, the Pd-catalyzed acetoxylation has also been used as a terminal reaction to quench the palladium(II) species to give functionalized products. Bäckvall and co-workers found that the oxidative acetoxylation/carbocyclizations of allene-substituted 1,3-dienes can be achieved to furnish acetoxylated triene products with catalytic amount of Pd(OAc)2 and p-benzoquinone (BQ) as an oxidant (Scheme 2). 10 A detailed mechanistic study revealed the reaction was initiated by allene attack on Pd(II) through allylic C-H bond cleavage followed by alkene insertion to give a π-allylpalladium species I-1, which is attacked by an acetate to furnish acetoxylated product (Scheme 2, A). This methodology was later extended to oxy-nucleophiles other than acetate/acetic acid (Scheme 2, B). 11 The reaction proceeded well with an excess of C6F5OH and carboxylic acids in acetone, while other nucleophiles such as phenol and benzyl alcohol were unsuccessful. Furthermore, it turned out later that water can also serve as suitable nucleophile to attack π-allylpalladium complexes to give hydroxylated cyclic compound. 12 Scheme 2. Pd-Catalyzed Oxidative Acetoxylation and Carboxylation/Carbocyclization of Allenynes

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H E

A) E

E

AcO

10 mol% Pd(OAc)2 2 equiv. BQ

H E

E

E 9 examples 44-87% yields

via

4 equiv. LiOAc HOAc, RT, 4 h E = CO2Me or H

H

H

LnPdII

I-1 H E AcO

H E E

AcO

H

H E

H E E

AcO

AcO

E

H

E

H Bu

H

Pr (56:44) 60% yield

77% yield

44% yield, E/Z=75:25

B) E

H E

E

Nu

10 mol% Pd(OAc)2 5 equiv Li2CO3, 2 equiv. BQ 20 equiv. NuH acetone, RT, 20 h E = CO2Me H E BzO

H E O

E

85% yield

H

H E

E

O H

7 examples 15-85% yields

H

H E E

C6F5O

E

O

H

50% yield

E

O

15% yield

H 19% yield

Furthermore, by employing allenynes as substrates, Bäckvall and co-workers were able to conduct the carboxylation/carbocyclization with various carboxylic acids in the presence of 5 mol% Pd(OAc)2 and BQ (1.2eq), which furnished potentially synthetically useful acyloxylated vinylallenes (Scheme 3). 13 In this transformation, a competing propargylic C-H bond cleavage would produce vinylpalladium intermediate I-2, and followed by the intramolecular vinylpalladation of the allene moiety to generate π-allylpalladium intermediate I-4, which is attacked by an acetate nucleophile to give final products, although a pallada(IV)cyclopentene intermediate with competing β-eliminations can also not be ruled out. Furthermore, an aerobic version of this transformation with few examples using a catalytic amount of BQ has been demonstrated. Similarly, Pd(II)-catalyzed oxidative carbo-chlorocyclization and dichlorination of 1,3-diene substrates proceeded in the similar reaction pathway. 14 Scheme 3. Pd-Catalyzed Oxidative Acetoxylation and Carboxylation/Carbocyclization of Enallenes

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R1 E

E

R1

O

E

E O

nBu

Me E

E

F

E

nPr


R O

nBu

nBu

OAc

E

O

E

OAc

O

O 74%

E

acetone, 60 oC, 17 h E = CO2Me

5 equiv.

E

E

5 mol% Pd(OAc)2 1.2 equiv. BQ

+ RCO2H

yield[a]

52% yield[b]

66% yield[a]

75% yield

[a]

5mol% Pd(OAc)2, BQ (1.2 equiv), allenyne (1.0 equiv), HOAc, 60 oC, 17 h [b] 5mol% Pd(OAc) , BQ (1.2 equiv), allenyne (1.0 equiv), HOAc (5.0 equiv), acetone, 60 oC, 17 h 2

Proposed mechanism with the example of acetoxylation/carbocyclization: HQ substrate BQ

Pd(OAc)2

Pd0+HOAc R

product

OAc

HOAc

E

PdII

OAc

E E I-2

E PdOAc BQ

R -HOAc

+HOAc

I-4 E

PdOAc BQ

E I-3

The oxidative Pd(II)-catalyzed cascade protocol for carboxylation/carbocyclization can also be achieved via a sp2 C−H bond activation. Yang and co-workers firstly reported the oxidative monocarboxylation/carbocyclization of butenylated arenes in the presence of Pd(OAc)2 with Selectfluor as the oxidant (Scheme 4). 15 Treatment of various butenylated arenes with different carboxylic acids as nucleophilic reagents afforded 2-tetralyl carboxylic esters in good yields under mild conditions. The authors proposed that the transformation involves a Pd(II)/Pd(IV) catalytic process. Scheme 4. Pd(II)-Catalyzed Oxidative Monocarboxylation/Carbocyclization of Butenylated Arenes

Subsequently, Bäckvall et al. reported an example of tandem oxidative acetoxylation/carbocyclization of arylallenes using 5 mol% of Pd(OAc)2 in the presence of 1.7 equiv. of BQ in acetic acid, in which an allene moiety not only acted as directing group 6


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for intramolecular aryl sp2 C−H bond activation, but also directly involved in a carbocyclization process (Scheme 5). 16 The catalytic protocol is highly selective and provided access to construct functionalized indene frameworks. Mechanistic investigations showed that vinyl Pd(II)-intermediate I-6 generated from the nucleophilic attack by acetate on the coordinated allene underwent a subsequent acetate-assisted C−H activation of the ortho arene C−H bond to provide intermediate I-8, which would produce final product after a reductive elimination. Notably, it is the first example of such carbocyclization process where an allene moiety acts as directing group for intramolecular aryl sp2 C−H bond activation. Scheme 5. Pd(II)-Catalyzed Oxidative Acetoxylation/Carbocyclization of Arylallenes E

E

R H R1

R2

E

E

E

R

E


OAc

R

E

2 1R

E

Me

OBn

BnO OAc

OAc

OAc

E

E

10 mol% Pd(OAc)2 1.7 equiv. BQ 2 equiv. DMSO-d6 AcOH, 60 oC,16 h E=CO2Et

OAc

F3C 65% yield

56% yield

Proposed mechanism:

HQ

substrate

Pd0

product

E

E

R

E

R2 Pd L R1 I-5

AcO

E L=DMSO L'=L or BQ

R2 Pd R1 L' L OAc I-8

AcO-

R AcOH

35% yield

Pd(OAc)2

BQ

R

54% yield

E

R

R2

R1 H Pd OAc L O O I-7

E

E

E Pd AcO

L

R2 R1 OAc

I-6

Me

By combining other appropriate coupling partners with Pd(II)-catalyzed oxidative carbocyclizations, various functionalized cyclic compounds such as organoboronate compounds,17a-b tetrasubstituted enyne17c and ynones17d-e, which are easily handled for further transformations, could be prepared efficiently by carbocyclization/borylation, 18,19 carbocyclization/arylations, 20, 21 carbocyclization/alkynylation, 22 carbocyclization/carbonylation23 and carbocyclization/carbonylation/alkynylation tandem sequences.24 Bäckvall and co-workers have contributed seminal works by employing allene derivatives as substrates on this subject. 18-24 Typically, they found that the oxidative carbocyclizations of enallenes or allenynes with a Pd(II) catalyst coupled with external reagents such as bis(pinacolato)diboron (B2pin2), arylboronic acid, terminal alkyne, carbon monoxide (CO)/alcohol (ROH) or carbon monoxide (CO)/terminal alkyne to afford various cyclopentane derivatives (Scheme 6). Scheme 6. Pd(II)-Catalyzed Oxidative Tandem Carbocyclization with Various Coupling Partners 7


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For instance, when enallenes (substituted 1,5-enallenes) were employed, the oxidative carbocyclizations of enallenes with a Pd(II) catalyst led to give the δ-alkylpalladium(II) species I-10 via allylic C-H activation, which can be intercepted by a transmetalation reagent such as B2pin2 or arylboronic acid to afford functionalized cyclic compounds (Scheme 7). On the basis of these, they reported a palladium(II)-catalyzed oxidative borylative carbocyclization of enallenes to furnish alkylboronates in good yields with excellent steroselectivities (cis addition to the olefin) (Scheme 7, eq-1).18 Combining with arylboronic acids, they demonstrated a stereoselective carbocyclization/arylation to produce arylated five-memebred ring carbocycles, which showed wide tolerance toward highly functionalized arylboronic acids (Scheme 7, eq-2).20 Scheme 7. Pd(II)-Catalyzed Oxidative Carbocyclization/Borylation and Carbocyclization/Arylation of Enallenes

E

E

1 mol% Pd(OAc)2 1 equiv. B2pin2 1.2 equiv. BQ Toluene, 40 oC,10 h E=CO2Me

E

E 13 examples 5-89% yields

eq-1


eq-2

Bpin

1 mol% Pd(OAc)2 1.0-1.3 equiv. ArB(OH)2 1.1 equiv. BQ THF, 60 oC, 2-24 h E=CO2Me

E

E

Ar

E

E

E

E

E

E

Me

Bpin

E

Bpin

E

Ph 68% yield

63% yield

88% yield

61% yield

Proposed mechanism (Ligands omitted for clarity): substrate

Pd(OAc)2 Oxidation BQ+H+ E

E

0

Pd

PdII I-9

E E

cis insertion

product B2pin2 or ArB(OH)2

PdII I-10

Subsequently, this method has been extended to the tandem oxidative carbocyclization/carbonylation and carbocyclization/carbonylation/alkynylation processes, 23,24 in which various γ, δ-unsaturated esters and ynones containing five-membered ring

8


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frameworks were obtained in good yields in the presence of Pd(II) salt in low catalytic amounts under ambient temperature and pressure (1 atm of carbon monoxide) (Scheme 8). Scheme 8. Pd(II)-Catalyzed Oxidative Carbocyclization/Borylation and Carbocyclization/Arylation of Enallenes

On the other hand, when allenynes (substituted 1,5-allenynes) were employed for the oxidative carbocyclization combining with B2pin2 or arylboronic acid, either functionalized triene products or vinylallene products can be obtained. For examples, a controllable selective oxidative Scheme 9. Pd(II)-Catalyzed Oxidative Carbocyclization/Borylation of Allenynes

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E 2 mol% Pd(OAc)2 1.1 equiv. BQ E

E

E

R'


20 mol% LiOAc 2H2O DCE, 50 oC

Bpin

B2pin2

E

E


R' E=CO2Me

20 mol% BF3 Et2O THF, 50 oC

E

E nC

R' E

E

E

E

E

Bpin Bpin

92% yield


Bpin

5H11

Bpin

E

Bpin

nBu

Me

81% yield

77% yield

70% yield

Possible reaction pathway (ligands omitted for clarity): R

R

OAc

allylic C-H cleavage X

PdII

BQ

OAc

PdII B2pin2 trienes BQ

X

R allenynes (

)

I-13

I-12

Pd(II) PdII(OAc)2

X

R I-11

R

OAc

propargylic C-H cleavage

PdII

X

I-14

BQ

X

B2pin2

vinylallenes

AcOPdII BQ I-15

carbocyclization/borylation reactions of allenynes with B2pin2 enabled the preparation either borylated trienes or borylated vinylallenes with excellent regioselectivities, by using of LiOAc·2H2O in 1,2-dichloroethane (DCE) or BF3·Et2O in THF under Pd(II) catalysis with BQ as the oxidant (Scheme 9). 19 Based on the results of deuteriumlabeling experiments, the reaction of allenynes was proposed to proceed through competing allylic and propargylic C-H bond cleavage pathways (I-12 and I-14) to give borylated trienes and borylated vinylallenes, respectively. This strategy can be extended to the oxidative arylating carbocyclization of allenynes, in which either vinylallenes or cross conjugated trienes can be obtained in good yields with high selectivities, depending on the structural differences in the starting material (Scheme 10).21 This arylating carbocyclization may involve the formation of a pallada(IV)cyclopentene intermediate I-16 which followed different β-H elimination to give triene or vinylallene products. Scheme 10. Pd(II)-Catalyzed Oxidative Carbocyclization/Arylation of Allenynes

10


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R 1 or 5 mol% Pd(OAc)2 1.1 equiv. BQ E

Ar E 17 examples 45-81% yields

E E

1.3 equiv ArB(OH)2 THF, RT or reflux, 20 h R=H or Ar

E


R E=CO2Me

1.3 equiv ArB(OH)2 THF, RT, 20 h R=Alkyl

tBu

E

H

Ar

Ph

H

R

E

E

E

75% yield

E

nBu

E Me

77% yield

Me

E

E

E


Ph

65% yield

68% yield

Possible reaction pathway : ArB(OH)2 + Pd(OAc)2

-HOAc AcOB(OH)2 allenynes

R

ArPdOAc BQ

Ar PdII

β elimination E

trienes

E I-17

OAc PdIV BQ Ar

E

BQ

R'

E I-16

Ar PdII

β elimination E -HOAc R=CH2R'

E I-18

vinylallenes

BQ

Recently, a Pd(II)-catalyzed domino carbocyclization/carbonylation reaction of allenynes has also been achieved in a similar controllable manner. Treatment of allenynes with alcohols and carbon monoxide (1 atm) in the presence of low catalytic amounts of Pd(OAc)2 and BQ as the oxidant under ambient temperature provided cyclic α, β-unsaturated esters or vinylallene esters in good to high yields (Scheme 11, A). 23 The use of DMSO as an additive was found to be important for this transformation. A wide range of alcohols as trapping reagents was used to give the corresponding esters in good yields. The mechanism of these transformations is proposed to operate in analogy to the corresponding arylative carbocyclization reaction (Scheme 10). However, in contrast to the forementioned regioselective carbocyclizations of allenynes involving borylation, arylation and carbonylation, Pd(II)-catalyzed aerobic oxidative domino carbocyclization/alkynylation of allenynes with terminal alkynes gave a single alkynyl-substituted product with high regioselectivity, irrespective of using BQ as sole oxidant or aerobic oxidative system (20 mol% of BQ and 5 mol% of Cobalt(salophen) under 1 atm of O2) (Scheme 11, B). 22 Scheme 11. Pd(II)-Catalyzed Oxidative Carbocyclization/Carbonylation and Carbocyclization/Alkynylation

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In contrast to the carbocyclizations of enallenes and allenynes, Gabriele et al. developed an alternative tandem Pd-catalyzed oxidative carbamoylation/carbocyclization process (Scheme 12). 25 In this sequence, the carbamoylation of 2-(2- ethynylbenzyl)malonates with carbon monoxide, a secondary amine, and oxygen, followed by carbocyclization through intramolecular addition of the in situ formed carbanion to the proiolamide moiety furnished functionalized indane derivatives. Here PdI2-catalyzed oxidative carbomylation of the triple bond of 2-(2-ethynylbenzyl)malonates and cyano malonate analogs leads to propiolamide intermediates A, which then undergo highly selective carbocyclization to give the E-isomer products. Scheme 12. Tandem Pd-Catalyzed Cascade Oxidative Carbamoylation/Carbocyclization Process

12


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In addition, the tandem cyclizations of enallenes and allenynes are not only applicable to construct five-membered ring systems, but also prepare other size-ring analogues. Cyclobutene motifs are widely occurred in many biologically relevant compounds and natural products.26 Moreover, they proved to be useful synthetic units in number of transformations due to their high strain.27 By using enallenes as substates, Bäckvall group developed an efficient Pd(II)-catalyzed oxidative borylation for the selective formation of cyclobutene derivatives as the exclusive products in MeOH in the presence of H2O and Et3N (Scheme 13, eq-3). 28 The generated vinylpalladium intermediate I-20, could undergo an olefin insertion to form cyclobutene intermediate I-21. Subsequent transmetalation of I-21 with B2pin2 would give I-22, which can produce Scheme 13. Preparation of Cyclobutene Derivatives by Pd(II)-Catalyzed Oxidative Carbocyclization/Borylation

13


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cyclobutene derivative upon reductive elimination. In the presence of AcOH, fully-substituted alkenylboron compounds can be obtained when the transmetalation of I-20 with B2pin2, followed by reductive elimination (Scheme 13, eq-4). In this case, the coordination of the olefin unit to palladium is not only crucial for activation of the allene attack to occur, but also enabled the insertion of the olefin to give a cyclobutene. The reactions showed a broad substrate scope and good tolerance for various functional groups. The potential applications Scheme 14. Synthetic Applications of Cyclobutenes

of the borylated cyclobutene products were demonstrated. 28 Borylated cyclobutene can undergo [4+2]-cycloaddition, oxidation and [1,5]-H migration to furnish various functionalized cyclic compounds (Scheme 14). 14


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Recently, by using similar olefin-assisted strategy, the same group demonstrated a highly selective Pd(II)-catalyzed oxidative carbocyclization/borylation of enallenes containing an extra olefin to afford borylated cyclohexenes via remote olefin insertion (Scheme 15). 29 Furthermore, quenching δ-alkyl-Pd(II) intermediate I-23 with other nucleophiles such as arylboronic acid or carbon monoxide (CO)/alcohol (ROH) providing the corresponding arylated or carbonylated carbocycles can also be accomplished (Scheme 15). Scheme 15. Preparation of Cyclohexenes by Palladium-Catalyzed Oxidative Tandem Carbocyclization of Enallenes 5 mol% Pd(OAc)2 1.3 equiv. B2pin2

R 11 examples 60-91% yields

1.1 equiv. BQ DCE, RT, 4-20 h

Bpin R

2 mol% Pd(OAc)2 1.3 equiv. ArB(OH)2

R

R 10 examples 58-90% yields

Bpin 90% yield

CO2R1

EtO2C

EtO2C

EtO2C

Bpin

Ph

75% yield

88% yield

55% yield

EtO2C

EtO2C

CO2Me

CO2Me 80% yield

OAc I-23

Ar

1.1 equiv. BQ 20 mol% DMSO RT, 12-18 h

Ph

PdII


1.1 equiv. BQ DCE, RT or 50 oC 12-24 h

2 mol% Pd(OAc)2 CO(1 atm) + R1OH

via

R

90% yield

77% yield

CO2Et 73% yield

Besides, Bäckvall group found that treatment of bisallenes and arylboronic acids under Pd(II)-catalyzed oxidative conditions can afford cyclohexadiene derivatives through a highly efficient and regioselective carbocyclization/arylation sequence, since the chemoselectivity of insertion of organopalladium(II) intermediate I-24 with allene moiety may take place either on C2-C3 or C1-C2 of the allene which would lead to either cyclopentene or cyclohexene intermediate (Scheme 16). 30 The reaction conditions were compatible with a wide range of functional groups, and exhibited broad substrate scope. Scheme 16. Preparation of Cyclohexenes by Pd(II)-Catalyzed Oxidative Carbocyclization/Arylation of Bisallenes

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The direct oxidative Heck arylation can trigger a tandem Pd-catalyzed oxidative carbocyclization via C-C bond formation reaction. Kim and co-workers developed a Pd(II)-catalyzed one-pot arylative cyclization of 3-(γ, δ-disubstituted)allylidene-2-oxindoles, which afforded spirodihydronaphthalene-2-oxindoles via an oxidative Heck arylation/allylic palladium migration/aryl C-H bond functionalization/arylation sequence (Scheme 17).31 The plausible mechanism for the formation of spirooxindoles was proposed as follow: alkylpalladium intermediates I-25 from the carbopalladation with PhPd(OPiv) species can be converted to intermediate I-26, which underwent an aryl C-H bond activation and reductive elimination to produce final product. Scheme 17. Pd(II)-Catalyzed Oxidative Heck arylation/Carbocyclization

Very recently, Bäckvall and co-workers reported an olefin-assisted Pd(II)-catalyzed oxidative carbocyclization/alkoxycarbonylation of bisallenes to produce seven-membered carbocycles (Scheme 18). 32 Treatment of bisallene with CO and alcohol under the optimized reaction conditions provided ester as single product with chemo- and regioselectivity. This dehydrogenative coupling reaction showed excellent substrate scope and functional group compatibility. The ligand exchange of olefin with the second allene moiety proved to be pivotal for the formation of the 7-membered ring I-31, which was trapped by CO and alcohol to produce product. Furthermore, mechanistic studies have shown that the allenic C-H bond cleavage occurred during a rate-limiting step. Scheme 18. Construction of Seven-Membered Carbocycles by Pd(II)-Catalyzed Oxidative Carbocyclization/Alkoxycarbonylation of Bisallenes

16


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ACS Catalysis

R1

R2

R2 5 mol% Pd(OAc)2 1.5 equiv. BQ + CO + ROH 20 mol% DMSO (1 atm) (5 equiv) DCE, RT, 6 h

Bn

CO2R R1 nPr

nPr

CO2Me

EtO2C

nPr

CO2Cy

CO2Me

HO

68% yield

71% yield

Possible reaction pathway (ligands omitted for clarity): HQ HOAc+BQ product

CO2Me

EtO2C

EtO2C

80% yield

50% yield

bisallene

Pd(OAc)2 R2

Pd0

R1 I-28

PdII R2

I-32


COOR PdII

-HOAc R1

R1

R2 PdII I-29

CO ROH

R2

R2

PdII

PdII R1 I-31

R1 I-30

2. CARBOCYCLIZATIONS INTERRUPTED WITH “EXTERNAL REAGENTS” In contrast to the aforementioned tandem carbocyclizations, in which external reagents either incorporated into tandem process prior to or posterior to the ring-closure, an alternative tandem carbocyclization in which direct ring-closure step via C-C bond formation is interrupted by external reagents is also applicable. On the basis of previous works on Pd(II)-catalyzed carbocyclization reactions, Bäckvall group developed an efficient Pd(II)-catalyzed oxidative carbonylation/carbocyclization/carbonylation/alkynylation reaction of enallenes under mild reaction conditions, which involved sequential insertion of carbon monoxide, olefin and carbon monoxide (CO) with concomitant overall four C-C bond formations (Scheme 19). 33 In this process, generated carbonyl palladium complex I-34 from the insertion of CO into the C-Pd bond of I-33 underwent a subsequent carbocyclization via olefin insertion to produce I-35, which was subjected to the carbonylative coupling reaction to produce ynones. Several possible side reactions which may stem from the coupling reactions of terminal alkyne with palladium species I-33, I-34, or I-35, have been well inhibited. Scheme 19. Pd(II)-Catalyzed Oxidative Carbonylation/Carbocyclization/ Carbonylation−Alkynylation of Enallenes

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A further extension of this carbocyclization to formation of spirocarbocyclic scaffolds which are frequently occurred in a wide range of natural products and pharmaceutical ingredients, has also been accomplished by interrupting the vinyl-Pd species with the intramolecular insertion of alkene moiety by the same group (Scheme 20). 34 In this cascade reaction, the direct transformation of dienallenes to spirocyclobutenes bearing a carbon-substituted quaternary carbon center as single diastereoisomers can be achieved though the efficient formation of overall four C-C bonds with insertion of olefin, olefin and CO by means of palladium(II) salt (Scheme 20, eq-5). Additionally, under slightly different reaction conditions (BQ, DCE), an additional CO insertion can take place to give spiro[4.4]nonenes with formation of overall five C-C bonds (Scheme 20, eq-6). Scheme 20. Preparation of Spirocyclobutenes by Pd(II)-Catalyzed Oxidative Double Carbocyclization/Carbonylation/Alkynylation R R

5 mol% Pd(TFA)2 1.1 equiv. F4 BQ

R

R1 via

CH3CN, 80 oC

I-37

O 20 examples 55-83% yields

+

eq-5

PdX

CO (1 atm) + R1

R

5 mol% Pd(TFA)2 1.1 equiv. BQ DCE, RT

(1.5 equiv.)

O

eq-6 PdX

9 examples 72-93% yields 95/5-88/12 d.r. CO2Et

CO2Et

R

via O R1

CO2Et

O I-38 AcO

CF3 TMS

Ph

O

O 77% yield

O

79% yield

CO2Et

O

80% yield CO2Et

68% yield Ph

O

O

O

O Ph

93% yield, 91/9 d.r.

Ph

O O

R1 R1 = 3-thienyl: 78% yield, 88/12 d.r. 1 R = 2-Methoxyl: 80% yield, 90/10 d.r.

18


Ph 88% yield, 88/12 d.r.

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ACS Catalysis

Besides, alkene, arenes and alkyne derivatives have been reported to be inserted intermolecularly during ring-closure step. By employing a range of aromatic enynes with olefins, Loh and Feng demonstrated a highly efficient and mild Pd(II)-mediated bisolefination of C-C triple bonds in DMSO at 110 oC under atmospheric pressure of O2 (Scheme 21).35 The use of an alkene as the initiator for intramolecular nucleopalladation of aromatic enyne followed by intermolecularly coupling with another alkene with O2 as the sole oxidant enabled the concise construction of naphthalene derivatives. With different types of olefin (such as acrylate, vinyl acetate and styrene) employed, this reaction terminated in diverse fashions. An investigation of the substrate scope revealed that the α-methyl group on the styrene moiety is crucial to the accomplishment of this catalytic process in an efficient manner due to its the role in stabilization of the benzylic cation generated (intermediate I-39, Scheme 21). Scheme 21. Pd-Catalyzed Bis-olefination of Aromatic Enynes with Alkenes

Moreover, by means of Pd(II)/Pd(IV) catalytic cycle, Cheng et al. disclosed a direct C-H activation triggered tandem oxidative reaction of sec-alkyl aryl ketones with aryl iodides in the presence of 10 mol% of Pd(OAc)2 and one equivalent of Ag2O in TFA (Scheme 22). 36 This reaction provided a facile way to access

19


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Scheme 22. Pd-Catalyzed Oxidative Cyclization of Ketones with Aryl Iodides

phenanthrone derivatives. The catalytic process involved ortho-C-H activation to form five-membered palladacycle I-41 and subsequent oxidative addition of aryl iodide to I-41 to give Pd(IV) intermediate I-42. Reductive elimination followed by another C-H activation afforded the seven-membered palladacycle I-43. Subsequent enolization/C-H activation and reductive elimination gave final product. In the presence of Pd(II) salt and oxidant, catalytic cycloaromatizations of arenes (or alkenes) coupled with the intermolecular alkyne insertion has emerged as a powerful strategy for the generation of structurally diverse aromatic and heteroaromatic compounds. 3d, 37 However, unlike such cycloaromatization reaction, Jiao and co-workers described a palladium-catalyzed oxidative carbocyclization of indoles with alkynes through dual C-H bond activations concomitant with ring-expansion reaction, using O2 as the oxidant, which leads to tetrahydroquinoline derivatives with highly substituted cyclopentadienyl cores (Scheme 23).38 Treatment of indoles with disubstitued ethynes in the presence of Pd(OAc)2 in CH3CN/AcOH under O2 atmosphere exclusively afforded polysubstituted 4,5-dihydroquinolines. It is worth noting that this ring-expansion reaction involves a dual C-H bond activation, one C-C bond cleavage, and five new C-C bond formations. Scheme 23. Palladium-Catalyzed Aerobic Ring-Expansion Reaction of Indoles with Alkynes to Prepare Tetrahydroquinoline Derivatives 20


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In addition, Pd(II)-catalyzed oxidative tandem reaction could be extended to prepare the polyheterocycles. For example, Zhang and co-workers developed a palladium-catalyzed oxidative domino reaction of diyne-enones and substituted indoles for the preparation of polyheterocycles (Scheme 24). 39 This reaction involved the formation of three new rings via two direct C-H functionalizations using air as the oxidant, in which the syn-addition of generated furanylpalladium intermediate to the acetylene to give a bicyclic vinylpalladium intermediate I-45, and followed a nucleophilic attack by the indole and a subsequent direct C-H functionalization at the 2-position constituted the key steps for the generation of final products. Scheme 24. Pd(II)-Catalyzed Oxidative Tandem Reaction for Polyheterocycles E E

O

R1

R1

O

R1

R2 R2

10 mol% [PdCl2(CH3CN)2] R4 50 mol% LiBr H2O

R3

+

via

E

CH3CN, 40 oC, air E=CO2Me

R4

E

XPd

N R3 R5 17 examples 46-84% yields

N R5

O

R2

E

E

R3 I-45 Cl

Ph

Cl

O

Ph

Ph

Ph

O

E

E

O

O

Ph Me

E

Ph E

E N Me 84% yield

E CF3

E

N Me

N Ph H 70% yield

79% yield

E N Ph Me 62% yield

3. USING Pd COMBINED WITH OTHER CATALYST FOR PROMOTING OXIDATIVE CARBOCYCLIZATIONS As the forementioned processes, the tandem sequences were mediated by Pd(II) salt and oxidant. Since cooperative catalysis40 has emerged as a powerful tool to access useful synthetic compounds, combination of Pd-catalyzed reactions with other metal-catalysis or organocatalysis has been extended to oxidative carbocyclizations, and some preliminary results displayed the promising potential for the preparation of carbocyclic compounds. In 2014, Ma and co-workers reported a Palladium/Copper-catalyzed aerobic tandem cyclization of enediyne compounds 1 and alkynes (Scheme 25).41 Unlike the previous analogues, Cu(II) not only promoted the aerobic oxidation of Pd(0) to Pd(II) by using O2 as the terminal oxidant, but also facilitated the subsequent one-electron oxidation of the enol 21


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moiety of species. According to the proposed mechanism, generated vinylpalladium species I-46 through 5-endo cyclization of enediyne-imides would undergo a syn carbopalladation onto external alkyne to afford intermediate I-47, which was subjected to the regioselective nucleophilic attack of H2O on the triple bond, and followed by reductive elimination to provide enol I-49 and a Pd(0) species. By using O2 as the terminal oxidant with the aid of Cu(II) salt, Pd(0) species could be oxidized to the Pd(II) catalyst. Subsequent one-electron oxidation of the enol moiety of I-49 promoted by Cu(II) species and followed the aromatization would afford benzyl radical I-51, which could react with O2 to produce isoindolinones. This tandem reaction enabled efficiently assembling a class of o-acylbenzoic acids by employing a set of readily accessible enediyne-carboxylic acids with inner alkynes.

Scheme 25. Palladium/Copper-Catalyzed Aerobic Intermolecular Cyclization of Enediyne Compounds and Alkynes

22


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NT s

On the basis of the previous works on the development of oxidative carbocyclization reactions using allenes, Bäckvall and co-workers demonstrated a chiral counter anion-induced asymmetrical carbocyclization/borylation of enallenes by the combination of chiral phosphoric acid-based anions with Pd(II) catalysis (Scheme 26). 42 In this process, by exchanging the acetate (ligand) with a chiral counter anion, the migratory insertion of the alkene into the Pd-C bond through a syn-carbopalladation occurred in an enantioselective manner, which led to a vinylpalladium(II) intermediate bearing a new stereogenic center. Subsequent borylation gave chiral borylated carbocycles in high enantiomeric excess (Scheme 26, A). The use of biphenol-type chiral phosphoric acids in combination with Pd(II) induced the highest enantioselectivity for the carbocyclization transformation. A number of chiral borylated carbocycles were synthesized in high enantiomeric excess. Recently, by using similar strategy, the same group demonstrated an enantioselective Pd(II)-catalyzed oxidative carbocyclization/borylation of enallenes with an extra alkene unit via a remote olefin insertion to afford cyclohexenes with moderate enantioselectivity (Scheme 26, B). 29 Scheme 26. Palladium(II)/Brønsted Acid-Catalyzed Enantioselective Oxidative Carbocyclization–Borylation of Enallenes

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Córdova and co-workers developed a novel highly enantioselective Pd-catalyzed oxidative cascade carbocyclization transformation by merging Pd(II)/Pd(0) catalyzed aerobic oxidation with Pd/amine43 cocatalyzed dynamic Michael/carbocyclization44 domino reactions (Scheme 27).45 In this process, a Pd(II)/Pd(0) catalyzed aerobic oxidation of allylic alcohols led to α, β-unsaturated aldehydes I-52, which underwent a reversible amine-catalyzed conjugate addition of propargyl nucleophiles to generate enaminyne intermediate I-54. Next, irreversible intramolecular C-C bond formation with the alkyne moiety of I-54 by the synergistic action of a Pd(II) catalyst followed by isomerization of the resulting double bond furnished the final products. Scheme 27. Palladium/Amine Co-catalyzed Carbocyclization of Allylic Alcohol with Alkynes

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ACS Catalysis

O

17 mol% cat.-2 17 mol% C6H5COOH 1.7 equiv., 1a ,RT

R O

R

OH

5 mol% Pd(PPh3)4

cat.-2:

N H

O N H

1a N H

Toluene, O2, 70 oC

NC

10 examples 59-79% yields 91-99% ee

NC MeO2C

20 mol% cat.-2 1 equiv., 1b, RT

Ph Ph OTMS

R

CO2Me

O 1b O

O

NC MeO2C O N H 88% yield, 81:19 dr 88% ee

O N H 76% yield, 83:17 dr 97% ee [a]

NC MeO2C O

O

63% yield, 86:14 dr 95% ee[a]

68% yield, 83:17 dr 96% ee[a]

Cl

Pd0-Amp-CPG (5 mol %) was used as the Pd catalyst.

Proposed mechanism (ligands omitted for clarity): H2O

E

O2

product

E PdIIL2

R H+

R1 N

R1 HN R2 Cat.

I-57

R2

E E

L2Pd(II)

L2Pd(0)

R

O

R

OH

I-52

R

PdII R1 N R2

R

I-56

I-53 E

E

E R

I-55

R1 N R2

E 1a or 1b

R PdII 1 N R R2

PdL2

R2

N R1 I-54

The mechanistic investigation based on density functional theory (DFT) calculations and experimental studies on the C−C bond forming step of this carbocyclization revealed that the 5-exo-dig cyclization proceeded via a Pd(II)-catalyzed pathway where the Pd(0) catalyst is first oxidized to Pd(II) by molecular oxygen or air. Next, the Pd(II) species activates the alkyne by acting as a Lewis acid. Number of valuable chiral pyrrolidines and spirocyclic oxindoles, with up to three quaternary stereocenters can be obtained from simple alcohols in a highly enantioselective fashion (95:5 to >99.5:0.5 e.r.). In addition, the combination of heterogeneous Pd(0) species (Pd(0)-aminopropyl-mesocellular foam (Pd0-Amp-MCF)) or Pd(0)-aminopropyl-controlled pore glass (Pd0-Amp-CPG))/chiral aminocatalysis also exhibited a wide substrate scope under the same conditions in comparison to the case when Pd(PPh3)4 is used as a homogeneous cocatalyst. 46 4. CONCLUSION In summary, Pd-catalyzed oxidative cascade carbocyclization with external reagents by the aid of stoichiometric oxidant, has emerged as an efficient protocol for the preparation of carbocyclic compounds via introducing diverse functionalities concomitant with mutli-C-C bond formations. These cascade processes which benefit from the versatile Pd-catalyzed 25


ACS Catalysis

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oxidative C-C and C-X bond-forming reactions demonstrate good functional group compatibility and wide substrate scope under mild reaction conditions. In addition, by combination of Pd catalysis and organocatalysis or other transition-metal catalysis, these cascade carbocyclizations enable efficient preparation of functionalized carbocyclic compounds with high efficiency and selectivity. Therefore, these carbocyclizations will undoubtedly play an important role in the construction functionalized carbocyclic scaffolds in future. Acknowledgements The Berzelii Center EXSELENT was financially supported by VR and the Swedish Governmental Agency for Innovation Systems (VINNOVA). The European Union is also acknowledged for financial support. W.-W.L. thanks NSFC (No. 21772063) and the Open Project of State Key Laboratory for Supramolecular Structure and Materials (sklssm201716) for financial support.

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References: 1. For selected examples, see: (a) Green, D.; Goldberg, I.; Stein, Z.; Ilan, M.; Kashman, Y. Nat. Prod. Lett. 1992, 1, 193-199. (b) Enqusit Jr, J. A.; Stoltz, B. M. Nature. 2008, 453, 1228-1231. (c) Kingston, D. G. I. J. Org. Chem. 2008, 73, 3975-3984. (d) Daum, R. S.; Kar, S.; Kirkpatrick, P. Nat. Rev. Drug Discovery. 2007, 6, 865-866. 2. For selected reviews involving carbocyclization reaction, see: (a) Trost, B. M.; Tanoury, G. J.; Lautens, M.; Chan, C.; MacPherson, D. T. J. Am. Chem. Soc. 1994, 116, 4255-67. (b) Trost, B. M.; Romero, D. L.; Rise, F. J. Am. Chem. Soc. 1994, 116, 4268-78. (c) Trost, B. M.; Toste, F. D.; Pinkerton, A. B. Chem. Rev. 2001, 101, 2067-2096. (d) Méndez, M.; Echavarren, A. M. Eur. J. Org. Chem. 2002, 15-28. (e) Zhang, D. H.; Zhang Z.; Shi, M. Chem. Commun. 2012, 48, 10271-10279. (f) Aubert, C.; Fensterbank, L.; Garcia, P.; Malacria, M.; Simonneau, A. Chem. Rev. 2011, 111, 1954-1993. (g) McDonald, R. I.; Liu, G.; Stahl, S. S. Chem. Rev. 2011, 111, 2981-3019. (h) Guo, L.-N.; Duan, X.-H.; Liang, Y.-M. Acc. Chem. Res. 2011. 44, 111-122. (i) Wang, Y.; Yu, Z.-X. Acc. Chem. Res. 2015, 48, 2288-2296. 3. For selected reviews involving palladium oxidative carbocyclization, see: (a) Beccalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S. Chem. Rev. 2007, 107, 5318-5365. (b) Dénès, F.; Pérez-Luna, A.; Chemla, F. Chem. Rev. 2010, 110, 2366-2447. (c) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215-1292. (d) Deng, Y.; Persson, A. K. Å.; Bäckvall, J.-E. Chem. - Eur. J. 2012, 18, 11498-11523. 4. For selected reviews, see: (a) Müller, T. J. J. Topics in Organometallic Chemistry: Metal Catalyzed Cascade Reactions; Springer-Verlag: Berlin Heidelberg, 2006. (b) Tietze, L. F.; Brasche, G.; Gericke, K. Domino Reactions in Organic Synthesis; Wiley-VCH: Weinheim, 2006. (c) Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G. Angew. Chem., Int. Ed. 2006, 45, 7134-7186. (d) Grondal, C.; Jeanty, M.; Enders, D. Nat. Chem. 2010, 2, 167-178. 5. (a) Tsuji, J. Palladium Reagents and Catalysts: Innovations in Organic Synthesis; John Wiley & Sons: Chichester, 1995. (b) Tsuji, J. Palladium Reagents and Catalysts: New Perspectives for the 21st Century; John Wiley & Sons: Chichester, 2004. 6. (a) Vlaar, T.; Ruijter, E.; Orru, R. V. A. Adv. Synth. Catal. 2011, 353, 809-841. (b) Lautens, M.; Alberico, D.; Bressy, C.; Fang, Y.-Q.; Mariampillai, B.; Wilhelm, T. Pure Appl. Chem. 2006, 78, 351-361. 7. For selected reviews, see: (a) Shao, Z.; Zhang, H. Chem. Soc. Rev. 2009, 38, 2745-2755. (b) Zhong, C.; Shi, X. Eur. J. Org. Chem. 2010, 2999-3025. (c) Ambrosini, L. M.; Lambert, T. H. ChemCatChem. 2010, 2, 1373-1380. (d) Allen, A. E.; MacMillan, D. W. C. Chem. Sci. 2012, 3, 633-658. (e) Afewerki, S.; Córdova, A. Chem. Rev. 2016, 116, 13512-13570. 8. Antonsson, T.; Moberg, C.; Tottie, L. J. Org. Chem. 1989, 54, 4914-4929. 9. (a) Antonsson, T.; Malmberg, C.; Moberg, C. Tetrahedron Lett. 1988, 29, 5973-5974. (b) Moberg, C.; Nordstörm, K.; Helquist, P. Synthesis. 1992, 7,685-689. 10. Löfstedt, J.; Franzén, J.; Bäckvall, J.-E. J. Org. Chem. 2001, 66, 8015-8025. 11. Löfstedt, J.; Närhi, K.; Dorange, I.; Bäckvall, J.-E. J. Org. Chem. 2003, 68, 7243-7248. 12. Piera, J.; Persson, A.; Caldentey, X.; Bäckvall, J.-E. J. Am. Chem. Soc. 2007, 129, 14120-14121. 13. Deng, Y.; Bäckvall, J.-E. Angew. Chem., Int. Ed. 2013, 52, 3217-3221. 14. (a) Castaño, A. M.; Bäckvall, J.-E. J. Am. Chem. Soc. 1995, 117, 560-561. (b) Castaño, A. M.; Persson, B. A.; Bäckvall, J.-E. Chem. - Eur. J. 1997, 3, 482-490. (c) Bäckvall, J.-E.; Nilsson, Y. I. M.;

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Andersson, P. G.; Gatti, R. G. P.; Wu, J. Tetrahedron Lett. 1994, 35, 5713-5716. 15. Liu, R.; Lu, Z.-H.; Hu, X.-H.; Li, J.-L.; Yang, X.-J. Org. Lett. 2015, 17, 1489-1492. 16. Mazuela, J.; Banerjee, D; Bäckvall, J.-E. J. Am. Chem. Soc. 2015, 137, 9559-9562. 17. (a) Hall, D. G. Boronic Acids: Preparation and Applications in Organic Synthesis and Medicine; Wiley-VCH: Weinheim, Germany, 2005. (b) Stang, P. J.; Diederich, F. Modern Acetylene Chemistry; Wiley-VCH Verlag GmbH & Co.: Weinheim, Germany, 1995. (c) Diederich, F.; Stang, P. J.; Tykwinski, R. R. Acetylene Chemistry; Wiley-VCH Verlag GmbH: Weinheim, Germany, 2005. Selected examples of synthetic application of ynones: (d) Karpov, A. S.; Merkul, E.; Rominger, F.; Müller, T. J. J. Angew. Chem., Int. Ed. 2005, 44, 6951-6956. (e) Ahmed, M. S. M.; Kobayashi, K.; Mori, A. Org. Lett. 2005, 7, 4487-4489. 18. Persson, A. K. Å.; Jiang, T.; Johnson, M. T.; Bäckvall, J.-E. Angew. Chem., Int. Ed. 2011, 50, 6155-6159. 19. Deng, Y.; Bartholomeyzik, T.; Bäckvall, J.-E. Angew. Chem., Int. Ed. 2013, 52, 6283-6287. 20. Jiang, T.; Persson, A. K. Å.; Bäckvall, J.-E. Org. Lett. 2011, 13, 5838-5841. 21. (a) Deng, Y.; Bartholomeyzik, T.; Persson, A. K. Å.; Sun, J.; Bäckvall, J.-E. Angew. Chem., Int. Ed. 2012, 51, 2703-2707. For palladium oxidative cascade carbocyclizations involving 5-exo-trig and 6-exo-trig cyclizations of enynes see: (b) Jiang, M.; Jiang, T. Bäckvall, J.-E. Org. Lett. 2012, 14, 3538-3541. (c) Murthy, A. S.; Donikela, S.; Reddy, C. S.; Chegondi, R. J. Org. Chem. 2015, 80, 5566-5571. (d) Liu, B.; Song, R.-J.; Ouyang, X. H.; Li, Y.; Hu, M.; Li, J.-H. Chem. Commun. 2015, 51, 12819-12822. and references therein. 22. Volla. C. M. R.; Bäckvall, J.-E. Angew. Chem., Int. Ed. 2013, 52, 14209-14213. 23. Volla. C. M. R.; Mazuela, J.; Bäckvall, J.-E. Chem. - Eur. J. 2014, 20, 7608-7612. 24. Volla. C. M. R.; Bäckvall, J.-E. Org. Lett. 2014, 16, 4174-4177. 25. Gabriele, B.; Veltri, L.; Mancuso, R.; Carfagna, C. Adv. Synth. Catal. 2014, 356, 2547-2558 26. Selected examples, see: (a) Frébault, F.; Luparia, M.; Oliveira, M. T.; Goddard, R.; Maulide, N. Angew. Chem., Int. Ed. 2010, 49, 5672-5676. (b) Sadana, A. K.; Saini, R. K.; Billups, W. E. Chem. Rev. 2003, 103, 1539-1602. 27. Meijere, A. D. Houben-Weyl Methods in Organic Chemistry; Thieme Medical Publishers: Stuttgart, Germany, 1997. 28. Qiu, Y.-A.; Yang, B.; Zhu, C.; Bäckvall, J.-E. Angew. Chem., Int. Ed. 2016, 55, 6520-6524. 29. Qiu, Y.-A.; Yang, B.; Zhu, C.; Bäckvall, J.-E. Chem. Sci. 2017, 8, 616-620. 30. Volla. C. M. R.; Bäckvall, J.-E. ACS Catal. 2016, 6, 6398-6402. 31. Kim, K. H.; Moon, H. R.; Lee, J.; Kim, J. N. Adv. Synth. Catal. 2015, 357, 701-708. 32. Zhu, C.; Yang, B.; Qiu, Y.-A.; Bäckvall, J.-E. Angew. Chem., Int. Ed. 2016, 55, 14405-14408. 33. Zhu, C.; Yang, B.; Bäckvall, J.-E. J. Am. Chem. Soc. 2015, 137, 11868-11871. 34. Qiu, Y.-A.; Yang, B.; Zhu, C.; Bäckvall, J.-E. J. Am. Chem. Soc. 2016, 138, 13846-13849. 35. Feng, C.; Loh, T.-P. J. Am. Chem. Soc. 2010, 132, 17710-17712. 36. Gandeepan, P.; Parthasarathy, K.; Cheng, C.-H. J. Am. Chem. Soc. 2010, 132, 8569-8571. 37. Selected recent examples: (a) Peng, S. Y.; Gao, T.; Sun, S. F.; Peng, Y. H.; Wu, M. H.; Guo, H. B.; Wang, J. Adv. Synth. Catal. 2014, 356, 319-324. (b) Peng, S. Y.; Wang, L.; Wang, J. Chem. - Eur. J. 2013, 19, 13322-13327. (c) Ghosh, S. K.; Kuo, B.-C.; Chen, H.-Y.; Li, J.-Y.; Liu, S.-D.; Lee, H. M. Eur. J. Org. Chem. 2015, 4131-4142. (d) Su, T.; Han, X. L.; Lu, X.Y. Tetrahedron Lett. 2014, 55,

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27-30. 38. Shi, Z.-Z.; Zhang, Bo; Cui, Y.-X.; Jiao, N. Angew. Chem., Int. Ed. 2010, 49, 4036-4041. 39. Liu, R.; Zhang, J. Adv. Synth. Catal. 2011, 353, 36-40. 40. (a) Kanai, M.; Kato, N.; Ichikawa, E.; Shibasaki, M. Synlett 2005, 1491–1508. (b) Lee, J. K.; Kung, M. C.; Kung, H. H. Top. Catal. 2008, 49, 136–144. (c) Bruggink, A.; Schoevaart, R.; Kieboom, T. Org. Process Res. Dev. 2003, 7, 622−640. (d) Wende, R. C.; Schreiner, P. R. Green Chem. 2012, 14, 1821−1849. (e) Afewerki, S.; Córdova, A. Chem. Rev., 2016, 116,13512–13570. 41. Ling, F.; Li, Z.-X.; Zheng, C.G.; Liu, X.; Ma, C. J. Am. Chem. Soc. 2014, 136, 10914-10917. 42. Jiang, T.; Bartholomeyzik, T.; Mazuela, J.; Willersinn, J.; Bäckvall, J.-E. Angew. Chem., Int. Ed. 2015, 54, 6024-6027. 43. Ibrahem, I.; Córdova, A. Angew. Chem. Int. Ed. 2006, 45, 1952-1956. 44. (a) Yang, T.; Ferrali, A.; Campbell, L.; Dixon, D. J. Chem. Commun. 2008, 2923−2925. (b) Zhao, G.-L.; Ullah, F.; Deiana, L.; Lin, S.; Zhang, Q.; Sun, J.; Ibrahem, I.; Dziedzic, P.; Córdova, A. Chem. - Eur. J. 2010, 16, 1585−1591. (c) Lin, S.; Zhao, G.-L.; Deiana, L.; Sun, J.; Zhang, Q.; Leijonmarck, H.; Córdova, A. Chem. - Eur. J. 2010, 16, 13930−13934. (d) Deiana, L.; Afewerki, S.; Palo-Nieto, C.; Verho, O.; Johnston, E. V.; Córdova, A. Sci. Rep. 2012, 2, 851. (e) Sun, W.; Zhu, G.; Hong, L.; Wang, R. Chem. - Eur. J. 2011, 17, 13958−13962. (f) Sun, W.; Zhu, G.; Wu, C.; Hong, L.; Wang, R. Chem. - Eur. J. 2012, 18, 6737−6741. (g) Yu, C.; Zhang, Y.; Zhang, S.; He, J.; Wang, W. Tetrahedron Lett. 2010, 51, 1742−1744. 45. Santoro, S.; Deiana, L.; Zhao, G.-L.; Lin, S. Z.; Himo, F.; Córdova, A. ACS Catal. 2014, 4, 4474-4484. 46. (a) Deiana, L.; Jiang, Y.; Palo-Nieto, C.; Afewerki, S.; Incerti-Pradillos, C. A.; Verho, O.; Tai, C.-W.; Johnston, E. V.; Córdova, A. Angew. Chem., Int. Ed. 2014, 53, 3447-3451. (b) Deiana, L.; Ghisu, L.; Córdova, O.; Afewerki, S.; Zhang, R.; Córdova, A. Synthesis. 2014, 46, 1303-1310. (c) Córdova, A. Pure Appl. Chem. 2015, 87, 1011.

FG1

FG1

Ca

Ca or

Ca Cb

PdII, [O] external reagent

Cb

Cb

FG2

FG1, FG2: carboxyl, chloro, aryl, boryl et al.

(or + Co-catalyst) Ca

Ca FG1 or

Cb

FG1 Cb

FG1, FG2: carbon based FG

FG2 FG = functional group

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Recent Developments in Palladium-Catalyzed Oxidative Cascade

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