Carbene catalysts

Abstract

The use of N-heterocyclic carbenes as catalysts for organic transformations has received increased attention in the past 10 years. A discussion of catalyst development and nucleophilic characteristics precedes a description of recent advancements and new reactions using N-heterocyclic carbenes in catalysis.

Figure 1

Orbital representation of carbenes

Scheme 1

Lapworth’s proposed mechanism of the benzoin reaction

Scheme 2

Breslow’s proposed mechanism of the benzoin reaction

Scheme 3

Catalyst development in the benzoin reaction

Scheme 3

Catalyst development in the benzoin reaction

Scheme 4

Proposed mechanism for the acyl silane cross-benzoin reaction

Scheme 5

Suzuki and co-workers synthesis of (+)-sappanone B

Scheme 6

Murry, Frantz and co-workers trapping of in situ formed imines

Scheme 6

Murry, Frantz and co-workers trapping of in situ formed imines

Scheme 7

Synthesis of imidazoles

Scheme 8

Miller and co-workers aldehyde imine cross-coupling catalyzed by thiazolylalanine-derived catalysts

Scheme 9

Proposed mechanism for the Stetter reaction

Scheme 10

Intramolecular Stetter reaction

Scheme 11

Thiazolylidene vs. triazolinylidene steric capacities

Scheme 12

Cyclization of β,β-disubstituted aliphatic substrates

Scheme 13

Intramolecular protonation

Scheme 14

Complementary diastereoselectivity

Scheme 15

Desymmetrization of cyclohexadienones

Scheme 16

Bach and Miller catalysts

Scheme 17

Tomioka’s catalyst in the Stetter

Scheme 18

Enders et al intermolecular Stetter reaction

Scheme 19

Synthesis of furans via one-pot multicomponent reaction

Scheme 20

Aromatic substitution reaction catalyzed by NHCs

Scheme 21

Stetter and Kuhlmann’s synthsis of cis-jasmone and dihydrojasmone

Scheme 22

Trost et al synthesis of (±)-hirsutic acid C

Scheme 23

Roth et al synthesis of LIPITOR^®

Scheme 24

Tius and co-workers synthesis of roseophilin

Scheme 25

Grée and co-workers synthesis of haloperidol

Scheme 25

Grée and co-workers synthesis of haloperidol

Scheme 26

Nicolaou et al formal synthesis of (±)-platensimycin

Scheme 27

Rovis and Orellana’s efforts toward the synthesis of FD-838

Scheme 28

Proposed mechanism for the formation of β-hydroxy esters

Scheme 29

Rovis and co-workers acylation reaction via activated carboxylate XXXVII

Scheme 30

Base dependent reactivity

Scheme 31

Redox esterification of chiral enantioenriched formylcyclopropanes

Scheme 32

Proposed catalytic cycle of the redox amidation of α,α-dichloroaldehydes

Scheme 33

Synthesis of β-hydroxy amides catalyzed by NHCs

Scheme 34

Synthesis of γ-buturolactones

Scheme 35

Proposed mechanism of NHC catalyzed formation of γ-butyrolactone

Scheme 36

Synthesis of γ-butyrolactones from trifluoromethyl ketones and enals

Scheme 37

Proposed mechanism of trisubstituted cyclopentene formation

Scheme 38

Proposed intermediates leading to cis-cyclopentenes

Scheme 39

Desymmetrization of 1,3-diketones

Scheme 40

Scheidt and co-workers formal [3+3] of enals and azomethine

Scheme 41

Proposed intermediates leading to esters

Scheme 42

Movassaghi et al proposed catalytic cycle for amidation reaction

Scheme 43

Maruoka et al enantioselective acylation of secondary alcohols

Scheme 44

NHC promoted synthesis of γ-butyrolactones

Scheme 45

Proposed mechanism for ROP

Scheme 46

Ring opening of aziridines catalyzed by NHCs

Scheme 47

Proposed mechanism of aziridine ring opening under aerobic reaction conditions catalyzed by NHC

Scheme 48

Proposed mechanism for cyanosilylation of aldehydes and ketones

Scheme 49

Representative products formed via cyanation of aldehydes

Scheme 49

Representative products formed via cyanation of aldehydes

Scheme 50

Formation of benzopyranone via S_N2 reaction catalyzed by NHC

Scheme 51

NHC catalyzed substitution reaction

Scheme 52

Reaction scope of the aza-Morita-Baylis-Hillman catalyzed by NHCs

Scheme 53

NHC promoted O→C acyl transfer