Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

Abstract

N-Heterocyclic carbenes (NHCs) have emerged as a powerful class of organocatalysts that mediate a variety of organic transformations. The Benzoin reaction constitutes one of the earliest known carbon-carbon bond-forming reactions catalysed by NHCs. The rapid growth of NHC catalysis in general has resulted in the development of a variety of benzoin and benzoin-type reactions. An overview of such NHC-catalysed benzoin reactions is presented.

Keywords: N-heterocyclic carbenes; acyloin reaction; benzoin reaction; organocatalysis; umpolung.

Scheme 1

Breslow’s proposal on the mechanism of the benzoin condensation.

Scheme 2

Imidazolium carbene-catalysed homo-benzoin condensation.

Scheme 3

Homo-benzoin condensation in aqueous medium.

Scheme 4

Homobenzoin condensation catalysed by bis(benzimidazolium) salt 8.

Scheme 5

List of assorted chiral NHC-catalysts used for asymmetric homobenzoin condensation.

Scheme 6

A rigid bicyclic triazole precatalyst 15 in an efficient enantioselective benzoin reaction.

Scheme 7

Inoue’s report of cross-benzoin reactions.

Scheme 8

Cross-benzoin reactions catalysed by thiazolium salt 17.

Scheme 9

Catalyst-controlled divergence in cross-benzoin reactions.

Scheme 10

Chemoselective cross-benzoin reactions catalysed by a bulky NHC.

Scheme 11

Selective intermolecular cross-benzoin condensation reactions of aromatic and aliphatic aldehydes.

Scheme 12

Chemoselective cross-benzoin reaction of aliphatic and aromatic aldehydes.

Scheme 13

Cross-benzoin reactions of trifluoromethyl ketones developed by Enders.

Scheme 14

Cross-benzoin reactions of aldehydes and α-ketoesters.

Scheme 15

Enantioselective cross-benzoin reactions of aliphatic aldehydes and α-ketoesters.

Scheme 16

Dynamic kinetic resolution of β-halo-α-ketoesters via cross-benzoin reaction.

Scheme 17

Enantioselective benzoin reaction of aldehydes and alkynones.

Scheme 18

Aza-benzoin reaction of aldehydes and acylimines.

Scheme 19

NHC-catalysed diastereoselective synthesis of cis-2-amino 3-hydroxyindanones.

Scheme 20

Cross-aza-benzoin reactions of aldehydes with aromatic imines.

Scheme 21

Enantioselective cross aza-benzoin reaction of aliphatic aldehydes with N-Boc-imines.

Scheme 22

Chemoselective cross aza-benzoin reaction of aldehydes with N-PMP-imino esters.

Scheme 23

NHC-catalysed coupling reaction of acylsilanes with imines.

Scheme 24

Thiazolium salt-mediated enantioselective cross-aza-benzoin reaction.

Scheme 25

Aza-benzoin reaction of enals with activated ketimines.

Scheme 26

Isatin derived ketimines as electrophiles in cross aza-benzoin reaction with enals.

Scheme 27

Aza-benzoin reaction of aldehydes and phosphinoylimines catalysed by the BAC-carbene.

Scheme 28

Nitrosoarenes as the electrophilic component in benzoin-initiated cascade reaction.

Scheme 29

One-pot synthesis of hydroxamic esters via aza-benzoin reaction.

Scheme 30

Cookson and Lane’s report of intramolecular benzoin condensation.

Scheme 31

Intramolecular cross-benzoin condensation between aldehyde and ketone moieties.

Scheme 32

Intramolecular crossed aldehyde-ketone benzoin reactions.

Scheme 33

Enantioselective intramolecular crossed aldehyde-ketone benzoin reaction.

Scheme 34

Chromanone synthesis via enantioselective intramolecular cross-benzoin reaction.

Scheme 35

Intramolecular cross-benzoin reaction of chalcones.

Scheme 36

Synthesis of bicyclic tertiary alcohols by intramolecular benzoin reaction.

Scheme 37

A multicatalytic Michael–benzoin cascade process for cyclopentanone synthesis.

Scheme 38

Enamine-NHC dual-catalytic, Michael–benzoin cascade reaction.

Scheme 39

Iminium-cross-benzoin cascade reaction of enals and β-oxo sulfones.

Scheme 40

Intramolecular benzoin condensation of carbohydrate-derived dialdehydes.

Scheme 41

Enantioselective intramolecular benzoin reactions of N-tethered keto-aldehydes.

Scheme 42

Asymmetric cross-benzoin reactions promoted by camphor-derived catalysts.

Scheme 43

NHC-Brønsted base co-catalysis in a benzoin–Michael–Michael cascade.

Scheme 44

Divergent catalytic dimerization of 2-formylcinnamates.

Scheme 45

One-pot, multicatalytic asymmetric synthesis of tetrahydrocarbazole derivatives.

Scheme 46

NHC-chiral secondary amine co-catalysis for the synthesis of complex spirocyclic scaffolds.