Reactions aza-benzoin

The aza-benzoin reaction is the addition of aldehydes to imines to give a-amino ketones. The difference in reactivity between an aldehyde and an imine can be tuned because of the trivalency of nitrogen. In 2005, Miller and coworkers reported the asymmetric crosscoupling reactions of aldehydes 18 with imines generated in situ from atylsulfonylamides 19. In the presence of 15 mol% of peptide-derived NHC A2, the reaction afforded the 

In 2013, the Ye group found the bifunctional NHC catalyst C2 containing a hydrmg l group to be an efficient precatalyst for the enantioselective 

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Cross-aza-benzoin reactions of aldehydes with imines have also been developed to afford a-amido ketones. The difference in reactivity between aldehydes and imines is inherently greater but also tunable because of the trivalency of nitrogen. Furthermore, a-amido ketones represent an important class of medicinal agents and are an important synthon for the ubiquitous 1,2-amino alcohol motif. 

Recently, the Chi group disclosed an NHC-promoted asymmetric inter-molecular cross-aza-benzoin reaction of enals with isatin-derived ketimines to afford chiral quaternary 3-aminooxindoles (18 examples, with up to 76% yield, 96% ee). The chemoselectivity is controlled by the NHC catalysts, with electron-deficient and sterically non-congested carbene catalysts favoring the enal acyl anion reaction pathway and aza-benzoin, allowing convenient access to products of different scaffolds by starting from the same set of readily available substrates (Scheme 7.16). 

Scheme 7.13 Catal)4ic asymmetric cross-aza-benzoin reactions of aliphatic aldehydes with N-Boc-protected imines reported by Rovis.

Scheme 7.15 NHC-catalyzed aza-benzoin reaction of enals with activated ketimines reported by Ye.

In 2012, a highly enantioselective cross-aza-benzoin reaction of aliphatic aldehydes and imines was developed by Rovis et A variety of aliphatic aldehydes that contained a diverse range of functionality proved suitable for the reaction, resulting in formation of the desired products 23 in high yield and excellent enantioselectivily, but a-branched aldehydes did not participate in the reaction (Scheme 20.12). 

Recently, Chi and coworkers disclosed the enantioselective cross-aza benzoin reaction of enals with isatin-derived ketimines, affording the 3-aminooxindoles 29 bearing a quaternary stereogenic centre with high enantioselectivities. The electron-deficient and sterically noncongested car-bene catalyst H2 was shown to favour the pathway of enal acyl anion leading to an aza-benzoin reaction (Scheme 20.14). 

An enantioselective aza-benzoin reaction of enals with activated ketimines employs an NHC catalyst incorporation of appropriate steric hindrance in the catalyst blocks competing reaction through the homo-enolate route. ... 

Bis(amino)cyclopropenylidene (743) has been found to catalyse the aza-benzoin reaction between aromatic imines (740) and aromatic aldehydes (741). The reaction provided excellent chemoselectivity favoring aza-benzoin products (742) (Scheme 207). ... 

Scheme 18.7 Aza-benzoin reactions to access a-amino ketones.

During the preparation of this chapter, enantioselecdve triazolium-calalyzed aza-benzoin reactions were reported ... 

NHCs have been used to promote reactions of enals with A -substimted isatini-mines ° ° and oxindole-derived a, -unsaturated imines to form spirocyclic y-lactam oxindoles. Asymmetric cross-aza-benzoin reactions of aliphatic aldehydes with A-Boc-protected aryl imines to form RCOCH(Ar)NHBoc have also been NHC catalysed. ... 

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