Aza-cross-benzoin reaction

Benzoin, Cross-benzoin and Aza-cross-benzoin Reaction... 

Unactivated imines were also found be suitable acceptor for the aza-cross-benzoin reaction. In 2007, You and co-workers [36] demonstrated that aromatic aldehydes 28 react well with unactivated imines 29 to give the corresponding a-aminoketones 30 in good yields (Scheme 7.18). The reaction was demonstrated to be thermodynamically controlled. 

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 7.16 NHC-catalyzed chemoselective cross-aza-benzoin reaction of enals with isatin-derived ketimines reported by Chi.

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). 

In 2005, the asymmetric cross-coupling reactions of aldehydes 33 with arylsul-fonylamides 34 were reported by Miller and co-workers [37]. In the presence of 15 mol% of peptide-derived NHC 32, the corresponding aza-benzoin adduct 35 was obtained in good yields with good enantioselectivities (Scheme 7.19). 

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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