Catalytic Asymmetric Aminoallylation of Aldehydes

Significance

Here, Ren and Wulff developed a Brønsted acid catalyzed direct asymmetric aminoallylation of both aromatic and aliphatic aldehydes. The catalytic system consists of VANOL-based catalyst I and benzoic acid, the latter being essential to obtain good enantioselection. Under optimized conditions enantioselectivities of 90:10 or above are obtained in all reported cases except α-quaternary pivaldehyde (er = 86:14). The reaction proceeds by condensation of the aldehyde substrate 1 with amine 2 and subsequent aza-Cope rearrangement of the intermediate aldimine to its more stable ketimine isomer 3. Ketimine 3 can be isolated or directly hydrolyzed to yield the aminoallylation product 4 as its hydrochloride. The benzophenone side product as well as the VANOL ligand can be efficiently recycled.