Direct asymmetric vinylogous Michael addition of cyclic enones to nitroalkenes via dienamine catalysis.

ABSTRACT: In spite of the many catalytic methodologies available for the asymmetric functionalization of carbonyl compounds at their ? and ? positions, little progress has been achieved in the enantioselective carbon-carbon bond formation ? to a carbonyl group. Here, we show that primary amine catalysis provides an efficient way to address this synthetic issue, promoting vinylogous nucleophilicity upon selective activation of unmodified cyclic ?,?-unsaturated ketones. Specifically, we document the development of the unprecedented direct and vinylogous Michael addition of ?-substituted cyclohexenone derivatives to nitroalkenes proceeding under dienamine catalysis. Besides enforcing high levels of diastereo- and enantioselectivity, chiral primary amine catalysts derived from natural cinchona alkaloids ensure complete ?-site selectivity: The resulting, highly functionalized vinylogous Michael adducts, having two stereocenters at the ? and ? positions, are synthesized with very high fidelity. Finally, we describe the extension of the dienamine catalysis-induced vinylogous nucleophilicity to the asymmetric ?-amination of cyclohexene carbaldehyde.

SUBMITTER: Bencivenni G 

PROVIDER: S-EPMC2996419 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature