Enantioselective, Organocatalytic, Dissymmetric 1,4- and 1,2-Addition of Malononitrile to a Keto-bisenone Followed by an Oxa-Michael Addition Cascade

Abstract

An unprecedented enantioselective dissymmetric 1,4- and 1,2-addition of malononitrile to a keto-bisenone followed by an oxa-Michael addition cascade to trap the in situ generated unstable tertiary alcohol have been developed. The quinine-derived amino-squaramide bifunctional organocatalyst worked efficiently and provides the oxa-spiro-[4,4]-nonanes in good yields and excellent diastereo- and enantioselectivities (up to 99:1 dr and 99% ee). Notably, a complete chemoselective addition of a methylene unit to an aliphatic-tethered enone over the aromatic-tethered enone was observed.