Controlling the α/γ-Reactivity of Vinylogous Ketone Enolates in Organocatalytic Enantioselective Michael Reactions

Abstract

The first regio-, diastereo-, and enantioselective direct Michael reaction of β,γ-unsaturated ketones with nitroolefins is enabled by Brønsted base/hydrogen-bonding bifunctional catalysis. A squaramide-substituted tertiary amine catalyzes the reaction of a broad range of β,γ-unsaturated ketones to proceed at the α-site exclusively, giving rise to adducts with two consecutive tertiary carbon stereocenters in diastereomeric ratios of up to >20:1 and enantioselectivities generally in the 90-98 % ee range.

Keywords: Brønsted bases; conjugate additions; ketones; organocatalysis; regioselectivity.