Enantioselective Rhodium-Catalyzed Allylic Alkylation of β,γ-Unsaturated α-Amino Nitriles: Synthetic Homoenolate Equivalents

Abstract

An enantioselective rhodium-catalyzed allylic alkylation of β,γ-unsaturated α-amino nitriles is described. This protocol provides a novel approach for the construction of β-stereogenic carbonyl derivatives via the catalytic asymmetric alkylation of a homoenolate equivalent. The particularly challenging nature of this transformation is highlighted by the fact that three modes of selectivity must be manipulated, namely regio- and enantioselectivity, in addition to geometrical control. The γ-stereogenic cyanoenamine products can be readily hydrolyzed in situ to afford the β-substituted carboxylic acids, which in turn provide expedient access to a number of related carbonyl derivatives. In addition, control experiments indicate that the chiral rhodium-allyl intermediate facilitates the selective formation of the E-cyanoenamine products, which is critical since the Z-isomer affords significantly lower enantiocontrol. As a consequence, garnering excellent E-selectivity in the alkylation step is vital for the development of a practical process.