Enantioselective Rhodium- Catalyzed Allylic Alkylation of b, gUnsaturated a- Amino Nitriles: Synthetic Homoenolate Equivalents

An enantioselective rhodium-catalyzed allylic alkylation of b, g-unsaturated a-amino nitriles is described. This protocol provides a novel approach for the construction of bstereogenic 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 g-stereogenic cyanoenamine products can be readily hydrolyzed in situ to afford the b-substituted carboxylic acids, which in turn provide expedient access to a number of related carbonyl derivatives. Additionally, 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.