Strategy for Employing Unstabilized Nucleophiles in Palladium-Catalyzed Asymmetric Allylic Alkylations

We report a strategy for the employment of highly unstabilized anions in palladium-catalyzed asymmetric allylic alkylations (AAA). The hard 2-methylpyridyl nucleophiles studied are first reacted in situ with BF(3)center dot OEt(2)., subsequent deprotonation of the resulting complexes with LiHMDS affords soft anions that are competent nucleophiles in AAA reactions. The reaction is selective for the 2-position of methylpyridines and tolerates bulky aryl and alkyl substitution at the 3-, 4-, and 5-positions. Investigations into the reaction mechanism demonstrate that the configuration of the allylic stereocenter is retained, consistent with the canonical outer sphere mechanism invoked for palladium-catalyzed allylic substitution processes of stabilized anions.