Stereospecific Nucleophilic Substitution with Arylboronic Acids as Nucleophiles in the Presence of a CONH Group

Abstract

Stereospecific nucleophilic substitution was achieved for the first time with arylboronic acids as nucleophiles. This transition-metal-free coupling between chiral α-aryl-α-mesylated acetamides and arylboronic acids provided access to a series of chiral α,α-diaryl acetamides with excellent enantioselectivity and moderate to good yields. The CONH functionality proved to be crucial for bridging the reactants and promoting the reaction. Efficient syntheses of a cannabinoid CB₁ receptor ligand, the antidepressant (S)-diclofensine, and a key chiral building block of the inhibitor implitapide were successfully accomplished by using this method.