Sulfone–Metal Exchange and Alkylation of Sulfonylnitriles

The first general sulfonyl metal-exchange is described. Treating substituted 2-pyridylsulfonylacetonitriles with BuLi or Bu3MgLi generates metalated nitriles that alkylate a variety of electrophiles to efficiently install quaternary centers. The 2-pyridylsulfone is critical for the sulfone-metal exchange, anchoring the organometallic proximal to the electrophilic, tetrasubstituted sulfone to override complex-induced deprotonation. Alkylating commercial 2-pyridinesulfonylacetonitrile with mild bases, K2CO3 or DBU, followed by alkylation-sulfonyl-metal exchange rapidly assembles quaternary nitriles through three alkylations, only one of which requires an organometallic.