Rationalizing the Role of NaOtBu in Copper-Catalyzed Carboboration of Alkynes: Assembly of Allylic All-Carbon Quaternary Stereocenters

A preliminary mechanistic approach to the Cu-catalyzed carboboration of alkynes using B2(pin)2 was used as a blueprint for the rational design and development of a regiocontrolled, stereoselective carboboration of internal alkynes by reaction with a β,β-disubstituted acrylate fragment to provide synthetically versatile and densely functionalized pyrrolidines. Experimental observations and computational analysis relevant to understanding the activation role of the alkoxide functionality in this type of carboboration process were instrumental in developing a synthetic method broad in scope and functional group tolerance. Compounds obtained by this strategy feature a stereochemically defined tetrasubstituted vinyl boronate, together with an all-carbon quaternary stereocenter. This procedure involves a tandem regioselective, chemoselective, and diastereoselective borylcupration of unsymmetrical dialkyl alkynes, followed by migratory insertion of an activated olefin to a C–Cu bond.