Re-Orienting Coupling of Organocuprates with Propargyl Electrophiles from S2' to S2 with Stereocontrol.

Diorganocuprate(I) reagents derived from lithiated heterocycles and CuCN react with enantioenriched secondary propagryl bromides to give the corresponding propargylated heterocycles. While propargyl electrophiles typically undergo S2' displacement, this transformation represents the first example of the reaction of hard carbanions with propargyl eletrophiles in an S2 fashion and occurs with excellent levels of stereoinversion. The new method was applied to the formal synthesis of (+)-frondosin B.