Re-orienting coupling of organocuprates with propargyl electrophiles from SN2′ to SN2 with stereocontrol

Diorganocuprate(I) reagents derived from lithiated heterocycles and CuCN react with enantioenriched secondary propargyl bromides to give the corresponding propargylated heterocycles. While propargyl electrophiles typically undergo S(N)2' displacement, this transformation represents the first example of the reaction of hard carbanions with propargyl electrophiles in an S(N)2 fashion and occurs with excellent levels of stereoinversion. The new method was applied to the formal synthesis of (+)-frondosin B.