Catalytic Cyclopropanol Ring Opening for Divergent Syntheses of gamma-Butyrolactones and delta-Ketoesters Containing All-Carbon Quaternary Centers

Catalytic ring opening cross coupling reactions of strained cyclopropanols have been useful for the syntheses of various beta-substituted carbonyl products. Among these ring opening cross coupling reactions, the formation of alpha,beta-unsaturated enone byproducts often competes with the desired cross coupling processes and has been a challenging synthetic problem to be addressed. Herein, we describe our efforts in developing divergent syntheses of a wide range of gamma-butyrolactones and delta-ketoesters containing all-carbon quaternary centers via copper-catalyzed cyclopropanol ring opening cross couplings with 2-bromo-2,2-diallcyl esters. Our mechanistic studies reveal that unlike the previously reported cases, the formation of alpha,beta-unsaturated enone intermediates is actually essential for the gamma-butyrolactone synthesis and also contributes to the formation of the delta-ketoester product. The gamma-butyrolactone synthesis is proposed to go through an intermolecular radical conjugate addition to the in situ generated alpha,beta-unsaturated enone followed by an intramolecular radical cyclization to the ester carbonyl double bond. The reactions are effective to build all-carbon quaternary centers and have broad substrate scope.