Synthetic studies of 2-acetoxyfuran and 2(3H)-furanone as pronucleophiles in the asymmetric synthesis of butenolides

Enantioselective synthesis of gamma-substituted butenolides is desirable due to the prevalence of these functionalities in medicinally important natural products. As organic synthons, butenolides contain four carbon atoms, each of which is capable of undergoing regioselective modification. Two complementary approaches for the construction of gamma-substituted butenolides have been developed in the present work. The trapped dienolate, 2-acetoxyfuran, couples with aldehydes under mild conditions with diastereocontrol determined by the nature of catalyst, solvent, and temperature employed. An even more efficient synthesis of the butenolide architecture has been developed by the direct coupling of 2(3H)-furanone to aldehydes. Enantioselectivity is afforded by use of Takemoto's bifunctional thiourea catalysts. The simplicity and versatility of these reactions demonstrate the strong potential that the pronucleophiles 2-acetoxyfuran and 2(3H)-furanone offer for the synthesis of gamma-butenolides.