61st Annual Report on Research 2016

We have made significant progress in the proposed projects and published five research papers in internationally renowned journals including two in Journal of the American Chemical Society and three in Organic Letters. In the catalytic carbonylation of olefin project, we have developed a novel tandem palladium-catalyzed Heck carbonylative macrolactonization to synthesize fused-macrolides. In the carbonylation of cyclopropanol project, we have developed an unprecedented palladium-catalyzed cascade carbonylative spirolactonization of hydroxycyclopropanols to efficiently synthesize oxaspirolactones common to many complex natural products of important therapeutic value. Collaboration with the Waymouth and Zare groups at Stanford University enabled mechanistic studies utilizing high-resolution electrospray ionization mass spectrometry (ESI-MS) to identify several key intermediates in the catalytic cycle, as well as those intermediates related to catalyst decomposition and competitive pathways. The mechanistic results provide important insights for guiding new reaction development. While conducting the research of the carbonylation reaction of cyclopropanols, we have discovered a series of copper-catalyzed cyclopropanol ring opening cross coupling reactions to introduce a variety of substituents such as trifluoromethyl, trifluoromethylthiol, amino, and (fluoro)alkyl at the beta-positions of carbonyls. These methods provide new avenues to access medicinally important molecules, which are often difficult to access with other synthetic methods.