| Described herein are two complementary rhodium--catalyzed methods for the synthesis of substituted pyridines from unsaturated oxime derivatives and alkenes. In the first, formal [4+2] cycloaddition of O--pivaloyl alpha,beta--unsaturated oxime esters and activated terminal alkenes was discovered to proceed in high yields and with excellent selectivity for 6--substituted pyridine products. Mechanistic experiments were found to be consistent with a reversible C--H activation step and a C--N bond forming, N--O bond cleaving process en route to pyridine formation. Rhodium-catalyzed coupling using unactivated alkene substrates was shown to present important information regarding the influence of the alkene component on product distribution. In a second method, access to 5--substituted pyridine derivatives was achieved by decarboxylative annulation of alpha,beta--unsaturated oxime esters and beta--substituted acrylic acid derivatives. In this case, carboxylic acids were found to serve as traceless activating groups for selective alkene incorporation. A wealth of mechanistic insight was gained by identification of and decomposition studies regarding catalytically relevant rhodium complexes. |
