Reactions utilizing palladium-catalyzed carbene insertion intermediates

This dissertation deals with the development of palladium-carbene reactions originating from diazo compounds. We have shown that trimethylsilyldiazomethane can serve as a carbene equivalent in carbenylative cyclization reactions leading to indenes. Two types of aryl halide substrates were examined: aryl halides with pendant olefins and aryl halides with pendant allenes. Both types of substrates generate benzylpalladium intermediates through carbene insertion and these benzylpalladium intermediates undergo intramolecular carbapalladation to produce indenes. The respective fates of these indenyl intermediates, however, are different. Substrates with pendant olefins regenerate the palladium(0) catalyst through beta-hydride elimination, whereas substrates with pendant allenes regenerate palladium(0) through attack of a nucleophile on an eta 3-allylpalladium intermediate. While we were able to generate indene products through carbenylative Heck cyclizations the product distributions were difficult to control. Protodesilylation reactions can be facile under the conditions of the reaction, demonstrating that trimethylsilyldiazomethane can serve as either a trimethylsilylmethylene equivalent or a methine equivalent.;In addition, we have developed a powerful new method for the synthesis of alpha,beta-unsaturated gamma-amino esters through a palladium-catalyzed three-component coupling reaction. We believe the key step in the catalytic cycle involves migratory insertion of a carbene unit into a vinyl-palladium bond to generate an eta3-allylpalladium intermediate. This unique transformation is important because it complements the multistep synthesis of alpha,beta-unsaturated gamma-amino acids and it can be used to synthesize variants with both natural and non-natural side chains.