Studies on the formation of C-N and C-O bonds using transition metal catalysts

Abstract

1. Stereoselective Synthesis of Z-Enamide using Wacker System An efficient procedure for the preparation of Z-enamides has been developed via coupling primary amides with conjugated olefins using Wacker system. In the process of optimization, additives such as phosphine oxides and phosphonates, proved to increase the efficiency of the reaction. The major product, of Z-enamides, can be synthesized in high yields with excellent stereoselectivity catalyzed by Pd/Cu biometallic system in nonpolar solvents under an oxygen atmosphere. The oxidative amidation reaction has a broad substrate scope, allowing alkyl, aryl, and vinyl amides to react with olefins conjugated with ester, amide, phosphonate, and ketone groups. The notable preference for the formation of Z-enamides is presumably due to the presence of an intramolecular hydrogen bond between the amido proton and the carbonyl oxygen. The energy difference between two plausible α-alkylamido-palladium intermediates, leading to Z- and E-isomeric enamide products, respectively, was calculated to be 4.18 kcal/mol. The β-hydride elimination step is assumed to be a stereochemistry-determining step in the overall oxidative amidation process, with the energy level for the transition state leading to the Z-enamide being 5.35 kcal/mol lower than that leading to the E-isomer. The efficiency of photoisomerization between Z- and E-enamides was observed to be largely dependent on the substrates’ substituents, and certain E-enamides could be obtained in synthetically useful yields by photoirradiation of Z-isomers. Synthetic application of the present method was successfully demonstrated by a direct formal synthesis of cis-CJ-15,801. 2. Benzylic and Allylic C-H Bonds Activation via Radical Pathway to Form C-O Bonds. We have developed a highly efficient protocol for the C-H bond functionalization of benzylic and allylic hydrocarbons to form C-O bond. A wide range of alkanes and alkenes was coupled with N-hydroxyphthalim...