Development of transitional metal-catalyzed reactions for organic synthesis

Abstract

Chapter 1. A general catalyst system for the synthesis of tetra-ortho-substituted biaryls via the Suzuki-Miyaura cross-coupling reaction is described. It was found that the most efficient catalyst system is based on a phenanthrene-substituted biaryl phosphine ligand. Utilizing this ligand, a number of tetra-ortho-substituted biaryls were synthesized in good to excellent yields. Chapter 2. A procedure for the arylation of methyl and cyclic ketone enolates with o-halonitroarenes was developed. An unusual additive effect of phenols on the outcome of the reaction was observed and explored. This process has provided for the regioselective synthesis of a wide variety of substituted indoles from commercially available materials. Chapter 3. The first method for the asymmetric copper-catalyzed conjugate reduction of [alpha] ,[beta] unsaturated esters containing [beta]-heteroatoms was developed. We found that this system tolerated the presence of both lactams as well as azaheterocycles in the [beta]-position of various enoates. This has led to the asymmetric synthesis of a number of interesting [5- amino acid derivatives. Chapter 4. A copper-catalyzed conjugate reduction reaction that allows for a variety of [gamma]-aryl containing [alpha], [beta]-unsaturated butenolides to be reduced in both high enantiomeric and diastereomeric excess was developed. While a number of catalysts based on chiral bisphosphines were found to successfully perform this transformation, optimal enantioselectivity was obtained when employing the commercially SYNPHOS ligand.