Advances in Palladium-Catalyzed Benzylation, Propargylation, and 1,3-Dienylation of Enolates

Abstract

Presented herein is the development and application of several methods for the palladium-catalyzed decarboxylative benzylation, propargylation, and 1,3-dienylation of various enolate nucleophiles. In chapter 1 and 2, a brief review of many previously reported methods for benzylation and propargylation is presented, with an emphasis on decarboxylative coupling strategies. These chapters review these previously developed methodologies, as well as discuss any shortfalls inherent. In contrast, chapters 3 and 4 focuses on the presentation of the reaction methods developed in the Tunge group over the last several years. In chapter 3, we present a palladium-catalyzed decarboxylative coupling of enol carbonates with diarylmethyl electrophiles that are derived from secondary benzylic alcohols, allowing for the generation of a variety of β-diaryl ketones with high yields and enantioselectivities. Further, extensive experimentation is described that allowed us to propose a mechanistic pathway that involves a rare intramolecular decarboxylative coupling. In chapter 4, we present a palladium-catalyzed decarboxylative propargylation and 1,3-dienylation of both 1,3-dicarbonyl compounds and benzoyl acetonitrile derivatives. The dienylated 1,3-dicarbonyl products were further utilized in Diels-Alder coupling reactions, which allows us to illustrate the usefulness of these coupling reactions. Further, timed reactions and deuterium labeling studies allowed us to probe the mechanism of these reactions.