The Development of Palladium-Catalyzed Regio- and Enantioselective Hydrofunctionalizations of Conjugated Dienes and Enynes

Abstract

The construction of complex structural motifs from simple precursors is a compelling goal in organic synthesis. Within this context, enantioselective hydrofunctionalization of carbon–carbon multiple bonds is an attractive strategy due to the broad accessibility and/or simple preparation of starting materials and because of the inherent atom economy of this process. The hydrofunctionalization of conjugated multiple bonds provides additional opportunities and challenges. Conjugated dienes and enynes can be more reactive in transition metal catalysis than isolated olefins or alkynes; however, such hydrofunctionalization processes frequently give rise to multiple stereo- and regioisomers. Achieving both site and facial selectivity for nucleophile additions to these requires careful catalyst design. This research describes the development of palladium catalysts bearing electron-deficient phosphinooxazoline (PHOX) ligands for highly efficient regio- and enantioselective addition of amine and carbon-based nucleophiles to conjugated dienes and enynes. These reactions proceed under exceptionally mild conditions to afford a variety of high-value enantioenriched products. Throughout these studies, questions regarding the mechanisms of these transformations have been answered using an experimental approach.