Mechanistic Investigations into the Palladium-Catalyzed Decarboxylative Allylic Alkylation of Ketone Enolates Using the PHOX Ligand Architecture

Citation

Sherden, Nathaniel Haynes (2011) Mechanistic Investigations into the Palladium-Catalyzed Decarboxylative Allylic Alkylation of Ketone Enolates Using the PHOX Ligand Architecture. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/QEAX-9N40. https://resolver.caltech.edu/CaltechTHESIS:05312011-072858726

Abstract

Palladium-catalyzed asymmetric allylic alkylation has become a large and important field for chemical synthesis. Many methodologies in this field offer mild conditions under which challenging and important molecular features can be reliably synthesized, including chiral all-carbon quaternary stereocenters. As a result, palladium- catalyzed asymmetric allylic alkylation has found significant use in total synthesis, and growing use in industry. While the general process of palladium-catalyzed asymmetric allylic alkylation has been studied for decades, there have been a number of recent modifications and developments, such as asymmetric versions of decarboxylative allylic alkylation procedures that are not yet well understood. The development of future implementations and improvements to palladium-catalyzed asymmetric allylic alkylation and related methodologies is expected to be facilitated by a better understanding of these more recent developments, and thus further mechanistic investigation is warranted.

Reported herein is a set of investigations into the palladium-catalyzed decarboxylative asymmetric allylic alkylation of ketone enolates using the PHOX ligand architecture. By monitoring the reaction via 31P NMR, a series of previously unidentified key intermediates is discovered. Two representatives of these key intermediates are isolated and characterized. The solution behavior of these species under reaction-like conditions is studied along with a few novel and related complexes. The role of these intermediates and their impact on the behavior of the reaction and product formation is discussed. Previously confounding experimentally observed behavior for this methodology is rationalized via the properties elucidated for these discovered intermediates.

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