Development of Enantioselective Transition-Metal Catalyzed Allylic Alkylation Methodologies

Abstract

Research in the Stoltz group is directed, generally, at the development of synthetic methods for the preparation of stereochemically rich molecules, and the total synthesis of complex natural products. One major theme of our group’s methods development is transition-metal catalyzed allylic alkylation, of which we have reported Pd, Ir, Cu, and Ni catalyzed strategies. Described in this thesis are projects related to these interests, primarily focused on new approaches toward acyclic stereocenters via palladium catalysis; however also include an iridium-catalyzed formal γ-alkylation of malonates and β-ketoesters, as well as an Overman rearrangement strategy for synthesizing α-amino ketones. A majority of asymmetric enolate functionalization methods, developed by our group and others, pertain to cyclic systems in which only one enolate geometry isomer is possible due to the constrained ring. In acyclic systems, however, this issue of enolate geometry becomes a major challenge that must be addressed. When one seeks to prepare a tetrasubstituted acyclic enolate, which would lead to a fully-substituted stereocenter following functionalization, one must contend with the issue of non-selective formation of a mixture of enolates which generally leads toward less selective transformations. Strategies toward overcoming this issue, as well as new insights gained regarding the palladium-catalyzed alkylation of acyclic enolates, are described in the subsequent chapters.