UC Berkeley

The following dissertation discuss the development of iridium-catalyzed asymmetric allylic substitution reactions with unstabilized enolates and prochiral enolates. These reactions include the enantioselective allylic substitutions with silyl ketene acetals, diastereo- and enantioselective allylic substitutions with α-alkoxy ketones, and stereodivergent allylic substitutions with aryl acetic acid esters, azaaryl acetamides and azaaryl acetates.

Chapter 1 provides a brief overview of transition-metal-catalyzed asymmetric allylic substitutions with enolates. This overview focused on the mechanism of allylations of enolates catalyzed by palladium complexes and iridium complexes. Additionally, methodologies for asymmetric allylations of unstabilized enolates are discussed in detail. Furthermore, this overview highlights the challenges and the strategies for the control of diastereoselectivity for the allylic substitutions with prochiral enolates.

Chapter 2 describes the development of iridium-catalyzed enantioselective allylic substitution reactions with silyl ketene acetals, the silicon enolates of esters, under relatively neutral conditions. The ester products contain a quaternary carbon atom at the nucleophile moiety and a chiral tertiary carbon atom at the electrophile moiety.

Chapter 3 describes the study on diastereoselective and enantioselective allylic substitution reactions with acyclic α-alkoxy ketones. A metallacyclic iridium complex catalyzes the allylation of unstabilized copper(I) enolates generated in situ from acyclic α-alkoxy ketones to form products with contiguous stereogenic centers.

Chapter 4 describes the development of stereodivergent allylic substitutions with aryl acetic acid esters catalyzed synergistically by a metallacyclic iridium complex and a Lewis base co-catalyst. Through permutations of the enantiomers of the two chiral catalysts, all four stereoisomers of the products bearing two adjacent stereocenters are accessible with high diastereoselectivity and enantioselectivity. A stereochemical model is provided to understand the origin of high stereoselec-tivity.

Chapter 5 describes a combination of catalysts that enable stereodivergent allylic substitution reactions with azaaryl acetamides and acetates. This combination of catalysts comprises a chiral metallacyclic iridium complex and a chiral bisphosphine-ligated copper(I) complex, which individually control the configuration of the electrophilic and nucleophilic carbon atoms, respectively.

Chapter 6 extends from the work discussed in Chapter 5 and demonstrates iridium and copper complexes synergistically catalyze stereodivergent allylations to construct vicinal fully substituted and tertiary stereogenic centers in acyclic structures. In particular, fluorine-containing fully substituted stereocenters are readily constructed from fluorinated acetates.