An Anion-Binding Approach to Enantioselective Catalytic Reactions of Cationic Transition-Metal and Cation Radical Intermediates

Abstract

In Chapter 1, we describe a new approach to inducing enantioselectivity in transition-metal-catalyzed reactions. This strategy relies on the association of chiral hydrogen-bond donors with anions of achiral metal complexes to achieve enantiocontrol and rate enhancement through ion-pairing and other noncovalent interactions. A chiral bis-thiourea hydrogen-bond donor is identified to impart enantioselectivity to ruthenium-catalyzed intramolecular propargylic substitution reactions, yielding chromane derivatives in up to 99% enantiomeric excess. Mechanistic investigations of the developed catalytic system show that the association between the bis-thiourea hydrogen-bond donor and diruthenium complexes relies on anion binding and does not involve any dative bonding interactions with the metal center. Spectroscopic, kinetic, and computational studies reveal attractive interactions between the electron-deficient arene components of the hydrogen-bond donor and the ligands of the metal complex, which contribute to enantioinduction and the observed acceleration effect. In Chapter 2, we describe the application of anion-binding catalysis with chiral hydrogen-bond donors as a new strategy to achieve enantiocontrol in photoredox reactions proceeding through cation radical intermediates. Cooperative catalysis between aryl-pyrrolidine tert-leucine hydrogen-bond donors and pyrylium salts enables cycloaddition reactions of electron-rich alkene substrates to provide enantioenriched 3–6-membered carbocyclic products. The synthetic utility of the developed (2+2) cycloaddition reaction is demonstrated through its application to the synthesis of the enantiomer of a glucocorticoid receptor binder, (+)-endiandrin A, in 99% enantiomeric excess.