Reaction Mechanisms for Chiral-Phosphate-Catalyzed Transformations Involving Cationic Intermediates and Protic Nucleophiles

Abstract

Recent strategies for enantioinduction often focus on employing a chiral catalyst to noncovalently interact with the substrate. By restricting the number of low energy diastereomeric transition states the reacting components can adopt, stereoselectivity can be achieved. Many of these noncovalent interactions include a significant dispersive component and these types of contacts have historically been difficult to model accurately. Modern computational methods have been designed to overcome such limitations. Using our computational work in chiral phosphate catalysis, we discuss the reasons for enantioselectivity in diverse reaction space.

The Hydrated Structure Factor in Additive Effect on Enantioselective Organocatalytic Transfer Hydrogenation Reactions with Hantzsch Esters

“…And a weak hydrogen (from the adjacent carbon of the achiral amine moiety)-oxygen (from TRIP anion) bonding was initially proposed to play a key role in the stabilization of the imine cation-acid anion complex in the organic solution (21, Scheme 5). 10 A very recent work by the Reid group 23 and the Goodman group 24 on reaction mechanisms for chiral phosphoric acid-catalyzed transformations involved cationic intermediates and protic nucleophiles proposed a dual activation pathway; an imine cationic carbon hydrogen-oxygen (from TRIP anion) bonding and a hydrogen (protic nucleophile)-oxygen (from another oxygen of TRIP anion) bonding were found to be the most probable non-covalent interactions governing the stereochemistry and reactivity via a computational method (22, Scheme 5). Still the generated water molecule via an imine condensation was not included in the proposed non-covalent interactions.…”