Toward Direct Design of Transfer Hydrogenation Catalysts

California State University Northridge, Northridge CA

Investigators

Linked publications & trials

Abstract

In general terms, the purpose of this project is to expand a new class of catalysts for pharmaceutical synthesis that are[unreadable] more safe and economical than traditional catalysts and also have potential for direct customization to specific[unreadable] reactions. These compounds could benefit drug development by reducing development time and production cost.[unreadable] Enantioselective transfer hydrogenation of ketones to chiral alcohols is an important process in the production of[unreadable] Pharmaceuticals. Homogeneous catalysts have been developed to support these reactions using alcohol solvents as[unreadable] safe and convenient hydrogen sources, but these existing systems rely on hydride and proton-transfer to and from[unreadable] weakly associated substrates that necessitates base co-catalysts to maintain sufficiently strong proton acceptors and[unreadable] requires cooperative intermolecular interactions for good selectivity. Basic co-catalysts limit these systems to base[unreadable] tolerant substrates, and the subtleties of the intermolecular forces behind alcohol association often requires significant[unreadable] development time to optimize catalyst design for good selectivity. The long-term goal of the proposed program is to[unreadable] advance a new and novel catalyst family that utilizes an alternative inner-sphere hydride and proton transfer that[unreadable] resolves both issues through alcohol coordination to a highly labilized metal binding site. These ruthenium complexes[unreadable] are bifunctional each with a hydride acceptor site and a pendent proton acceptor that flank the substrate binding site.[unreadable] The binding itself is also highly labilized for rapid reactant/product exchange by cooperative trans and cis-effects from[unreadable] the surrounding ligand set. The direct coordination of alcohols boosts their acidity so modest pendent bases can be[unreadable] employed without base co-catalysts. Direct coordination also better defines the steric interactions between bound[unreadable] substrate and surrounding ligands allowing more deliberate design control over selectivity (and enantioselectivity). The[unreadable] proposed research will begin from a set of three existing 2,2':6',2"-terpyridine supported complexes and will specifically:[unreadable] A. Determine the impact of the geometry and strength of incorporated pendent bases on catalyst selectivity and[unreadable] co-catalyst dependence.[unreadable] B. Assess the influence of anionic and/or electron donating substituents of customized 2,2':6',2"-terpyridine ligands on[unreadable] the rate of catalytic hydrogen transfer.[unreadable] C. Explore analogous catalyst designs with other tight-bite-angle tridentate ligands in place of terpyridines that are[unreadable] more amenable to design variations.[unreadable] D. Incorporate chiral versions of tridentate ligands into catalysts and correlate the coordination enforced ligandsubstrate[unreadable] interactions to the resulting enantioselectivity.[unreadable] The proposed program will advance this promising catalyst family toward pharmaceutical relevance and provide a[unreadable] quality and relevant research environment for the participation of underrepresented students in the MARC ITSTAR and[unreadable] chemistry and biochemistry major programs.