title: Reaction Optimization, Scalability, and Mechanistic Insight on the Catalytic Enantioselective Desymmetrization of 1,1-Diborylalkanes via Suzuki-Miyaura Cross-Coupling.
abstract: A method for enantioselective desymmetrization of 1,1-diborylalkanes through a stereoselective Pd-catalyzed Suzuki-Miyaura cross-coupling has been thoroughly optimized. The most effective ligand was found to be a α,α,α,α-tetra-aryl-1,3-dioxolane-4,5-dimethanol (TADDOL)-derived phosphoramidite. Results show that in order to achieve high selectivity, a suitable balance between the sterics of the aryl groups and the amino group on the ligand must be achieved. While the base has been known to facilitate transmetallation in cross-coupling reactions, mechanistic studies on this desymmetrization process reveal that the base, in the presence of KHF2, likely plays an additional role in the hydrolysis of the pinacol boronates to the corresponding boronic acids. Through an in depth optimization of the chiral ligand and mechanistic studies, it was possible to obtain ee values over 90% for several aryl bromides and to develop a reliably scalable process (up to one gram of 1,1-diborylalkane substrate).
authors.affiliation: Department of Chemistry, University of Alberta, 11227 Saskatchewan Drive, Edmonton AB, T6G 2G2 (Canada).
authors.forename: Ho-Yan
authors.initials: HY
authors.lastname: Sun
authors.affiliation: Faculty of Engineering, Hokkaido University, Kita 13 Nishi 8, Sapporo 060-8628 (Japan).
authors.forename: Koji
authors.initials: K
authors.lastname: Kubota
authors.affiliation: Department of Chemistry, University of Alberta, 11227 Saskatchewan Drive, Edmonton AB, T6G 2G2 (Canada). dennis.hall@ualberta.ca.
authors.forename: Dennis G
authors.initials: DG
authors.lastname: Hall
keywords: catalysis; cross-coupling; organoboron; palladium; stereoselectivity