title: Highly selective asymmetric hydrogenation using a three hindered quadrant bisphosphine rhodium catalyst.
abstract: A concise synthesis of both enantiomers of ligand 2 and rhodium complex 5 is presented. The crux of the synthesis is a chiral HPLC separation of the enantiomers of 4. Rhodium complex 5 possesses three hindered quadrants in the steric environment within which a substrate binds. Evidence is presented that this configuration leads to high enantioselectivity (>99% ee) for rhodium-catalyzed asymmetric hydrogenation of alpha-acetamido dehydroamino acids, 6a-e. High enantioselectivities are also reported for the hydrogenation of a substrate precursor, 8, of pharmaceutical candidate, pregabalin. Advantages for large-scale hydrogenation of 8 using catalyst 5a vs Rh-Me-DuPhos are discussed.
authors.affiliation: Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, Michigan 48105, USA. garrett.hoge@pfizer.com
authors.forename: Garrett
authors.initials: G
authors.lastname: Hoge
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Wu
authors.forename: William S
authors.initials: WS
authors.lastname: Kissel
authors.forename: Derek A
authors.initials: DA
authors.lastname: Pflum
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Greene
authors.forename: Jian
authors.initials: J
authors.lastname: Bao