Efficient, enantioselective synthesis of a β,β-disubstituted carboxylic acid by Ru-XylPhanePhos-catalyzed asymmetric hydrogenation

• Published in: Tetrahedron letters Vol. 49; no. 36; pp. 5328 - 5331
• Main Authors: Grasa, Gabriela A., Zanotti-Gerosa, Antonio, Ghosh, Shyamali, Teleha, Christopher A., Kinney, William A., Maryanoff, Bruce E.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.09.2008
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2008.06.068

Enantioselective preparation of a key α vβ 3 integrin antagonist intermediate was accomplished via catalytic asymmetric hydrogenation of the corresponding β,β-disubstituted α,β-unsaturated carboxylic acid bearing a 3-quinolinyl moiety. The successful application of a Ru-( R)-XylPhanePhos catalyst to this type of substrate is unprecedented. In situ NMR experiments of pre-catalyst formation/activation by CH 3CO 2H, and reaction parameter modification, revealed that [Ru(COD)(CF 3CO 2) 2] 2/( R)-XylPhanePhos is a highly active and efficient catalytic system.