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

✍ Scribed by Gabriela A. Grasa; Antonio Zanotti-Gerosa; Shyamali Ghosh; Christopher A. Teleha; William A. Kinney; Bruce E. Maryanoff

• Publisher: Elsevier Science
• Year: 2008
• Tongue: French
• Weight: 189 KB
• Volume: 49
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/j.tetlet.2008.06.068

✦ Synopsis

Enantioselective preparation of a key a v b 3 integrin antagonist intermediate was accomplished via catalytic asymmetric hydrogenation of the corresponding b,b-disubstituted a,b-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 3 CO 2 H, and reaction parameter modification, revealed that [Ru(COD)(CF 3 CO 2 ) 2 ] 2 /(R)-XylPhanePhos is a highly active and efficient catalytic system.