Synthesis of Ro 25-8210 via an enantioselective oxazaborolidine-catalyzed reduction

✍ Scribed by Kenneth G. Hull; Mike Visnick; William Tautz; Allen Sheffron

• Book ID: 104208024
• Publisher: Elsevier Science
• Year: 1997
• Tongue: French
• Weight: 552 KB
• Volume: 53
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(97)00802-8

✦ Synopsis

Prochiral ketones which contain nitrogen atoms have been reduced enantioselectively with chiral oxazaborolidines in the presence of excess borane. However, the pyridine system has been shown to be a poor substrate for this asymmetric reduction. For example, catalytic reduction of 2acetylpyridine with a chiral oxazaborolidine provided the product alcohol in only 28% ce. We wish to report the enantioselective reduction of 2-(bromoacetyl)-pyridine 1 with chiral oxazaborolidines. Good enantiomeric excess was obtained in the reductions (80% ce) and could be improved to ->95% ce upon recrystallization. Subsequently, bromohydrin 6 was used to prepare Ro 25-8210.