SYNTHESIS OF RO-25-8210 VIA AN ENANTIOSELECTIVE OXAZABOROLIDINE-CATALYZED REDUCTION

Prochiral ketones which contain nitrogen atoms have been reduced enant ioselectively with chiral oxazaborolidines in the presence of excess b orane. However, the pyridine system has been shown to be a poor substr ate for this asymmetric reduction. For example, catalytic reduction of 2-acetylpyridine with a chiral oxazaborolidine provided the product a lcohol in only 28% ee. We wish to report the enantioselective reductio n of 2-(bromoacetyl)-pyridine 1 with chiral oxazaborolidines. Good ena ntiomeric excess was obtained in the reductions (80% ee) and could be improved to greater than or equal to 95% ee upon recrystallization. Su bsequently, bromohydrin 6 was used to prepare Ro 25-8210. (C) 1997 Els evier Science Ltd.