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

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 2-acetylpyridine with a chiral oxazaborolidine provided the product alcohol in only 28% ee. We wish to report the enantioselective reduction of 2-(bromoacetyl)-pyridine 1 with chiral oxazaborolidines. Good enantiomeric excess was obtained in the reductions (80% ee) and could be improved to greater than or equal to 95% ee upon recrystallization. Subsequently, bromohydrin 6 was used to prepare Ro 25-8210. (C) 1997 Elsevier Science Ltd.