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 ≤95% ee upon recrystallization. Subsequently, bromohydrin 6 was used to prepare Ro 25-8210.
Hull, K. G., Visnick, M., Tautz, W., & Sheffron, A. (1997). Synthesis of Ro 25-8210 via an enantioselective oxazaborolidine-catalyzed reduction. Tetrahedron, 53(37), 12405–12414. https://doi.org/10.1016/S0040-4020(97)00802-8