Tetrahedron Letters,Vol.24,No.lO,pp 1015-1018,1983 0040-4039/83/101015-04$03.0@/0 Printed in Creat Britain 01983 Pergamon Press Ltd. REDUCTION OF KETONES BY SODIUM BOROHYDRIDE IN THE ABSENCE OF PROTIC SOLVENTS. INTER VERSUS INTRAMOLECULAR MECHANISM Margaret M. Kayser* and Sonia Eliev Departement de chimie, Universite de Moncton, Moncton, N.B., Canada Odile Eisenstein Department of Chemistry, University of Michigan, Ann Arbor, MI 48109 U.S.A. Abstract: Acetone, acetophenone and benzophenone react with sodium borohydride in the absence of protic solvent to give the corresponding tetraalkoxyborates. In view of these res-ults, the possibility of the 4-centre mechanism for these reductions is discussed. Sodium borohydride, because of its convenience as well as its efficiency is an attractive and widely used reducing agent. Nonetheless, the mechanism of boro- hydride reduction of carbonyl function remains the subject of much controversyl. Initially, the reaction was assumed to follow a stepwise hydride ion transfer to the carbonyl carbon atom, resulting in the formation of a tetraalkoxyborate 2 which was subsequently hydrolyzed during the workup procedure to yield alcohol 1 . _ 4 R,CO + BHGO --- tR2CH0)4B@ - H20 4 R,CHOH The mechanistic studies reported in the following years probed the origin of stereoselectivity3, early versus late transition statc4, solvent anc cation in- fluences' and the kinetics of these reactions 6 . The large number of facts and hypotheses amassed over the years served only to cloud the issue and no consensus as to the mechanism of these reactions has been reached. Recently Wigfield demonstrated that during carbonyl reductions in alcohol solvents, the alkoxyborate anion intermediate contains the solvent alkoxide rather than that of the product and that the ketone is reduced to the free 7 alcohol . Our ab initio study of BH4- -~ addition to formaldehyde suggested that the non- synchronous 4-centre transition state may be implicated under the circumstances where the protic solvent is not available zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONM a . To investigate such a possibility we have studied NaBH4 reductions of acetone, acetophenone and benzophenone in the absence of a protic solvent. NaBH4 (BDH) was crystallized from boiling dry isopropyl alcohol, dried overnight at 200°C, and handled under nitrogen. Acetone and acetophenone were dried, purified and distilled. The reduction were carried out neat at 1015