Mechanism of borohydride reductions. Evidence for lack of disproportionation in the reduction of ketones

Abstract

/t,retr/ oJ'Clret~~i.s/ry, Cnr.le/otr U t r i~~e~. s i / )~, Ottcrn,tr, Otr/. , Cntrcrtltr KIS 586 Received Septernbe1.26, 1977 DONALD C. WIGFIELD and FREDERICK W. GOWLAND. Can. J. Chem. 56,786(1978).Examination of unreacted sodium borohydride after reduction of ketones by mixtures of NaBH, and NaBD, shows that it is still isotopically pure and that no detectable species NaBH,D,-, have been formed. Disproportionation of intermediates back to NaBH, therefore plays no significant role in the reduction. DONALD C. WIGFIELD et FREDERICK W. GOWLAND. Can. J. Chem. 56,786 (1978).Un examen du borohydrure de sodium qui n'a pas reagit lors de la reduction de cetones par des melanges de NaBH, et de NaBD, indique que ce dernier est encore isotopiquement pur et I'on n'a pas detecte la formation d'entites NaBH,,D,-,,. La dismutation d'intermtdiaires pour reconduire a NaBH, ne joue donc aucun r61e important.[Traduit par le journal] Little is known about the mechanism of borohydride reductions of ketones. Three major questions, of increasing level of molecular detail, exist. Firstly, given the 4:l stoichion~etry, what are the structures of the reducing agents for reduction of each of the four ketone molecules? Secondly, given the structure of the reducing agent(s), what is the mechanism of reduction: is it cyclic or acyclic; does it differ for each reducing species; what role, if any, d o the metal cation and the solvent play? Thirdly, given the reducing agent and the mechanism for each reducing species, where on the reaction coordinate d o the transition states occur: are they reactant-like, product-like, or somewhere in between? Finally, if one knew the answers to the above questions, presumably the problem of understanding the striking stereoselectivity of the reactions could at least be approached on a rational basis.With several notable exceptions (see for example refs. 1-3), investigations in this area seem to be a persistent case of the cart before the horse. Speculations concerning the cause of stereoselectivity have been discussed for over twenty years. Speculators d o not seem to have been greatly troubled by the almost total lack of knowledge of the reaction mechanism. Similarly, a good deal of effort has been expended to define the degree of hydride transfer in the transition state but the answer to this question is still unsettled. In contrast, little attention has been paid to the first two, rather more fundamental, questions posed above. The questions are not intangible and this communication is aiined a t the first of these: what is(are) the structure(s) of the reducing agent(s)? Results and Discussion The ProbletnAll four hydrides of sodium borohydride are available for reduction of simple ketones.' While there is not much doubt that the reduction is initiated by reaction of NaBH, itself with a molecule of ketone, considerable uncertainty exists about what happens then. We have recently shown that the hydroxylic solvent plays a crucial role in this first step (5, 6) and it may therefore be represented as ...