Directive effect of the 2- and 3-axial hydroxy groups that appeared in the complex metal hydride reduction of cyclohexanones

Article abstract of DOI:10.1246/bcsj.73.237

A directive effect of the 2-axial hydroxy group appeared in the LiAlH₄, NaBH₄, and Zn(BH₄)₂ reduction of cyclohexanone, while the 3-axial hydroxy group exhibited a steric hindrance. The distance between the carbonyl carbon and the hydroxy group interacting with the hydride reagent was responsible for such a difference. In the reduction of Na[B(OAc)₃H], the 2- and 3-axial hydroxycyclohexanones gave the products obtained by the hydride approaching from the side of the hydroxy group. The key point of the stereoselectivity was the formation of Na[B(OAc)₂(OR)H, which was more reactive than the parent hydride, by exchanging the acetate ion with the alkoxide. Although the reduction was performed under the condition that the hydride/substrate ratio was 1, the conversion of the hydroxy ketone to an alcohol were < 50% for the LiAlH₄, NaBH₄, and Zn(BH₄)₂ reductions in tetrahydrofuran. The conversions in the NaBH₄ reduction in ethanol were > 90%.