Enantioselectivity improvement induced by β-cyclodextrin in the NaBH4 reduction of acetophenone through the formation of a three-component inclusion β-cyclodextrin–acetophenone–triethylamine complex

Abstract

Stoichiometric amounts of triethylamine (TEA) were found to enhance the chiral induction by β-cyclodextrin (β-CD) in the reduction of acetophenone (ACPH) by aqueous NaBH₄ and to invert the face selectivity. The enantioselectivity obtained depends upon the molar ratio β-CD∶ACPH∶TEA and on the reaction temperature. For example, R(+)-1-phenylethanol was predominantly produced at -10 °C in 56% enantiometric excess for a molar ratio β-CD∶ACPH∶TEA of 2∶1∶2 vs. the S(-) enantiomer in 5% enantiomeric excess in the absence of TEA, other experimental conditions remaining unchanged. Evidence for the formation of a three-component inclusion compound was obtained from detailed ¹H and ²H NMR studies. TEA partially binds to the β-CD∶ACPH molecular edifice in such a way that the conformational mobility of the acetyl group is reduced. The restriction of the rotational motion of the prochiral centre probably accounts for the strong enhancement of the chiral induction observed.