Chiral Brønsted acid-catalysed enantioselective allylboration of sterically hindered aldehydes enabled by multiple hydrogen bonding interactions†

Abstract

Chiral phosphoric acids (CPAs) are an important class of chiral Brønsted acid catalysts that can accomplish highly effective enantioselective allylborations of aldehydes. However, traditional CPA-catalysed allyboration has difficulty utilizing sterically hindered aldehydes, where the corresponding products of enantioenriched secondary alcohols adjacent to a quaternary carbon are important moieties in biologically active natural products. To overcome this issue, we employed a chiral phosphoramide catalyst for allylation and crotylation reactions of the allyl boronic acid pinacol ester with sterically hindered aldehydes to benefit from multiple hydrogen bonding interactions between the chiral phosphoramide and substrates. As a result, not only the sterically hindered aldehydes, but the less sterically hindered ones, could also be subjected to enantioselective allylboration using the chiral phosphoramide catalyst by “interaction strategy”. Indeed, conventional CPAs were ineffective for the reactions presented here, resulting in low conversions and enantioselectivities. Computational studies revealed that the most stable transition state comprises weak attractive interactions between phosphoramide and substrates. These interactions did not exist in traditional allylborations with chiral phosphoric acids. In conclusion, the sum of weak interactions, including SO⋯H–C and two C–F⋯H–C hydrogen bonding interactions, substantially impacts the enantioselectivity of the allylboration of sterically hindered aldehydes.