Chiral Brønsted Acid-Catalysed Enantioselective Allylboration of Sterically Hindered Aldehydes Enabled by Multiple Hydrogen Bonding Interactions

Abstract

Chiral phosphoric acids (CPAs) are privileged chiral Brønsted acid catalysts that have accomplished enantioselective allylborations of aldehydes in highly efficient manner. However, traditional CPA-catalysed allyboration is difficult to utilize sterically hindered aldehydes, in which generating corresponding enantioenriched secondary alcohols adjacent to a quaternary carbon that are important moieties in biologically active natural products. In order to overcome this issue, we employed a chiral phosphoramide catalyst for allylation and crotylation reactions of allylboronic acid pinacol ester with sterically hindered aldehydes to take advantage of multiple hydrogen bonding interactions between the chiral phosphoramide and substrates. As a result, not only sterically hindered aldehydes but also less sterically hindered aldehydes could be performed for the present enantioselective allylboration using the chiral phosphoramide catalyst by “interaction strategy”. Indeed, conventional CPAs were ineffective for the present reactions, resulting in low conversions and enantioselectivities. Computational studies revealed that the most stable transition state is stabilized by weak attractive interactions between phosphoramide and substrates, in which these interactions were not existed in traditional allylborations using chiral phosphoric acids. Namely, the sum of weak interactions including S=O···H–C and two C–F···H–C hydrogen bonding interactions substantially impacts the enantioselectivity in the allylboration of sterically hindered aldehydes.