Facile access to functionalized chiral secondary benzylic boronic esters <i>via</i> catalytic asymmetric hydroboration

Abstract

Allylic and homoallylic phosphonates bearing an aryl or heteroaryl substituent at the γ- or δ-position undergo rhodium-catalyzed asymmetric hydroboration by pinacolborane to give functionalized chiral secondary benzylic boronic esters in yields up to 86% and enantiomer ratios up to 99 : 1. Compared to minimally-functionalized terminal and 1,1-disubstituted vinyl arenes, there are relatively few reports of efficient catalytic asymmetric hydroboration (CAHB) of more highly functionalized internal alkenes. Phosphonate substrates bearing a variety of common heterocyclic ring systems, including furan, indole, pyrrole and thiophene derivatives, as well as those bearing basic nitrogen substituents (<i>e.g.</i>, morpholine and pyrazine) are tolerated, although donor substituents positioned in close proximity of the alkene can influence the course of the reaction. Stereoisomeric (<i>E</i>)- and (<i>Z</i>)-substrates afford the same major enantiomer of the borated product. Deuterium-labelling studies reveal that rapid (<i>Z</i>)- to (<i>E</i>)-alkene isomerization accounts for the observed (<i>E</i>/<i>Z</i>)-stereoconvergence during CAHB. The synthetic utility of the chiral boronic ester products is illustrated by stereospecific C-B bond transformations including stereoretentive electrophile promoted 1,2-B-to-C migrations, stereoinvertive S_E2 reactions of boron-ate complexes with electrophiles, and stereoretentive palladium- and rhodium-catalyzed cross-coupling protocols.