Phosphonate-Directed Catalytic Asymmetric Hydroboration: Delivery of Boron to the More Substituted Carbon, Leading to Chiral Tertiary Benzylic Boronic Esters.

Abstract

Phosphonate-directed catalytic asymmetric hydroboration (CAHB) of β-aryl/heteroaryl methylidenes and trisubstituted alkenes by pinacolborane enables facile access to functionalized, chiral tertiary benzylic boronic esters. Hydroboration is catalyzed by a chiral rhodium catalyst prepared in situ from a Rh(I)-precursor in combination with a simple TADDOL-derived chiral cyclic monophosphite in a 1:1 ratio. The regio- and stereochemistry arises from the combined effects of the relative disposition of the directing group to the alkene, the alkene substitution pattern, and the necessity of an aryl substituent attached to the alkene. A range of aryl and heteroaryl substituents can be accommodated, and for several chiral substrates, the reactions are efficiently catalyst-controlled enabling the choice of diastereomeric products as desired. Stereospecific transformations of the chiral boronic ester afford chiral phosphonates bearing a quaternary carbon stereocenter. The synthetic utility of the products is further demonstrated by α-oxidation of the phosphonate leading to hydroxy- and oxo-phosphonates; the latter readily undergo elimination/substitution reactions to unmask the phosphonate functionality with the formation of aldehydes, alcohols, esters, amides, acids and ketones.