Diastereo- and Enantioselective Allylation of α‑Hydroxy Ketones Enabled by Palladium/Borinic Acid Dual Catalysis

Asymmetric allylation reactions between unsymmetrical
allyl carbonates
and α-hydroxy ketones synergistically catalyzed by a palladium/borinic
acid catalytic platform have been developed. The reaction proceeds
through nucleophilic activation of α-hydroxy ketone by an achiral
borinic acid to form a tetracoordinated enediol boronate complex and
its subsequent interception of an electrophilic π-allyl palladium
complex generated from a chiral Pd catalyst and an allyl component.
A broad scope of substrates was suitable in this reaction, providing
a series of allyl-substituted α-hydroxy ketones bearing vicinal
stereocenters with high enantioselectivities (up to 99% ee) and diastereoselectivities
(up to 24:1 dr). The methodology also achieved effective kinetic resolution
of 1,3-disubstituted allylic carbonates, with the unreacted substrates
being recovered with high ee values. A plausible mechanism and model
for chiral induction in this reaction are proposed. The diastereo-
and enantioselectivites observed in this reaction were rationalized
by density functional theory studies. The utility of this method was
demonstrated by a gram-scale reaction and subsequent elaboration of
the allylation products.