Palladium-Catalyzed Regio- and Enantioselective Hydrosulfonylation of 1,3-Dienes with Sulfinic Acids: Scope, Mechanism, and Origin of Selectivity

Chiral
sulfones are important structural motifs in organic synthesis
because of their widespread use in pharmaceutical chemistry. In particular,
chiral allylic sulfones have drawn particular interest because of
their synthetic utility. However, enantioselective synthesis of 1,3-disubstituted
unsymmetrical chiral allylic sulfones remains a challenge. In this
article, we report a protocol for (R)-DTBM-Segphos/Pd-catalyzed
regio- and enantioselective hydrosulfonylation of 1,3-dienes with
sulfinic acids, which provides atom- and step-economical access to
1,3-disubstituted chiral allylic sulfones. The reaction occurs under
mild conditions and has a broad substrate scope. Combined experimental
and computational studies suggest that the reaction is initiated by
a ligand-to-ligand hydrogen transfer followed by a C–S bond
reductive elimination via a six-membered transition state. Steric
repulsion between the olefinic C–H of the substrate and the tert-butyl group of (R)-DTBM-Segphos was
found to be a key factor in the enantiocontrol.