Dynamic Kinetic Resolution of Indole-Based Sulfenylated Heterobiaryls by Rhodium-Catalyzed Atroposelective Reductive Aldol Reaction

A highly enantio-
and diastereoselective dynamic kinetic resolution
(DKR) of configurationally labile 3-aryl indole-2-carbaldehydes is
described. The DKR proceeds via a Rh-catalyzed intermolecular asymmetric
reductive aldol reaction with acrylate esters, with simultaneous generation
of three stereogenic elements. The strategy relies on the labilization
of the stereogenic axis that takes place thanks to a transient Lewis
acid–base interaction (LABI) between the formyl group and a
thioether moiety strategically located at the ortho′ position. The atropisomeric indole products present a high degree
of functionalization and can be further converted to a series of axially
chiral derivatives, thereby expanding their potential application
in drug discovery and asymmetric catalysis.