Methylene Thiazolidinediones as Alkylation Reagents in Catalytic C–H Functionalization: Rapid Access to Glitazones

The straightforward and rapid incorporation of a thiazolidinedione
scaffold into prefunctionalized (hetero)aromatic compounds is in demand
for the development of antidiabetic glitazones and other pharmaceuticals.
Herein, we report the unprecedented N- and O-directed C–H alkylation
of various (hetero)arenes with methylene thiazolidinediones under
rhodium(III) catalysis. The applicability of the developed protocol
in challenging contexts is exhibited by the late-stage installation
of a methylene thiazolidinedione moiety on the C–H bond of
commercially available drug molecules. Combined mechanistic investigations
aided the elucidation of a plausible reaction mechanism.