Ketone homologation via palladium-catalysed decarboxylative rearrangement

The decarboxylative semi-pinacol rearrangement of β-hydroxy carboxylic acids under electrochemical oxidation conditions was first reported in 1960¹. However, its further development has remained limited owing to stepwise radical and carbocationic pathways that induce side reactions and result in the loss of stereochemical information at the α-carbon. Herein, we demonstrate that this transformation can instead be realized through a concerted mechanism under Pd(II)/Pd(IV) catalysis. The reaction proceeds via the formation of a six-membered Pd(IV) chelate, which undergoes fragmentation accompanied by β-to-α carbon migration and carbon dioxide extrusion, with Pd(IV) serving as the redox center. This closed-shell pathway enables precise stereochemical control: the migrating carbon retains its absolute configuration, while the α-stereocenter undergoes inversion. For unsymmetrical ketones, the reaction displays markedly higher migrating-group selectivity than the classical Tiffeneau-Demjanov² and Büchner-Curtius-Schlotterbeck reactions³. Broadly applicable to cyclic and acyclic ketones and aldehydes, this method avoids hazardous diazo reagents. Its utility is illustrated by a concise total synthesis of (+)-rupestine D, where the rearrangement serves as a key carbon-skeleton-editing step.