C═C/N═O Metathesis Enables Oxidative Decarboxylation

Metathesis reactions proceeding through a (2 + 2) cycloaddition - (2 + 2) cycloreversion sequence are of great importance in synthetic chemistry. However, to date, this type of reactivity has only been demonstrated for a limited set of compatible substrate classes. We present herein the design and development of a novel reaction of this class, an iron(II)-catalyzed C═C/N═O metathesis, and its application to the mild oxidative decarboxylation of carboxylic acids. The reaction proceeds under air in a one-pot fashion, utilizing readily available, inexpensive reagents, and features an earth-abundant, environmentally benign iron catalyst. The reaction exhibits broad functional group tolerance, is efficiently scalable, and its late-stage applicability was showcased through the streamlined oxidative decarboxylation of 12 drug molecules. Divergent and convergent reactivity was demonstrated relying on the complementary C═C/O═N metathesis counterpart providing access to imines instead of ketones, and the method was extended to the synthesis of esters from α-aryloxy and α-alkoxy carboxylic acids. Results of preliminary mechanistic experiments, reaction profile analysis with ReactIR, and computational studies are presented to provide further insight into the transformation.