Synthesis of Cyclic Anhydrides via Ligand-Enabled C-H Carbonylation of Simple Aliphatic Acids

The development of C(sp(3))-H functionalizations of free carboxylic acids has provided a wide range of versatile C-C and C-Y (Y=heteroatom) bond-forming reactions. Additionally, C-H functionalizations have lent themselves to the one-step preparation of a number of valuable synthetic motifs that are often difficult to prepare through conventional methods. Herein, we report a beta- or gamma-C(sp(3))-H carbonylation of free carboxylic acids using Mo(CO)(6) as a convenient solid CO source and enabled by a bidentate ligand, leading to convenient syntheses of cyclic anhydrides. Among these, the succinic anhydride products are versatile stepping stones for the mono-selective introduction of various functional groups at the beta position of the parent acids by decarboxylative functionalizations, thus providing a divergent strategy to synthesize a myriad of carboxylic acids inaccessible by previous beta-C-H activation reactions. The enantioselective carbonylation of free cyclopropanecarboxylic acids has also been achieved using a chiral bidentate thioether ligand

Automated summary

The development of C(sp(3))-H functionalizations of free carboxylic acids has provided a wide range of versatile reactions, enabling convenient synthesis of cyclic anhydrides using Mo(CO)(6) as a solid CO source and a bidentate ligand. Succinic anhydride products serve as versatile intermediates for introducing various functional groups at the beta position of parent acids, offering a divergent strategy for synthesizing carboxylic acids inaccessible by previous beta-C-H activation reactions. Furthermore, enantioselective carbonylation of free cyclopropanecarboxylic acids has been achieved using a chiral bidentate thioether ligand.