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

• Published in: Angewandte Chemie International Edition 2021-07, Vol.60 (30), p.16382-16387
• Main Authors: Zhuang, Zhe, Herron, Alastair N., Yu, Jin‐Quan
• Format: Article
• Language: English
• Subjects: Acids; Anhydrides; Carbon monoxide; carbonylation; Carbonyls; Carboxylic acids; C–H activation; Divergence; Enantiomers; Functional groups; ligand design; Ligands; palladium
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202104645

The development of C(sp3)–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 β‐ or γ‐C(sp3)–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 β position of the parent acids by decarboxylative functionalizations, thus providing a divergent strategy to synthesize a myriad of carboxylic acids inaccessible by previous β‐C–H activation reactions. The enantioselective carbonylation of free cyclopropanecarboxylic acids has also been achieved using a chiral bidentate thioether ligand PdII‐catalyzed β‐ or γ‐C(sp3)–H carbonylation of free carboxylic acids, a new method for the synthesis of a wide range of cyclic anhydrides, is reported. Decarboxylative functionalization of the installed carboxyl group provides access to diverse β‐functionalized aliphatic acids. The enantioselective C–H carbonylation of cyclopropanecarboxylic acids is also achieved.