Synthesis of 3,3′-Disubstituted Isobenzofuran-1(3H)-Ones via Cs0.5H2.5PW12O40-Catalyzed Difunctionalization of Carbonyls

We reported a method for the synthesis of 3,3'-disubstituted isobenzofuran-1(3H)-ones via the carbonyl difunctionalization of 2-acylbenzoic acids. A range of nucleophiles was reacted with 2-acylbenzoic acids to furnish the functionalized isobenzofuran-1(3H)-ones with the factual yield range of 61-96%. The reaction uses Cs0.5H2.5PW12O40 as a catalyst and produces water as the sole by-product. Various functional groups could be introduced to the isobenzofuran-1(3H)-one skeletons via the C-P/C-N/C-O/C-C bond formation, which would provide opportunities for the synthesis of potential biologically active molecules. Based on the preliminary experiments, a plausible mechanism is proposed.

Automated summary

We reported a method for the synthesis of 3,3'-disubstituted isobenzofuran-1(3H)-ones via the carbonyl difunctionalization of 2-acylbenzoic acids. The reaction yielded functionalized isobenzofuran-1(3H)-ones with a range of nucleophiles, achieving factual yield of 61-96%. The reaction was catalyzed by Cs0.5H2.5PW12O40 and water was the only by-product. The method enables the introduction of various functional groups to the isobenzofuran-1(3H)-one skeletons, offering opportunities for the synthesis of potential biologically active molecules.