Photocatalytic Phosphine-Mediated Thioesterification of Carboxylic Acids with Disulfides

Herein, a practical and effective synthesis of thioesters from readily available carboxylic acids and odorless disulfides was developed under photocatalytic conditions. This approach involves phosphoranyl radical-mediated fragmentation to generate acyl radicals and allows for incorporation of both S atoms of the disulfides into the desired products. In addition to batch reactions, a continuous-flow reactor was employed, enabling rapid thioester synthesis on a gram scale. Preliminary experimental mechanistic studies and the rapid synthesis of dalcetrapib are also demonstrated.

Automated summary

A practical and effective method for synthesizing thioesters from readily available carboxylic acids and odorless disulfides under photocatalytic conditions was developed. This method involves phosphoranyl radical-mediated fragmentation to generate acyl radicals and incorporates both sulfur atoms of the disulfides into the desired products. In addition to batch reactions, a continuous-flow reactor was utilized for rapid gram-scale thioester synthesis. Preliminary experimental mechanistic studies and the rapid synthesis of dalcetrapib were also demonstrated.