Metal-Free Thiocarbamation of Quinolinones: Direct Access to 3,4-Difunctionalized Quinolines and Quinolinonyl Thiocarbamates at Room Temperature.

Abstract

A novel and practical method for the preparation of difunctionalized quinolines, bearing a thiocarbamate group at the C3-position and an acyloxyl group at the C4-position, and quinolinonyl thiocarbamates from quinolinones, tetraalkylthiuram disulfides, and hypervalent iodine(III) reagents has been developed via thiocarbamation of quinolinones at room temperature. The present method features mild reaction conditions, good tolerance with diverse functional groups, and a wide substrate scope, providing the desired products in good yields. Furthermore, this transformation is easy to scale up, and the desired products can be readily converted to heterocyclic thiols. Most importantly, this protocol allows for the late-stage thiocarbamation of bioactive compounds. Mechanistic studies show that radicals may be involved in this transformation, water is probably the oxygen source of thiocarbamates, and difunctionalized quinolines are possibly formed via nucleophilic attack of carboxylic anions, which derive from hypervalent iodine(III) reagents.