Umpolung C(3)–H Functionalization of Indoles via I(III) Intermediates: Synthesis of Indol‐3‐yl Xanthates

Abstract

Herein, we report a transition‐metal‐free strategy for the synthesis of O‐alkyl‐S‐(indol‐3‐yl) xanthates, valuable surrogates for indol‐3‐yl thiols. The method relies on the in situ formation of electrophilic (3,5‐dimethylisoxazol‐4‐yl)(indol‐3‐yl)iodonium salts via highly chemo‐ and regioselective C(3)–H functionalization of indoles with (3,5‐dimethylisoxazol‐4‐yl)–I(OH)OTs, a Koser's type reagent. These electrophilic intermediates readily react with potassium O‐alkyl xanthates, delivering the corresponding O‐alkyl‐S‐(indol‐3‐yl) xanthates in good‐to‐high yields. The protocol exhibits good functional group compatibility and is well‐suited for late‐stage functionalization of complex bioactive molecules, as demonstrated by the derivatization of the antiviral agent CCG‐203926 and estradiol, a steroid hormone. This operationally simple protocol provides an efficient approach to otherwise inaccessible indol‐3‐yl xanthates that are both a class of compounds of considerable interest due to their potential biological activity and valuable precursors for other indole derivatives containing organosulfur functional groups at the C(3) position.