Atom-economical and workup-free multiparticipation of p-TsOH in yne-ynamide skeletal reshuffle: access to regiospecific, chemospecific, and stereospecific (E)-alkenyl sulfonate/ketone-tethered indoles

Abstract

Transition metal-free organic transformations that do not involve/generate hazardous waste are of great interest in organic synthesis. In this regard, p-toluenesulfonic acid monohydrate (p-TsOH·H₂O) is an ecofriendly reagent for efficiently synthesizing diverse heterocyclic compounds. Using p-TsOH·H₂O as a multipurpose reagent, we synthesized highly substituted, sensitive, stereospecific alkenyl sulfonate/ketone derivatives from the same precursors (yne-ynamides) via skeletal rearrangement. This strategy is notable because it is transition metal- and additive-free, atom-economical, scalable, operationally simple, regioselective, and chemoselective. Furthermore, it avoids tedious workup procedures, has a broad substrate scope, uses environmentally friendly and commercially available p-TsOH·H₂O, and prevents hazardous waste generation. The alkenyl sulfonate synthesis is an acceptable green and economical organic synthesis process based on green chemistry metrics (E-factor of 1.72) and EcoScale (64.5 on a scale of 0–100). Moreover, this protocol demonstrates further synthetic transformations of the synthesized ketone products.