Transition‐Metal‐Free One‐Pot [3+3] Heteroannulative Coupling of Thioamides with Epichlorohydrin: Access to Diverse 1,3‐Thiazinanes

Abstract

An operationally simple and efficient cascade approach to access a series of 1,3‐thiazinanes has been developed through intermolecular [3+3] heteroannulative coupling employing β‐ketothioamide as a C1 N1S1 unit and epichlorohydrin as a C3 unit at room temperature for the first time. The reaction proceeds by nucleophilic attack of thiocarbonyl sulfur to less hindered primary carbon of oxirane followed by sequential intramolecular N‐cyclization and dehydrochlorination enabling the coupling by cleavage of C−O bond and formation of two new C−S and C−N bonds in one stretch. This protocol not only avoids potential toxicity and tedious work up procedures, but also features open atmosphere, good to high yields, gram‐scalability, and easy performance from inexpensive, readily available starting materials under transition‐metal‐free conditions. A probable mechanism for the formation of 1,3‐thiazinanes has been suggested.

PIDA-promoted metal-free [3 + 2] heteroannulation of β-ketothioamides with 4-hydroxy coumarins: chemo-/regioselective access to furo[3,2-c]chromen-4-ones at room temperature

“…One such synthon are β-ketothioamides (KTAs), which have proven to be a versatile class of strategic precursors due to their intrinsic synthetic tunability with fitting partners in a chemo- and regioselective manner, for the construction of various heterocycles. 17 Due to our constant efforts to develop new protocols towards heterocyclic frameworks utilizing KTA as a synthon, 18 we envisioned further expanding their synthetic repertoire by reacting them with 4-hydroxy coumarin as a coupling partner. Herein, we report the synthesis of furo[3,2- c ]coumarins from 4-hydroxy coumarins and β-ketothioamides via an intermolecular cross-coupling and intramolecular cyclization strategy mediated by the eco-friendly hypervalent iodine reagent phenyliodine( iii ) diacetate (PIDA), at room temperature under open air, in a highly efficient, rapid and pot-/step-economical manner (Scheme 1d).…”