Regioselective and stereospecific synthesis of functionalized 3,4-dihydro-2H-1,4-thiazines by catalyst-free [3 + 3] annulation of pyridinium 1,4-zwitterionic thiolates and aziridines

Abstract

A regioselective and stereospecific [3 + 3] annulation between pyridinium 1,4-zwitterionic thiolates and aziridines has been developed, allowing the practical and enantio-retained preparation of functionalized 3,4-dihydro-2H-1,4-thiazines. This reaction proceeds smoothly via a domino S_N2 ring-opening/N-Michael addition cyclization/retro-Michael addition/Py extrusion procedure under mild conditions without a metal and a strong base. The regioselectivity is greatly affected by the nature of the substituents on aziridines. Moreover, biologically interesting sulfoxide and sulfone analogues could also be conveniently obtained via selective oxidation of the produced 3,4-dihydro-2H-1,4-thiazines using m-CPBA.