A novel stereoselective one-pot synthesis of 2-susbstituted amino-5,6-dihydro-4H-1,3-thiazines via primary allylamines afforded from Morita–Baylis–Hillman acetates

Abstract

A new stereoselective synthesis of 2-susbstituted amino-5,6-dihydro 4H-1,3-thiazines using primary allylamines obtained from the Morita–Baylis–Hillman (MBH) acetates is described. The primary allylamines react with aryl isothiocyanates to afford the title compounds via sequential thiourea formation and intramolecular sulfa-Michael reaction in a one-pot process under two different experimental conditions. Two steps during the reactions between the allylamines derived from the MBH adducts of benzaldehyde or electron-donating group bearing substituted benzaldehydes and aryl isothiocyanates proceed in a cascade sequence to directly afford the anti-isomer of the title compounds. In contrast reactions between the allylamines generated from the MBH adducts of electron-withdrawing group containing substituted benzaldehydes and aryl isothiocyanate result in allyl thioureas which undergo Lewis acid-mediated intramolecular sulfa-Michael cyclization to afford syn or anti-products depending on the placement of the substitution on the phenyl ring. A plausible mechanism is proposed to explain the observed stereoselectivity amongst the prepared 1,3-thiazines.