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.