Unprecedented one-pot stereoselective synthesis of Knoevenagel-type derivatives via in situ condensation of N-methyleniminium salts of ethylenethiourea and ethyleneurea with active methylene reagents

A facile stereoselective synthesis of Knoevenagel-type compds. I (e.g., X = O, S, Y = CN, COMe, CO2Me, COPh, Z = CN, CO2Me, PO(OEt)2, CONH2, COMe, CO2Et, SO2Ph) was accomplished through a 1-pot two-step procedure. The reaction of ethylenethiourea (2-imidazolidinethione, 1) and ethyleneurea (2-imidazolidone, 2) with benzoyl chloride-DMF complex in DMF gave the corresponding isolable ternary N-methyleniminium chlorides II, along with HOBz (5) as a byproduct. Hydrolysis of salts II yielded the N-formyl derivs. 6 and 7, thus confirming the N-methyleniminium structure. Salts II condensed in situ at 120° with a variety of acyclic active methylene reagents Y-CH2-Z (Y = or ≠ Z), in the presence of 5 (Procedure A) or of 5 and NEt3 (1.5 equiv) (Procedure B), afforded α,β-unsatd. compds. I. The overall yields ranged from poor to good. Mechanistic hypotheses concerning the formation of II and the origin of the stereoselectivity are also discussed