Ethenetricarboxylic acid diester 1a is a useful compound bearing two reactive sites, a CO2H group and a Michael acceptor. Reactions of 1a and reagents with oxygen and nitrogen nucleophilic moieties have been examined. The reaction of 1a with 2-aminoalcohols in the presence of EDCI and HOBt in one pot gave N,O-containing heterocyclic compounds, regioselectively. The stepwise method has also been carried out. Deprotection of N-Boc protected aminoesters, followed by basic aqueous workup, gave various 1,4-oxazine derivatives. Deprotection of the O-TBS protected amides also leads to spontaneous cyclization and affords 1,4-oxazine derivatives. They have the opposite regiochemistry to those from the one-pot reaction. Thus, both ester or amide regioisomers can be prepared. These synthetic methods represent a new general strategy for the construction of diverse heterocyclic systems such as morpholine-derived heterocycles.
