An Efficient and Simple Entry toN-Substituted β-Enamino Acid Derivatives from 2-Alkyl-2-oxazolines and 2-Alkyl-2-thiazolines

Abstract

Reaction of azaenolates of 2-alkyl-oxa(thia)zolines 6 with imidoyl chlorides 7 as electrophiles to furnish masked N-substituted β-enamino acid derivatives 1−2 in 70−90% yield is described. Alternative routes are discussed. Compounds 1−2 generally appear in one tautomeric form, imino or enamino, depending on the nature of the imidoyl chloride. The configuration of the enamino moiety (Z) and the conformation (s-cis) of compounds 1−2 obtained were established by an NMR study and unequivocally set by nuclear Overhauser effect difference experiments. An X-ray structure of compound 1e is also reported, showing a strong intramolecular NH···N hydrogen bond. Ab initio calculations (HF/3-21G and HF/3-21+G) have been carried out on several representative examples (1e, 1p, and 1l) in an attempt to support and provide the correct geometry of these derivatives. Structural considerations among the possible isomers of compounds 1 are discussed. From these studies it was concluded that the theoretical calculations agree with the experimental results. In addition, a very simple one-pot procedure for the preparation of masked N-substituted α-alkylated β-enamino acid derivatives 2 from 6, 7, and different alkyl halides (R³Y) is described.