Systematic study on acylation of methyl 3-aminocrotonate with acid chlorides of aliphatic, aromatic and α, β-unsaturated acids: A comparative evaluation of the preference for regio- and stereoselectivity vis - à - vi s 3-aminocrotononitrile

Acylation of methyl 3-aminocrotonate 1a in benzene with a variety of aliphatic and aromatic acid chlorides including α, β-unsaturated acid chloride in the presence of an added organic base, (either pyridine or triethylamine) is reported. The preferred N, C-site selectivity in these reactions has been compared with the terminal selectivity of the products obtained previously on acylation of methyl 3-aminocrotononitrile 1b . A strong preference either for N- or C- selectivity in N, C-acylation has been observed for both 1a and 1b based on the choice of acid chlorides and added organic base. Interestingly, irrespective of the enamine 1a or 1b , acylation with α, β-unsaturated acid chlorides in the presence of triethylamine afforded 3,4-dihydropyridin-(2 H )-one via [3.3] sigmatropic rearrangement of the corresponding intermediary N(E)-enamide. Accrued results show methyl 3-aminocrotonate to be a better precursor for preparation of enamides (N-acylated products) whereas 3-aminocrotononitrile is found to be a preferred choice for preparation of enaminones (C-acylated products). An attempt is made to offer a preliminary theoretical interpretation for observed site selectivity.