Enamine Chemistry—XXIV.: Synthesis, thiation, and reduction of lactams

Abstract

Enamines, 1, prepared from cyclohexanones or cyclopentanones are reacted with acrylamide to give lactams, the condensed 2-piperidones, 2. Ethyl 2-(1-pyrrolidinyl)-2-cyclohexene-1-propanoate, 3, when treated with primary amines, produces the corresponding N-substituted 2-piperidones, 4. Ethyl 2-(1-pyrrolidinyl)-2-cyclohexene-1-ethanoates and ethyl 2-(1-pyrrolidinyl)-2-cyclopentene-1-ethanoate, 5, react with primary amines to give condensed N-substituted 2-pyrrolidones, 6, and non-cyclic imines, 7. The starting enamines, 1, treated with 2-bromo acetamides only afford the N-alkylated compounds 8 (2-pyrrolidino acetamides), and the regioselectivity of this reaction is rationalized in terms of the HSAB-principle. Compound 1 undergoes an exchange reaction (aminolysis) when reacted with primary amines to give the imines 9. Thiation of the lactams 2 and 6 with the Lawesson reagent (LR), affords the corresponding thiolactams, 10. Reduction of the lactams and thiolactams, 2, 6, and 10 by LAH gives the imines, 11, and the enamines, 16. Further reduction of 11 (LAH) affords the saturated amines, 15. The stereochemistry for the formation of 15 is discussed using the torsion angle notation and the principal of least torsional distortion. In a one-pot reaction using LAH-acetic anhydride the lactams, 2, and the thiolactams, 10, are transformed into the enamides, 14. Compound 14 was also obtained from 11 by direct acetylation with acetic anhydride in the presence of triethylamine.