Intramolecular Michael-type additions. II. Synthesis of derivatives of 7-thia-2-azabicyclo[3.2.1]oct-3-ene, a novel heterocyclic ring system

Abstract

The isothiouronium salt derived from dimethyl 4-chloromethyl-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate reacted with ammonium hydroxide to give dimethyl 7-thia-2-aza-1,3-dimethylbicyclo[3.2.1]oct-3-ene-4,8-dicarboxylate, which could be converted back to a dihydropyridine using iodomethane. Replacement of ammonium hydroxide by sodium hydroxide afforded a tetrahydro- and a dihydrothieno[3,4-c]pyridine as by-products. 3,5-Diacetyl-4-chloromethyl-1,4-dihydro-2,6-dimethylpyridine reacted with thiourea, followed by ammonium hydroxide, to give 3-acetyl-2-methylpyrrole, 4-acetyl- and 4,8-diacetyl-7-thia-2-aza-1,3-dimethylbicyclo[3.2.1]oct-3-ene. The structure and stereochemistry of the novel 7-thia-2-azabicyclo[3.2.1]octenes are established using spectroscopic methods. The mechanism of their formation is discussed in terms of Baldwin's rules.