Synthesis of bridgehead nitrogen heterocycles via cyclization of α-ammonio 5-hexenyl radicals

Ring-closure of the 2,2-dimethyl-2-azonia-5-hexenyl radical (4) proceeds smoothly and efficiently to give the g-exo isomer essentially quantitatively, in accordance with predictions based on MP4SDTQ/6-31G* ab initio calculations on the thermodynamic stability of alpha-ammonio radicals. The corresponding 5-hexynyl radical species 15 and its B-phenyl derivative 19 display similar behavior affording the analogous 5-exo-3-methylenepyrrolidinium salts in high yield. In none of these cases were the products of reduction were detected. All of the radical intermediates were generated conveniently by treatment of the iodomethyl and/or phenylselenomethyl salts with tributyltin hydride. Application of this procedure to monocyclic precursors such as 1-methyl-1-iodomethyl-4-methylene-1-azoniacyclohexyl iodide (31) provided an attractive entry into quaternary derivatives of the 1-azabicyclo[2.2.1]heptyl system in good yield via a three-step sequence from 1-methylpiperidone. Dequaternization of the bicyclic salts so obtained unexpectedly leads to rupture of one of the rings rather than loss of the N-methyl group. The 1-azabicyclo[2.2.1]heptane could be accessed readily via tin hydride-induced cyclization of the corresponding N-phenylethylammonium salt 54, followed by Hofmann elimination with potassium tert-butoxide.