Synthesis of nitrogen bridgehead bicyclic heterocycles via ring-closure of beta-ammonio 5-hexenyl radicals

The 2(3-methylenepiperidinyl)ethyl radical (6) displays considerable reluctance to ring-closure under conditions which its carbocyclic analog, the 2-(3-methylenecyclohexyl)ethyl radical (2), cyclizes essentially completely. Molecular mechanics calculations suggest that the increased activation barrier associated with ring-closure of 6 is the result of a higher than expected transition state energy. A study of the behavior of beta-ammonio-substituted 5-hexenyl radicals, such as the 3,3-dimethyl-3-azonia-5-hexenyl radical (22), reveals that cyclization occurs readily. Treatment of 1-methyl-1-(2-(phenylselenyl)ethyl)-3-methylenepiperidinium iodide (20) with tributyltin hydride in tert-amyl alcohol yields the bridgehead nitrogen bicyclic heterocycle, 1,5-dimethyl-1-azoniabicyclo-[3.2.1]octane iodide (26), in excellent yield and without contamination, thus providing an attractive synthetic route to this hitherto unknown heterocyclic system.