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.
Della
Ernest W.
EW
Department of Chemistry, Flinders University, Bedford Park, South Australia 5042.
Knill
Andrew M.
AM