Synthesis of 7-azabicyclo[2.2.1]heptane, exo-2-chloro-7-azabicyclo[2.2.1]heptane, and derivatives

Abstract

A synthesis of 7-azabicyclo[2.2.1]heptane (1) in five steps and an overall yield of 18% has been achieved. An alternative five-step route which gives 1 in 36% yield but which requires large amounts of platinum oxide has also been developed. In comparison, the only previous synthesis of this compound gave less than a 1% overall yield of an impure product. Several N-acyl derivatives and the N-nitroso derivative have been prepared, and the barriers to rotation about the N—CO bond of the acetyl derivative and the N—NO bond of the nitroso derivative have been determined. The barriers were found to be 1.2 and 6.5 kcal less, respectively, than in their unstrained analogs. exo-2-Chloro-7-azabicyclo [2.2.1]heptane has also been synthesized.