Synthesis of the new 2-azatricyclo[3.3.0.03,6]octane skeleton as a constrained proline analogue

Abstract

The synthesis of the tricyclic amino ester 12 is described. This constrained proline analogue contains the formerly unknown 2-azatricyclo[3.3.0.03,6]octane skeleton. A short 5 step sequence was developed allowing the production of 12 on a multi-gram scale. The key step consists of a stereoselective synthesis of a hydantoin that, after conversion to the amino ester, can be brominated and ring closed to the 2-azatricyclo[3.3.0.03,6]octane skeleton.