Synthesis and isolation of a monoamine having a thermodynamically stabilized pseudo-chirotopic nitrogen

We have synthesized a tricyclic monoamine, (1S,4R)-(E)-7,3′-heptenylene-2,3:5,6-dibenzo-7-azabicyclo[2.2.1]heptane (1), by applying a ring-closing metathesis reaction in the key step of the synthetic route and by using preparative chiral HPLC for the separation. The X-ray crystallographic analysis of its salt with (1R)-camphor-10-sulfonic acid showed that the geometry and absolute configuration are (E) and (1S,4R), respectively. The theoretical calculations revealed that the inversion of the nitrogen atom at the 7-position of (1S,4R)-(E)-1 thus isolated takes place through a very slow process and that the configuration of the N(7) is highly biased to (R), indicating that (1S,4R)-(E)-1 is a thermodynamically controlled N-pseudo-chirotopic compound ((1S,4R,7R): (1S,4R,7S) = 99.68:0.32 at 120 °C).