Preparation of novel bicyclic piperazines by reduction of bicyclo[4.2.2]diketopiperazines: rearrangement involving 1,2-bond migration

Reduction of (1 R ,6 R )-7,9-diazabicyclo[4.2.2]dec-3-ene-8,10-dione ( 5 ) with lithium aluminum hydride gave a mixture of the expected (1 R ,6 R )-7,9-diazabicyclo[4.2.2]dec-3-ene ( 2 ) as well as 7,9-diazabicyclo[4.3.1]dec-3-ene ( 3 ), resulting from 1,2-σ (C–C) migration of the pendant cis -2-butenyl ring. More of the rearranged product was observed in polar solvents and upon the addition of HMPA. The relief of ring strain imparted by the olefin may promote this rearrangement, as it was not observed when the olefin was reduced prior to the reduction.