Theoretical study of the mechanism of highly diastereoselective formation of a strained 3-azabicyclo[3.2.0]heptane derivative.

The mechanism of multicomponent reactions, especially stereoselective ones is of special importance in organic synthesis. The mechanism of diastereoselective formation of a highly strained 3-azabicyclo[3.2.0]heptane derivative through a catalyst-free multistep reaction is studied by DFT calculations in solution phase. The calculations on the two proposed mechanisms (pathways A and B) showed that the iminium ion, the relatively high energy species is not the approprite reaction intermediate. On the other hand, the lower activation energy of pathway B, as compared to that of pathway A, makes it as the preferred mechanism. The high stereoselectivity of the stepwise reaction may be attributed to the fact that the rate limiting and stereodifferentiating steps are the same. These findings may also account the formation of by-product in the experimental observations.