Synthesis of 4-membered ring alkaloid analogues via intramolecular [2+2] cycloaddition involving keteniminium salt intermediates

We have developed a very straightforward method for the synthesis of 4-membered ring alkaloid analogues via intramolecular 2+2] cycloadditions. This involves the cyclization of a keteniminium salt in which an alkene is linked by the nitrogen atom, and where, the resulting cyclobutane iminium is reduced in a diastereoselective manner. Competition reactions have been performed to fully understand the features of this sequence. Moreover, DFT calculations have verified that the 2+2] cycloaddition step is driven by kinetic and not thermodynamic factors confirming all the experimental observations.