Stereoretentive Formation of Cyclobutanes from Pyrrolidines: Lessons Learned from DFT Studies of the Reaction Mechanism.

The stereoselective synthesis of cyclobutanes that possess an array of stereocenters in a contiguous fashion has attracted the wide interest of the synthetic community. Cyclobutanes can be generated from the contraction of pyrrolidines through the formation of 1,4-biradical intermediates. Little else is known about the reaction mechanism of this reaction. Here, we unveil the mechanism for this stereospecific synthesis of cyclobutanes by means of density functional theory (DFT) calculations. The rate-determining step of this transformation corresponds to the release of N from the 1,1-diazene intermediate to form an open-shell singlet 1,4-biradical. The formation of the stereoretentive product is explained by the barrierless collapse of this open-shell singlet 1,4-biradical. The knowledge of the reaction mechanism is used to predict that the methodology could be amenable to the synthesis of [2]-ladderanes and bicyclic cyclobutanes.