Computational evidence of a bifurcation in a Cope rearrangement proximate to a forbidden electrocyclization

Bifurcations are important features on the potential energy surface (PES) of chemical reactions. In particular, post-transition state bifurcations (PTSB) are increasingly observed in pathways relevant for the synthesis of complex chemical structures. In these reactions, the pathway bifurcates after a single transition structure (TS), resulting in a distribution of two distinct products. Recognizing the presence of PTSB in chemical reactions is crucial for predicting reaction outcomes. This importance stems from the need to move away from the conventional one-dimensional view of reaction pathways. We investigate the Cope rearrangement of 3,4-divinylcyclobut-1-ene, a versatile scaffold used in the synthesis of natural products. While this rearrangement was previously thought to proceed via a single pathway based on DFT calculations, our complete active space self-consistent field (CASSCF) approach has uncovered a PTSB in this pathway. This is due to the presence of a Woodward-Hoffmann (WH) forbidden 8π electrocyclization, which alters the PES, producing a TS similar in energy to the Cope TS. Our findings emphasize the importance of multi-reference methods and the role of forbidden WH pathways in this well-studied class of reactions, providing new insights into the selectivity between different products in the Cope rearrangement.