Photocatalysis as a mechanistic probe for the Staudinger β-lactam synthesis

In this study, we demonstrate that a visible-light-mediated energy transfer process can serve as a mechanistic probe in the Staudinger cyclization. Ikeda demonstrated that N-acyl enaminone substrates undergo diastereoselective cyclization to form β-lactams under UV irradiation. We reinvestigated this process, employing energy transfer catalysis and Hammett studies, which enabled us to conclude that these reactions proceed in the T₁ state via the formation of a zwitterionic intermediate. This is in contrast to previous explanations, which suggest that the reaction proceeds via the S₁ state and involves a ground-state open-shell biradical. In-depth computational investigations support the zwitterionic hypothesis, with the final ring-closing process being radical. The rate of intersystem crossing was found to be critical in controlling the geometry of the zwitterionic intermediate, being ultimately responsible for the observed diastereoselectivity. Finally, a crossover experiment confirms reversibility in formation of the zwitterionic intermediate, experimentally validating a long-standing hypothesis.