Programmable Regiodivergent Light-Driven Cyclisation of Acyclic 1,5-Dienes Unlocks Rigid Bicyclic Architectures

Controlling regioselectivity in radical cyclisations remains a major challenge in synthetic chemistry, hindering the efficient assembly of strained, rigid bicyclic architectures from simple acyclic precursors. Herein, we report a visible-light-mediated intramolecular [2+2] photocycloaddition of aza-1,5-dienes that successfully overcomes the classical “rule-of-five” selectivity governing radical cyclisations. By tuning the electronic properties of an easily removable amide N-substituent, we reprogram the initial energy-transfer-driven cyclisation event, diverging from the usually kinetically favoured 5-exo-trig to the 6-endo-trig pathway. As a result, closely related substrates can be selectively directed to generate either bridged bicyclo[2.1.1] or vastly underexplored fused bicyclo[2.2.0] architectures, both of which offer rich downstream derivatisation potential. Furthermore, an extensive computational study of this transformation revealed how the intricate interplay of electronic effects controls reaction regioselectivity. Overall, this work establishes a programmable, light-driven cyclisation strategy that enables precise and selective construction of distinct bicyclic frameworks within a unified reaction manifold.