Triple energy transfer-enabled dearomative cycloaddition/rearrangement cascade of bicyclic azaarenes to structurally complex products

Abstract

Pyridine-fused, C(sp3)-rich bridged frameworks are privileged scaffolds in natural products and pharmaceutical compounds, yet their synthesis remains a formidable challenge due to prevailing step-intensive routes. Energy transfer (EnT)-catalysed dearomative cycloadditions offer a milder approach to increase saturation in feedstock (hetero)arenes. Current methods exploiting the 1,4-biradical reactivity of bicyclic azaarenes mainly focus on [4+2] cycloadditions. However, achieving higher-order cycloadditions, such as [4+n] (n > 2), to construct pyridine-fused/bridged motifs, remains challenging. Here we report a cascade reaction combining a higher-order dearomative [5+4] photocycloaddition of bicyclic azaarenes and vinyl cyclopropanes with a formal [3,3]-sigmatropic rearrangement and a subsequent [2+2] photocycloaddition. This triple EnT-catalysed cascade provides a mild, one-pot protocol for efficiently accessing complex pyridine-fused/bridged pentacyclic motifs with excellent selectivity. Notably, the EnT-mediated formal [3,3]-sigmatropic rearrangement unveils a mechanistic paradigm in photochemical cascades. Mechanistic experiments and density functional theory studies support involvement of three sequential EnT steps, rationalizing the origin of regioselectivity and diastereoselectivity. (Figure presented.)