Triple energy transfer-enabled dearomative cycloaddition/rearrangement cascade of bicyclic azaarenes to structurally complex products
Abstract
Pyridine-fused, C( sp 3 )-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.
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BibTeX
@article{chahar2026triple,
title = {{Triple energy transfer-enabled dearomative cycloaddition/rearrangement cascade of bicyclic azaarenes to structurally complex products}},
author = {Preeti Chahar and Utpal Kundu and Subhabrata Dutta and Niklas Hölter and Florian Boser and Fabian Hugel and Luca Stadtmann and Constantin Daniliuc and Frank Glorius},
journal = {Nature Catalysis},
year = {2026},
month = jul,
doi = {10.1038/s41929-026-01566-z},
url = {https://hal.science/hal-05796256v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Triple energy transfer-enabled dearomative cycloaddition/rearrangement cascade of bicyclic azaarenes to structurally complex products
AU - Preeti Chahar
AU - Utpal Kundu
AU - Subhabrata Dutta
AU - Niklas Hölter
AU - Florian Boser
AU - Fabian Hugel
AU - Luca Stadtmann
AU - Constantin Daniliuc
AU - Frank Glorius
PY - 2026
DA - 2026/07/09
JO - Nature Catalysis
DO - 10.1038/s41929-026-01566-z
UR - https://hal.science/hal-05796256v1
AB - Pyridine-fused, C( sp 3 )-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.
SN - 2520-1158
ER -