Substituent-Controlled Divergent Photocyclization of Aza-1,5 Dienes to Access Three Distinct Cyclic Frameworks
Abstract
Rigid, three-dimensional cyclic scaffolds are highly valued in medicinal chemistry, yet selectively accessing dis tinct cyclic frameworks from a common class of simple acyclic precursors remains a significant challenge. Herein, we report a precious-metal-free photochemical cyclization of aza-1,5-dienes that enables the substituent-controlled, divergent synthe sis of three distinct cyclic frameworks: bridged bicyclo[2.1.1]hexanes, fused bicyclo[2.2.0]hexanes, and six-membered lac tams. N-Aryl-substituted substrates preferentially undergo 5-exo-trig cyclization to afford bridged bicyclo[2.1.1]hexanes, whereas substrates bearing electron-withdrawing N-substituents such as acetyl or tosyl groups favor the 6-endo-trig pathway to furnish fused bicyclo[2.2.0]hexanes. Notably, this strategy was further extended to the synthesis of six-membered lactams from N-methyl-substituted aza-1,5-dienes under photosensitizer-free conditions. This work establishes a mild, substituent controlled strategy for skeletal divergence, enabling the selective synthesis of structurally diverse cyclic scaffolds of potential value in medicinal chemistry.
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BibTeX
@misc{zhang2026substituentcontrolled,
title = {{Substituent-Controlled Divergent Photocyclization of Aza-1,5 Dienes to Access Three Distinct Cyclic Frameworks}},
author = {Jun-Wei Zhang and Cui-Lian Zeng and Wei-Jun Dou and Yun-He Xu},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15009858/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009858/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Substituent-Controlled Divergent Photocyclization of Aza-1,5 Dienes to Access Three Distinct Cyclic Frameworks
AU - Jun-Wei Zhang
AU - Cui-Lian Zeng
AU - Wei-Jun Dou
AU - Yun-He Xu
PY - 2026
DA - 2026/10/05
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009858/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009858/v1
AB - Rigid, three-dimensional cyclic scaffolds are highly valued in medicinal chemistry, yet selectively accessing dis tinct cyclic frameworks from a common class of simple acyclic precursors remains a significant challenge. Herein, we report a precious-metal-free photochemical cyclization of aza-1,5-dienes that enables the substituent-controlled, divergent synthe sis of three distinct cyclic frameworks: bridged bicyclo[2.1.1]hexanes, fused bicyclo[2.2.0]hexanes, and six-membered lac tams. N-Aryl-substituted substrates preferentially undergo 5-exo-trig cyclization to afford bridged bicyclo[2.1.1]hexanes, whereas substrates bearing electron-withdrawing N-substituents such as acetyl or tosyl groups favor the 6-endo-trig pathway to furnish fused bicyclo[2.2.0]hexanes. Notably, this strategy was further extended to the synthesis of six-membered lactams from N-methyl-substituted aza-1,5-dienes under photosensitizer-free conditions. This work establishes a mild, substituent controlled strategy for skeletal divergence, enabling the selective synthesis of structurally diverse cyclic scaffolds of potential value in medicinal chemistry.
ER -