Substituent-Controlled Divergent Photocyclization of Aza-1,5 Dienes to Access Three Distinct Cyclic Frameworks
Year: 2026
Type: preprint
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.
Source: ChemRxiv
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Award: G6263739292
OpenAlex ID: W7220360845