Yinjiao Zhao,^† Yang Cheng,^† Shu-Lin Zhang, Le Yu,, David Lee Phillips, Jiani Ma*, and Yu Fang. J. Phys. Chem. Lett. 2025 DOI: https://doi.org/10.1021/acs.jpclett.5c03347

The efficient synthesis of heterocyclic compounds is crucial for the development of pharmaceuticals and functional materials. In recent years, photoirduced carbene reactions have emerged as a mild, catalyst-free, and green synthetic pathway, providing efficient methods for constructing complex heterocyclic systems. Among them, diazo compounds (e.g., α-diazo esters, α-diazo ketones) and acylsilanes, as two important types of photoactive precursors, have attracted considerable attention due to their ability to undergo rearrangement and cyclization under visible light.

Taking the diazo compound C1 as an example, its reaction pathway can be precisely controlled by the solvent: it efficiently converts into benzofused five-membered heterocycles in solvents such as acetonitrile, toluene, or DMF, while only trace amounts of products are observed in ethanol. Similar selectivity has been observed in studies on acyl silanes. For instance, olefin-functionalized acyl silane C2 undergoes intramolecular [2+1] cycloaddition under visible light to efficiently construct cyclopropane frameworks, whereas its carbon-chain-shortened analog C3 tends to yield pyran derivatives derived from silyl enol ethers. The underlying mechanisms remain to be fully elucidated, such as how solvents affect the electronic states of carbenes, how side-chain length determines the cyclization mode, and the dynamic behavior of key intermediates.

Figure 1. (A) Two types of carbene. (B) Photochemical reactions of the diazo compound and acylsilanes. (C) Our work uses fs-TA spectroscopy combined with DFT to unravel the photochemical reaction mechanisms of C1, C2, and C3.

To address these questions, the research team selected C1, C2, and C3 as model systems and combined femtosecond transient absorption spectroscopy with density functional theory calculations to systematically uncover the regulatory roles of solvent and chemical structure on carbene photoreactivity. The study reveals that solvents can effectively modulate carbene spin states: C1 tends to form triplet carbenes that undergo Stevens rearrangement in polar aprotic solvents, while in protic solvents, the system favors a singlet pathway leading to Wolff rearrangement. This finding clarifies the physical mechanism by which solvents switch reaction channels through influencing carbene spin states. At the same time, side-chain length was confirmed to determine reaction outcomes: C2, with its longer side chain, undergoes cycloaddition, whereas the shorter side chain of C3, due to spatial constraints, promotes a retro-Michael/Michael cascade reaction. This reveals that side-chain length can steer reactions toward different cyclization modes by modulating the stability of key intermediates.

Based on these results, a general principle is proposed: carbene reactivity is not solely determined by precursor structure but can be finely tuned through the synergistic effects of solvation and substituents. By establishing a direct correlation among excited-state dynamics, carbene spin states, and product selectivity, this work provides a mechanistic blueprint for developing green, catalyst-free, photo-driven cyclization strategies, which holds promise for advancing the design of precise synthetic methods targeting specific heterocyclic frameworks.

First Author: Zhao Yinjiao, master’s student, Cheng Yang, doctoral candidate, Shaanxi Normal University

Correspondence Author: Prof. Ma Jiani, Shaanxi Normal University

Full Text Link: https://doi.org/10.1021/acs.jpclett.5c03347