Yang Cheng, Shu-Lin Zhang, Jessika Lammert, Le Yu, Yinjiao Zhao, Armido Studer,* Jiani Ma,* and Yu Fang. JACS Au, 2025, DOI: 10.1021/jacsau.5c01342

Photolabile protecting groups (PPGs), featuring light-triggered and spatiotemporally precise activation, have found broad applications in drug delivery, light-controlled synthesis, optogenetics, and related fields. Traditional carbonate-based photocaging strategies, however, suffer from laborious synthesis, the need for thermal decarboxylation after photolysis, and limited spatiotemporal precision. Benzoyl diisopropyl silane (BDIPS) has emerged as a new class of silicon-based, visible-light-responsive PPGs. Yet researchers have observed that BDIPS ethers with different structures yield distinct photoproducts: while some molecules successfully release alcohols, BDIPS ethers containing benzylic or allylic moieties exclusively produce ketone derivatives. This phenomenon lacks a unified mechanistic explanation, which has hindered the broader application of BDIPS.

Figure 1. Reactivity overview of photoexcited species of (A) carbonyl compounds, (B) acylsilanes, (C) alkoxyaroylsilanes and (D) The schematic outline of this work.

To address this challenge, the present study combines femtosecond transient absorption (fs-TA) spectroscopy with density functional theory (DFT) calculations to elucidate the photoreaction pathways of three model compounds (1a, 1b, and 1c). The results reveal that BDIPS ethers lacking activated α-hydrogens—such as 1a and 1c–1f (Figure 1)—favor a 1,2-silyl shift upon photoexcitation. This pathway proceeds with an almost negligible barrier, rapidly forming a highly reactive siloxycarbene intermediate, which subsequently undergoes O–H insertion with methanol, efficiently leading to alcohol deprotection. In contrast, BDIPS ethers containing activated α-hydrogens—such as benzylic or allylic groups (e.g., 1b, 1g, and 1h, Figure 1)—predominantly undergo 1,5-hydrogen atom transfer (1,5-HAT). The presence of α-H significantly lowers the HAT barrier, giving this pathway a clear kinetic advantage. Once a biradical intermediate is formed, it undergoes cyclization, protonation, and ring opening to yield a stable rearranged ketone.

A particularly representative discovery concerns the reaction mechanism of 1c, which forms an alcohol in methanol but yields a ketone derivative in acetonitrile. Potential energy surface analysis shows that the energy barriers for silyl migration and HAT are comparable in 1c, making it a prototypical “dual-pathway competitive system.” Methanol, with strong hydrogen-donating capability and hydrogen-bonding interactions, accelerates carbene insertion, rendering the silyl-shift pathway dominant. In contrast, acetonitrile provides a less stabilizing environment for the carbene, allowing the HAT pathway to prevail, thus favoring ketone formation. These findings fundamentally reveal how solvent environments regulate photochemical pathway selection.

Overall, this study fully elucidates the photochemical mechanism of BDIPS-based PPGs and introduces a new design principle based on structure–solvent cooperative control. Under identical photoexcitation conditions, selective formation of alcohol or ketone products can be achieved simply by tuning molecular structure and solvent environment. This insight shifts photochemical outcomes from passive consequences to actively programmable processes, offering valuable theoretical and practical guidance for applications in photocontrolled drug delivery, stimuli-responsive materials, and light-driven polymerization.

First Author: Cheng Yang, doctoral candidate, Shaanxi Normal University

Correspondence Authors: Prof. Ma Jiani, Shaanxi Normal University; Assoc. Prof. Armido Studer, University of Münster

Full Text Link: https://doi.org/10.1021/jacsau.5c01342