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. 2025 Nov 28;5(12):6334–6342. doi: 10.1021/jacsau.5c01342

Photoinduced Alcohol and Ketone Generation from Alkoxyaroylsilanes: Mechanistic Insights into Competing Radical Pathways

Yang Cheng †, Shu-Lin Zhang †, Jessika Lammert ‡, Le Yu §, Yinjiao Zhao †, Armido Studer ‡,*, Jiani Ma †,*, Yu Fang †
PMCID: PMC12728622  PMID: 41450625

Abstract

Acylsilanes represent a unique class of organosilicon compounds with distinctive photochemical reactivities, including hydrogen atom transfer (HAT) and silyl shift pathways. Recently, a new photolabile protecting group (PPG) benzoyldiisopropylsilane (BDIPS) featuring an acylsilane functionality was introduced for alcohol protection. While the photomediated deprotection of aliphatic silyl ethers in methanol provided the free alcohols, BDIPS-protected benzyl or allyl alcohols resulted in rearranged ketones upon photoexcitation in acetonitrile. In this work, we systematically investigate the photochemical behavior of different BDIPS-ethers, focusing on the mechanistic divergence leading to either alcohol release as PPG or rearranging ketone formation. Through a combined approach of femtosecond transient absorption spectroscopy and density functional theory calculations, we elucidate the competing reaction pathways for model compounds 1a, 1b, and 1c. Our results reveal that the presence of an α-hydrogen adjacent to an olefinic moiety kinetically favors the HAT pathway, yielding rearranged ketone products, while its absence promotes a silyl shift mechanism that results in efficient alcohol photodeprotection. Furthermore, solvent-dependent studies demonstrate distinct photoreaction behaviors for 1c in methanol and acetonitrile, underscoring the role of the local chemical environment in steering reaction outcomes. This study provides fundamental insights into the structure–reactivity relationships of acylsilane-based PPGs and offers a strategic basis for the rational design of photoresponsive systems with programmable release properties.

Keywords: photolabile protecting group, theoretical calculations, ultrafast spectroscopy, photochemistry, acylsilane

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Introduction

Acylsilanes constitute a unique class of organosilicon compounds characterized by a carbonyl group directly bonded to a silicon atom (R1–C­(O)–SiR3). − Acylsilanes exhibit distinct electronic and structural properties compared with conventional aromatic carbonyl compounds. These distinctive structural features give rise to novel reactivity patterns, most notably through photochemical hydrogen atom transfer (HAT) and facile silyl shift. The HAT process is among the most extensively studied photoreactions in aromatic carbonyl chemistry, with well-established mechanisms in benzophenone and anthraquinone derivatives serving as paradigmatic examples. Upon photoexcitation, the triplet excited state of an aromatic carbonyl group undergoes intra- or intermolecular HAT. Conversely, the polarization of the aromatic carbonyl groupenhanced by the adjacent silicon atom via the β-silicon effectenables photoinduced 1,2-silyl shifts in acylsilanes. , This process generates reactive siloxycarbene intermediates upon excitation, further expanding their synthetic utility.

Photolabile protecting groups (PPGs) for diverse functional groups hold significant promise in synthetic and biological chemistry. − Their successful applications in total synthesis, controlled drug release, optogenetics, photolithography, photoimaging, and other fields have spurred the development of new PPGs with enhanced and diversified functionalities. Hydroxy groups can be effectively protected by various PPGs, such as 2-nitrobenzyl, 3,5-dimethoxybenzoin, phenacyl, and silyl ether derivatives. , However, the poor leaving group ability of alcohols generally necessitates their conjugation to PPGs through carbonate linkages. , Although conceptually straightforward, this strategy has notable drawbacks: carbonates are often less synthetically accessible than ether linkages. Moreover, following photolytic cleavage, the released carbonic acid monoalkyl esters typically undergo subsequent thermal decarboxylation, which compromises the precise temporal control afforded by photoactivation.

Recently, Studer and co-workers developed a new PPG platform based on benzoyldiisopropylsilane (BDIPS), featuring alkyl-group substitutions (like 1a and 1c-1f in Scheme ) for alcohol protection. This class of PPGs can be readily synthesized on a large scale and exhibited good photostability. Direct and efficient release of alcohols (photodeprotection efficiency of 87–99%) is achieved upon visible-light (456 nm) irradiation in protic solvents such as methanol (MeOH). It is proposed that upon photoexcitation a silyl shift occurs to generate siloxycarbene (Scheme B), which undergoes insertion into the O–H bond with the assistance of MeOH, forming unstable acetals. Finally, the deprotection of alcohols occurs after a solvolysis process. On the other hand, for BDIPS-protected benzyl or allyl alcohols (like 1b, 1g, and 1h in Scheme ), photoexcitation in acetonitrile (ACN) results in ketones with concomitant C–C bond formation. Based on the NMR studies, it is assumed that a 1,5-HAT from the activated benzylic or allylic C–H bond occurs with the generation of a diradical species, which undergoes a Norrish type II process to yield a silaoxetane, followed by decomposition to the corresponding ketone product. 1c presents an intriguing case: while it retains the HAT channel through its CH2 group adjacent to oxygen (similar to 1b), the photodeprotection of alcohol is detected like that for 1a.

1. Reactivity Overview of Photoexcited Species of (A) Carbonyl Compounds, (B) Acylsilanes, and (C) Alkoxyaroylsilanes and (D) the Schematic Outline of This Work.

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The behavior of 1c triggered us to unravel the factors that dictate the divergent reactivity patterns for BDIPS-ethers under photoexcitation. We start our mechanistic investigation from the selected BDIPS-ethers 1a and 1b as model substrates for the photodeprotection of alcohol and photoinduced ketone formation, respectively. With this benchmark knowledge in hand, we move on to investigate the unexpected behaviors of 1c. With the help of femtosecond transient absorption (fs-TA) and density functional theory (DFT) as well as time-dependent DFT (TD-DFT) calculations, it is revealed that the presence of an α-hydrogen adjacent to an olefinic moiety kinetically favors hydrogen atom transfer, yielding ketone products, while its absence promotes a silyl shift that results in efficient alcohol photodeprotection. Furthermore, solvent-dependent studies demonstrate distinct photoreaction behaviors for 1c in MeOH (releasing alcohol) and ACN (forming rearranged ketone), underscoring the role of the local chemical environment in steering reaction outcomes. The mechanistic insights presented here not only advance the fundamental understanding of the solvent-dependent and chemical structure-related acylsilane photochemistry but also provide a strategic foundation for the rational design of photoresponsive systems with programmable release properties.

Results and Discussion

Photophysical Properties of 1a, 1b, and 1c

Figure illustrates the frontier orbitals, electronic structures, and photophysical properties of compounds 1a, 1b, and 1c as determined by DFT calculations. The experimental ultraviolet–visible (UV–vis) spectras of 1a, 1b, and 1c are displayed in Figure S4 (see the Supporting Information). The excellent agreement between the experimental and computed UV–vis absorption spectra (Figure S4) confirms the reliability of the computational method. As shown in Figure A, the first singlet excitation (S1) of the three molecules involves an n → π* transition from the highest occupied molecular orbital (HOMO) to the lowest unoccupied molecular orbital (LUMO). Usually, the n → π* transition is weakly allowed or even formally forbidden, often regarded as “dark state”. For 1a, 1b, and 1c, natural bond orbital (NBO) analysis reveals pronounced donor–acceptor hyperconjugative interactions. Specifically, all three molecules exhibit notable σ­(Si–C) → π*­(C–C) hyperconjugative interactions, as evidenced by significant electron delocalization and corresponding second-order perturbation energies E(2) of 4.53, 4.52, and 4.61 kcal·mol–1, respectively. These interactions reduce the HOMO–LUMO gaps in 1a, 1b, and 1c, thereby enabling photochemical reactions under visible-light irradiation.

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(A) Frontier orbitals and orbital energies, (B) schematic illustration of the σ­(Si–C) → π*­(C–C) hyperconjugation effect with the corresponding NBO second-order perturbative stabilization energies (E(2)), and (C) calculated photophysical processes including ISC rates and spin-orbit coupling matrix element, for compounds 1a, 1b, and 1c.

As shown in Figure C, the energy level diagram illustrates adiabatic excitation from the ground state (S0) to S1, followed by intersystem crossing (ISC) to the T2 state for all three molecules. The relatively small singlet–triplet energy gaps (ΔE(S1 – T2)) and substantial spin–orbit coupling (SOC) matrix elements suggest efficient ISC transformation in each compound. The T2 state then rapidly relaxes to the T1 state via internal conversion, from which the subsequent photochemical reactions are predominantly initiated.

Investigation of the Photorelease Reaction Mechanism of 1a

When we performed the fs-TA test for 1a in MeOH (Figure A), as the absorbance at 345 nm decreased, the signal at 455 nm was populated with the isosbestic point at 400 nm. Based on the TD-DFT simulated electronic absorption spectra (Figure S5), the intermediate absorbing at 345 nm is assigned to the S1 state of 1a, while the subsequently generated species is identified as its triplet state 1a­(T 1 ). Later, 1a­(T 1 ) decayed, and a new intermediate species was formed with characteristic signals at 420 and 455 nm. The free energy diagram for 1a was mapped using (TD)­B3LYP-D3/6–311+G** (MeOH) computations (Figure B). Upon formation, 1a­(T 1 ) undergoes a 1,2-silyl shift reaction (ΔG = −12.75 kcal·mol–1) to generate triplet α-siloxycarbene intermediate 1a–a, with a minimal activation barrier of 0.30 kcal·mol–1. We therefore compared the TA spectrum of the emerging intermediateobserved after the decay of 1a­(T 1 )with TD-DFT simulated spectrum of 1a–a. The good correlation leads to the assignment of the intermediate showing up at 420 and 455 nm to form 1a–a. Thereafter, 1a–a undergoes an ISC process to produce a singlet-carbene 1a–b, which abstracts a proton from the solvent MeOH molecule by overcoming an energy barrier of 4.79 kcal·mol–1, thereby forming the ion pair 1a–c. Subsequently, recombination of the ions across a barrierless process to give 1a–d. This process is consistent with previous studies regarding the reactivity of a carbene with MeOH. The reaction sequence concludes with the MeOH-mediated deprotection of adamantanol.

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(A) fs-TA spectra of 1a in MeOH (λex = 266 nm), (B) the free energy diagram of the photodeprotection of the alcohol pathway for 1a, and (C) the proposed photochemical reaction mechanism of 1a.

Notably, MeOH facilitates the photodeprotection reaction through dual roles: (a) serving as a reagent for the carbene insertion and then (b) a second equivalent is used for the solvolysis of the bissilyl ether intermediate. On the other hand, MeOH is known to act as a hydrogen-donating solvent capable of engaging in photochemical intermolecular HAT with the triplet state of aromatic carbonyl oxygen. To test the possibility of this pathway for 1a, we compared the fs-TA results in MeOH with that in ACN (Figure S6), an inert organic solvent. The identical spectral features suggest that the same photochemical reaction is probed for 1a regardless of the solvent environment. This conclusion is further supported by DFT calculations, which unravel a high activation barrier (ΔG ‡ = 19.2 kcal·mol–1, Figure S7) for intermolecular HAT between 1a­(T 1 ) and MeOH, in contrast to the nearly barrierless 1,2-silyl shift (ΔG ‡ = 0.30 kcal·mol–1). Overall, the 1,2-silyl shift reaction is the dominant pathway, estimated to proceed approximately 1013 times faster than the intermolecular HAT reaction.

Investigation of the Photoinduced Ketone Formation Mechanism of 1b

Our attention then turned to investigate the photochemical reaction mechanism for the benzyl-substituted molecule 1b. Analysis of the fs-TA spectra for 1b in both MeOH (Figure A) and ACN (Figure S8) reveals spectral features remarkably similar to those observed for 1a. This similarity initially indicates that a 1,2-silyl shift might occur following triplet state formation for 1b as that for 1a. However, this hypothesis is totally contradictory to the steady-state experimental results, where 1b yields a ketone product instead of the alcohol product obtained for 1a. To resolve the discrepancy between the TA and steady-state results and to elucidate the factors governing the divergent product formation of these structurally analogous compounds, we mapped the free energy diagram for the photoinduced ketone formation of 1b by using (TD)­DFT calculations.

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(A) fs-TA spectra of 1b in MeOH (λex = 266 nm), (B) the free energy diagram of the photoinduced ketone generation pathway for 1b, and (C) the proposed photochemical reaction mechanism of 1b.

As illustrated in Figure , after forming 1b­(T 1 ), it further reacts through a 1,5-HAT generating 1b-a­(T). Then, triplet biradical 1b–a­(T) undergoes intersystem crossing to singlet state and cyclization reaction leads to structure 1b–b. For 1b–b, there are two possible diastereoisomers (for each diastereoisomer, two major conformations were found). Among them, the relative configuration with the two phenyl groups at opposite site of the 4-membered ring as shown in the figure corresponds to the more stable one, as expected for steric reasons. The two most stable conformations and relative energies of the two diastereoisomers are provided in Figure S9. Thereafter, 1b–b is protonated in the presence of hydrochloric acid forming 1b–c, which then fragments overcoming a tiny reaction energy barrier of 3.49 kcal·mol–1 to generate (Z)-1,2-diphenylethen-1-ol (1b–d). Finally, 1b–d tautomerizes to its ketone form 1b–e with the assistance of MeOH. Briefly, the photoinduced generation of ketone from 1b goes exothermically through the following processes: (1) HAT (−14.24 kcal·mol–1), (2) cyclization reaction (−23.27 kcal·mol–1), (3) protonation (−19.86 kcal·mol–1), (4) fragmentation reaction (−9.27 kcal·mol–1), and (5) enol-keto tautomerization (−10.33 kcal·mol–1).

Based on the above mechanistic studies on 1a and 1b, 1,2-silyl shift is identified as the essential step leading to the alcohol formation, whereas ketone formation proceeds via the 1,5-HAT process. To elucidate why no alcohol product was detected for 1b, DFT calculations were performed (Figure S10). The analysis revealed an obvious higher energy barrier for the 1,2-silyl shift pathway (ΔG ‡ = 8.83 kcal·mol–1) compared to that for the 1,5-HAT process (ΔG ‡ = 2.54 kcal·mol–1). This kinetic preference results in a calculated product ratio of 4.1 × 104 favoring ketone over alcohol formation, well explaining the experimental observation of exclusive ketone generation upon photoexcitation of 1b. However, how can we account for the identical fs-TA spectral features observed for both 1b and 1a? Intriguingly, the simulated electronic absorption spectrum for the HAT-derived triplet intermediate 1b–a showed remarkable similarity to that of the siloxycarbene intermediate produced from the 1,2-silyl shift (Figure S11). Thus, the nearly identical TA signals observed for 1b and 1a can be attributed to this spectral similarity, even though the two compounds undergo fundamentally different photochemical reaction pathways. The remaining final question is whether 1b would undergo an intermolecular HAT reaction from MeOH if it is used as the solvent? Our DFT calculations revealed that the energy barrier for the intermolecular HAT from MeOH to excited 1b (18.01 kcal·mol–1, Figure S12) is significantly higher than that for the intramolecular process (2.54 kcal·mol–1), thereby precluding the intermolecular pathway.

Elucidating the Photochemical Reaction Mechanisms of 1c

Unexpectedly, 1c exhibited different photochemical reaction behaviors in MeOH and ACN. Figure S13 presents the time-dependent evolution of the steady-state absorption spectra of compound 1c under 266 nm light irradiation in MeOH and ACN. As irradiation time increases in MeOH, the spectra display prominent absorption signals at 255 and 425 nm, which rapidly diminish over time, with no emergence of new signals. In contrast, irradiation in ACN results in a similar decrease of the signals at 255 and 425 nm, but also induces the emergence of a new absorption band at 360 nm. Complementary NMR and mass spectrometric (Figures S14–S17) analyses further confirm that 1c follows different photoreaction pathways in MeOH and ACN. In MeOH, it undergoes photodeprotection to afford the corresponding alcohol, whereas in ACN, it yields a ketone product.

Compound 1c exhibits nearly identical fs-TA signals in MeOH and ACN (Figure S18). This phenomenon arises from the close resemblance between the simulated electronic absorption spectrum of the HAT-derived intermediate and that of the siloxycarbene formed via the 1,2-silyl shift (Figure S19), even though 1c undergoes fundamentally different photochemical pathways in the two solvents. DFT calculations were performed (Figure ) to rationalize the distinct reactivities of 1c in MeOH and ACN. The calculated free energy of 1,5-HAT and silyl shift reaction for 1c both in ACN and MeOH are summarized in Table S1. It is noted that the two pathways of 1c exhibited comparable energy barriers. To rule out possible functional dependence, the calculations were performed using ωB97XD and CAM-B3LYP functionals, respectively (Table S2). The results show that the calculated energy barriers are only slightly affected by the choice of functional. On one hand, the photorelease reaction in MeOH occurs following a reaction pathway similar to that observed for 1a, with the exception that the energy barrier of the 1,2-silyl shift (8.74 kcal·mol–1) is higher compared to that for 1a. In the silyl shift reaction, the strong inductive electron-withdrawing effect of the 1-adamantyloxy group in 1a reduces the electron density at silicon and weakens the Si–C bond, whereas the cyclohex-3-en-1-yloxy substituent in 1c, with weaker electron withdrawal and partial π-conjugation, strengthens the bond. Consequently, the silyl shift barrier of 1a is significantly lower than that of 1c. On the other hand, for the photoinduced ketone formation in ACN, the 1,5-HAT barrier of 1c is 5.81 kcal·mol–1 higher than that of 1b. Notably, NBO analysis (Figure S21) reveals that the C–H bonds at the benzylic or allylic positions are perturbed by the adjacent CC bond, resulting in σ-electron delocalization. This delocalization weakens the C–H bonds, facilitating their cleavage and promoting the HAT process, thereby accounting for the observed difference in HAT barriers between 1b and 1c. We currently assume that both the 1,5-HAT and also the silyl shift are reversible for 1c and in the presence of MeOH only the H–O-insertion reaction takes place, while in ACN, only ketone formation can occur.

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Free energy diagram of (A) the photoinduced ketone generation pathway, (B) photodeprotection of the alcohol reaction pathway for 1c, and (C) the proposed photochemical reaction mechanism of 1c.

With this mechanistic understanding of the photochemistry of 1a–1c in hand, we subsequently examined the substituent effects. Computational analyses (Table ) reveal that a substituent featuring an α-H adjacent to an olefinic moiety (allylic or benzylic) facilitates activation of the corresponding C–H bond, thereby favoring the HAT pathway kinetically, as demonstrated in compounds 1b, 1g, and 1h. However, in the absence of an α-H, or when the α-H is not activated by a π-system, the photochemical reaction of BDIPS-ether proceeds through a distinct pathway. Compounds 1d-1f exhibit energy barriers similar to those of 1c, further supporting the generality of the proposed mechanism on these molecular systems.

1. Summary of Energy Barriers and ΔG Values for HAT and Si-Shift Reactions of Compounds 1a-1g in MeOH.

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Conclusions

In summary, this study provides a comprehensive mechanistic elucidation of the photochemical reactivity of BDIPS-based PPGs, highlighting the critical factors that govern the competition between HAT and silyl shift pathways. Alcohol release proceeds via a 1,2-silyl shift that generates siloxycarbenes, whereas rearrangement to form a ketone arises from an intramolecular 1,5-HAT process. Substituent effects play a decisive role: the presence of α-hydrogens adjacent to olefinic groups lowers the HAT barrier and favors ketone formation, while their absence promotes the silyl shift pathway. Solvent polarity further modulates these competing channels, as exemplified by the distinct reactivity of compound 1c in MeOH and ACN.

These insights establish the dual role of silicon in PPG design: enabling bathochromic absorption via σ-π* hyperconjugation and facilitating selective bond cleavage through β-silicon assistance. By circumventing the limitations of carbonate-type systems, BDIPS scaffolds offer a promising platform for developing protecting groups with controlled and efficient release. Future optimization should focus on enhancing light-harvesting capability and excited-state reactivity through π-extension or substituent engineering. Overall, our mechanistic framework provides a rational basis for designing next-generation silicon-based PPGs with tunable photochemical outcomes and expanded functional scope.

Experimental Section

Synthesis of Compounds

1a, 1b, and 1c were prepared following the reported methods.

1a. 1H NMR (400 MHz, CDCl3): δ = 8.15 (dt, J = 6.8, 1.6 Hz, 2H), 7.53 – 7.43 (m, 3H), 2.17 – 2.09 (m, 3H), 1.87 (d, J = 3.2 Hz, 6H), 1.60 (s, 6H), 1.30 (hept, J = 7.3 Hz, 2H), 1.08 (d, J = 7.3 Hz, 6H), 1.05 (d, J = 7.3 Hz, 6H).

1b. 1H NMR (400 MHz, CDCl3): δ = 8.07 – 8.05 (m, 2H), 7.55 – 7.51­(m, 1H), 7.44 – 7.29 (m, 7H), 4.96 (s, 2H), 1.38 (hept, J = 7.4 Hz, 2H), 1.13­(d, J = 7.4 Hz, 6H), 1.10 (d, J = 7.4 Hz, 6H).

1c. 1H NMR (400 MHz, CDCl3): δ = 8.08 – 8.06 (m, 2H), 7.54 – 7.47 (m, 3H), 5.70 (d, J = 2.4 Hz, 2H), 3.73 (d, J = 6.0 Hz, 2H), 2.18 – 2.07 (m, 3H), 1.89–1.81 (m, 3H), 1.34 – 1.25 (m, 3H), 1.10 (d, J = 7.3 Hz, 6H), 1.06 (d, J = 7.3 Hz, 6H).

fs-TA Experiment

A femtosecond regenerative amplified Ti:sapphire laser system was applied to carry out the fs-TA experiments. A white continuum light was selected as the probe pulse, which was generated in a CaF2 crystal by about 5% of the amplified 800 nm output obtained from the laser system. The probe pulse was divided into two beams; one beam would pass the sample solution sealed in a 2 mm path-length cuvette, and the other was used as a reference to monitor the stability of the probe pulse. A 266 nm laser beam was employed to excite 1a, 1b, and 1c.

DFT Calculations

All the calculations have been performed using the Gaussian 16 package within the time-dependent and density functional theory frameworks, to model the excited-state and ground-state intermediate properties, respectively. The (U)­B3LYP-D3/6–311+G** level was used to optimize structures and vibrational frequencies for intermediates and transition states (TSs) involved in the reaction pathways. The structures of the TSs have only one imaginary frequency, while the reactants, complexes, intermediates, and products have all positive vibrational frequencies. Intrinsic reaction coordinate (IRC) calculations were performed to confirm the connectivity between the transition state and the appropriate reactant or product. Potential energy surface scans were used to find suitable transition states and lower energy or lowest guess structures. All of the geometry optimizations have been carried out in respective solvent systems, utilizing the implicit solvation model based on density (SMD) to estimate the effect of the environment. The spin–orbit coupling matrix elements (SOCME) were calculated at the TD-DFT/B3LYP/6–311G** level of theory with spin–orbit mean-field (SOMF) methods and the ISC rates with ESD­(ISC) model employing the ORCA 5.0.3 program. The spin densities and NBO analysis were performed using Multiwfn software. For the simulated electronic absorption spectra, a half-width of 1800 cm–1 and the scale factor of 1.0 was applied consistently to all computed spectra.

Supplementary Material

au5c01342_si_001.pdf (2.3MB, pdf)

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacsau.5c01342.

  • Synthetic route of compounds with the 1H NMR spectra discussed in the text; fs-TA spectra for intermediate species in different solvents; calculated free energy diagrams and structural isomers of key intermediates; MS and 1H NMR characterization before and after irradiation; and hyperconjugation and C–H bond energy analyses (PDF)

∥.

Y.C. and S.L.Z. contributed equally to this work. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. CRediT: Yang Cheng data curation, formal analysis, investigation, methodology, visualization, writing - original draft; Shu-Lin Zhang formal analysis, methodology, writing - review & editing; Jessika Lammert methodology, writing - review & editing; Le Yu supervision, writing - review & editing; Yinjiao Zhao methodology, writing - review & editing; Armido Studer investigation, supervision, validation, writing - review & editing; Jiani Ma data curation, investigation, resources, supervision, validation, writing - review & editing; Yu Fang resources, writing - review & editing.

The research was supported by grants from the National Natural Science Foundation of China for Excellent Young Scholars (22322301) to Jiani Ma.

The authors declare no competing financial interest.

References

  1. Zhang H.-J., Priebbenow D. L., Bolm C.. Acylsilanes: valuable organosilicon reagents in organic synthesis. Chem. Soc. Rev. 2013;42(21):8540–8571. doi: 10.1039/c3cs60185d. [DOI] [PubMed] [Google Scholar]
  2. Hong W. P., Lim H. N., Shin I.. Recent progress and perspectives in photo-induced organic reactions of acylsilanes. Org. Chem. Front. 2023;10(3):819–836. doi: 10.1039/D2QO01772E. [DOI] [Google Scholar]
  3. Zhang Y., Zhou G., Liu S., Shen X.. Radical Brook rearrangement: past, present, and future. Chem. Soc. Rev. 2025;54(4):1870–1904. doi: 10.1039/D4CS01275E. [DOI] [PubMed] [Google Scholar]
  4. Li N.-Y., Zhang W., Yang D.-N., Wang P., Han M.-Y.. Visible-light-induced radical reaction of acylsilanes through solvent-controlled Norrish type I cleavage. Org. Biomol. Chem. 2025;23(37):8452–8458. doi: 10.1039/D5OB01095K. [DOI] [PubMed] [Google Scholar]
  5. Dantas J. A., Correia J. T. M., Paixão M. W., Corrêa A. G.. Photochemistry of carbonyl compounds: Application in metal-free reactions. ChemPhotoChem. 2019;3(7):506–520. doi: 10.1002/cptc.201900044. [DOI] [Google Scholar]; Turro, N. J. ; Ramamurthy, V. ; Scaiano, J. C. . Modern Molecular Photochemistry of Organic Molecules; University Science Books, 2010. [Google Scholar]; Situ Z., Lu M., Chen W., Xie Z., Chen S. L., Dang L., Li M.-D.. Boosting the release of leaving group from blebbistatin derivative photocages via enhancing intramolecular charge transfer and stabilizing cationic intermediate. J. Phys. Chem. Lett. 2023;14(51):11580–11586. doi: 10.1021/acs.jpclett.3c02970. [DOI] [PubMed] [Google Scholar]; Fréneau M., Lefebvre C., Gómez Fernández M. A., Richard C., Hoffmann N.. Photochemical reactivity of phenyl (methyl-tetrazolyl) ketone – hydrogen atom transfer vs. electron transfer. New J. Chem. 2019;43(44):17151–17158. doi: 10.1039/C9NJ03061A. [DOI] [Google Scholar]; Zhang X., Ma J., Phillips D. L.. To photoredox or not in neutral aqueous solutions for selected benzophenone and anthraquinone derivatives. J. Phys. Chem. Lett. 2016;7(23):4860–4864. doi: 10.1021/acs.jpclett.6b02403. [DOI] [PubMed] [Google Scholar]
  6. Dormán G., Nakamura H., Pulsipher A., Prestwich G. D.. The life of Pi star: Exploring the exciting and forbidden worlds of the benzophenone photophore. Chem. Rev. 2016;116(24):15284–15398. doi: 10.1021/acs.chemrev.6b00342. [DOI] [PubMed] [Google Scholar]; Ma J., Zhang X., Phillips D. L.. Time-resolved spectroscopic observation and characterization of water-assisted photoredox reactions of selected aromatic carbonyl compounds. Acc. Chem. Res. 2019;52(3):726–737. doi: 10.1021/acs.accounts.8b00619. [DOI] [PubMed] [Google Scholar]
  7. Flegel M., Lukeman M., Huck L., Wan P.. Photoaddition of water and alcohols to the anthracene moiety of 9-(2’-hydroxyphenyl)­anthracene via formal excited state intramolecular proton transfer. J. Am. Chem. Soc. 2004;126(25):7890–7897. doi: 10.1021/ja039078g. [DOI] [PubMed] [Google Scholar]
  8. Brook A. G.. Triphenylsilyl phenyl ketone. J. Am. Chem. Soc. 1957;79(16):4373–4375. doi: 10.1021/ja01573a036. [DOI] [Google Scholar]; Priebbenow D. L.. Insights into the stability of siloxy carbene intermediates and their corresponding oxocarbenium ions. J. Org. Chem. 2019;84(18):11813–11822. doi: 10.1021/acs.joc.9b01698. [DOI] [PubMed] [Google Scholar]; Kirmse W., Guth M., Steenken S.. Production of α-siloxycarbenium ions by protonation of photochemically generated α-siloxycarbenes. Formation mechanism and reactivities with nucleophiles. J. Am. Chem. Soc. 1996;118(44):10838–10849. doi: 10.1021/ja9603970. [DOI] [Google Scholar]; Holownia A., Apte C. N., Yudin A. K.. Acyl metalloids: conformity and deviation from carbonyl reactivity. Chem. Sci. 2021;12(15):5346–5360. doi: 10.1039/D1SC00077B. [DOI] [PMC free article] [PubMed] [Google Scholar]; Lambert J. B., Zhao Y., Emblidge R. W., Salvador L. A., Liu X., So J.-H., Chelius E. C.. The β effect of silicon and related manifestations of σ conjugation. Acc. Chem. Res. 1999;32(2):183–190. doi: 10.1021/ar970296m. [DOI] [Google Scholar]
  9. Klán P., Solomek T., Bochet C. G., Blanc A., Givens R., Rubina M., Popik V., Kostikov A., Wirz J.. Photoremovable protecting groups in chemistry and biology: reaction mechanisms and efficacy. Chem. Rev. 2013;113(1):119–191. doi: 10.1021/cr300177k. [DOI] [PMC free article] [PubMed] [Google Scholar]; Weinstain R., Slanina T., Kand D., Klan P.. Visible-to-NIR-light activated release: from small molecules to nanomaterials. Chem. Rev. 2020;120(24):13135–13272. doi: 10.1021/acs.chemrev.0c00663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Wang P.. Photolabile protecting groups: structure and reactivity. Asian J. Org. Chem. 2013;2(6):452–464. doi: 10.1002/ajoc.201200197. [DOI] [Google Scholar]; Xiong H., Xu Y., Kim B., Rha H., Zhang B., Li M., Yang G.-F., Kim J. S.. Photo-controllable biochemistry: Exploiting the photocages in phototherapeutic window. Chem. 2023;9(1):29–64. doi: 10.1016/j.chempr.2022.11.007. [DOI] [Google Scholar]; Li H., Wang J., Jiao L., Hao E.. BODIPY-based photocages: rational design and their biomedical application. Chem. Commun. 2024;60(45):5770–5789. doi: 10.1039/D4CC01412J. [DOI] [PubMed] [Google Scholar]; Shrestha P., Kand D., Weinstain R., Winter A. H.. meso-Methyl BODIPY photocages: Mechanisms, photochemical properties, and applications. J. Am. Chem. Soc. 2023;145(32):17497–17514. doi: 10.1021/jacs.3c01682. [DOI] [PubMed] [Google Scholar]; Nguyen H. D., Abe M.. Crucial roles of leaving group and open-shell cation in photoreaction of (coumarin-4-yl)­methyl derivatives. J. Am. Chem. Soc. 2024;146(15):10993–11001. doi: 10.1021/jacs.4c02880. [DOI] [PubMed] [Google Scholar]; Liu Y., Wang T., Wang W.. Photopharmacology and photoresponsive drug delivery. Chem. Soc. Rev. 2025;54:5792–5835. doi: 10.1039/D5CS00125K. [DOI] [PubMed] [Google Scholar]; Schulte A. M., Alachouzos G., Szymanski W., Feringa B. L.. The fate of the contact ion pair determines the photochemistry of coumarin-based photocleavable protecting groups. Chem. Sci. 2024;15(6):2062–2073. doi: 10.1039/D3SC05725A. [DOI] [PMC free article] [PubMed] [Google Scholar]; Dissanayake K. C., Walid M. K. I., Austin M., Smith E. A., Winter A. H.. A structurally compact aqueous soluble oxypicolinium photocage with high photosensitivity. Chem. Sci. 2025;16(15):6418–6424. doi: 10.1039/D5SC00204D. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Pirrung M. C., Fallon L., Zhu J., Lee Y. R.. Photochemically removable silyl protecting groups. J. Am. Chem. Soc. 2001;123(16):3638–3643. doi: 10.1021/ja002370t. [DOI] [PubMed] [Google Scholar]
  12. Specht A., Goeldner M.. 1-(o-Nitrophenyl)-2,2,2-trifluoroethyl ether derivatives as stable and efficient photoremovable alcohol-protecting groups. Angew. Chem., Int. Ed. 2004;43(15):2008–2012. doi: 10.1002/anie.200353247. [DOI] [PubMed] [Google Scholar]
  13. Pirrung M. C., Ye T., Zhou Z., Simon J. D.. Mechanistic studies on the photochemical deprotection of 3′,5′-dimethoxybenzoin esters. Photochem. Photobiol. 2006;82(5):1258–1264. doi: 10.1562/2006-02-07-RA-798. [DOI] [PubMed] [Google Scholar]
  14. Yang Y.-Q., Lu Z., Xu X.. Phenacyl xanthates: A photoremovable protecting group for alcohols under visible light. Asian J. Org. Chem. 2019;8(12):2192–2195. doi: 10.1002/ajoc.201900576. [DOI] [Google Scholar]
  15. Literák J., Wirz J., Klán P.. 2,5-Dimethylphenacyl carbonates: A photoremovable protecting group for alcohols and phenols. Photochem. Photobiol. Sci. 2005;4(1):43–46. doi: 10.1039/b408851d. [DOI] [PubMed] [Google Scholar]; Schulte A. M., Vivien Q., Leene J. H., Alachouzos G., Feringa B. L., Szymanski W.. Photocleavable Protecting Groups Using a Sulfite Self-Immolative Linker for High Uncaging Quantum Yield and Aqueous Solubility. Angew. Chem., Int. Ed. 2024;63(47):e202411380. doi: 10.1002/anie.202411380. [DOI] [PubMed] [Google Scholar]
  16. Papageorgiou G., Barth A., Corrie J. E. T.. Flash photolytic release of alcohols from photolabile carbamates or carbonates is rate-limited by decarboxylation of the photoproduct. Photochem. Photobiol. Sci. 2005;4(2):216–220. doi: 10.1039/b417153e. [DOI] [PubMed] [Google Scholar]; Guo Y., Song Q., Wang J., Ma J., Zhang X., Phillips D. L.. Unraveling the photodeprotection mechanism of anthraquinon-2-ylmethoxycarbonyl-caged alcohols using time-resolved spectroscopy. J. Org. Chem. 2018;83(21):13454–13462. doi: 10.1021/acs.joc.8b02252. [DOI] [PubMed] [Google Scholar]
  17. Lind F., Markelov K., Studer A.. Benzoyldiisopropylchlorosilane: a visible light photocleavable alcohol protecting group. Chem. Sci. 2023;14(44):12615–12620. doi: 10.1039/D3SC04975B. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Feng R., Yu X., Autschbach J.. Spin–orbit natural transition orbitals and spin-forbidden transitions. J. Chem. Theory Comput. 2021;17(12):7531–7544. doi: 10.1021/acs.jctc.1c00776. [DOI] [PubMed] [Google Scholar]
  19. Costa P., Sander W.. Hydrogen bonding switches the spin state of diphenylcarbene from triplet to singlet. Angew. Chem., Int. Ed. 2014;53(20):5122–5125. doi: 10.1002/anie.201400176. [DOI] [PubMed] [Google Scholar]
  20. Frisch, M. J. ; Trucks, G. W. ; Schlegel, H. B. ; Scuseria, G. E. ; Robb, M. A. ; Cheeseman, J. R. ; Scalmani, G. ; Barone, V. ; Petersson, G. A. ; Nakatsuji, H. ; Li, X. ; Caricato, M. ; Marenich, A. ; Bloino, J. ; Janesko, B. G. ; Gomperts, R. ; Mennucci, B. ; Hratchian, H. P. ; Ortiz, J. V. ; Izmaylov, A. F. ; Sonnenberg, J. L. ; Williams-Young, D. ; Ding, F. ; Lipparini, F. ; Egidi, F. ; Goings, J. ; Peng, B. ; Petrone, A. ; Henderson, T. ; Ranasinghe, D. ; Zakrzewski, V. G. ; Gao, J. ; Rega, N. ; Zheng, G. ; Liang, W. ; Hada, M. ; Ehara, M. ; Toyota, K. ; Fukuda, R. ; Hasegawa, J. ; Ishida, M. ; Nakajima, T. ; Honda, Y. ; Kitao, O. ; Nakai, H. ; Vreven, T. ; Throssell, K. ; Montgomery, J. A. ; Peralta, J. E. ; Ogliaro, F. ; Bearpark, M. ; Heyd, J. J. ; Brothers, E. ; Kudin, K. N. ; Staroverov, V. N. ; Keith, T. ; Kobayashi, R. ; Normand, J. ; Raghavachari, K. ; Rendell, A. ; Burant, J. C. ; Iyengar, S. S. ; Tomasi, J. ; Cossi, M. ; Millam, J. M. ; Klene, M. ; Adamo, C. ; Cammi, R. ; Ochterski, J. W. ; Martin, R. L. ; Morokuma, K. ; Farkas, O. ; Foresman, J. B. ; Fox, D. J. . Gaussian 16, Revision A.03; Gaussian, Inc.: Wallingford CT, 2016. [Google Scholar]
  21. Stephens P. J., Devlin F. J., Chabalowski C. F., Frisch M. J.. Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields. J. Phys. Chem. A. 1994;98(45):11623–11627. doi: 10.1021/j100096a001. [DOI] [Google Scholar]
  22. Fukui K.. Formulation of the reaction coordinate. J. Chem. Phys. 1970;74(23):4161–4163. doi: 10.1021/j100717a029. [DOI] [Google Scholar]; Fukui K.. The path of chemical reactions-the IRC approach. Acc. Chem. Res. 1981;14(12):363–368. doi: 10.1021/ar00072a001. [DOI] [Google Scholar]
  23. Berning A., Schweizer M., Werner H.-J., Knowles P. J., Palmieri P.. Spin-orbit matrix elements for internally contracted multireference configuration interaction wavefunctions. Mol. Phys. 2000;98(21):1823–1833. doi: 10.1080/00268970009483386. [DOI] [Google Scholar]; Heß B. A., Marian C. M., Wahlgren U., Gropen O.. A mean-field spin-orbit method applicable to correlated wavefunctions. Chem. Phys. Lett. 1996;251(5–6):365–371. doi: 10.1016/0009-2614(96)00119-4. [DOI] [Google Scholar]
  24. Neese F.. The ORCA program system. WIREs Comput. Mol. Sci. 2012;2(1):73–78. doi: 10.1002/wcms.81. [DOI] [Google Scholar]
  25. Lu T., Chen F.. Multiwfn: A multifunctional wavefunction analyzer. J. Comput. Chem. 2012;33(5):580–592. doi: 10.1002/jcc.22885. [DOI] [PubMed] [Google Scholar]; Lu T.. A comprehensive electron wavefunction analysis toolbox for chemists, Multiwfn. J. Chem. Phys. 2024;161(8):082503. doi: 10.1063/5.0216272. [DOI] [PubMed] [Google Scholar]

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