Hydrogen bonding mediated electron donor-acceptor acceptor catalysis in hydrosulfonylation and sulfonyl dehydrogenation of olefins

Domain: biology
Published: 2026-03-23
Editorial outcome: minor_revision

Abstract
Electron donor-acceptor (EDA) accept or catalysis remains significantly less developed than
donor catalysis. Herein, a hydrogen-bond-mediated EDA acceptor catalysis using readily available
4,4'-di-tert-butyl-2,2'-dipyridyl (dtbbpy) or 4-tert-butylpyridine as the acceptor catalyst is devel-
oped, enabling the hydrosulfonylation of unactivated olefins and sulfonyl dehydrogenation of sty-
renes, utilizing sodium sulfinate as the sulfonyl source. The reaction proceeds under mild condi-
tions. A broad range of functional groups is well tolerated, affording good to excellent yields. Pre-
liminary mechanistic investigations, including both computational studies and experiments, indi-
cate that hydrogen bonding between sulfinic acid and the acceptor catalyst may facilitate the for-
mation of a photoresponsive EDA complex and the subsequent photo-induced radical generation.
This work represents a distinct feature compared to previously known modes of EDA acceptor
catalysis.

Introduction
In recent years, photoredox catalysis has emerged as a powerful strategy for constructing a
variety of otherwise challenging chemical bonds via radical intermediates under mild conditions.[1–
5] Among them, carbon radical generation through photo-active electron donor−acceptor (EDA)
complexes has drawn significant attention, primarily because this method does not require exoge-
nous photoredox catalysts.[6,7] In the early stage, stoichiometric donors and acceptors are re-
quired.[8–15] Recently, catalytic EDA complex photochemistry has rapidly advanced, generating a
certain number of successful examples of EDA donor catalysis for the transformation of electron-
deficient substrates[16–19]; in sharp contrast, successful examples of EDA acceptor catalysis remain
relatively scarce.[20] More specifically, eElectron-deficient species such as I
2
[21], B(C
6
F
5
)
3
[22,23], and
highly electron-deficient aromatic compounds including 1,2-dibenzoylethylene[24], tetrachlroph-
thalimide[25], 4-nitrophthalonitrile[26], 1,2-dinitrobenzene[27], and methyl viologen[28] typically
form EDA complexes with the electron-rich donors through weak noncovalent orbital interactions
(e.g., n–π and π–π interactions). However, hydrogen-bonding-mediated catalytic acceptor EDA
complexes are still relatively underexplored, despite the successful development of hydrogen-
bonding-mediated non-catalytic EDA approaches that have proven efficient in several transfor-
mations (Fig. 1a).[29–31]

In general, the catalytic acceptor EDA process involves the following key mechanistic steps:
(1) formation of a ground-state EDA complex through noncovalent interactions between the cata-
lyst and the electron-rich substrates; (2) photoexcitation of the EDA complex, resulting in electron
transfer from the substrates to the acceptor catalyst, generating radical species and the reduced
form of the catalyst (“e-pool”); and (3) the resulting radicals trigger the subsequent reactions, ac-
companied by electron donation from the “e-pool” to the reaction system to regenerate the catalyst
and close the catalytic cycle (Fig. 1b).[25] We envisioned that pyridine would serve as an ideal
acceptor catalyst to explore hydrogen-bonding-mediated catalytic acceptor EDA complexes with
an appropriate hydrogen bond donor based on the following considerations: first, the nitrogen atom
in pyridine is an excellent hydrogen-bond acceptor capable of interacting with various hydrogen-
bond donors;[32–34] second, hydrogen-bond complex would promote the electron transfer;[35–41]
third, the electron-deficient pyridine ring can readily accept electrons to generate the electron
added “e-pool”; and finally, the electron-ad ded pyridine can subsequently transfer its extra elec-
tron back to either the reaction intermediates or other synergistic catalysts[42,43](Fig. 1c).

Herein, we select sulfinic acid or the combination of readily available and cost-effective so-
dium sulfinate[44] with an appropriate proton source as the electron-rich and hydrogen bond donor
substrate to investigate the hydrogen-bonding-mediated EDA acceptor catalysis. An unactivated
olefin or styrene was utilized as the coupling partner, with a thiol serving as a co-catalyst for proton
transfer.[45–49] The proposed catalytic cycle is illustrated in Fig. 1d. Initially, sulfinic acid and the
pyridine catalyst (Py) were assembled through a hydrogen bond to form the EDA complex. Upon
photoirradiation, proton and electron transfer from sulfinic acid to pyridine occurs, generating an
electron-added, protonated pyridine intermediate (PyH•) and a sulfonyl radical (Int-1). Subse-
quently, the sulfonyl radical adds to the olefin, forming an alkyl radical (Int-2), which abstracts a
hydrogen atom from the thiol co-catalyst ArSH to form the olefin hydrosulfonylation product (P1)
and a thiol radical (ArS•). The thiol radical is then reduced by the intermediate PyH•, generating a
thiophenolate anion and the protonated pyridine catalyst (PyH+). Finally, proton transfer from
PyH+ to the thiophenolate anion closes the catalytic cycle (Fig. 1d, left cycle). Additionally, we
speculate that the redox-active intermediate (PyH•) can reduce a high-valent cobalt catalyst [e.g.,
chloro(pyridine)cobaloxime(III)] to generate a Co(II) species. Consequently, a dehydrogenation
reaction could be expected after the sulfonyl radical addition through the alkyl recombination with
the Co(II) catalyst, the Co(III) promoted β-hydride elimination and H extrusion sequence (Fig.
1d, right cycle).[50–53] This strategy exhibits several distinctive features. First, it exploits hydrogen
bonding as noncovalent interaction in catalytic acceptor EDA complexes. Second, the realization
of this approach can facilitate the synthesis of synthetically valuable sulfone derivatives[54,55] from
readily available sodium sulfinate, whereas current methods heavily rely on photocatalysts[56–59].

Results
Reaction development
We proceeded to experimentally validate the hypothesis (Table 1). The reaction between p-
toluenesulfinic acid (2a) and unactivated olefin but-3-en-1-ylbenzene (1a), using dtbbpy (cat-1)
as the EDA acceptor catalyst and TRIP (2,4,6-triisopropylbenzenethiol) as the hydrogen transfer
catalyst, was initially evaluated. The desired anti-Markovnikov hydrosulfonylation product (3a)
was obtained in 12% yield (entry 1). Switching the thiol co-catalyst to diphenyl disulfide (PhSSPh)
improved the reaction efficiency (entry 2), and 4-(tert-butyl)pyridine (cat-5) exhibited comparable
catalytic performance (entry 3). In both cases (entries 2 and 3), the overall yield could be improved
to >80% by extending the reaction time to 48 h. Considering cost-effectiveness, we then explored
the feasibility of using sodium sulfinate (2b) along with a suitable proton source to generate the
corresponding sulfinic acid in situ. After extensive condition optimization (for details, see SI), we
identified that the combination of TMSCl and H O as a proton source,[60] along with PhSSPh as
2
the hydrogen atom transfer catalyst, provided the best results (entry 4). Control experiments were
subsequently performed to clarify the role of each component based on the conditions in entry 4.
Unsuprisely, the reaction was completely shut down under light-free conditions (entry 5). Cat-1
was found to be important for the transformation, as its absence led to a significant decrease in
efficiency (entry 6). The low yield (21%) ob served without dtbbpy (cat-1) could be attributed to a
“background” reaction involving the direct excitation of the in-situ generated p-toluenesulfinic
acid (for details, see SI).[61] TOther pyridines and bipyridines with varying electronic properties,
except for 4-(tert-butyl)pyridine (cat-5), exhibited inferior performance (entry 7). TMSCl, PhSSPh
and H O are all critical for the reaction (entries 8–10). TESCl proved less effective than TMSCl
2
(entry 11), which might be due to its lower reactivity toward water in generating HCl. Direct ad-
dition of HCl (3.0 equiv, 11.5 N in H O) as the proton source resulted in a slightly lower yield
2
(entry 12). The decreased yield may be attributed to the formation of an EDA complex between
excess HCl and sulfinic acid 2a, which could in turn reduce the overall efficiency (for details, see
SI).[30] Performing the reaction under open-air conditions resulted in only trace amounts of product
formation (entry 13). Finally, the hydrate form of 2b is not essential when using a water-containing
solvent system (entry 14).

Substrate scope
With the optimized conditions in hand, the scope of unactivated olefin hydrosulfonylation
was systematically explored (Fig. 2). Terminal mono-substituted alkenes were found to be excel-
lent substrates for the transformation, affording anti-Markovnikov hydrosulfonylation products in
good to excellent yields (3a–3w). The standard example could be scaled up to 4.0 mmol scale
without any erosion of the efficiency (3a). In addition to alkenes bearing a distal phenyl group,
purely aliphatic alkenes also showed high reactivity (3b). A wide range of functional groups, in-
cluding nucleophile-sensitive primary alkyl bromides (3c, 3d), oxidant-sensitive aldehyde (3e),
ketone (3f), esters (3g), nitrile (3h), amide (3i), and sulfamides (3j) were well tolerated. In addition,
heterocycles like acid- and oxidant-sensitive indole (3k) remained intact under the current reaction
conditions. A number of functional groups on the phenyl, such as aryl fluoride (3m), chloride (3n),
bromide (3o), iodine (3p), and phenyl (3q) were well tolerated in this transformation. Substrates
containing ring systems, including strained four-membered carbon rings (3r), as well as five- and
six-membered carbocyclic and oxygen, sulfur-containing rings, also reacted efficiently (3s–3w).
Furthermore, several sterically hindered terminal 1,1-disubstituted alkenes were examined and
found to react smoothly with moderate to good yields (3x–3aa). Notably, amide (3x) and nucleo-
phile-sensitive primary alkyl tosylate (3y) remained intact. Strained 1,1-ring-disubstituted alkenes
proved to be good substrates (3z, 3aa). Finally, internal alkenes were evaluated. Both the disub-
stituted cyclohexene (3ab) and the tetrasubstituted 2,3-dimethylbut-2-ene (3ac) were productive,
albeit in only synthetically useful yields. The scope of sodium sulfinates was subsequently
investigated. The electronic properties of the aryl ring in aryl sodium sulfinates were found to be
crucial for the reaction. Electron-neutral (3ad) and electron-deficient (3ae–3ag) sulfinates reacted
smoothly, whereas the electron-rich aryl sodium sulfinate bearing a methoxy substituent (3ah) was
significantly less effective. Aliphatic sodium sulfinates reacted efficiently (3ai–3ak). Notably, the
cyclopropane ring adjacent to the sulfur atom was preserved under the reaction conditions. The
generality of the current reaction was further demonstrated through the modification of complex
molecules and drug derivatives (3al–3as). Notably, several mono-substituted terminal alkenes de-
rived from pharmaceuticals—including Ciprofibrate (3al), Febuxostat (3am), Fenofibric acid
(3an), Probenecid (3ao), Oxaprozin (3ap), and Indometacin (3aq), successfully afforded the cor-
responding sulfone products in excellent yields, highlighting the strong potential of this method
for pharmaceutical applications. In addition, densely oxygen-substituted sugar derivatives were
also well tolerated under the reaction conditions (3ar, 3as).

The acceptor EDA catalysis coupled Co(III) mediated dehydrogenation (vide supra, right cy-
cle in Fig. 1d) was next validated using 1-methyl-1,1-disubstituted styrene 4a as the model sub-
strate (Table 2). Optimal conditions were identified as the addition of 10 mol% of the dehydro-
genation catalyst Co(dmgH) PyCl and an extra 2.0 equivalents of pyridine[62] as a base to the
2
standard hydrosulfonylation conditions (entry 1). Quick control experiments indicated that all re-
actants and light irradiation are indispensable for the reaction (entries 2–7), while
Co(dmgH)(dmgH )Cl proved slightly less effective under the tested conditions (entry 8). The
2 2
scope of the sulfonyl dehydrogenation reaction was subsequently explored (Fig. 3). 1,1-
Disubstituted styrenes bearing aryl fluoride (5b), aryl chloride (5c), aryl methoxyl (5d), and naph-
thyl (5e) substituents reacted smoothly, affording the corresponding products in moderate yields.
Aryl sodium sulfinates bearing electron-neutral or electron-withdrawing groups (5f–5i) performed
better than those with electron-donating substituents, which is similar to the hydrosulfonylation.
Aliphatic sodium sulfinates were also compatible with the current conditions (5j, 5k). Notably, the
cyclopropane ring adjacent to the sulfur atom stayed untouched (5k). Branched 𝛼-olefins derived
from densely oxygen-substituted sugar derivatives (5l, 5m) successfully underwent the reaction,
demonstrating the good functional group compatibility.

Preliminary mechanistic studies & Computational studies
Next, preliminary mechanistic studies were conducted experimentally (Fig. 4). The key point
is to identify the formation of the donor-acceptor complex and the presence of hydrogen bonding.
A radical trapping experiment by adding 2.0 equivalents of TEMPO to the reaction significantly
suppressed the productive pathway and led to the formation of 6 (Fig. 4a), which was possibly
generated through the SO extrusion of sulfonyl radical and TEMPO trapping.[63] Deuterium-la-
2
beling experiments were conducted to identify the hydrogen source involved in the reaction (Fig.
4b). When substrates 2b or 2c were subjected to the standard reaction conditions using D O in
2
place of H O, the yields decreased significantly, and deuterium incorporation was detected in the
2
final products. The observed reduction in yield may be attributed to the influence of hydrogen
bonds or the photo-induced proton and electron transfer process (vide infra) by replacing O–H
with O–D.[64] Additionally, the low deuterium incorporation observed with 2b as the substrate
might result from residual crystal water, which may serve as a proton source in the reaction system
(Fig. 4b, eq. 2). The role of TMSCl was investigated by monitoring the reaction progress. After 1
h, TMSOH was observed in 90% yield, and this yield remained unchanged after 5 h (Fig. 4c).
These results suggest that the hydrolysis of TMSCl occurs rapidly, and the generated HCl partici-
pates in the reaction. Job’s plot analysis suggested a 1:2 ratio between cat-1 and 2a, 1:1 ratio
between cat-5 and 2a (Fig.4d, 4e). When the reaction mixture was irradiated with green light (λ
max
= 520 nm), a wavelength not absorbed by either the catalysts or the substrates, the desired product
was still formed, albeit in low yield (Fig. 4f). This observation further supports that the reaction
proceeds via an EDA pathway,[25] and the direct excitation of cat-1 or 2a, followed by a direct
hydrogen-bonding-mediated O−H cleavage -initiated approach, may be less likely. Finally, UV–
Vis spectra of 2a, the acceptor catalyst, and their mixture at concentrations identical to those used
in the reaction were recorded. After mixing the catalyst cat-1 or cat-5 with 2a, a redshift in ab-
sorption was observed for the mixture, suggesting ground-state interaction between the compo-
nents (Fig. 4g, 4h). Constant irradiation was required, as no conversion was observed during the
dark period through the light on-off experiment (Fig. 4i). Taken together, these results support that
the olefin hydrosulfonylation reaction proceeds through radical addition and HAT process and the
formation of a donor-acceptor complex.

To gain further insight into the reaction mechanism, computational studies were carried out
(Fig. 5). Because 4-(tert-butyl)pyridine (cat-5) exhibited comparable catalytic performance in the
hydrosulfonylation reaction (Table 1, entry 3), cat-5 and p-toluenesulfinic acid (2a) were chosen
as the model substrates for DFT calculations. The PBE1W-D3 method has been reported to repro-
duce experimental UV–vis absorption spectra reasonably well in excited-state calculations of di-
hydrogen-bonded EDA systems[65]. Accordingly, our calculations were carried out at the
SMD(DCM), PBE1W-D3(BJ)/def2-TZVP//SMD(DCM), PBE0-D3(BJ)/def2-SVP level of theory
using Gaussian 16.[66] As is shown in Fig. 5a, the geometry optimization revealed a proton–pyri-
dine nitrogen distance of 1.56 Å, an O–H bond length of 1.04 Å, and an N–H–O bond angle of
170.8°, indicating excellent conformity with the geometric criteria of a hydrogen bond.[67,68] The
calculated binding energy was determined to be −11.8 kcal/mol. Further analysis of weak interac-
tions through IRI (interaction region indicator) [69–71] analysis confirmed the presence of a strong
hydrogen bond between the proton and the pyridine nitrogen atom, whereas the arene-arene inter-
action was found to be negligible. The HOMO of the complex is highly localized on the -SO
2
group, while the LUMO is mainly contributed by the pyridinium π* orbitals (Fig. 5b). These results
indicated the possible electron transfer from the -SO group to the pyridinium and that the key
2
excited state is the first singlet excited state (S state). As shown in Fig. 5c, the geometry optimi-
1
zation of the S state of the complex formed between cat-5 and 2a was performed using the
1
TDDFT method at the same level as the ground-state calculations. The results revealed a disruption
of the hydrogen bond, accompanied by a hydrogen transfer from 2a to the nitrogen atom of cat-5.
IRI analysis of the S state indicates that potential π–π stacking between the two phenyl rings was
1
observed, which might contribute to stabilizing this state. Electron-hole analysis[72] of the S ex-
1
cited state of the complex indicated electron localization on the pyridine moiety of cat-5 and hole
localization on the SO group of 2a. These results imply that both proton and electron transfers are
2
promoted by the photo-excitation.[73–75] We further calculated the energy profile associated with
radical generation (Fig. 5d). The vertical excitation (VE) energy of the S state is 80.5 kcal/mol,
0
and the S₁-minimum state energy is 27.4 kcal/mol. The formation of the sulfinyl radical (IM-1)
and protonated pyridine radical (IM-2) was found to be endothermic (13.2 kcal/mol). Additionally,
the reduction of PhS• by IM-2 to generate PhS− and protonated pyridine IM-3 was determined to
be significantly exothermic, with a free energy change of −25.8 kcal/mol. To conduct a more com-
prehensive study of the excitation process, we carried out a two-dimensional potential-energy sur-
face (2D-PES) scan to analyze the PES of S and S states as well as the vertical excitation surface
0 1
based on the S
0
surface (Fig. 5e) at the same level (for the results with other DFT functionals, see
SI). To clearly illustrate the character of the surface, the 1D-PES scan of the proton transfer was
shown in Fig. 5f based on the points taken along the diagonal in Fig. 5e. The 1D-PES scan results
show that the energy of the complex differs a little as the proton transfers between 2a and cat-5
(no more than 1.4 kcal/mol as is shown in Fig. 5e), while the VE energy goes down from 80.5
kcal/mol (indicating 355 nm) to 45.3 kcal/mol (46.2kcal/mol – 0.9 kcal/mol = 45.3 kcal/mol, indi-
cating 631 nm) as the proton transfers from 2a to cat-5. Thus, it’s rational to propose that the
excitation process might happen in the non-ground-state conformer. Although it’s difficult to know
the absorbance for different conformers due to the limitation of the TDDFT method, the large
wavelength coverage is consistent with the large wavelength range of the light used in the experi-
ments (up to 520 nm), which, in a way, supports the above proposal.

Methods
General procedure for the hydrogen bonding mediated Electron Donor-Acceptor acceptor
catalysis in hydrosulfonylation and sulfonyl dehydrogenation of olefins

General Procedure A: An oven-dried 8.0 mL screw-cap vial containing a magnetic stir bar was
transferred to a nitrogen-filled glovebox. Then, diphenyl disulfide (4.4 mg, 0.02 mmol, 0.1 equiv),
dtbbpy (5.4 mg, 0.02 mmol, 0.1 equiv), and sodium sulfonates (0.24 mmol, 1.2 equiv) were added
to the vial. Next, the respective alkene (0.2 mmol, 1.0 equiv), TMSCl (32.6 mg, 0.3 mmol, 1.5
equiv), and dichloromethane (DCM, 0.9 mL) were added. After sealing and removing the vial from
the glovebox, H O (108 μL, 6.0 mmol, 30.0 equiv) was added, and the reaction mixture was stirred
2
and irradiated with blue LEDs (20 W) for 24 h. Upon completion, the reaction was quenched by
opening the screw cap and stirring under an air atmosphere for 5 minutes. The reaction mixture
was concentrated under reduced pressure and purified by column chromatography on silica gel
with the specified solvent system to afford the title compounds.

General Procedure B: An oven-dried 8.0 mL screw-cap vial containing a magnetic stir bar was
transferred to a nitrogen-filled glovebox. Then, Co(dmgH) PyCl (8.0 mg, 0.02 mmol, 0.1 equiv),
2
dtbbpy (5.4 mg, 0.02 mmol, 0.1 equiv), and sodium sulfonates (0.2 mmol, 1.0 equiv) were added
to the vial. Next, the respective alkene (0.4 mmol, 2.0 equiv), pyridine (31.6 mg, 0.4 mmol, 2.0
equiv), and dichloromethane (DCM, 1.9 mL), TMSCl (32.6 mg, 0.3 mmol, 1.5 equiv) were added.
After sealing and removing the vial from the glovebox, H O (108 μL, 6.0 mmol, 30.0 equiv) was
2
added, and the reaction mixture was stirred and irradiated with blue LEDs (20 W) for 24 h. Upon
completion, the reaction was quenched by opening the screw cap and stirring under an air atmos-
phere for 5 minutes. The reaction mixture was concentrated under reduced pressure and purified
by column chromatography on silica gel with the specified solvent system to afford the title com-
pounds.

Peer review rounds
[{"round": 1, "reviewer_comments": {"reviewer_1": "The authors reported that readily available dtbbpy or simple pyridine derivatives could effectively catalyze the hydrosulfonylation of unactivated olefins and the sulfonylative dehydrogenation of styrenes, employing sodium sulfite/TMSCl/H2O or sulfinic acids as the sulfonyl source under blue LED irradiation. A distinctive feature of this study is the utilization of hydrogen bonding as the primary driving force to assemble the catalytic EDA complex, representing a significant difference from previously established modes of EDA acceptor catalysis. To support the hydrogen bonding mode, a series of experiments were conducted, including (i) determining the binding stoichiometry between sulfinic acid and the catalyst; (ii) using green light instead of blue light, which yielded a low yield of product formation; and (iii) recording the optical absorption spectra of the reaction mixture and individual reactants, where a redshift was observed in the mixture. Furthermore, computational studies were performed, which indicate that the major interaction between the sulfinic acid and the pyridine derivative catalyst is the hydrogen bond. From the synthetic value view, the substrate scope of hydrosulfonylation of unactivated olefins exhibited broad functional group tolerance, several complex molecules and drug derivatives also reacted well. A minor limitation of sulfonyl dehydrogenation is its relatively narrower substrate scope compared to hydrosulfonylation.\nOverall, considering the feature of hygron-bonding promoted EDA acceptor catalysis, this paper should gain a broad interest from organic chemists, especially those working on photoredox catalysis chemistry. I support its publication in Nature Communications after addressing the following issues.\n1.A light-on/off experiment is suggested to be conducted to see whether the radical chain process is involved or not in the reaction.\n2.The scope of the hydrosulfonylation of unactivated olefins is broad and attractive, and several heterocyclic substrates are compatible; however, no results of pyridyl-containing substrates are shown. Did the author try any pyridyl-containing substrates? How about furyl or thienyl-containing substrates?\n3.In the sulfonyl dehydrogenation part. What’s the result of a larger-scale reaction (e.g., 1.0 mmol)? Including one or two complex molecule derivatives as the substrates should be more attractive. I notice that unactivated olefins are not compatible in the sulfonyl dehydrogenation reaction. Are there any undesired products? Providing this information in the Supporting Information will assist readers and facilitate subsequent research.\n4.In page 12, Fig 2i, the color of the absorbance lines of the mixture in the first and second pictures is blue, which, however, is red in the third picture.\n5.The SI is well organized, and the spectra were of good quality in most cases; however, the 1H NMR spectra of 5k and 5j are not clean enough.", "reviewer_2": "The manuscript presents a hydrogen-bonding promoted electron donor–acceptor (EDA) catalysis strategy employing dtbppy as the acceptor catalyst to facilitate two distinct transformations: the hydrosulfonylation of unactivated olefins, and the sulfonyl dehydrogenation of styrenes in combination with a Co(III) co-catalyst. The authors demonstrate broad substrate scope and achieve a variety of synthetically valuable alkyl sulfone derivatives in good to excellent yields. The use of a readily available and cost-effective donor system comprising sodium sulfite and a proton source (TMSCl+water) to generate the EDA complex is both practical and efficient. Moreover, the proposed involvement of a PyH• radical intermediate in dual catalytic cycles adds mechanistic interest. I recommend publication of this manuscript in Nature Communications after the following points are addressed.\n(1) The use of sodium sulfite in combination with TMSCl and water as the electron donor system is a valuable feature of this work. However, the reported decrease in yield from 87% to 72% when using sulfinic acid (2a) as donor or using 2b with HCl as donor/proton source, raises mechanistic questions. The authors are encouraged to provide a more detailed discussion of this observation.\n(2) As the study proposes a newly formed hydrogen-bond-mediated EDA complex, it would be beneficial to include a more detailed discussion of its excited-state properties. Specifically, the key excited states involved in the reaction should be clearly assigned, along with the excitation energies that align with the experimental observations.\n(3) In Figure 3d, the authors assign the EDA complex* as the S₁-minimum after proton transfer, with an adiabatic excitation energy (E₀-₀) of 47.7 kcal/mol. To enhance this analysis, the following additional data should be provided: (a) The vertical excitation energy (from the ground-state geometry); (b) The S₁-minimum prior to proton transfer; (c) The energy barrier for proton transfer on the excited-state surface.", "reviewer_3": "The authors describe a hydrogen bonding-promoted Electron Donor-Acceptor (EDA) acceptor catalysis system utilizing readily available 4,4'-di-tert-butyl-2,2'-dipyridyl (dtbbpy) as the catalyst. This system facilitates the hydrosulfonylation of unactivated olefins and the sulfonyl dehydrogenation of styrenes using sodium sulfite as the sulfonyl source. The reactions proceed under mild conditions with broad substrate scope. Mechanistic investigations, including experimental and computational studies, were conducted to elucidate the reaction pathway. So, I think the following concerns should be addressed before publication.\n1. In entry 6, Table 1, a 21% yield of product was obtained without the catalyst, the authors should provide a reasonable explanation for the proposed mechanism.\n2. UV-Vis absorption spectra (Figure 2i) indicate that the catalyst and sulfonic acid absorb significantly below 400 nm. While blue light effectively drives the reaction, Figure 2h shows low yield of product formation even under 520 nm green light irradiation. To deep understand the photoactivation mechanism, the authors should provide supplementary UV-Vis absorption spectrum of individual reaction partners and that of combined reaction components (the olefin + the sulfonic acid, and the ternary mixture involving olefin + sulfonic acid + dtbbpy catalyst).\n3. As depicted in the proposed excited-state complex (Figure 3c), π, π-stacking may occur between the protonated pyridinium moiety and the phenyl ring of the benzenesulfinate anion. This potential interaction should be explicitly addressed and discussed within the manuscript.\n4. A fluorescence quenching study (Stern Volmer plots) is necessary to support the proposed catalytic cycle.\n5. Some related references should be cited: J. Am. Chem. Soc. 2024, 146, 2583; Org. Lett., 2024, 26, 3727; J. Org. Chem. 2025, 90, 2842."}, "author_response": "Response: We thank this reviewer for his/her positive evaluation and valuable comments!\nQ1: A light-on/off experiment is suggested to be conducted to see whether the radical chain process is involved or not in the reaction.\nResponse: Thank you very much for this valuable suggestion! A light-on/off experiment was conducted. Constant irradiation was required, as no conversion was observed during the dark period. This result has been included in the revised Figure 2j and SI (Section 7.6).\nFigure R1. Light-on/off experiment\nQ2: The scope of the hydrosulfonylation of unactivated olefins is broad and attractive, and several heterocyclic substrates are compatible; however, no results of pyridyl-containing substrates are shown. Did the author try any pyridyl-containing substrates? How about furyl or thienyl-containing substrates?\nResponse: We appreciate this suggestion very much! Pyridyl-, furyl-, and thienyl-containing substrates were further investigated. Hydrosulfonylation of furyl- and thienyl-containing alkenes afforded products 3v and 3w in 71% and 68% isolated yields, respectively. These results have been included in the revised Table 2. The pyridyl-containing alkene, however, showed no reactivity under the standard conditions and is also included in failed examples in the revised SI (Section 5.3).\nQ3: In the sulfonyl dehydrogenation part. What’s the result of a larger-scale reaction (e.g., 1.0 mmol)? Including one or two complex molecule derivatives as the substrates should be more attractive. I notice that unactivated olefins are not compatible in the sulfonyl dehydrogenation reaction. Are there any undesired products? Providing this information in the Supporting Information will assist readers and facilitate subsequent research.\nResponse: Thank you very much for these valuable suggestions! We conducted a 1.0 mmol scale test of the reaction, which resulted in a 50% yield of product 5a, this result has been added to the revised Table 3 and SI (Section 6.2). In addition, densely oxygen-substituted sugar derivatives were well tolerated under the reaction conditions, affording products 5l and 5m in 41% and 42% isolated yields, respectively. However, unactivated olefins showed no reactivity under the standard conditions and are included as failed examples in the revised SI (Section 5.3).\nQ4: In page 12, Fig 2i, the color of the absorbance lines of the mixture in the first and second pictures is blue, which, however, is red in the third picture.\nResponse: We appreciate this suggestion very much! We have made the adjustment of the color of the absorbance lines of the mixture in revised manuscript (Fig 2h).\nQ5: The SI is well organized, and the spectra were of good quality in most cases; however, the 1H NMR spectra of 5k and 5j are not clean enough.\nResponse: We appreciate this suggestion very much! The 1H NMR spectra of 5k and 5j have been updated in the revised SI.\nThe authors thank this reviewer for helpful comments and suggestions again.\n\nResponse: We thank this reviewer for his/her positive evaluation and valuable comments!\nQ1: The use of sodium sulfite in combination with TMSCl and water as the electron donor system is a valuable feature of this work. However, the reported decrease in yield from 87% to 72% when using sulfinic acid (2a) as donor or using 2b with HCl as donor/proton source, raises mechanistic questions. The authors are encouraged to provide a more detailed discussion of this observation.\nResponse: Thank you very much for the insightful comments!\nFirst, a comparable 81% yield of 3a was obtained when sulfinic acid (2a) was used as the sulfonyl source through extending the reaction time to 48 h, suggesting that the reaction of 2a should be similar to the combination of 2b/TMSCl/H2O. This result has been added in the revised Table 1.\nIn the case of 2b with HCl as the donor/proton source, the literature (Sci. Bull. 2024, 69, 345–353) suggests that large amounts of excessive HCl can form an EDA complex with sulfinic acid, generating E (vide infra, Table R1) through PCET and rearrangement processes, thereby affecting the yield of 3a. To clarify this point, we reanalyzed the reaction using 3.0 equiv of 11.5 N HCl and successfully isolated the byproduct E in 10% yield (Table R1, entry 1). However, under our optimized TMSCl/H2O conditions (TMSCl/2b = 1.25/1), as no significant excess of HCl is generated, the byproduct E was not detected (entry 2). Furthermore, when our reaction was conducted under TMSCl/2b = 0.5/1 conditions, a comparable yield of 3a (88%) was obtained (entry 3), indicating that an HCl-promoted EDA pathway is unlikely to be involved in our reaction.\nIn the revised manuscript, we added the following discussion: “Direct addition of HCl (11.5 N in H2O) as the proton source resulted in a slightly lower yield (entry 11), the decreased yield is likely attributed to the formation of an EDA complex between excessive HCl and sulfinic acid 2a, thereby affecting the overall efficiency (for details, see SI).” The aforementioned literature (Sci. Bull. 2024, 69, 345–353) was cited to support this point.\nQ2: As the study proposes a newly formed hydrogen-bond-mediated EDA complex, it would be beneficial to include a more detailed discussion of its excited-state properties. Specifically, the key excited states involved in the reaction should be clearly assigned, along with the excitation energies that align with the experimental observations.\nResponse: Thanks for your suggestion! In order to add a more detailed discussion of the excited-state and the excitation process, we have conducted more calculations and added the following details in the revised manuscript (page 12–16).\n“The HOMO of the EDA complex is highly localized on the -SO2 group, while the LUMO is mainly contributed by the pyridinium π* orbitals (Figure 3b). These results indicated the possible electron transfer from the -SO2 group to the pyridinium and that the key excited state is the first singlet excited state (S1 state).”\n“To conduct a more comprehensive study of the excitation process, we carried out a two-dimensional potential-energy surface (2D-PES) scan to analyze the PES of S0 and S1 states as well as the vertical excitation surface based on the S0 surface (Figure 3e) at the the SMD(DCM), PBE1W-D3(BJ)/def2-TZVP//SMD(DCM), PBE0-D3(BJ)/def2-SVP level of theory (for the results with other DFT functionals, see SI). To clearly illustrate the character of the surface, the 1D-PES scan of the proton transfer was shown in Figure 3f based on the points taken along the diagonal in Figure 3e. The 1D-PES scan results show that the energy of the complex differs a little as the proton transfers between 2a and cat-5 (no more than 1.4 kcal/mol as is shown in Figure 3e), while the VE energy goes down from 80.5 kcal/mol (indicating 355 nm) to 45.3 kcal/mol (46.2 kcal/mol – 0.9 kcal/mol = 45.3 kcal/mol, indicating 631 nm) as the proton transfers from 2a to cat-5. Thus, it’s rational to propose that the excitation process might happen in the non-ground-state conformer. Although it’s difficult to know the absorbance for different conformers due to the limitation of the TDDFT method, the large wavelength coverage is consistent with the large wavelength range of the light used in the experiments (up to 520 nm), which, in a way, supports the above proposal.”\nQ3: In Figure 3d, the authors assign the EDA complex* as the S₁-minimum after proton transfer, with an adiabatic excitation energy (E₀-₀) of 47.7 kcal/mol. To enhance this analysis, the following additional data should be provided: (a) The vertical excitation energy (from the ground-state geometry); (b) The S₁-minimum prior to proton transfer; (c) The energy barrier for proton transfer on the excited-state surface.\nResponse: Thanks for your suggestion!\nReplies to question (a): The vertical excitation energy (from the ground-state geometry) is 80.5 kcal/mol at the level of SMD(DCM), PBE1W-D3(BJ)/def2-TZVP//SMD(DCM), PBE0-D3(BJ)/def2-SVP. But it should be emphasized that, according to the PES scan, the excitation process might happen in the non-ground-state conformer.\nReplies to question (b) & (c): According to the 2D-PES scan, there is no so-called S₁-minimum prior to proton transfer since the energy profile goes down from the beginning to the end of the proton transfer process. And thus, the proton transfer is barrierless.\nThe authors thank this reviewer for helpful comments and suggestions again.\n\nResponse: We thank this reviewer for his/her positive evaluation and valuable comments!\nQ1: In entry 6, Table 1, a 21% yield of product was obtained without the catalyst, the authors should provide a reasonable explanation for the proposed mechanism.\nResponse: We appreciate this constructive suggestion very much! To gain insight into the mechanism, several additional control experiments were conducted (Table R2). When 2a was used as the sulfonyl source, a 15% yield of 3a was obtained in the absence of cat-1 (entry 2); however, no 3a was detected when both cat-1 and PhSSPh were omitted (entry 3), indicating that PhSSPh plays an important role in the reaction. A similar phenomenon was observed when 2b/TMSCl/H2O was employed as the sulfonyl source (entries 4 and 5).\nAccording to the literature (Green Chem. 2024, 26, 6578–6583; J. Org. Chem. 2025, 90, 5047–5051), arylsulfinic acid 2a can be directly excited under light irradiation from 365 to 450 nm in acetonitrile; however, the efficiency of excitation with a 450 nm light source is low. Consistent with this observation, control experiments revealed that 3a was obtained in much lower yield in the absence of cat-1, suggesting that direct photoexcitation of the in-situ generated p-toluenesulfinic acid may account for the minor “background” pathway. Based on the above control experiments and literature, we propose the following possible mechanism for the generation of the desired product 3a in the absence of cat-1 (Table R2, entry 4). Upon light irradiation, excitation of arylsulfinic acid 2a affords a bis-radical species A (Green Chem. 2024, 26, 6578–6583), which undergoes hydrogen atom transfer (HAT) with ground-state 2a to generate a putative S-centered radical B and sulfonyl radical C (Eur. J. Org. Chem. 2025, 28, e2500596). Radical C adds to the unactivated alkene to form a β-sulfonyl radical D, which may undergo a reverse HAT with ArSH to deliver the final product. On the other hand, the thiol radical can be reduced by intermediate B, generating a thiophenolate anion along with 2a.\nAccordingly, in the revised maintext, we have add the discussion to explain the yield observed in the absence of the catalyst: “The low yield observed without dtbbpy (cat-1) could be attributed to a “background” reaction involving the direct excitation of the in situ generated p-toluenesulfinic acid (for details, see SI).” and cite the reference (Green Chem. 2024, 26, 6578–6583 and Eur. J. Org. Chem. 2025, 28, e2500596) to support this point. In addition, we have included the above control experiments and proposed mechanism in the revised SI (Section 7.9).\nQ2: UV-Vis absorption spectra (Figure 2i) indicate that the catalyst and sulfonic acid absorb significantly below 400 nm. While blue light effectively drives the reaction, Figure 2h shows low yield of product formation even under 520 nm green light irradiation. To deep understand the photoactivation mechanism, the authors should provide supplementary UV-Vis absorption spectrum of individual reaction partners and that of combined reaction components (the olefin + the sulfonic acid, and the ternary mixture involving olefin + sulfonic acid + dtbbpy catalyst).\nResponse: We appreciate this suggestion very much! UV-Vis absorption spectra of cat-1, 2a and cat-1 + 2a (Figure R4), cat-5, 2a and cat-5 + 2a (Figure R5), 1a, cat-1, 2a and their mixtures (Figure R6) and 1a, cat-5, 2a and their mixtures (Figure R7) were recorded, and the results are included in the revised manuscript and SI (Section 7.3).\nAs shown in Figure R6, EDA complexes formed between 2a and cat-1 in DCM solvent and exhibits a pronounced redshift. However, the addition of 1a did not reveal a significant redshift, indicating 1a might not be involved in the formation of the EDA complex. Similar phenomena were observed when adding 1a into the mixture of 2a and cat-5 (Figure R7).\nQ3: As depicted in the proposed excited-state complex (Figure 3c), π, π-stacking may occur between the protonated pyridinium moiety and the phenyl ring of the benzenesulfinate anion. This potential interaction should be explicitly addressed and discussed within the manuscript.\nResponse: Thank you very much for this suggestion! We analyzed the weak interactions in the S1 state using the interaction region indicator (IRI). π–π stacking was observed between the phenyl ring of the protonated and electron-added pyridinium and the benzenesulfinate radical. In the revised manuscript, we have replaced the original Figure 3c with the new Figure R8 below and added the following discussion: “IRI analysis of the S1 state indicates that potential π–π stacking between the two phenyl rings was observed, which might contribute to stabilizing this state.”\nQ4: A fluorescence quenching study (Stern Volmer plots) is necessary to support the proposed catalytic cycle.\nResponse: We appreciate this insightful suggestion very much! In fluorescence quenching studies, the ideal case involves selectively exciting one species while quenching with another that is not appreciably excited at the same wavelength. In our reaction system, however, mixing 2a and cat-1 leads to the formation of a hydrogen-bonded complex that exhibits a pronounced red shift and broad absorption in the UV–vis region. Consequently, it may be difficult to identify a wavelength that excites only cat-1 or 2a without also exciting the complex in the mixture. Therefore, fluorescence quenching experiments may not provide constructive mechanistic insights in this case.\nHowever, we took this reviewer’s suggestion seriously and conducted the following experiment to further support the proposed complex formation and the proposed catalytic cycle.\nFirst, the emission spectra of cat-5 (excitation at 300 nm), 2a (excitation at 370 nm), and cat-5 + 2a (excitation at 400 nm) were recorded (Figure R9). Subsequently, mixed solutions of cat-5 and 2a with varying cat-5/2a ratios (0.50 to 1.33) were subjected to emission spectroscopy (excitation at 370 nm), and the results are shown in Figure R10. From the recorded spectra, upon addition of 2a to the solution, a new emission peak appeared. As the cat-5/2a ratio increased, this peak became more pronounced, suggesting the formation of a new excited species, which may be attributable to the hydrogen-bonded complex of cat-5 and 2a.\nIn the revised manuscript and SI, the above Figure R10 has been included as Figure 2i and Figure S16 (Section 7.8), and the following description and discussion have been added: “Mixed solutions of cat-5 and 2a with varying cat-5/2a ratios (0.50 to 1.33) were subjected to emission spectroscopy. Upon addition of 2a to the solution of cat-5, a new emission peak appeared, suggesting the formation of a new excited species, which may be attributable to the hydrogen-bonded complex of cat-5 and 2a.”\nQ5: Some related references should be cited: J. Am. Chem. Soc. 2024, 146, 2583; Org. Lett., 2024, 26, 3727; J. Org. Chem. 2025, 90, 2842.\nResponse: Thank you very much for this suggestion. The abovementioned references have been cited as refs 17, 18, and 19 in the revised manuscript.\nThe authors thank this reviewer for helpful comments and suggestions again."}, {"round": 2, "reviewer_comments": {"reviewer_1": "The authors addressed all of my feedback thoroughly, and I now believe the manuscript is ready to be accepted for publication.", "reviewer_2": "I thank the authors for their careful and comprehensive revision.\nThe additional data and clarifications have addressed my earlier concerns, and the manuscript is now clearer and more convincing.\nI have no further comments, and I am satisfied with this revised version.", "reviewer_3": "The revised manuscript has been significantly improved and looks better, so I recommend acceptance of the manuscript for publication in its current form."}, "author_response": ""}]

Decision letter