Light-Mediated Difluoromethylthiolation of Aldehydes with a Hydrogen Atom Transfer Photocatalyst

Article abstract of DOI:10.1021/acs.orglett.0c02902

A mild general method for difluoromethylthiolation of aldehydes with PhSO2SCF2H and a decatungstate photocatalyst under redox-neutral conditions has been developed. This reaction is highly efficient, scalable, and oxidant-free. The broad substrate scope and excellent functional group tolerance of the reaction make it suitable for generating libraries of difluoromethyl thioesters. We demonstrated the utility and sustainability of the method by synthesizing several structurally complex difluoromethyl thioesters.

Full text of DOI:10.1021/acs.orglett.0c02902

pubs.acs.org/OrgLett
Letter
Light-Mediated Difluoromethylthiolation of Aldehydes with a
Hydrogen Atom Transfer Photocatalyst
Jianyang Dong, Fuyang Yue, Xiaochen Wang, Hongjian Song, Yuxiu Liu, and Qingmin Wang*
Cite This: https://dx.doi.org/10.1021/acs.orglett.0c02902
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: A mild general method for difluoromethylthiolation
of aldehydes with PhSO2SCF2H and a decatungstate photocatalyst
under redox-neutral conditions has been developed. This reaction
is highly efficient, scalable, and oxidant-free. The broad substrate
scope and excellent functional group tolerance of the reaction make
it suitable for generating libraries of difluoromethyl thioesters. We
demonstrated the utility and sustainability of the method by
synthesizing several structurally complex difluoromethyl thioesters.
ecause the incorporation of a fluorinated group (e.g., CF3,
OCF3, SCF3, or SCF2H) into a molecule tends to alter its
B
physiochemical properties and biological activity,1 methods for
synthesizing fluorinated molecules are important for the
discovery of new agrochemicals and pharmaceuticals.2 In
recent years, difluoromethylthiolated molecules have generated
considerable interest for several reasons. First, because the
acidic proton of the SCF2H group can participate in hydrogen
bonds,3 incorporation of this group can increase the binding
selectivity of a drug toward its target enzymes or proteins.4
Second, because this group is electron-withdrawing, it can
increase the metabolic stability of a drug molecule. Finally, the
distinctive Hansch parameter of this group (ΠR = 0.68) means
that it can be used to adjust the lipophilicity of a drug
molecule.5 Therefore, organic chemists have directed much
research effort toward synthesizing SCF2H-containing mole-
cules,6,7 and several difluoromethyl thioethers and difluor-
omethanesulfonamides have shown promising activity, such as
the antibiotic flomoxef sodium, the insecticide pyriprole,8 and
the herbicides pyrimisulfan and triafamone (Figure 1).9
Figure 1. Biologically active molecules with SCF2H and SCH2F
groups.
affording the desired difluoromethyl thioester and a PhSO2
radical (Scheme 1A). However, the strong oxidant makes
readily oxidized functionalities incompatible with these
reactions, and various byproducts can be generated by radical
addition reactions. Consequently, the use of these approaches
for complicated aldehydes is problematic. Therefore, a mild
redox-neutral protocol for the introduction of SCF2H groups
into structurally complex aldehydes is urgently needed. Given
that the PhSO2 radical has been used as the sole oxidant in
photoredox radical reactions,13 we envisioned that it might be
suitable for generating acyl radicals from aldehydes so that the
use of excess oxidant could be avoided. However, the challenge
However, to our knowledge, no bioactive difluoromethyl
thioesters have been reported, even though monofluoromethyl
thioester groups are present in common drugs such as the anti-
inflammatory drug fluticasone and its propionate derivative
(Figure 1).10 Because the chemical properties of difluor-
omethyl thioesters differ from those of difluoromethyl
thioethers, difluoromethanesulfonamides, and monofluoro-
methyl thioesters, one might expect difluoromethyl thioesters
to have different bioactivities as well, and this expectation has
motivated the development of efficient methods for their
preparation. For example, the Wang group11 and the Shen
group12 prepared difluoromethyl thioesters by reactions of
aldehydes and PhSO2SCF2H with excess di-tert-butyl peroxide
or PIFA/NaN3, respectively, as an oxidant. In these reactions,
the excess oxidant generates an acyl radical, and then acyl
radical abstracts the SCF2H group from PhSO2SCF2H,
Received: August 31, 2020
https://dx.doi.org/10.1021/acs.orglett.0c02902
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

Organic Letters
pubs.acs.org/OrgLett
Letter
Scheme 1. Preparation of Difluoromethyl Thioesters from
Aldehydes
Table 1. Optimization of the Conditions for Photoredox
Difluoromethylthiolation
a
b
entry
variation from the standard conditions
yield (%)
1
2
3
4
5
6
7
8
9
none
90
64
71
58
77
74
71
45
NR
14
NR
16
Na2CO3 instead of NaHCO3
K3PO4 instead of NaHCO3
DCE instead of CH3CN
1.5 equiv of 2
2 mol % TBADT
20 mol % NaHCO3
no NaHCO3
470 nm LED
air
no light
no TBADT
10
11
12
we needed to overcome is that PhSO2 radical cannot abstract
the hydrogen atom from the aldehyde because of the polarity
mismatch.14
a
Reaction conditions: 1 (0.2 mmol), 2 (0.6 mmol), tetrabutylammo-
We hypothesized that this challenge could be overcome with
a hydrogen atom transfer (HAT) photocatalyst. As part of our
ongoing work on photoredox catalysis,15 we recently
developed a protocol for deuteration reactions of aldehydes
mediated by a synergistic combination of photoredox HAT
and thiol catalysis; in these reactions, the HAT photocatalyst
generates the acyl radical and is subsequently oxidized by a
thiol radical to complete the photoredox cycle.16 On the basis
of that previous work, we wondered whether a PhSO2 radical
could oxidize the HAT photocatalyst, and we set about
exploring this possibility. Herein we report that difluorome-
thylthiolation of aldehydes with PhSO2SCF2H can be
accomplished with a decatungstate photocatalyst under
oxidant-free conditions (Scheme 1B).
At the outset, we investigated the difluoromethylthiolation
of 2-naphthaldehyde (1a) (1.0 equiv) with PhSO2SCF2H (2)
(3.0 equiv) in the presence of a base at 30 °C with
tetrabutylammonium decatungstate (TBADT) as the HAT
photocatalyst under irradiation with 36 W, 390 nm LEDs
(Table 1). We began by screening several bases with
acetonitrile as the solvent. With NaHCO3 (1.5 equiv) as the
base, the desired difluoromethyl thioester 3a was obtained in
90% yield (entry 1); the other tested bases led to lower yields
(entries 2 and 3). Using 1,2-dichloroethane as the solvent
decreased the yield (entry 4), as did reducing the amount of
PhSO2SCF2H, TBADT, or NaHCO3 (entries 5−7). When the
base was omitted, 3a was obtained in 45% yield (entry 8).
There was no reaction when a 470 nm LED was used (entry
9), and the reaction under an air atmosphere gave 3a in 14%
yield (entry 10). Control experiments showed that light and
the HAT photocatalyst were necessary for the reaction (entries
11 and 12).
nium decatungstate (TBADT) (0.008 mmol), NaHCO3 (0.3 mmol),
b
CH3CN (1 mL), Ar atmosphere. DCE = 1,2-dichloroethane. Yields
were determined by 18F NMR spectroscopy using fluorobenzene as
the internal standard. NR = no reaction.
particularly encouraged by the outcome of reactions of
halogenated aldehydes (3c−f) since 50% of the market-leading
drugs contain halogens because their reduced susceptibility to
oxidation by cytochrome P450.17 Moreover, halogenated
molecules can rapidly generate molecular complexity via
cross-coupling reactions.18 A fluorine atom and a trifluor-
omethyl group, which may improve the activity of
pharmaceutical lead compounds, were suitable for this
reaction, affording moderate yields of 3f and 3g (64% and
49%, respectively). In addition, benzaldehydes with electroni-
cally neutral functional groups, for example, isopropyl, tert-
butyl, and phenyl, were also compatible with the reaction,
giving good yields of 3h−k. Moreover, electron-rich
benzaldehydes were reactive (3l−p, 44−72% yield). Especially
3l and 3p, which have an active hydrogen, are compatible with
this reaction in moderate yields. However, 3l and 3p were
obtained in lower yields with previously reported conditions.11
A benzaldehyde with an electron-withdrawing ester group was
smoothly transformed into the corresponding difluoromethyl
thioester 3q in 51% yield. Intriguingly, benzaldehydes with
relatively sensitive yet versatile alkyne (3r) and cyclic ether
(3s) functional groups tolerated the difluoromethylthiolation
conditions well. Polysubstituted aldehydes afforded the
corresponding difluoromethyl thioesters in moderate yields
(3t−v). Heteroaromatic moieties are prevalent motifs in drugs,
and we found that S- and N-heteroarenes were also compatible
with the difluoromethylthiolation conditions (3w−y). In
addition, when the reaction was scaled up to 6 mmol, 3d
was isolated in 65% yield.
With the optimized reaction conditions in hand, we explored
the scope of aldehydes (Scheme 2). First, we found that
difluoromethyl thioester 3a could be isolated in 86% yield,
which indicated that decomposition of the difluoromethyl
thioester was minimal. The reaction has a broad substrate
scope and was amenable to oxidant-sensitive functional groups,
for example, an alkyne; −OMe, −SMe, −OH, and −OBn
groups; an amide; and a cyclic ether. Specifically, 6-methoxy-2-
naphthaldehyde afforded 3b in 81% yield. Benzaldehydes
bearing substituents with various electronic and steric
properties afforded difluoromethyl thioesters 3c−v. We were
Aliphatic aldehydes constitute a greater part of the −CHO
family compared with aromatic aldehydes. We were pleased to
find that in addition to aromatic aldehydes, several aliphatic
aldehydes were suitable substrates for our protocol, affording
difluoromethyl thioester products 3z−cc in 49−67% yield, and
no products of CO dissociation were observed (Scheme 2). It
is worth mentioning that 3bb, which has an oxidant-sensitive
position, tolerated the difluoromethylthiolation conditions
B
https://dx.doi.org/10.1021/acs.orglett.0c02902
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
a
Scheme 2. Substrate Scope of the Difluoromethylthiolation Reaction
a
Reaction conditions: aldehyde (0.2 mmol), 2 (0.6 mmol), TBADT (0.008 mmol), NaHCO3 (0.3 mmol), and CH3CN (1 mL) under an Ar
b
atmosphere. Reaction conditions: aldehyde (0.75 mmol), 2 (0.5 mmol), TBHP (1.0 mmol, 70 wt % in H2O), and CH3CN (2.5 mL) at 82 °C
under an air atmosphere. Isolated yields are given. See the Supporting Information for experimental details.
well. α,β-Unsaturated aldehydes such as (−)-myrtenal and (E)-
non-2-enal were also amenable to the difluoromethylthiolation
conditions (Scheme 2), affording the corresponding difluor-
omethyl thioesters 3dd and 3ee were obtained in moderate
yields.
As mentioned above, the introduction of a SCF2H group
into complex aldehydes is generally a difficult synthetic task.
However, the oxidant-free reaction conditions make our
protocol suitable for generating complex difluoromethyl
thioesters. For example, L-menthol-, fenbufen-, ibuprofen-,
and dehydrocholic acid-derived difluoromethyl thioesters
(3ff−ii) could be obtained in moderate yields (Scheme 2).
Next, we turned our attention to the reaction mechanism
(Scheme 3). The reaction was completely suppressed when we
used 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) as the
radical scavenger, and the corresponding radical-trapping
product 2,2,6,6-tetramethylpiperidin-1-yl 2-naphthoate (4)
was isolated in 16% yield (Scheme 2A). 2,6-Di-tert-butyl-4-
C
https://dx.doi.org/10.1021/acs.orglett.0c02902
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
difluoromethyl thioesters, which are highly valuable in the field
of drug discovery.
Scheme 3. Mechanistic Experiments
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c02902.
Experimental procedures, reaction optimization, mech-
anistic investigation, characterization data, and NMR
spectra (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Qingmin Wang − State Key Laboratory of Elemento-Organic
Chemistry, Research Institute of Elemento-Organic Chemistry,
College of Chemistry, Nankai University, Tianjin 300071,
People’s Republic of China; Collaborative Innovation Center of
Chemical Science and Engineering (Tianjin), Tianjin 300071,
People’s Republic of China; orcid.org/0000-0002-6062-
3766; Email: angqm@nankai.edu.cn
((phenylsulfonyl)methyl)phenol (5) and (2-(phenylsulfonyl)-
ethene-1,1-diyl)dibenzene (6) were observed by mass
spectrometry when 2-(tert-butyl)-6-isopropyl-4-methylphenol
(BHT) or 1,1-diphenylethylene was used as the radical
scavenger (Scheme 2B,C). These results suggest that an acyl
radical and a PhSO2 radical were generated. Furthermore, light
on/off experiments revealed that the reaction ceased in the
absence of light but began again when irradiation was
recommenced (Figure S8), indicating that any chain-
propagation process was short-lived.
Authors
Jianyang Dong − State Key Laboratory of Elemento-Organic
Chemistry, Research Institute of Elemento-Organic Chemistry,
College of Chemistry, Nankai University, Tianjin 300071,
People’s Republic of China
Fuyang Yue − State Key Laboratory of Elemento-Organic
Chemistry, Research Institute of Elemento-Organic Chemistry,
College of Chemistry, Nankai University, Tianjin 300071,
People’s Republic of China
On the basis of our experimental results, a proposed
mechanism is depicted in Scheme 4. First, photoexcitation of
Xiaochen Wang − State Key Laboratory of Elemento-Organic
Chemistry, Research Institute of Elemento-Organic Chemistry,
College of Chemistry, Nankai University, Tianjin 300071,
People’s Republic of China
Scheme 4. Proposed Mechanism for the Catalytic
Photoredox Difluoromethylthiolation Reaction
Hongjian Song − State Key Laboratory of Elemento-Organic
Chemistry, Research Institute of Elemento-Organic Chemistry,
College of Chemistry, Nankai University, Tianjin 300071,
People’s Republic of China; orcid.org/0000-0001-7105-
1196
Yuxiu Liu − State Key Laboratory of Elemento-Organic
Chemistry, Research Institute of Elemento-Organic Chemistry,
College of Chemistry, Nankai University, Tianjin 300071,
People’s Republic of China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c02902
Notes
TBADT (7) produces triplet excited state 8, which abstracts
the formyl hydrogen atom from 1a, affording decatungstate
species 9 and reactive nucleophilic formyl radical 10. Radical
10 abstracts the SCF2H group from 2 to afford the desired
difluoromethyl thioester 3a and PhSO2 radical (11).19 Finally,
a single electron transfer (SET) process between reduced
decatungstate 9 (E([W10O32]4−/[W10O32]5−) = −0.97 V vs
SCE)20 and 11 (PhSO2·/PhSO2Na, E1re/d2 = +0.50 V vs SCE)21
occurs to regenerate the active HAT photocatalyst 7.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (21732002 and 21672117) and the Tianjin Research
Innovation Project for Postgraduate Students (2019YJSB085)
for generous financial support for our programs.
In conclusion, a mild protocol for the preparation of
difluoromethyl thioesters by means of reactions of aldehydes
and PhSO2SCF2H mediated by a polyoxometalate HAT
catalyst has been developed. This oxidant-free reaction is
practical for generating complex difluoromethyl thioesters. We
anticipate that it will facilitate access to a wide range of
REFERENCES
■
(1) (a) O’Hagan, D. Understanding organofluorine chemistry. An
introduction to the C−F bond. Chem. Soc. Rev. 2008, 37, 308.
(b) O’Hagan, D.; Rzepa, H. S. Some influences of fluorine in
bioorganic chemistry. Chem. Commun. 1997, 645. (c) Chambers, R.
D. Fluorine in Organic Chemistry; Blackwell Publishing: Oxford, U.K.,
D
https://dx.doi.org/10.1021/acs.orglett.0c02902
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
of a spot-on formulation of pyriprole on dogs infested with Sarcoptes
scabiei. Vet. Rec. 2010, 167, 442.
(9) (a) Yoshimura, T.; Ikeuchi, T.; Ohno, S.; Asakura, S.; Hamada,
Y. Research and development of a novel rice herbicide, pyrimisulfan. J.
Pestic. Sci. 2013, 38, 171. (b) Jeanmart, S.; Edmunds, A. J. F.;
Lamberth, C.; Pouliot, M. Synthetic approaches to the 2010−2014
new agrochemicals. Bioorg. Med. Chem. 2016, 24, 317.
(10) Larsson, K.; Rosenhall, L. Anti-inflammatory treatment in
clinical practice: a summary. Clin. Exp. Allergy 1996, 26, 18.
(11) Guo, S.-H.; Zhang, X.-L.; Pan, G.-F.; Zhu, X.-Q.; Gao, Y.-R.;
Wang, Y.-Q. Synthesis of Difluoromethyl thioesters from Aldehydes.
Angew. Chem., Int. Ed. 2018, 57, 1663.
(12) Xu, B.; Li, D.; Lu, L.; Wang, D.; Hu, Y.; Shen, Q. Radical
fluoroalkylthiolation of aldehydes with PhSO2SRf (Rf = CF3, C2F5,
CF2H or CH2F): a general protocol for the preparation of
fluoroalkylthioesters. Org. Chem. Front. 2018, 5, 2163.
(13) (a) Noble, A.; MacMillan, D. W. C. Photoredox α-Vinylation of
α-Amino Acids and N-Aryl Amines. J. Am. Chem. Soc. 2014, 136,
11602. (b) Amaoka, Y.; Nagatomo, M.; Watanabe, M.; Tao, K.;
Kamijo, S.; Inoue, M. Photochemically induced radical alkenylation of
C(sp3)−H bonds. Chem. Sci. 2014, 5, 4339.
(14) (a) Le, C.; Liang, Y.; Evans, R. W.; Li, X.; MacMillan, D. W. C.
Selective sp3 C−H alkylation via polarity-match-based cross-coupling.
Nature 2017, 547, 79. (b) Roberts, B. P. Polarity-reversal catalysis of
hydrogen-atom abstraction reactions: concepts and applications in
organic chemistry. Chem. Soc. Rev. 1999, 28, 25.
(3) (a) Erickson, J. A.; McLoughlin, J. I. Hydrogen Bond Donor
Properties of the Difluoromethyl Group. J. Org. Chem. 1995, 60, 1626.
(b) Prakash, G. K. S.; Mandal, M.; Schweizer, S.; Petasis, N. A.; Olah,
G. A. Stereoselective Synthesis of anti-α-(Difluoromethyl)-β-amino
Alcohols by Boronic Acid Based Three-Component Condensation.
Stereoselective Preparation of (2S,3R)-Difluorothreonine. J. Org.
Chem. 2002, 67, 3718.
(4) Manteau, B.; Pazenok, S.; Vors, J.-P.; Leroux, F. R. New trends in
the chemistry of α-fluorinated ethers, thioethers, amines and
phosphines. J. Fluorine Chem. 2010, 131, 140.
(5) (a) Hansch, C.; Leo, A.; Unger, S. H.; Kim, K. H.; Nikaitani, D.;
Lien, E. J. Aromatic substituent constants for structure-activity
correlations. J. Med. Chem. 1973, 16, 1207. (b) Rico, I.; Wakselhan,
C. Synthese de composes aromatiques comportant les groupements
(15) (a) Dong, J.; Wang, Z.; Wang, X.; Song, H.; Liu, Y.; Wang, Q.
Ketones and aldehydes as alkyl radical equivalents for C−H
functionalization of heteroarenes. Sci. adv. 2019, 5, No. eaax9955.
(b) Dong, J.; Lyu, X.; Wang, Z.; Wang, X.; Song, H.; Liu, Y.; Wang,
Q. Visible-light-mediated Minisci C−H alkylation of heteroarenes
with unactivated alkyl halides using O2 as an oxidant. Chem. Sci. 2019,
10, 976. (c) Xia, Q.; Dong, J.; Song, H.; Wang, Q. Visible-Light
Photocatalysis of the Ketyl Radical Coupling Reaction. Chem. - Eur. J.
2018, 25, 2949. (d) Dong, J.; Yue, F.; Xu, W.; Song, H.; Liu, Y.;
Wang, Q. Visible-Light-Mediated Minisci C−H Alkylation of
Heteroarenes with 4-Alkyl-1,4-dihydropyridines Using O2 as an
Oxidant. Green Chem. 2020, 22, 5599.
(16) Dong, J.; Wang, X.; Wang, Z.; Song, H.; Liu, Y.; Wang, Q.
Formyl-selective deuteration of aldehydes with D2O via synergistic
organic and photoredox catalysis. Chem. Sci. 2020, 11, 1026.
(17) Ford, M. C.; Ho, P. S. Computational Tools To Model
Halogen Bonds in Medicinal Chemistry. J. Med. Chem. 2016, 59,
1655.
(18) (a) Cernak, T.; Dykstra, K. D.; Tyagarajan, S.; Vachal, P.;
Krska, S. W. The medicinal chemist’s toolbox for late stage
functionalization of drug-like molecules. Chem. Soc. Rev. 2016, 45,
546. (b) Blakemore, D.; Castro, L.; Churcher, I.; Rees, D. C.;
Thomas, A. W.; Wilson, D. M.; Wood, A. Organic synthesis provides
opportunities to transform drug discovery. Nat. Chem. 2018, 10, 383.
(19) (a) Lu, Q.; Zhang, J.; Wei, F.; Qi, Y.; Wang, H.; Liu, Z.; Lei, A.
Aerobic Oxysulfonylation of Alkenes Leading to Secondary and
Tertiary β-Hydroxysulfones. Angew. Chem., Int. Ed. 2013, 52, 7156;
Angew. Chem. 2013, 125, 7297. (b) Amaoka, Y.; Nagatomo, M.;
Watanabe, M.; Tao, K.; Kamijo, S.; Inoue, M. Photochemically
induced radical alkenylation of C(sp3)−H bonds. Chem. Sci. 2014, 5,
4339. (c) Li, H.; Shan, C.; Tung, C.-H.; Xu, Z. Dual gold and
photoredox catalysis: visible light-mediated intermolecular atom
transfer thiosulfonylation of alkenes. Chem. Sci. 2017, 8, 2610.
(d) Denes, F.; Pichowicz, M.; Povie, G.; Renaud, P. Thiyl Radicals in
Organic Synthesis. Chem. Rev. 2014, 114, 2587.
́
OCF2Br et SCF2BrI - Action du dibromodifluoronethane sur les
́
́
thiophenate et phenate de potassium. Tetrahedron Lett. 1981, 22, 323.
(c) Wu, J.; Liu, Y.; Lu, C.; Shen, Q. Palladium-catalyzed
difluoromethylthiolation of heteroaryl bromides, iodides, triflates
and aryl iodides. Chem. Sci. 2016, 7, 3757.
(6) For a recent review, see: Xiong, H.-Y.; Pannecoucke, X.; Besset,
T. Recent Advances in the Synthesis of SCF2H- and SCF2FG-
Containing Molecules. Chem. - Eur. J. 2016, 22, 16734.
(7) (a) Fujiwara, Y.; Dixon, J. A.; Rodriguez, R. A.; Baxter, R. D.;
Dixon, D. D.; Collins, M. R.; Blackmond, D. G.; Baran, P. S. A New
Reagent for Direct Difluoromethylation. J. Am. Chem. Soc. 2012, 134,
1494. (b) Bayarmagnai, B.; Matheis, C.; Jouvin, K.; Goossen, L. J.
Synthesis of Difluoromethyl Thioethers from Difluoromethyl
Trimethylsilane and Organothiocyanates Generated In Situ. Angew.
Chem., Int. Ed. 2015, 54, 5753; Angew. Chem. 2015, 127, 5845.
(c) Wu, J.; Gu, Y.; Leng, X.; Shen, Q. Copper-Promoted Sandmeyer
Difluoromethylthiolation of Aryl and Heteroaryl Diazonium Salts.
Angew. Chem., Int. Ed. 2015, 54, 7648; Angew. Chem. 2015, 127, 7758.
(d) Ismalaj, E.; Le Bars, D.; Billard, T. Direct Electrophilic
(Benzenesulfonyl)Difluoromethylthiolation with a Shelf-Stable Re-
agent. Angew. Chem., Int. Ed. 2016, 55, 4790; Angew. Chem. 2016, 128,
4868. (e) Zhu, D.; Shao, X.; Hong, X.; Lu, L.; Shen, Q. PhSO2SCF2H:
A Shelf-Stable, Easily Scalable Reagent for Radical Difluoromethylth-
iolation. Angew. Chem., Int. Ed. 2016, 55, 15807; Angew. Chem. 2016,
128, 16039. (f) Zhu, D.; Shao, X.; Hong, X.; Lu, L.; Shen, Q.
PhSO2SCF2H: A Shelf-Stable, Easily Scalable Reagent for Radical
Difluoromethylthiolation. Angew. Chem., Int. Ed. 2016, 55, 15807.
(g) Zhao, Q.; Lu, L.; Shen, Q. Direct Monofluoromethylthiolation
with S-(Fluoromethyl) Benzenesulfonothioate. Angew. Chem., Int. Ed.
2017, 56, 11575. (h) Shen, F.; Lu, L.; Shen, Q. Electrophilic
fluoroalkylthiolation induced diastereoselective and stereospecific 1,2-
metalate migration of alkenylboronate complexes. Chem. Sci. 2020,
11, 8020. (i) Xu, B.; Wang, D.; Hu, Y.; Shen, Q. Silver-catalyzed ring-
opening difluoromethylthiolation/trifluoromethylthiolation of cyclo-
alkanols with PhSO2SCF2H or PhSO2SCF3. Org. Chem. Front. 2018,
5, 1462.
(20) Persson, B. Anodic Oxidation of Benzenesulfinate Ion. Acta
Chem. Scand. 1977, 31b, 88.
(21) (a) Renneke, R. F.; Pasquali, M.; Hill, C. L. Polyoxometalate
systems for the catalytic selective production of nonthermodynamic
alkenes from alkanes. Nature of excited-state deactivation processes
and control of subsequent thermal processes in polyoxometalate
photoredox chemistry. J. Am. Chem. Soc. 1990, 112, 6585. (b) Waele,
V. D.; Poizat, O.; Fagnoni, M.; Bagno, A.; Ravelli, D. Unraveling the
(8) (a) Ito, M.; Ishigami, T. The meaning of the development of
flomoxef and clinical experience in Japan. Infection 1991, 19, S253−
S257. (b) Fourie, J. J.; Horak, I. G.; de la Puente Redondo, V. Efficacy
E
https://dx.doi.org/10.1021/acs.orglett.0c02902
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Key Features of the Reactive State of Decatungstate Anion in
Hydrogen Atom Transfer (HAT) Photocatalysis. ACS Catal. 2016, 6,
7174.
F
https://dx.doi.org/10.1021/acs.orglett.0c02902
Org. Lett. XXXX, XXX, XXX−XXX