Decarboxylative Thiolation of Redox-Active Esters to Thioesters by Merging Photoredox and Copper Catalysis

Article abstract of DOI:10.1021/acs.orglett.0c01180

Thioesters and related thiols are critically important to biological systems and also widely employed in the synthesis of pharmaceutically important molecules and polymeric materials. However, known synthetic methods often suffer from the disadvantage of

Full text of DOI:10.1021/acs.orglett.0c01180

pubs.acs.org/OrgLett
Letter
Decarboxylative Thiolation of Redox-Active Esters to Thioesters by
Merging Photoredox and Copper Catalysis
Tianxiao Xu, Tianpeng Cao, Mingcheng Yang, Ruting Xu, Xingliang Nie, and Saihu Liao*
Cite This: https://dx.doi.org/10.1021/acs.orglett.0c01180
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: Thioesters and related thiols are critically important to
biological systems and also widely employed in the synthesis of
pharmaceutically important molecules and polymeric materials.
However, known synthetic methods often suffer from the disadvantage
of being specific only to certain substrates. Herein, we describe a facile
decarboxylative thioesterification of alkyl acid derived redox-active
esters by merging photoredox catalysis and copper catalysis. This
reaction is applicable to a wide range of carboxylic acids, as well as
natural products and drugs, allowing for the synthesis of various thioesters with diverse structures, including tertiary ones that are not
accessible via traditional nucleophilic substitution from tertiary halides. Moreover, product utilization is demonstrated with a direct
transformation of thioesters to sulfonyl fluorides.
hioesters and related thiols widely exist in nature and
T
biological systems,1 and they are also extensively employed
for the synthesis of sulfur-containing drugs and polymer
materials.2,3 In the past decades, the thiolation chemistry has
been a prominent and active branch of synthetic organic
chemistry.3,4 However, even though many methods are known
for thioester and thiol synthesis, they often suffer from the
disadvantage of being specific only to certain substrates. For
example, the traditional nucleophilic substitution reaction of
alkyl halides with sulfur nucleophiles is one of the most
employed methods, but failed when applied to tertiary halides
due to the steric hindrance and the competing elimination
reaction.5 Recently, alkyl carboxylic acid derived redox-active
esters (RAEs), such as N-hydroxyphthalimide (NHPI, A*)
esters, have been recognized as ideal type of alkyl radical
precursors for synthesis, by virtue of their wide availability and
structural diversity.6 Accordingly, a large number of decarbox-
ylative C(sp3)−C and C(sp3)−X (e.g., B, N, O, F etc.) bond
formation reactions have been developed in the past years.6−10
And the corresponding decarboxylative thiolation reactions9,10
have also been reported, including earlier studies by Barton in
the 1980s (Figure 1a).10 However, the pyridine or aryl groups in
the thioether products are difficult to remove to release the
corresponding alkyl free thiols, impeding further diversification
to other important thiol derivatives.
Figure 1. Photoinduced decarboxylative thiolation to sulfides (previous
work) and thioesters (this work).
expected is the ability to utilize tertiary carboxylic acids.9
However, in our initial trials on the decarboxylative thioester-
ification with thiobenzoic acid under Fu’s reaction conditions9b
for decarboxylative thiolation or the conditions for a photo-
induced deaminative thiolation,11b we only observed a trace
As a continuum of our effort on the development of diversity-
oriented decarboxylative reactions,11a we became interested in
transferring the structural diversity of abundant carboxylic acids
to thioesters, which are regarded as masked thiols1 and can be
readily converted to various pharmaceutically important groups
such as sulfides, sulfonamides, and sulfonyl fluorides.2 And, an
advantage of the radical decarboxylative thiolation over
traditional nucleophilic substitution reactions that can be
Received: April 2, 2020
https://dx.doi.org/10.1021/acs.orglett.0c01180
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

Organic Letters
pubs.acs.org/OrgLett
Letter
a
amount of the desired thioester product (Figure 1b), suggesting
the reactivity of thioacids (RCOSH) might be substantially
different from aryl thiols (ArSH). Therefore, we decided to
integrate a copper catalytic cycle12 into this transformation to
facilitate the C−S bond formation step. Herein, we report our
efforts toward this goal and the invention of an efficient
decarboxylative thioesterification reaction of redox-active esters
by merging photoredox catalysis and copper catalysis (Figure
1c). This reaction is applicable to a wide range of carboxylic
acids, including primary, secondary, and tertiary carboxylic
acids, as well as natural products and several pharmaceuticals. In
addition, the product utilization has been further demonstrated
in a direct transformation of thioesters to sulfonyl fluorides,
which are highly in demand recently in the related study in
chemical biology and molecular pharmacology.13
Scheme 1. Substrate Scope
We commenced our study by using cyclohexanecarboxylic
acid derived redox-active ester (1) as the model substrate and
commercially available thiobenzoic acid (2) as the sulfur source
(Table 1). After an extensive screening of photocatalyst, copper
Table 1. Reaction Conditions for Decarboxylative
a
Thioesterification
b
entry
variations from the standard conditions
yield
1
2
3
4
5
6
7
8
none
No light
No CuBr
No Et3N
No Ru(bpy)3Cl2·H2O
No bpy
86%
N.R.
trace
16%
46%
52%
63%
72%
No Ph3P
No 3 Å MS
a
Reaction conditions: 0.05 mmol scale in MeCN (0.5 mL), rt, under
b
1
the irradiation of 6 W blue LEDs. Determined by H NMR with
benzyl ether as an internal standard. N.R. = no reaction.
salt, ligand, solvent, base, light source, component ratio, etc. (for
details, please see the Supporting Information), a high yield was
finally accomplished for this decarboxylative thioesterification
by using [Ru(bpy)3]Cl2·6H2O as the photocatalyst and CuBr as
the copper catalyst with bipyridine/triphenyl phosphine (bpy/
Ph3P) as the ligands, in the presence of blue light irradiation
(Table 1, entry 1). The light proved to be critical to this
transformation. No reaction was observed when the reaction was
carried out in the dark (entry 2). Among the copper salts
screened,14 CuBr is crucial and gave the highest yields (entry 3).
Without triethylamine (Et3N) or [Ru(bpy)3]Cl2·6H2O, the
reactions became slow and yields dramatically dropped to 16%
and 46%, respectively. Notably, a range of common nitrogen and
oxygen ligands were examined14 aiming to improve the yield of
the desired product 3, and the combination of bpy and Ph3P was
found to give a clean reaction and the highest yield (entry 6 and
7 vs entry 1). The addition of molecular sieves (MS) is also
beneficial, which can suppress the hydrolysis of the product
(entry 8).
a
Reactions were performed on 0.2 mmol scale, and all yields represent
isolated yields.
85% isolated yield. Other cyclic carboxylic acids with different
ring sizes (4−14), including cyclopropane (4 and 5), cyclo-
butane (6), cyclopentane (7), and cycloheptane (8), are also
suitable substrates. Notably, cyclic substrates with fluoride
substitution (9), a C−C double bond on the ring (10 and 12), a
ketone carbonyl group (11), and also a bridge cycle (14) all
reacted well under the standard conditions. Acyclic secondary
carboxylic acids (15 and 16) also reacted well with thiobenzoic
acid. Notably, tertiary acids such as simple pivalic acid (17) and
adamantane-1-carboxylic acid (18) are also suitable substrates,
including those with the carboxylic acid group at the five- and
six-membered ring site (19 and 20), which are difficult to
synthesize via traditional nucleophilic substitution from tertiary
With the catalytic system successfully established, we next
examined the reaction scope with a variety of primary,
secondary, and tertiary acids (Scheme 1). The model reaction
proceeded well on 0.2 mmol scale, giving desired thioester 3 in
B
https://dx.doi.org/10.1021/acs.orglett.0c01180
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
halides. In cases of primary acids, we could see a good functional
group tolerance to C−C double bond (22) or triple bond (23),
chloride (24), ether linker (25), ketone (26), and also ester (27
and 28). Dihydrocinnamic acids (29−31) and the acids with
one carbon extension (33) or abridged (34) also reacted well.
To our delight, this decarboxylative thioesterification can be well
applied to the modification of naturally occurring carboxylic
acids and several drugs (35−44). The transformation of amino
acid proline gave the thioester (38) in 45% isolated yield, while
the side-chain carboxylic acid group of aspartic acid and glutamic
acid could also be modified (39 and 40). Furthermore, the
carboxylic groups of drugs such as Fenbufen (41), Gemfibrozil
(42), and Indometacin (44) could be transformed readily to the
corresponding thioesters in good to high yields. As outlined in
Scheme 1, under this tandem photoredox and copper catalytic
system, various primary, secondary, and tertiary carbon radicals,
including benzylic radicals (16, 20, and 34) can all be readily
generated from the corresponding redox-active esters and
coupled subsequently with thiobenzoic acid to afford the
desired thioester products, allowing for a facile access to
thioesters and their important derivatives2 with diverse
structures.
from the photoinduced decarboxylation was trapped by
TEMPO instead (53, Figure 2, a), suggesting a radical pathway
The past few years have witnessed a fast-growing research
activity on the study of sulfonyl fluorides as selective probes in
the context of chemical biology and molecular pharmacology.13
Thiols are important precursors for the synthesis of sulfonyl
fluorides.13a,15 As exemplified in a scaled up reaction (Scheme
2a), the free thiol can be readily obtained upon in situ hydrolysis
Scheme 2. Hydrolysis to Free Thiol and Direct Conversion of
Thioesters to Sulfonyl Fluorides
Figure 2. Mechanistic studies and a possible mechanism.
is operative. We next conducted a series of fluorescence
quenching experiments with the photocatalyst [Ru(bpy)3]Cl2·
6H2O.14 Although no apparent fluorescence decrease was
observed with either CuBr or bpy/Ph3P ligand alone, the
addition of the CuBr/bpy/Ph3P combination resulted in a
significant fluorescent quenching (Figure 2b, left), indicating the
ligand coordination could make the Cu(I) more reducing. In
fact, Cu(I) complexes have been reported as a photoredox
catalyst able to reduce the redox-active ester via a single electron
transfer (SET).7f,12d,16 Notably, in contrast to the nitrogen or
oxygen nucleophiles,12d−g the thiobenzoic acid that was found
can effectively quench the fluorescence of the excited [RuII]
photocatalyst and, thus, could also act as an electron donor to
generate the highly reducing [RuI] which is required to reduce
the NHPI ester. Based on these results and the related
mechanistic studies in literature,12d−g,17 a possible mechanism
was outlined in Figure 2c. Under light irradiation, the
photocatalyst [RuII] is first excited and then accepts an electron
from LnCu(I) species (A), which can be easily formed from
CuBr and thiobenzoic acid by anion exchange in the presence of
base,18 to afford the corresponding highly reducing [RuI] and
the key CuII species (B). A single electron transfer from [RuI] to
the redox-active ester delivers the alkyl radical (R·), which can
be trapped by CuII B to generate the key intermediate C, which
then undergoes a reductive elimination to afford the desired
thioester products, while the incoming thiobenzoic acid can
regenerate A. Alternatively, *[RuII] can be reductively quenched
by thiobenzoic acid17b to generate [RuI], and the PhCOS·
generated concurrently can be trapped by LnCu(I)X species to
form B as well (for simplicity, not shown in the catalytic cycle).
with aq. NaOH after the decarboxylative thioesterification
finished. Considering the instability and unpleasant smell of free
thiols, we became interested to develop a direct conversion of
thioester to sulfonyl fluorides. After examined several reaction
conditions, we found that Selectcfluor (chloromethyl-4-fluoro-
1,4-diazoniabicyclo [2.2.2] octane bis(tetrafluoroborate)) is a
suitable reagent for this goal (Scheme 2, b). With this protocol,
primary, secondary, and also tertiary thioesters can be readily
converted to the corresponding sulfonyl fluorides (46−52) in
one step.
To gain a better understanding about this decarboxylative
thioesterification reaction, we first conducted a radical trapping
reaction with TEMPO under the standard conditions, which
showed no thioester 3 formed. The cyclohexyl radical generated
C
https://dx.doi.org/10.1021/acs.orglett.0c01180
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
ligation concept. Nat. Rev. Chem. 2018, 2, 1−17. (b) Bondalapati, S.;
Jbara, M.; Brik, A. Expanding the chemical toolbox for the synthesis of
large and uniquely modified proteins. Nat. Chem. 2016, 8, 407.
In conclusion, by merging photoredox catalysis and copper
catalysis, a visible light-mediated decarboxylative thiolation of
redox-active esters to thioesters has been successfully developed
for the first time. The reaction is applicable to a variety of alkyl
carboxylic acids, including primary, secondary, and tertiary ones,
as well as several amino acids and drugs, allowing for a facile
access to various thioesters and related thiol derivatives, which
are important compounds in medicinal and materials chemistry.
Moreover, product utilization has be demonstrated with a direct
transformation of the thioesters to sulfonyl fluorides. We
anticipate that this radical decarboxylative thioesterification will
provide a useful, complementary new approach to traditional sp3
C−S alkylation methods.
́
(c) Gongora-Benítez, M.; Tulla-Puche, J.; Albericio, F. Multifaceted
Roles of Disulfide Bonds. Peptides as Therapeutics. Chem. Rev. 2014,
114, 901−926. (d) Cheng, Z.; Zhang, J.; Ballou, D. P.; Williams, C. H.,
Jr. Reactivity of Thioredoxin as a Protein Thiol-Disulfide Oxidor-
eductase. Chem. Rev. 2011, 111, 5768−5783. (e) Kent, S. B. H. Total
chemical synthesis of proteins. Chem. Soc. Rev. 2009, 38, 338−351.
(2) For reviews on drugs, see: (a) Scott, K. A.; Njardarson, J. T.
Analysis of US FDA-Approved Drugs Containing Sulfur Atoms. Top.
Curr. Chem. 2019, 376 (5), 1−34. (b) Feng, M.; Tang, B.; Liang, S.;
Jiang, X. Sulfur Containing Scaffolds in Drugs: Synthesis and
Application in Medicinal Chemistry. Curr. Top. Med. Chem. 2016, 16,
1200−1216. (c) Ilardi, E. A.; Vitaku, E.; Njardarson, J. T. Data-Mining
for Sulfur and Fluorine: An Evaluation of Pharmaceuticals to Reveal
Opportunities for Drug Design and Discovery: Miniperspective. J. Med.
Chem. 2014, 57, 2832−2842.
ASSOCIATED CONTENT
* Supporting Information
■
sı
(3) (a) Naowarojna, N.; Cheng, R.; Chen, L.; Quill, M.; Xu, M.; Zhao,
C.; Liu, P. Mini-Review: Ergothioneine and Ovothiol Biosyntheses, an
Unprecedented Trans-Sulfur Strategy in Natural Product Biosynthesis.
Biochemistry 2018, 57, 3309−3325. (b) Dunbar, K. L.; Scharf, D. H.;
Litomska, A.; Hertweck, C. Enzymatic Carbon−Sulfur Bond Formation
in Natural Product Biosynthesis. Chem. Rev. 2017, 117, 5521−5577.
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c01180.
Experimental procedures and characterization data
(PDF)
́
̀
(c) Denes, F.; Pichowicz, M.; Povie, G.; Renaud, P. Thiyl Radicals in
Organic Synthesis. Chem. Rev. 2014, 114, 2587−2693. (d) Dreaden, E.
C.; Alkilany, A. M.; Huang, X.; Murphy, C. J.; EI-Sayed, M. A. The
golden age: gold nanoparticles for biomedicine. Chem. Soc. Rev. 2012,
41, 2740−2779. (e) Franc, G.; Kakkar, A. K. Click” methodologies:
efficient, simple and greener routes to design dendrimers. Chem. Soc.
Rev. 2010, 39, 1536−1544. (f) Hoyle, C. E.; Bowman, C. N. Thiol−Ene
Click Chemistry. Angew. Chem., Int. Ed. 2010, 49, 1540−1573.
AUTHOR INFORMATION
Corresponding Author
■
Saihu Liao − Key Laboratory of Molecule Synthesis and Function
Discovery, College of Chemistry, Fuzhou University, Fuzhou
350116, P. R. China; Beijing National Laboratory for Molecular
Sciences (BNLMS), Beijing 100190, P. R. China; orcid.org/
0000-0002-0251-8757; Email: shliao@fzu.edu.cn
(4) For selected recent studies, see: (a) Wang, X.; Wang, B.; Yin, X.;
Yu, W.; Liao, Y.; Ye, J.; Wang, M.; Hu, L.; Liao, J. Palladium-Catalyzed
Enantioselective Thiocarbonylation of Styrenes. Angew. Chem., Int. Ed.
2019, 58, 12264−12270. (b) Ouhib, F.; Grignard, B.; van den Broeck,
E.; Luxen, A.; Robeyns, K.; van Speybroeck, V.; Jerome, C.;
Detrembleur, C. A Switchable Domino Process for the Construction
of Novel CO2-Sourced Sulfur Containing Building Blocks and
Polymers. Angew. Chem. 2019, 131, 11894−11899. (c) Kang, Y. S.;
Zhang, P.; Li, M. Y.; Chen, Y. K.; Xu, H. J.; Zhao, J.; Sun, W. Y.; Yu, J.
Q.; Lu, Y. Ligand-Promoted RhIII-Catalyzed Thiolation of Benzamides
with a Broad Disulfide Scope. Angew. Chem., Int. Ed. 2019, 58, 9099−
9103. (d) Laudadio, G.; Barmpoutsis, E.; Schotten, C.; Struik, L.;
Authors
Tianxiao Xu − Key Laboratory of Molecule Synthesis and
Function Discovery, College of Chemistry, Fuzhou University,
Fuzhou 350116, P. R. China
Tianpeng Cao − Key Laboratory of Molecule Synthesis and
Function Discovery, College of Chemistry, Fuzhou University,
Fuzhou 350116, P. R. China
Mingcheng Yang − Key Laboratory of Molecule Synthesis and
Function Discovery, College of Chemistry, Fuzhou University,
Fuzhou 350116, P. R. China
Ruting Xu − Key Laboratory of Molecule Synthesis and Function
Discovery, College of Chemistry, Fuzhou University, Fuzhou
350116, P. R. China
̈
Govaerts, S.; Browne, D. L.; Noel, T. Sulfonamide Synthesis through
Electrochemical Oxidative Coupling of Amines and Thiols. J. Am.
Chem. Soc. 2019, 141, 5664−5668. (e) Liu, D.; Ma, H.-X.; Fang, P.;
Mei, T.-S. Nickel-Catalyzed Thiolation of Aryl Halides and Heteroaryl
Halides through Electrochemistry. Angew. Chem., Int. Ed. 2019, 58,
5033−5037. (f) Yang, X.-H.; Davison, R. T.; Nie, S.-Z.; Cruz, F. A.;
McGinnis, T. M.; Dong, V. M. Catalytic Hydrothiolation: Counterion-
Controlled Regioselectivity. J. Am. Chem. Soc. 2019, 141, 3006−3013.
(g) Zhang, Y.; Xu, X.; Zhu, S. Nickel-Catalysed Selective Migratory
Hydrothiolation of Alkenes and Alkynes with Thiols. Nat. Commun.
2019, 10, 1752. (h) McKinnell, R. M.; Fatheree, P.; Choi, S.-K.;
Gendron, R.; Jendza, K.; Blair, B. O.; Budman, J.; Hill, C. M.; Hegde, L.
G.; Yu, C.; McConn, D.; Hegde, S. S.; Marquess, D. G.; Klein, U.
Discovery of TD-0212, an Orally Active Dual Pharmacology AT1
Antagonist and Neprilysin Inhibitor (ARNI). ACS Med. Chem. Lett.
2019, 10 (1), 86−91.
Xingliang Nie − Key Laboratory of Molecule Synthesis and
Function Discovery, College of Chemistry, Fuzhou University,
Fuzhou 350116, P. R. China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c01180
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge National Natural Science Founda-
tion of China (No. 21602028), Beijing National Laboratory for
Molecular Sciences (BNLMS201913), the Recruitment Pro-
gram of Global Experts, the Hundred-Talent Project of Fujian,
and Fuzhou University for the financial support.
(5) Wardell, J. L. In The Chemistry of the Thiol Group; Patai, S., Ed.;
Wiley: New York, 1974; pt. 1, pp 179−211.
(6) For selected reviews, see: (a) Xuan, J.; Zhang, Z.-G.; Xiao, W.-J.
Visible−Light−Induced Decarboxylative Functionalization of Carbox-
ylic Acids and Their Derivatives. Angew. Chem., Int. Ed. 2015, 54,
15632−15641. (b) Jin, Y.; Fu, H. Visible−Light Photoredox
Decarboxylative Couplings. Asian J. Org. Chem. 2017, 6, 368−385.
REFERENCES
■
̈
(1) (a) Kulkarni, S. S.; Sayers, J.; Premdjee, B.; Payne, R. J. Rapid and
efficient protein synthesis through expansion of the native chemical
(c) Schwarz, J.; Konig, B. Decarboxylative reactions with and without
light − a comparison. Green Chem. 2018, 20, 323−361. (d) Murarka, S.
D
https://dx.doi.org/10.1021/acs.orglett.0c01180
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
N−(Acyloxy)phthalimides as Redox−Active Esters in Cross−Coupling
Reactions. Adv. Synth. Catal. 2018, 360, 1735−1753.
Donor−Acceptor Complex Formation. Org. Lett. 2019, 21, 8673−
8678.
(7) For selected recent reports, see: (a) Fawcett, A.; Pradeilles, J.;
Wang, Y.; Mutsuga, T.; Myers, E. L.; Aggarwal, V. K. Photoinduced
Decarboxylative Borylation of Carboxylic Acids. Science 2017, 357,
283−286. (b) Candish, L.; Teders, M.; Glorius, F. Transition-Metal-
Free, Visible-Light-Enabled Decarboxylative Borylation of Aryl N-
hydroxyphthalimide Esters. J. Am. Chem. Soc. 2017, 139, 7440−7443.
(c) Wang, D.; Zhu, N.; Chen, P.; Lin, Z.; Liu, G. Enantioselective
Decarboxylative Cyanation Employing Cooperative Photoredox
Catalysis and Copper Catalysis. J. Am. Chem. Soc. 2017, 139, 15632−
15635. (d) Mao, R.; Frey, A.; Balon, J.; Hu, X. Decarboxylative C
(sp3)−N Cross-Coupling via Synergetic Photoredox and Copper
Catalysis. Nat. Catal. 2018, 1, 120−126. (e) Ma, J.; Lin, J.; Zhao, L.;
Harms, K.; Marsch, M.; Xie, X.; Meggers, E. Synthesis of β-Substituted
γ -Aminobutyric Acid Derivatives through Enantioselective Photoredox
Catalysis. Angew. Chem., Int. Ed. 2018, 57, 11193−11197. (f) Wang, C.;
Guo, M.; Qi, R.; Shang, Q.; Liu, Q.; Wang, S.; Zhao, L.; Wang, R.; Xu, Z.
Visible-Light-Driven, Copper Catalyzed Decarboxylative C(sp3)− H
Alkylation of Glycine and Peptides. Angew. Chem., Int. Ed. 2018, 57,
15841−15846. (g) Proctor, R. S. J.; Davis, H. J.; Phipps, R. J. Catalytic
Enantioselective Minisci-Type Addition to Heteroarenes. Science 2018,
360, 419−422. (h) Fu, M.-C.; Shang, R.; Zhao, B.; Wang, B.; Fu, Y.
Photocatalytic Decarboxylative Alkylations Mediated by Triphenyl-
phosphine and Sodium Iodide. Science 2019, 363, 1429−1434.
(8) (a) Qin, T.; Cornella, J.; Li, C.; Malins, L. R.; Edwards, J. T.;
Kawamura, S.; Maxwell, B. D.; Eastgate, M. D.; Baran, P. S. A General
Alkyl-Alkyl Cross-Coupling Enabled by Redox-Active Esters and
Alkylzinc Reagents. Science 2016, 352, 801−805. (b) Huihui, K. M.
M.; Caputo, J. A.; Melchor, Z.; Olivares, A. M.; Spiewak, A. M.;
Johnson, K. A.; DiBenedetto, T. A.; Kim, S.; Ackerman, S. L. K. G.;
Weix, D. J. Decarboxylative Cross-Electrophile Coupling of N-
hydroxyphthalimide Esters with Aryl Iodides. J. Am. Chem. Soc. 2016,
138, 5016−5019. (c) Xue, W.; Oestreich, M. Copper-Catalyzed
Decarboxylative Radical Silylation of Redox-Active Aliphatic Carbox-
ylic Acid Derivatives. Angew. Chem., Int. Ed. 2017, 56, 11649−11652.
(d) Liu, X.-G.; Zhou, C.-J.; Lin, E.; Han, X.-L.; Zhang, S.-S.; Li, Q.;
Wang, H. Decarboxylative Negishi Coupling of Redox−Active
Aliphatic Esters by Cobalt Catalysis. Angew. Chem., Int. Ed. 2018, 57,
13096−13100. (e) Zeng, X. J.; Yan, W. H.; Zacate, S. B.; Chao, T. H.;
Sun, X. D.; Cao, Z.; Bradford, K. G. E.; Paeth, M.; Tyndall, S. B.; Yang,
K. D.; Kuo, T. C.; Cheng, M. J.; Liu, W. Copper−Catalyzed
Decarboxylative Difluoromethylation. J. Am. Chem. Soc. 2019, 141,
11398−11403.
(12) For reviews, see: (a) Skubi, K. L.; Blum, T. R.; Yoon, T. P. Dual
Catalysis Strategies in Photochemical Synthesis. Chem. Rev. 2016, 116,
10035−10074. (b) Huang, H.; Jia, K.; Chen, Y. Radical Decarbox-
ylative Functionalizations Enabled by Dual Photoredox Catalysis. ACS
Catal. 2016, 6, 4983−4988. (c) Reed, N. L.; Herman, M. I.; Miltchev,
V. P.; Yoon, T. P. Tandem Copper and Photoredox Catalysis in
Photocatalytic Alkene Difunctionalization Reactions. Beilstein J. Org.
Chem. 2019, 15, 351−356. For selected examples: (d) Zhao, W.; Wurz,
R. P.; Peters, J. C.; Fu, G. C. Photoinduced, Copper-Catalyzed
Decarboxylative C−N Coupling to Generate Protected Amines: An
Alternative to the Curtius Rearrangement. J. Am. Chem. Soc. 2017, 139,
12153−12156. (e) Mao, R.; Balon, J.; Hu, X. Cross−Coupling of Alkyl
Redox−Active Esters with Benzophenone Imines: Tandem Photoredox
and Copper Catalysis. Angew. Chem., Int. Ed. 2018, 57, 9501−9504.
(f) Liang, Y.; Zhang, X.; MacMillan, D. W. C. Decarboxylative sp3 C−N
coupling via dual copper and photoredox catalysis. Nature 2018, 559,
83−88. (g) Mao, R.; Balon, J.; Hu, X. Decarboxylative C (sp3)−O
Cross−Coupling. Angew. Chem., Int. Ed. 2018, 57, 13624−13628.
(13) For reviews on SuFEx Chemistry, see: (a) Dong, J.; Krasnova, L.;
Finn, M. G.; Sharpless, K. B. Sulfur (VI) fluoride exchange (SuFEx):
another good reaction for click chemistry. Angew. Chem., Int. Ed. 2014,
53, 9430−9448. (b) Narayanan, A.; Jones, L. H. Sulfonyl fluorides as
privileged warheads in chemical biology. Chem. Sci. 2015, 6, 2650−
2659. (c) Barrow, A. S.; Smedley, C. J.; Zheng, Q.; Li, S.; Dong, J.;
Moses, J. E. The growing applications of SuFEx click chemistry. Chem.
Soc. Rev. 2019, 48, 4731−4758.
(14) For more details, please see the Supporting Information.
(15) (a) Krutak, J. J.; Burpitt, R. D.; Moore, W. H.; Hyatt, J. A.
Chemistry of ethenesulfonyl fluoride. Fluorosulfonylethylation of
organic compounds. J. Org. Chem. 1979, 44, 3847−3858. (b) Wright,
S. W.; Hallstrom, K. N. A Convenient preparation of heteroaryl
sulfonamides and sulfonyl fluorides from heteroaryl thiols. J. Org. Chem.
2006, 71, 1080−1084. (c) Laudadio, G.; Bartolomeu, A. d. A.;
̈
Verwijlen, L. M. H. M.; Cao, Y.; de Oliveira, K. T.; Noel, T. Sulfonyl
fluoride synthesis through electrochemical oxidative coupling of thiols
and potassium fluoride. J. Am. Chem. Soc. 2019, 141, 11832−11836.
(16) (a) Hossain, A.; Bhattacharyya, A.; Reiser, O. Copper’s rapid
ascent in visible-light photoredox catalysis. Science 2019, 364,
No. eaav9713. (b) Yu, X.-Y.; Zhao, Q.-Q.; Chen, J.; Chen, J.-R.;
Xiao, W.-J. Copper−Catalyzed Radical Cross−Coupling of Redox−
Active Oxime Esters, Styrenes, and Boronic Acids. Angew. Chem., Int.
Ed. 2018, 57, 15505−15509.
(17) (a) Weng, Z.; He, W.; Chen, C.; Lee, R.; Tan, D.; Lai, Z.; Kong,
D.; Yuan, Y.; Huang, K.-W. An Air−Stable Copper Reagent for
Nucleophilic Trifluoromethylthiolation of Aryl Halides. Angew. Chem.,
Int. Ed. 2013, 52, 1548−1552. (b) Liu, H.; Zhao, L.; Yuan, Y.; Xu, Z.;
Chen, K.; Qiu, S.; Tan, H. Potassium thioacids mediated selective
amide and peptide constructions enabled by visible light photoredox
catalysis. ACS Catal. 2016, 6, 1732−1736. (c) Soria-Castro, S. M.;
̈
(9) (a) Wimmer, A.; Konig, B. Photocatalytic Formation of Carbon−
Sulfur Bonds. Beilstein J. Org. Chem. 2018, 14, 54−83. (b) Jin, Y.; Yang,
H.; Fu, H. An N-(acetoxy) phthalimide Motif as a Visible-Light Pro-
photosensitizer in Photoredox Decarboxylative Arylthiation. Chem.
Commun. 2016, 52, 12909−12912. (c) Gianatassio, R.; Kawamura, S.;
Eprile, C. L.; Foo, K.; Ge, J.; Burns, A. C.; Collins, M. R.; Baran, P. S.
Simple Sulfinate Synthesis Enables C-H Trifluoromethylcyclopropa-
nation. Angew. Chem., Int. Ed. 2014, 53, 9851−9855.
́
Andrada, D. M.; Caminos, D. A.; Arguello, J. E.; Robert, M.; Penenory,
̈ ̃ ̃
A. B. Mechanistic insight into the Cu-catalyzed C−S cross-coupling of
thioacetate with aryl halides: A joint experimental-computational study.
J. Org. Chem. 2017, 82, 11464−11473.
(10) (a) Barton, D. H. R.; Crich, D.; Motherwell, W. B. New and
Improved Methods for the Radical Decarboxylation of Acids. J. Chem.
Soc., Chem. Commun. 1983, 939−941. (b) Barton, D. H. R.; Crich, D.;
Motherwell, W. B. The Invention of New Radical Chain Reactions. Part
VIII. Radical Chemistry of Thiohydroxamic Esters; A New Method for
the Generation of Carbon Radicals from Carboxylic Acids. Tetrahedron
1985, 41, 3901−3924. (c) Barton, D. H. R.; Bridon, D.; Fernandaz-
Picot, I.; Zard, S. Z. The Invention of Radical Reactions: Part XV. Some
Mechanistic Aspects of The Decarboxylative Rearrangement of
Thiohydroxamic esters. Tetrahedron 1987, 43, 2733−2740. (d) Barton,
D. H. R.; Lacher, B.; Misterkiewicz, B.; Zard, S. Z. The Invention of
Radical Reactions: Part XVII. A Decarboxylative Sulphonylation of
Carboxylic Acids. Tetrahedron 1988, 44, 1153−1158.
(18) The addition of thiobenzoic acid to the CuBr/ligand/Et3N
solution led to a quick color change from dark orange to light yellow,
and HRMS analysis indicated the bpyCu-SCOPh (m/z 378.9938)
formation.
(11) (a) Xu, R.; Xu, T.; Yang, M.; Cao, T.; Liao, S. A rapid access to
aliphatic sulfonyl fluorides. Nat. Commun. 2019, 10, 3752. (b) Yang,
M.; Cao, T.; Xu, T.; Liao, S. Visible-Light-Induced Deaminative
Thioesterification of Amino Acid Derived Katritzky Salts via Electron
E
https://dx.doi.org/10.1021/acs.orglett.0c01180
Org. Lett. XXXX, XXX, XXX−XXX