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Synthesis of aryl sulfides and diaryl sulfides

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Chan-Lam Coupling

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Leuckart Thiophenol Reaction

Sandmeyer-type Reaction

Ullmann Reaction

Recent Literature

A general palladium-catalyzed reaction using the CyPF-t-Bu ligand for the coupling of aryl halides and sulfonates with thiols exhibits extraordinary turnover numbers and high tolerance of functional groups.
M. A. Fernández-Rodríguez, Q. Shen, J. F. Hartwig, J. Am. Chem. Soc., 2006, 128, 2180-2181.

The well-defined palladium N-heterocyclic carbene (NHC) complex [Pd(IPr*OMe)(cin)(Cl)] provides high catalytic activity for carbon-sulfur cross-coupling reactions of nonactivated and deactivated aryl halides with a large variety of aryl- and alkylthiols.
G. Bastug, S. P. Nolan, J. Org. Chem., 2013, 78, 9303-9308.

A versatile and efficient Pd(OAc)2/1,1'-bis(diisopropylphosphino)ferrocene-catalyzed cross-coupling of thiols with aryl halides was developed. Aryl bromides and chlorides can be coupled to aliphatic and aromatic thiols - the widest substrate scope of any reported to date. This catalyst system also enables the coupling of secondary phosphines with aryl halides.
M. Murata, S. L. Buchwald, Tetrahedron, 2004, 60, 7397-7403.

A convenient method for C-S cross-coupling of aryl bromides with various thiols involves the use of a 1,1′-bis(diphenylphosphino)ferrocene (DPPF)-ligated palladium complex with N,N-diisopropylethylamine (DIPEA) as the base. This coupling tolerates a wide range of functional groups, including hydroxy, amino, cyano, nitro, formyl, and carboxyl groups.
T. Okauchi, K. Kuramoto, M. Kitamura, Synlett, 2010, 2891-2894.

Highly chemoselective C-S cross-couplings of aryl, benzyl, and alkyl thiols with aryl and heteroaryl iodides were achieved versus competitive C-O and C-N cross-couplings in the presence of an Ir-photoredox catalyst. The reactions exhibit remarkable functional group tolerance and can be carried out in the presence of molecular oxygen.
M. S. Oderinde, M. Frenette, D. W. Robbins, B. Aquila, J. W. Johannes, J. Am. Chem. Soc., 2016, 138, 1760-1763.

Alkyl radicals generated from hypervalent alkylsilicates serve as effective hydrogen atom abstractors from thiols, furnishing thiyl radicals. A subsequent nickel-mediated cross-coupling with aromatic bromides provides thioethers. This thioetherification of various aryl and heteroaryl bromides with a diverse array of thiols tolerates a wide range of functional groups due to the S-H selective H atom abstraction event.
M. Jouffroy, C. B. Kelly, G. A. Molander, Org. Lett., 2016, 18, 876-879.

A cobalt-catalyzed coupling of aryl halides with thiophenols and alkanethiols allows the preparation of various aryl sulfides in excellent yields under mild reaction conditions.
Y.-C. Wong, T. T. Jayanth, C.-H. Cheng, Org. Lett., 2006, 8, 5613-5616.

Y.-C. Wong, T. T. Jayanth, C.-H. Cheng, Org. Lett., 2006, 8, 5613-5616.

An efficient CuSO4-catalyzed S-arylation of thiols with aryl and heteroaryl boronic acids at room temperature is established. A wide variety of thiols and arylboronic acids can be converted in the presence of CuSO4 as the catalyst, inexpensive 1,10-phen·H2O as the ligand, oxygen as oxidant, and EtOH as environment-friendly solvent.
H.-J. Xu, Y.-Q. Zhao, T. Feng, Y.-S. Feng, J. Org. Chem., 2012, 77, 2649-2658.

A combination of copper(II) oxide and 1,10-phenanthroline catalyzes a microwave-promoted C-S bond formation of thiols and aryl iodides. Various aryl iodides react smoothly with thiols to provide the corresponding aryl sulfides in very good yields in water with a short reaction time. Amino, chloro, bromo, acetyl, and nitro groups are tolerated.
Y.-A. Chen. S. S. Badsara, W.-T. Tsai, C.-F. Lee, Synthesis, 2015, 47, 181-186.

A versatile photoinduced, copper-catalyzed method enables the coupling aryl thiols with aryl halides at 0°C using inexpensive CuI as a precatalyst without the need for an added ligand. The reaction is effective for a wide range of coupling partners. Mechanistic investigations are consistent with photoinduced C-S cross-couplings following a SET/radical pathway for C-X bond cleavage (via a Cu(I)-thiolate).
C. Uyeda, Y. Tan, G. C. Fu, J. C. Peters, J. Am. Chem. Soc., 2013, 135, 9548-9552.

Diaryliodonium triflates transfer an aryl group to the chalcogen atom of organic sulfides, selenides, and tellurides. The reaction works in the absence of a transition-metal catalyst, simply upon heating in chloroform or dichloroethane solution.
L. Racicot, T. Kasahara, M. A. Ciufolini, Org. Lett., 2014, 16, 6382-6385.

Inodorous stable Na2S2O3 is used as a sulfurating reagent in a Cu-catalyzed dual C-S bonds formation reaction, that proceeds in alcohol and water under air. This powerful strategy provides a practical and efficient approach to construct thioethers, using readily available aromatic amines and alkyl halides as starting materials. Sensitive and synthetic useful functional groups are tolerated.
Y. Li, J. Pu, X. Jiang, Org. Lett., 2014, 16, 2692-2695.

An acid-mediated coupling of thiols and thioethers with diaryliodonium salts enables the preparation of diaryl and alkyl aryl sulfides. The scope, limitations, and mechanism of the transformation are discussed.
A. M. Wagner, M. S. Sanford, J. Org. Chem., 2014, 79, 2263-2264.

The odorless and stable solid Na2S2O3·5H2O was used as a convenient and environmentally friendly source of sulfur in a Pd-catalyzed cross-coupling of aryl halides and alkyl halides to deliver aromatic sulfides.
Z. Qiao, J. Wei, X. Jiang, Org. Lett., 2014, 16, 1212-1215.

An efficient cross-coupling reaction of aryl/het-aryl/benzyl halides with stable and easily workable sulfonyl hydrazides as thiol substitutes delivers unsymmetrical sulfides in the presence [DBU][HOAc] and CuI under microwave irradiation.
N. Singh, R. Singh, D. S. Raghuvanshi, K. N. Singh, Org. Lett., 2013, 15, 5874-5877.

Cross-coupling of inexpensive ethyl potassium xanthogenate with aryl halides using recyclable CuO nanoparticles under ligand-free conditions followed by hydrolysis of the resulting xanthogenate ester and a subsequent cross coupling enables a synthesis of unsymmetrical sulfides in good to excellent yields. The copper oxide nanoparticles can be recovered and reused up to five cycles without loss of activity.
V. K. Akkilagunta, R. R. Kakulapati, J. Org. Chem., 2011, 76, 6819-6824.

In an efficient Cu-catalyzed one-pot approach for the synthesis of unsymmetrical diaryl thioethers through a Cu-catalyzed double arylation, the aryl thiols are generated in situ from an easily available xanthate and aryl halides. This strategy was further successfully utilized for the synthesis of symmetrical diaryl thioethers, aryl alkyl thioethers, and benzothiazoles.
D. J. C. Prasad, G. Sekar, Org. Lett., 2011, 13, 1008-1011.

An efficient coupling of arylboronic acids with dimethyldisulfide under metal-free conditions provides aryl methyl sulfides. The method offers operational simplicity, satisfactory yields, excellent functional-group tolerance, as well as mild reaction conditions.
X.-m. Wu, J.-m. Lou, G.-b. Yan, Synlett, 2016, 27, 2269-2273.

An Efficient Copper-Catalyzed One-Pot Synthesis of Diaryl Thioethers by Coupling of Arylboronic Acids with Potassium Ethyl Xanthogenate under Mild Conditions
L. Wang, W.-Y. Zhou, S.-C. Chen, M.-Y. He, Q. Chen, Synlett, 2011, 3041-3045.

Coupling of arylboronic acids with potassium ethyl xanthogenate enables a simple and environmentally benign one-pot synthesis of diaryl thioethers through a double arylation process. The aryl thiols were generated in situ, and the reactions proceeded smoothly to give the corresponding products in good to excellent yields under very mild conditions.
L. Wang, W.-Y. Zhou, S.-C. Chen, M.-Y. He, Q. Chen, Synlett, 2011, 3041-3045.

S-Alkyl, S-aryl, and S-vinyl thiosulfate sodium salts (Bunte salts), which can readily be prepared from sodium thiosulfate, react with Grignard reagents to give sulfides in good yields. The reaction is amenable to a broad structural array of Bunte salts and Grignard reagents. Importantly, this route to sulfides avoids the use of malodorous thiol starting materials or byproducts.
J. T. Reeves, K. Camara, Z. S. Han, Y. Xu, H. Lee, C. A. Busacca, C. H. Senanayaka, Org. Lett., 2014, 16, 1196-1199.

A single catalyst, derived from Pd(dba)2 and NiXantPhos, efficiently catalyzes a debenzylative synthesis of diaryl sulfides from aryl benzyl sulfides and aryl bromides in good to excellent yields via α-arylation of sulfides, C-S bond cleavage, and C-S bond formation in a tricatalytic cycle.
J. Mao, T. Jia, G. Frensch, P. J. Walsh, Org. Lett., 2014, 16, 5304-5307.

cis-1,2-Cyclohexanediol is an efficient and versatile bidentate O-donor ligand that provides a highly active Cu-catalytic system for cross-coupling reactions of alkyl, aryl, or heterocyclic thiols with either alkyl, aryl, heterocyclic, or substituted vinyl halides. This new catalytic system promoted the mild and efficient stereo- and regiospecific synthesis of biologically important vinyl sulfides.
M. S. Kabir, M. Lorenz, M. L. V. Linn, O. A. Namjoshi, S. Ara, J. M. Cook, J. Org. Chem., 2010, 75, 3626-3643.

An efficient ligand-free Cu2O-catalyzed C-S bond-formation reaction allows the assembling of a large number of diaryl sulfides and alkylaryl sulfides in good yields.
H.-J. Xu, X.-Y. Zhao, Y. Fu, Y.-S. Feng, Synlett, 2008, 3046-3052.

An aryl-sulfur bond formation between aryl iodides and thiophenols is catalyzed by a low amount of readily available and ligand-free copper iodide salt. Various diaryl thioethers are synthesized under relatively mild reaction conditions with good chemoselectivity and functional group tolerance.
E. Sperotto, G. P. M. van Klink, J. G. de Vries, G. van Koten, J. Org. Chem., 2008, 73, 5625-5628.

TAPC efficiently catalyzes the reaction of benzylic alcohols with aryl, heteroaryl, and alkyl thiols to afford thioethers in good to excellent yields. Furthermore, the reaction proceeds under metal-free and solvent-free conditions thus represents an interesting complement to known methods for thioether synthesis. A plausible mechanism is given.
K. Bahrami, M. M. Khodaei, N. Khodaboustan, Synlett, 2011, 2206-2210.

An efficient, indium triiodide-catalyzed substitution of the acetoxy group in alkyl, benzyl, allyl, and propargyl acetates with thiosilanes provides access to various thioethers.
Y. Nishimoto, A. Okita, M. Yasuda, A. Baba, Org. Lett., 2012, 14, 1846-1849.

Indium tri(organothiolate) derivatives are effective nucleophilic coupling partners in Pd-catalyzed C-S crosscoupling reactions to produce functionalized sulfides in excellent yields with high atom efficiency and complete regio- and chemoselectivity.
J.-Y. Lee, P. H. Lee, J. Org. Chem., 2008, 73, 7413-7416.

The use of copper(Ι) iodide as a catalyst, 4′-(4-methoxyphenyl)-2,2′:6′,2′′-terpyridine as ligand, and KOH as the base enables an efficient and convenient protocol for the copper-catalyzed reaction of aryl iodides with diorganyl disulfides and diselenides. Various symmetrical and unsymmetrical diaryl- and aryl alkyl chalcogenides were synthesized with good functional group tolerance and chemoselectivity.
B. Movassagh, Z. Hosseinzadeh, Synlett, 2016, 27, 777-781.

An eco-friendly coupling of diaryl disulfides and aryl iodides under ligand-free conditions with copper nanopowder as catalyst and PEG-400 as solvent enables the synthesis of varous unsymmetrical diaryl in very good yields. The process is odour-free and the copper nanopowder-PEG-400 catalytic system can be directly reused for four repetitive cycles.
X.-m. Wu, G.-b. Yan, Synlett, 2015, 26, 537-542.

Rongalite promotes a smoth, one-pot synthesis of aryl alkyl sulfides from disulfides and alkyl halides at room temperature. This protocol is metal-free, strong-base-free, and offers mild reaction conditions, operational simplicity, short reaction times and high yields of products.
R.-y. Tang, P. Zhong, Q.-l. Lin, Synthesis, 2007, 85-91.

Unsymmetrical diorgano-monosulfides, selenides, and tellurides can be synthesized by the coupling of dichalcogenides with aryl- or alkylboronic acids using a copper catalyst in air. The present reaction takes advantage of both organochalcogenide groups on the dichalcogenide.
N. Taniguchi, J. Org. Chem., 2007, 72, 1241-1245.

In three odorless methods for the thioarylation and thioalkylation of different nitroarenes using alkyl halides (Br, Cl), triphenyltin chloride, and arylboronic acids as the coupling partners, Na2S2O3·5H2O, S8/KF, and S8/NaOH systems are found to be effective sources of sulfur in the presence of copper salts. The methods offer use of green solvents, inexpensive catalysts, and user-friendly starting materials.
A. Rostami, A. Rostami, A. Ghaderi, J. Org. Chem., 2015, 80, 8694-8704.

In three odorless methods for the thioarylation and thioalkylation of different nitroarenes using alkyl halides (Br, Cl), triphenyltin chloride, and arylboronic acids as the coupling partners, Na2S2O3·5H2O, S8/KF, and S8/NaOH systems are found to be effective sources of sulfur in the presence of copper salts. The methods offer use of green solvents, inexpensive catalysts, and user-friendly starting materials.
A. Rostami, A. Rostami, A. Ghaderi, J. Org. Chem., 2015, 80, 8694-8704.

In situ nitrosation of anilines followed by reduction with ascorbic acid to form aryl radicals and thiolation with disulfides provided aryl sulfides. This mild, metal-free synthesis of aryl sulfides proceeded smoothly without heating or irradiation. This strategy can be expanded to the synthesis of aryl selenides.
M.-j. Bu, G.-p. Lu, C. Cai, Synlett, 2015, 26, 1841-1846.

The reaction of diazonium tetrafluoroborates and diaryl dichalcogenides including sulfides, selenides and tellurides on the surface of alumina under ball-milling enables a convenient, efficient, and general synthesis of a wide range of diaryl chalcogenides in high purity without any solvent or metal.
N. Mukherjee, T. Chatterjee, B. C. Ranu, J. Org. Chem., 2013, 78, 11110-11114.

1,1,1-Tris(hydroxymethyl)ethane as a New, Efficient, and Versatile Tripod Ligand for Copper-Catalyzed Cross-Coupling Reactions of Aryl Iodides with Amides, Thiols, and Phenols
Y.-J. Chen, H.-H. Chen, Org. Lett., 2006, 8, 5609-5612.

A mild, palladium-free method for C-S-bond formation is reported. The standard protocol gave aryl sulfides in excellent yields from thiols and iodides.
C. G. Bates, R. K. Gujadhur, D. Venkataraman, Org. Lett., 2002, 4, 2803-2806.

A nickel-catalyzed alkyl- or arylthiolation of aryl iodides with disulfides allows the preparation of various aryl sulfides. The in situ generated Ni(0)-bpy complex converts ArI into ArSR under neutral conditions. Furthermore, this system enables the use of only 0.5 eq. (RS)2.
N. Taniguchi, J. Org. Chem., 2004, 69, 6904-6906.

A selective single arylsulfanylation of aryl diiodides with aryl or hetaryl thiols gives a broad array of iodine-functionalized aryl and hetaryl sulfides.
Y. Liu, H. Wang, X. Cao, Z. Fang, J.-P. Wan, Synthesis, 2013, 45, 2977-2982.

2,2-Diphenyl-1,3-oxathiolane slowly liberates a vinyl sulfide anion under basic conditions, that can be effectively used in Pd/Xantphos-catalyzed reaction with a wide range of aryl bromides to provide aryl vinyl sulfides.
J. R. Schmink, S. A. B. Dockrey, T. Zhang, N. Chebet, A. van Venrooy, M. Sexton, S. I. Lew, S. Chou, A. Okazaki, Org. Lett., 2016, 18, 6360-6363.

A gold-catalyzed hydrothiolation of unactivated alkenes proceeds effectively to give anti-Markovnikov-selective adducts in good yields and in a regioselective manner.
T. Tamai, K. Fujiwara, S. Higashimae, A. Nomoto, A. Ogawa, Org. Lett., 2016, 18, 2114-2117.

The anti-Markovnikov addition of thiols to alkenes using CeCl3 as catalyst leads to products in very good yields. The reaction occurred under solvent-free conditions at room temperature.
C. C. Silveira, S. R. Mendes, F. M. Líbero, Synlett, 2010, 790-792.

A highly selective anti-Markovnikov addition of thiols to unactivated alkenes in water at room temperature without any additive is a very simple and efficient method for the synthesis of linear thioethers.
B. C. Ranu, T. Mandal, Synlett, 2007, 925-928.

Insertion of sulfoxonium ylides into the S-H bond of aryl thiols provides β-keto thioethers in excellent yield without the need for a catalyst. The method avoids the use of metal catalysts in combination with diazo compounds or toxic haloketones.
R. M. P. Dias, A. C. B. Burtoloso, Org. Lett., 2016, 18, 3034-3037.

A cinchona alkaloid-derived urea is an efficient organocatalyst for catalyzing enantioselective conjugate addition between thiols and various α,β-unsaturated ketones to provide optically active sulfides with high chemical yields and enantiomeric excess. The reaction was performed with 0.1 mol % of catalyst in toluene at room temperature.
N. K. Rana, S. Selvakumar, V. K. Singh, J. Org. Chem., 2010, 75, 2089-2091.

A rapid conjugate addition of thiols to α,β-unsaturated ketones is achieved in a hydrophobic ionic liquid [bmim]PF6/H2O solvent system in the absence of any acid catalyst. This mild and neutral method gave the corresponding Michael adducts in high yields with excellent 1,4-selectivity. The ionic liquid can be reused.
J. S. Yadav, B. V. S. Reddy, G. Baishya, J. Org. Chem., 2003, 68, 7098-7100.

CeCl3 • 7H2O/NaI supported on neutral alumina (Al2O3)  promotes heteroatom Michael additions under solvent-free conditions. The CeCl3 • 7H2O/NaI/Al2O3 system works well for hetero-Michael additions of weak nucleophiles such as imidazoles and carbamates to various acceptors.
G. Bartoli, M. Bartolacci, A. Giuliani, E. Marcantoni, M. Massaccesi, E. Torregiani, J. Org. Chem., 2005, 70, 169-174.

An efficient copper-catalyzed carbenoid insertion reaction of α-diazo carbonyl compounds into Si-H and S-H provides a broad range of α-silylesters and α-thioesters in high yields using 5 mol% of a simple copper(I) salt as catalyst. In addition, α-diazoketones can be converted to α-silylketones in moderate yields.
H. Keipour, A. Jalba, L. Delage-Laurin, T. Ollevier, J. Org. Chem., 2017, 82, 3000-3010.

A mild, versatile, palladium-free method for the synthesis of vinyl sulfides using the soluble copper(I) catalyst [Cu(phen)(PPh3)2]NO3 is reported. The desired vinyl sulfides are obtained with retention of stereochemistry in good to excellent yields.
C. G. Bates, P. Saejueng, M. Q. Doherty, D. Venkataraman, Org. Lett., 2004, 6, 5005-5008.

An efficient, mild and transition-metal-free N-arylation of amines, sulfonamides, and carbamates and O-arylation of phenols and carboxylic acids has been achieved by using various o-silylaryl triflates in the presence of CsF.
Z. Liu, R. C. Larock, J. Org. Chem., 2006, 71, 3198-3209.

A new synthetic method for the preparation of potassium organotrifluoroborates through nucleophilic substitution of potassium bromo- and iodomethyltrifluoroborates is described. Potassium halomethyltrifluoroborates have been prepared via in situ reaction of n-BuLi with dibromo- and diiodomethane, respectively, in the presence of trialkyl borates, followed by treatment with KHF2.
G. A. Molander, J. Ham, Org. Lett., 2006, 8, 2031-2034.

A regio and anti-selective copper-catalyzed 1,2-hydroxysulfenylation of alkenes can be carried out by the use of disulfides and acetic acid. Reoxidation of intermediate sulfides by oxygen enables the use of both organosulfide groups of the disulfides.
N. Taniguchi, J. Org. Chem., 2006, 71, 7874-7876.

In a highly enantioselective method for desymmetrization of meso-epoxides with aromatic thiols, epoxide activation is achieved using metal BINOL phosphates. β-Hydroxyl sulfides are obtained in excellent yield and enantioselectivity for a broad scope of substrates.
G. Ingle, M. G. Mormino, J. C. Antilla, Org. Lett., 2014, 16, 5548-5551.