Categories: C-S Bond Formation >
Synthesis of sulfoxides
Sulfur dioxide, delivered from the surrogate DABSO, combines as electrophile with an organometallic reagent to generate a sulfinate intermediate. In situ conversion of the sulfinate to a sulfinate silyl ester, using TMS-Cl, generates another electrophile, allowing addition of a second organometallic reagent. Both organolithium or Grignard reagents deliver sulfoxides in very good yields.
D. C. Lenstra, V. Vedovato, E. F. Flegeau, J. Maydom, M. C. Willis, Org. Lett., 2016, 18, 2086-2089.
The use of a chiral O,P-ligand (PC-Phos) enables an efficient palladium-catalyzed enantioselective arylation of both alkyl and aryl sulfenate anions to deliver various chiral sulfoxides in good yields with excellent enantioselectivities. The method offers general substrate scope and ease of scale-up.
L Wang, M. Chen, P. Zhang, W. Li, J. Zhang, J. Am. Chem. Soc., 2018, 140, 3467-3473.
A (JosiPhos)Pd-catalyzed reaction of aryl benzyl sulfoxides and aryl bromides provides chiral diaryl sulfoxides via an enantioselective arylation of aryl sulfenate anions. The method offers good functional group compatibility. A wide range of enantioenriched diaryl, aryl heteroaryl, and even diheteroaryl sulfoxides were generated.
T. Jia, M. Zhang, S. P. McCollom, A. Bellomo, S. Montel, J. Mao, S. D. Dreher, C. J. Welch, E. L. Regalado, R. T. Williamson, B. C. Manor, N. C. Tomson, P. J. Walsh, J. Am. Chem. Soc., 2017, 139, 8337-8345.
A phenyltrimethylammonium tribromide-mediated nucleophilic substitution/oxygen transformation reaction of benzyl halides with DMSO enables a convenient and direct synthesis of various benzyl methyl sulfoxides. In this transition-metal-free reaction, DMSO acts as not only a solvent but also a "S(O)Me" source.
D. Fu, J. Dong, H. Du, J. Xu, J. Org. Chem., 2020, 85, 2752-2758.
A palladium-catalyzed arylation of sulfenate anions generated from β-sulfinyl esters takes place under basic biphasic conditions. This reaction provides a simple, mild, and efficient route to aryl sulfoxides in good yields.
G. Maitro, S. Vogel, G. Prestat, D. Madec, G. Poli, Org. Lett., 2006, 8, 5951-5954.
The smooth generation of sulfenate salts by fluoride-mediated cleavage of 2-(trimethylsilyl)ethyl sulfoxides and subsequent reaction with alkyl halides gives stable sulfoxides.
F. Foucoin, C. Caupène, F.-F. Lohier, J. S. de Oliveira Santos, S. Perrio, P. Metzner, Synthesis, 2007, 1315-1324.
An oxidative variant of the thiol-ene reaction enables the direct addition of thiols to olefins to form sulfoxides in the presence of tert-butyl hydroperoxide as oxidant and methanesulfonic acid as catalyst. The latter is believed to catalyze the oxidation of the intermediate sulfide to the sulfoxide. Styrenes, acrylic acid derivatives, alkynes, and thiophenols gave the highest yields, while aliphatic olefins and thiols were less effective.
H.-L. Yue, M. Klussmann, Synlett, 2016, 27, 2505-2509.
A visible light mediated sulfurization of alkenes and alkynes with aromatic and heteroaromatic thiols enables a benign and metal-free functionalization using Eosin Y as photocatalyst and eco-friendly air (O2) as the sole oxidant. This selective approach shows good substrate generality to afford sulfoxides, β-hydroxysulfoxides, and β-keto sulfides in high yield.
R. Rahaman, M. T. Hoque, D. K. Maiti, Org. Lett., 2022, 24, 6885-6890.
Sulfoxides bearing a tert-butyl group can be activated using N-bromosuccinimide (NBS) under acidic conditions. Subsequent treatment with various nitrogen, carbon, or oxygen nucleophiles affords a wide range of sulfinic acid amides, new sulfoxides, and sulfinic acid esters.
J. Wei, Z. Sun, Org. Lett., 2015, 17, 5396-5399.
Several sulfoxides have been synthesized in excellent enantiopurities and high yields using sulfinyl transfer agents based on the cinchona alkaloids quinine and quinidine.
B. Z. Lu, F. Jin, Y. Zhang, X. Wu, S. A. Wald, C. H. Senanayake, Org. Lett., 2005, 7, 1465-1468.
A new synthetic approach to aryl and alkyl α,β-unsaturated sulfoxides is reported. The described procedure allows the synthesis of sulfoxides in good yields starting from readily available reagents, in a cost-effective procedure.
G. Signore, S. Samaritani, C. Malanga, R. Menicagli, Synthesis, 2006, 762-764.
Tetraphosphine cis,cis,cis-1,2,3,4-tetrakis[(diphenylphosphino)methyl]cyclopentane (Tedicyp) is an efficient ligand for the Heck reaction of sulfur-containing alkenes with aryl bromides. The rates and yields of the reactions strongly depend on the oxidation state of the sulfur atom.
A. Battace, T. Zair, H. Doucet, M. Santelli, Synthesis, 2006, 3495-3505.