Synthesis of alkyl sulfones
The addition of Grignard reagents or organolithium reagents to the SO2-surrogate DABSO generates a diverse set of metal sulfinates, which can be trapped in situ with a wide range of C-electrophiles, including alkyl, allyl, and benzyl halides, epoxides, and (hetero)aryliodoniums to give sulfone products.
A. S. Deeming, C. J. Russell, A. J. Henessy, M. C. Willis, Org. Lett., 2014, 16, 150-153.
A practical, rapid, and efficient microwave (MW) promoted nucleophilic substitution of alkyl halides or tosylates with alkali azides, thiocyanates or sulfinates in aqueous media tolerates various reactive functional groups.
Y. Ju, D. Kumar, R. S. Varma, J. Org. Chem., 2006, 71, 6697-6700.
A one-pot synthesis of aryl sulfones from primary alcohols is described. Alcohols were treated with N-bromosuccinimide and triphenylphosphine, followed by addition of sodium arenesulfinate with a catalytic amount of tetrabutylammonium iodide to afford the aryl sulfones in good to high yields.
T. Murakami, K. Furusawa, Synthesis, 2002, 479-482.
Cyanide mediates an in situ generation of a nucleophilic sulfinate ion from vinyl sulfones. Subsequent in situ S-alkylation provides sulfones in high yields. In the presence of N-bromosuccinimide, primary and secondary amines underwent sulfonamide formation.
T. Roy, J.-W. Lee, Synlett, 2020, 31, 455-458.
NaI catalyzes a highly chemoselective route to aryl methyl sulfones under mild conditions via an unexpected C-S bond formation between sulfonylhydrazides and dimethyl phosphite as a stable and readily available alkyl source. This transformation provides an alternative and metal-free pathway to various aryl methyl sulfones in very good yields.
T. Liu, S. Yu, X. Shen, Y. Li, J. Liu, C. Huang, F. Cheng, Synthesis, 2022, 54, 153-160.
2-(Phenylsulfonyl)-3-phenyloxaziridine, commonly known as the Davis reagent, enables a generation of sulfinate anions by oxidation of the corresponding thiolates. Subsequent S-alkylation of the sulfinates under phase-transfer catalysis affords sulfones in very good isolated yields.
F. Sandrinelli, S. Perrio, P. Beslin, Org. Lett., 1999, 1, 1107-1109.
A mild, late-stage conversion of primary sulfonamides to several other functional groups occurs via initial reductive deamination of sulfonamides to sulfinates via an NHC-catalyzed reaction of transiently formed N-sulfonylimines. This method tolerates common functional groups, as exemplified by the late-stage derivatization of several complex pharmaceutical compounds.
P. S. Fier, K. M. Maloney, J. Am. Chem. Soc., 2019, 141, 1441-1445.
An oxidation-free method provides sulfinic acids and sulfinate salts from easily prepared sulfone-substituted benzothiazole derivatives under mild reaction conditions. One-pot syntheses of sulfones and sulfonamides are also described.
J. J. Day, D. L. Neill, S. Xu, M. Xian, Org. Lett., 2017, 19, 3819-3822.
The use of inorganic sodium metabisulfite as the sulfur dioxide surrogate and di-tert-butyl peroxide as source of the methyl radical enables a direct C-H methylsulfonylation of alkenes. This method provides convenient access to (E)-2-methyl styrenyl sulfones in good yields.
F.-S. He, Y. Gong, P. Rojsitthisak, J. Wu, J. Org. Chem., 2019, 84, 13159-13163.
An [Ir(dF(CF3)ppy)2(dtbbpy)]PF6-mediated visible light photoredox catalysis enables an anti-Markovnikov hydrosulfonylation of unactivated alkenes with sodium sulfinates with the assistance of acetic acid. A variety of unactivated alkenes can be transformed into sulfones with good yield and high regioselectivity.
J.-J. Wang, W. Yu, Org. Lett., 2019, 21, 9236-9240.
Sulfination of aryl methyl ketones and aryl acetylenes with sodium sulfinates under mild electrochemical conditions provides β-ketosulfones in good yields. This strategy is convenient and environmentally friendly.
I. Yavari, S. Shaabanzadeh, Org. Lett., 2020, 22, 464-467.
A photoredox-catalyzed sulfonylation of silyl enol ethers with DABCO·(SO2)2 and thianthrenium salts provides diverse β-keto sulfones in moderate yields with good functional group compatibility. The use of a MeOH-derived methyl thianthrenium intermediate enables the synthesis of α-methylsulfonated ketones.
F.-S. He, P. Bao, Z. Zang, F. Yu, W.-P. Deng, J. Wu, Org. Lett., 2022, 24, 2955-2960.
Various sulfone tetrazoles were activated via iridium photoredox catalysis in the presence of DMAP to give dialkyl sulfones. The presumed sulfone radical intermediates were trapped by a range of electron-deficient olefins in generally good to excellent yields.
Y. Chen, N. McNamara, O. May, T. Pillaiyar, D. C. Blakemore, S. V. Ley, Org. Lett., 2020, 22, 5746-5748.
A three-component reaction of potassium alkyltrifluoroborates, DABCO·(SO2)2 as sulfur dioxide surrogate, and alkenes under photocatalysis provides diverse sulfones in very good yields at room temperature. This reaction works efficiently under mild conditions via generation of alkyl and alkylsulfonyl radicals as key intermediates, and a reductive single-electron transfer.
T. Liu, Y. Li, L. Lai, J. Cheng, J. Sun, J. Wu, Org. Lett., 2018, 20, 3605-3608.
A new protocol for the β-sulfonation of α,β-unsaturated carbonyl compounds with sodium p-toluenesulfinate employs FeCl3 as catalyst and TMSCl as additive.
B. Sreedhar, M. A. Reddy, P. S. Reddy, Synlett, 2008, 1949-1952.
Ethyl glyoxylate N-tosylhydrazone is an excellent sulfonyl anion surrogate in a DBU-catalyzed conjugate addition reaction with enones and enals for the synthesis of functionalized sulfones. The reaction provides γ-keto- and γ-hydroxy sulfones in a simple and reliable way through a sulfa-Michael reaction that proceeds with good yield and chemoselectivity.
M. Fernández, U. Uria, L. Orbe, J. L. Vicario, E. Reyes, L. Carrillo, J. Org. Chem., 2014, 79, 230-239.
Graphitic carbon nitride (p-g-C3N4) photocatalyzes a hydrosulfonylation of alkynes with the insertion of sulfur dioxide in aerobic conditions. Whereas the oxygen atom of the products is derviced from water, the O2 plays an important role by quenching the DABCO radical cation. Furthermore, this reaction could be carried out under solar light irradiation and was applicable for large scale.
B. Ni, B. Zhang, J. Han, B. Peng, Y. Shan, T. Niu, Org. Lett., 2020, 22, 636-641.
In an unprecedented oxidative radical process, dioxygen as the solely terminal oxidant triggers an aerobic oxidative difunctionalization of terminal alkynes toward β-keto sulfones with high selectivity. IR experiments revealed that pyridine not only acts as a base to successfully surpress ATRA (atom transfer radical addition) process, but also plays a vital role in reducing the activity of sulfinic acids.
Q. Lu, J. Zhang, G. Zhao, Y. Qi, H. Wang, A. Lei, J. Am. Chem. Soc., 2013, 135, 11481-11484.
A combination of o-iodoxybenzoic acid and iodine mediates a direct synthesis of β-keto sulfones from alkenes and arenesulfinates in good yields in a one-pot reaction.
N. Samakkanad, P. Katrun, T. Techajaroonjit, S. Hlekhlai, M. Pohmakotr, V. Reutrakul, T. Jaipetch, D. Soorukram, C. Kuhakarn, Synthesis, 2012, 44, 1693-1699.
A reaction of xanthates, DMSO, and Fenton’s reagent proceeds under very mild conditions to provide various β-keto sulfones in high yields.
P. N. Chalikidi, M. G. Uchuskin, I. V. Trushkov, V. T. Abaev, O. V. Serdyuk, Synlett, 2018, 29, 571-575.
An iron-catalyzed sulfonylation of aryl enol acetates with sulfonyl hydrazides enables the construction of β-keto sulfones under aerobic conditions. This environmentally benign approach utilizes an inexpensive iron salt as the catalyst, readily available sulfonyl hydrazides as the sulfonylating reagents, and air as oxidant under mild conditions.
V. K. Yadav, V. P. Srivastava, L. D. S. Yadav, Synlett, 2016, 27, 427-431.
A combination of o-iodoxybenzoic acid (IBX) and a catalytic amount of iodine promotes a facile one-pot deacylative sulfonylation reaction of 1,3-dicarbonyl compounds with sodium sulfinates to yield β-carbonyl sulfones in good yields.
P. Katrun, T. Songsichan, D. Soorukram, M. Pohmakotr, V. Reutrakul, C. Kuhakarn, Synthesis, 2017, 49, 1109-1121.
A cross-coupling reaction between sulfonyl hydrazides and diazo compounds provides various β-carbonyl sulfones in good yields. This methodology offers simple manipulation, easily available starting materials, and wide substrate scope.
Y. Wang, L. Ma, M. Ma, H. Zheng, Y. Shao, X. Wan, Org. Lett., 2016, 18, 5082-5085.
In a one-pot synthesis of optically active β-hydroxy sulfones, intermediate β-keto sulfones obtained via a nucleophilic substitution reaction of α-bromoketones and sodium sulfinates were reduced through Ru-catalyzed asymmetric transfer hydrogenation using HCOONa as a hydrogen source. This mild transformation in an aqueous medium provides chiral β-hydroxy sulfones with high yields and excellent enantioselectivities.
D. Zhang, T. Cheng, Q. Zhao, J. Xu, G. Liu, Org. Lett., 2014, 16, 5764-5767.
A nickel-catalyzed hydroxysulfonylation of alkenes using sodium sulfinates under air enabled the selective synthesis of β-hydroxysulfones in good yields and suppressed the formation of β-ketosulfones. On the contrary, sulfonylation of alkynes with sodium sulfonates afforded only β-ketosulfones.
N. Taniguchi, J. Org. Chem., 2015, 80, 7797-7802.
An efficient one-pot multistep strategy comprising auto-oxidative difunctionalization of alkenes, oxidation of sulfides, and a further reduction of peroxides enables the synthesis of complex β-hydroxysulfone derivatives from thiophenols and alkenes. This method offers readily available substrates, low-cost and environmental benign reagents, nontoxic and renewable solvents, and mild reaction conditions.
Y. Wang, W. Jiang, C. Huo, J. Org. Chem., 2017, 82, 10628-10634.
The photoredox catalyst fac[Ir(ppy)3] enables the synthesis of β-hydroxysulfones from sulfonyl chlorides and styrenes in the presence of water by a visible light mediated atom transfer radical addition (ATRA)-like process. This process could be combined with the visible light mediated synthesis of trifluoromethylated sulfonyl chlorides via an ATRA reaction between alkenes and CF3SO2Cl utilizing [Cu(dap)2Cl] as photoredox catalyst.
S. K. Pagire, S. Paria, O. Reiser, Org. Lett., 2016, 18, 2106-2109.
The reaction of p-toluenesulfonylmethyl isocyanide (TosMIC) with α-bromocarbonyl compounds efficiently provides α-sulfonated ketones, esters, and amides. TosMIC acts as the sulfonylating agent initiated by a Cu(OTf)2-catalyzed hydration to form a formamide intermediate, which undergoes facile C-S bond cleavage under the mediation of Cs2CO3.
J. Chen, W. Guo, Z. Wang, L. Hu, F. Chen, Y. Xia, J. Org. Chem., 2016, 81, 5504-5512.
An efficient cobalt-catalyzed reductive coupling reaction of alkyl halides with alkenes bearing electron-withdrawing groups in the presence of water and zinc powder in acetonitrile gave the corresponding Michael-type addition products in high yields. The mechanism is discussed.
P. Shukla, Y.-C. Hsu, C.-H. Cheng, J. Org. Chem., 2006, 71, 655-658.
A Zn/CuI-mediated coupling of alkyl halides with vinyl sulfones, vinyl sulfonates, and vinyl sulfonamides is described. Formamide is a superior solvent for obtaining high yields.
M. M. Zhao, C. Qu, J. E. Lynch, J. Org. Chem., 2005, 70, 6944-6947.