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Synthesis of S-Heterocycles

Synthesis of    


Cyclic Sulfides














Protecting Groups

1,3-Dithianes, 1,3-Dithiolanes

Recent Literature

Two complementary paths enable the synthesis of 3,4-disubstituted thietes in good yields via α-metalation or direct C-H functionalization.
M. Eisold, A. Müller-Deku, F. Reiners, D. Didier, Org. Lett., 2018, 20, 4654-4658.

Efficient acyl thiol-ene (ATE) or acyl thiol-yne (ATY) cyclization convert unsaturated thiocarboxylic acid derivatives into thiolactones in very good yields under mild conditions. The reactions offer high diastereoselectivity, excellent regiocontrol, and broad substrate scope.
R. O. McCourt, F. Dénčs, G. Sanchez-Sanz, E. M. Scanlan, Org. Lett., 2018, 20, 2948-2951.

An efficient reaction of carbon disulfide with oxiranes in the presence of sodium hydride (10 mol%) and methanol gives functionalized 1,3­oxathiolane-2-thiones in very good yields.
I. Yavari, M. Ghazanfarpour-Darjani, Z. Hossaini, M. Sabbaghan, N. Hosseini, Synlett, 2008, 889-891.

With CuI as the catalyst and K3PO4 • 3 H2O as the base, a highly efficient, ligand-free intramolecular S-vinylation of thiols with vinyl chlorides or bromides was successfully implemented. Moreover, competition experiments revealed that the 4-exo cyclization is fundamentally preferred over other modes (5-exo, 6-exo, and 6-endo) of cyclization.
Q. Zhao, L. Li, Y. Fang, D. Sun, C. Li, J. Org. Chem., 2009, 74, 459-462.

Reduction of a disulfide and subsequent trapping with thionyl chloride provides a trisulfide oxide. Heating this trisulfide oxide in the presence of dienes results in transfer of sulfur monoxide to form cyclic unsaturated sulfoxides in very good yields, along with recovery of the starting disulfide.
R. S. Grainger, A. Procopio, J. W. Steed, Org. Lett., 2001, 3, 3565-3568.

The reaction of donor-acceptor cyclopropanes with potassium p-toluenethiosulfonate enables a facile and efficient route to dithiolanes in good yields with high functional group tolerance. Upon treatment with an excess of mCPBA, the corresponding dithiolanes delivered four-membered thietane dioxides.
A. Jacob, P. Barkawitz, P. G. Jones, D. B. Werz, Org. Lett., 2022, 24, 3028-3032.

A highly efficient [3 + 2] cycloaddition of cyclopropenone derivatives and elemental chalcogens provides 1,2-dichalcogen heterocycles under mild reaction conditions. Different from other cyclopropenone derivatives, cyclopropenselenones undergo unprecedented rearrangement with elemental sulfur. This protocol offers excellent atom economy, gram-scale ability, and good regioselectivity.
J. Wu, W.-X. Gao, X.-B. Huang, Y.-B. Zhou, M.-C. Liu, H.-Y. Wu, Org. Lett., 2020, 22, 5555-5560.

The reaction of 3-sulfolene with arylboronic acids in the presence of a chiral diene-rhodium catalyst under highly basic conditions gave high yields of 3-arylsulfolanes with high enantioselectivity via a base-catalyzed isomerization to the more reactive 2-sulfolene.
K. M.-H. Lim, T. Hayashi, J. Am. Chem. Soc., 2015, 137, 3201-3204.

A catalytic asymmetric ring-closing 1,5-C-H amination of sulfamoyl azides provides chiral 1,2,5-thiadiazolidine-1,1-dioxides in up to 98% yield and up to 98% ee if the C-H bond is in a benzylic position. The reaction is catalyzed by a recently introduced simple chiral ruthenium bis(oxazoline) (pybox) complex.
X. Nie, Z. Yan, S. Ivlev, E. Meggers, J. Org. Chem., 2021, 86, 750-761.

A mild methodology provides 4-arylthiazol-2(3H)-ones and 5,5'-methylenebis[4-arylthiazol-2(3H)-ones] using benign solvents. Products can be isolated using a precipitation-recrystallization protocol. The overall methodology can be scaled up to pilot plant level.
J. F. Ortuńo, S. Poyraz, A. Belabbes, Ö. Kavas, S. Belveren, C. Altuğ, M. de Gracia Retamosa, F. Foubelo, C. M. Pask, J. M. Sansano, H. A. Döndaş, Synthesis, 2023, 55, 141-149.

A convenient base-catalyzed three-component reaction between chalcones, isothiocyanates, and elemental sulfur provides thiazole-2-thiones in very good yields.
T. B. Nguyen, P. Retailleau, Org. Lett., 2021, 23, 5344-5348.

An oxidative cascade cyclization strategy enables an unprecedented construction of thiazole-2-thiones from enaminones via a cascade of C(sp2)-H/C(sp2)-H bond sulfurations and C(sp3)-H bond thiocarbonylation. This transformation allows for the efficient synthesis of thiazole-2-thiones with broad tolerance in moderate to excellent yields from simple enaminones with elemental sulfur.
B. Zhan, D. Liu, Y. Sun, Y. Zhang, J. Feng, F. Yu, Org. Lett., 2021, 23, 3076-3082.

Pyridinium 1,4-zwitterionic thiolates with sulfenes generated in situ provide either 3H-1,2-dithiole 2,2-dioxides via a formal [3 + 2] pathway from alkylmethanesulfonyl chlorides, while 1,9a-dihydropyrido[2,1-c][1,4]thiazines were obtained via a stepwise [(5 + 2) - 1] pathway from arylmethanesulfonyl chlorides. 1,9a-dihydropyrido[2,1-c][1,4]thiazines can be converted into indolizines.
B. Cheng, Y. Li, X. Zhang, S. Duan, H. Li, Y. He, Y. Li, T. Wang, H. Zhai, Org. Lett., 2020, 22, 5817-5821.

A visible light-promoted three-component tandem annulation of α-bromoesters, amines, and aryl/alkyl isothiocyanates provides 2-iminothiazolidin-4-ones at room temperature in the absence of metal and photocatalyst. This [1 + 2 + 2] cyclization strategy offers broad substrate scope, excellent functional group tolerance, mild reaction conditions, step-economy, and simple operation.
W. Guo, M. Zhao, W. Tan, L. Zheng, K. Tao, L. Liu, X. Wang, D. Chen, X. Fan, J. Org. Chem., 2018, 83, 1402-1413.

A potassium-carbonate-mediated [3 + 2]-cycloaddition reaction of α-halohydroxamates with carbon disulfide provides functionalized rhodanine derivatives in very good yields. The present methodology offers a wide substrate scope as well as good functional group tolerance.
X. Lei, J. Feng, Q. Guo, C. Xu, J. Shi, Org. Lett., 2022, 24, 2837-2841.

An allenyl imide and alkynoates bearing good leaving groups are used as ketene precursors in tandem conjugate addition-elimination reactions promoted by nucleophilic phosphine catalysts. By utilizing thioamides as 1S,3N-bis-nucleophiles, [3+3] and [3+2] annulations provide rapid access to 1,3-thiazin-4-ones and 5-alkenyl thiazolones in high yields, respectively.
Y.-H. Wang, Z.-N. Zhao, S. J. Kalita, Y.-Y. Huang, Org. Lett., 2021, 23, 8147-8152.

A molecular iodine-catalyzed oxidative cyclization of 2-aminopyridine/amidine and isothiocyanate via N-S bond formation enables the synthesis of N-fused and 3,4-disubstituted 5-imino-1,2,4-thiadiazole derivatives at ambient temperature. This transition-metal-free protocol provides a facile and highly efficient regiospecific synthesis of various 1,2,4-thiadiazole derivatives with good to excellent yields using inexpensive I2 as a catalyst.
N. Tumula, N. Jatangi, R. K. Palakodety, S. Balasubramanian, M. Nakka, J. Org. Chem., 2017, 82, 5310-5316.

A simple P(NMe2)3-mediated annulation reaction of N-acyldiazenes with isothiocyanates provides 2-imino-1,3,4-thiadiazoles. N-acyldiazenes can be generated from hydrazides using iodine as oxidant and can be used without purification.
Z. Huang, Q. Zhang, Q. Zhao, W. Yu, J. Chang, Org. Lett., 2020, 22, 4378-4382.

A facile and scalable synthesis of δ-thiolactones from inexpensive and readily available γ-unsaturated esters incorporates a radical acyl thiol-ene reaction as the key C-S bond forming step. Cyclization is achieved via a Steglich-type thiolactonization of 5-mercaptopentanoic acids.
R. O. McCourt, E. M. Scanlan, Org. Lett., 2019, 21, 3460-3464.

An aza-Michael-addition/cyclization/condensation reaction sequence starting from sulfonimidamides and propargyl ketones provides 1,2,6-thiadiazine 1-oxides. These three-dimensional S,N-heterocycles have been further functionalized by standard cross-coupling reactions, selective bromination of the heterocyclic ring, and conversion into a β-hydroxy substituted derivative.
J.-H. Schöbel, M. T. Passia, N. A. Wolter, R. Puttreddy, K. Rissanen, C. Bolm, Org. Lett., 2020, 22, 2702-2706.

An allenyl imide and alkynoates bearing good leaving groups are used as ketene precursors in tandem conjugate addition-elimination reactions promoted by nucleophilic phosphine catalysts. By utilizing thioamides as 1S,3N-bis-nucleophiles, [3+3] and [3+2] annulations provide rapid access to 1,3-thiazin-4-ones and 5-alkenyl thiazolones in high yields, respectively.
Y.-H. Wang, Z.-N. Zhao, S. J. Kalita, Y.-Y. Huang, Org. Lett., 2021, 23, 8147-8152.

A three-component condensation gave 2-amino-4H-1,3-oxazines or 2-amino-4H-1,3-thiazines from alkynes, urea or thiourea, and aldehydes.
S. Huang, Y. Pan, Y. Zhu, A. Wu, Org. Lett., 2005, 7, 3797-3799.