The Synthesis of the Hydrogenated Thiophenes by [3+2] Cycloaddition Reaction of Thiocarbonyl Ylide

Tymofii V. Rudenko; Vadim M. Timoshenko

doi:10.24959/ophcj.23.283517

Authors

Tymofii V. Rudenko Institute of Organic Chemistry of the National Academy of Sciences of Ukraine; Enamine Ltd., Ukraine
Vadim M. Timoshenko Institute of Organic Chemistry of the National Academy of Sciences of Ukraine, Ukraine https://orcid.org/0000-0002-4879-604X

DOI:

https://doi.org/10.24959/ophcj.23.283517

Keywords:

cycloaddition, thiocarbonyl ylide, dipolarophile, dihydrothiophene, tetrahydrothiophene

Abstract

Aim. To study the use of chloromethyl trimethylsilylmethyl sulfide as a precursor of thiocarbonyl ylide in [3+2] cycloaddition reaction to a number of α,β-unsaturated compounds and to establish the regularities of the reaction course. To develop an effective method for the synthesis of new dihydro- and tetrahydrothiophene derivatives which are convenient for further modification.
Results and discussion. The synthetic approach to tetrahydrothiophenes with substituents in positions 3 and 4 was extended by the [3+2] cycloaddition reaction of thiocarbonyl ylide with a number of compounds containing an activated multiple bond. The stereoselectivity and limitations of this reaction were determined. Further functionalization of the obtained compounds was carried out.
Experimental part. Thiocarbonyl ylide was obtained by fluoride ion-promoted 1,3-desilylation of the known chloromethyl trimethylsilylmethyl sulfide. The synthesis of the target compounds involved the [3+2] cycloaddition of such an ylide to a series of compounds with an activated multiple bond. The stereochemistry of the target compounds was determined by ¹H NOESY experiments. Synthetic derivatives of thiolancarboxylic acids, in particular aldehydes, alcohols, amines, amidines, were obtained by functionalization of the [3+2] adducts.
Conclusions. The synthetic approach to functionalized tetrahydrothiophenes by the [3+2] cycloaddition reaction of thiocarbonyl ylide with a number of compounds containing an activated multiple bond has expanded the limits of application of this reaction and allows obtaining the target compounds in multigram quantities. A high stereoselectivity of this reaction was observed. The reaction products are convenient synthetic precursors to the various classes of organic compounds.

Supporting Agency

The authors received no specific funding for this work.

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References

Johnson, J. W.; Gretes, M.; Goodfellow, V. J.; Marrone, L.; Heynen, M. L.; Strynadka, N. J.; Dmitrienko, G. I. Cyclobutanone analogues of β-lactams revisited: Insights into conformational requirements for inhibition of serine- and metallo-β-lactamases. Am. Chem. Soc. 2010, 132, 2558–2560. https://doi.org/10.1021/ja9086374.
|
Monn, J. A.; Massey S. M.; Valli, M. J.; Henry, S.S.; Stephenson, G. A.; Bures, M.; Herin, M.; Catlow, J.; Giera, D.; Wright, R. A.; Johnson, B. G.; Andis, S. L.; Kingston, A.; Schoepp, D. D. Synthesis and metabotropic glutamate receptor activity of S-oxidized variants of (-)-4-amino-2-thiabicyclo-[3.1.0]hexane-4,6-dicarboxylate: Identification of potent, selective, and orally bioavailable agonists for mGlu2/3 receptors. Med. Chem. 2007, 50 (2), 233–240. https://doi.org/10.1021/jm060917u.
|
Lavrador, K.; Guillerm, D.; Guillerm, G. A new series of cyclic amino acids as inhibitors of S-adenosyl L-methionine synthetase. Med. Chem. Lett. 1998, 8 (13), 1629–1634. https://doi.org/10.1016/S0960-894X(98)00267-4.
|
Benetti, S.; De Risi, C.; Pollini, G. P.; Zanirato, V. Synthetic routes to chiral nonracemic and racemic dihydro- and tetrahydrothiophenes. Rev. 2012, 112 (4), 2129–2163. https://doi.org/10.1021/cr200298b.
|
Aono, M.; Hyodo, C.; Terao, Y.; Achiwa, K. Generation of thiocarbonyl ylides with release of disiloxane from bis(trimethylsilylmethyl) sulfoxides. Tetrahedron Lett. 1986, 27 (34), 4039–4042. https://doi.org/10.1016/S0040-4039(00)84905-9.
Aono, M.; Terao, Y.; Achiwa, K. New Method for Generation of Thiocarbonyl Ylides from Bis(trimethylsilylmethyl)sulfoxides and Their Application to Cycloadditions. Heterocycles 1995, 40 (1), 249–260. https://doi.org/10.3987/COM-94-S18.
Haut, F. L.; Habiger, C.; Speck, K.; Wurst, K.; Mayer, P.; Korber, J. N.; Müller, T; Magauer, T. Synthetic Entry to Polyfunctionalized Molecules through the [3+2]-Cycloaddition of Thiocarbonyl Ylides. Am. Chem. Soc. 2019, 141, 13352−13357. https://doi.org/10.1021/jacs.9b07729.
|
Li, D. B.; Rogers-Evans, M.; Carreira, E. M. Construction of multifunctional modules for drug discovery - synthesis of novel thia/oxa-azaspiro[3.4]octanes. Lett. 2013, 15 (18), 4766–4769. https://doi.org/10.1021/ol402127b.
|
Hosomi, A.; Matsuyama, Y.; Sakurai, H. Chloromethyl trimethylsilylmethyl sulphide as a parent thiocarbonyl ylide synthon. A simple synthesis of dihydro- and tetrahydro-thiophenes. Chem. Soc., Chem. Commun. 1986, 14, 1073–1074. https://doi.org/10.1039/C39860001073.
Hosomi, A.; Hayashi, S.; Hoashi, K.; Kohra, S. Unprecedented reaction of a thiocarbonyl ylide with carbonyl compounds: a novel synthesis of 1,3-oxathiolanes. Chem. Soc., Chem. Commun. 1987, 19, 1442–1443. https://doi.org/10.1039/C39870001442.
Hosomi, A.; Hayashi, S.; Hoashi, K.; Kohra, S. Intramolecular cyclization via onium salts – a novel synthesis of 1,3-thiazolidines from chloromethyl (trimethylsily1)methyl sulfide and nitrogen-containing heteroaromatic compounds. J. Org. Chem. 1987, 52 (19), 4423–4424. https://doi.org/10.1021/jo00228a062.
Karlsson, S.; Högberg, H. Enantiomerically pure trans-3,4-disubstituted tetrahydrothiophenes from diastereoselective thiocarbonyl ylide addition to chiral α,β-unsaturated amides. Org. Lett. 1999, 1 (10), 1667–1669. https://doi.org/10.1021/ol9910565.
Mykhaylychenko, S. S.; Markitanov, Y. N.; Rudenko, T. V.; Rusanov, E. B.; Shermolovich, Y. G. Synthesis of 4-polyfluoroalkyl-1,3-dithiolanes via [3+2] cycloaddition of thiocarbonyl ylide to polyfluoroalkanethioamides. Chem. Heterocycl. Compd. 2019, 55 (2), 189–192. https://doi.org/10.1007/s10593-019-02438-0.
Markitanov, Y. N.; Timoshenko, V. M.; Rudenko, T. V.; Rusanov, E. B.; Shermolovich, Y. G. 3-Functional substituted 4-trifluoromethyl tetrahydrothiophenes via [3 + 2]-cycloaddition reactions. J. Sulphur Chem. 2019, 40 (6), 629–640. https://doi.org/10.1080/17415993.2019.1633326.
Siryi, S. A.; Тimoshenko, V. М.; Rudenko, T. V.; Markitanov, Y. M.; Rusanov, E. B.; Shermolovich, Y. G. Synthesis of Monosubstituted Trifluoromethylated Derivatives of 2H-thiete, Dihydrothiophenes, and 2H-thiopyrans. Chem. Heterocycl. Comp. 2022, 58, 106–115. https://doi.org/10.1007/s10593-022-03063-0.
Stepaniuk, O. O.; Rudenko, T. V.; Vashchenko, B. V.; Matvienko V. O.; Kondratov, I. S.; Tolmachev, A. A., Grygorenko, O. O. Reaction of β-alkoxyvinyl α-ketoesters with acyclic NCN binucleophiles – Scalable approach to novel functionalized pyrimidines. Tetrahedron 2019, 75 (25), 3472–3478. https://doi.org/10.1016/j.tet.2019.05.005.
Johnson, J. W.; Evanoff, D. P.; Savard, M. E.; Lange G.; Ramadhar, T. R.; Assoud, A.; Taylor, N.J.; Dmitrienko, G.I. Cyclobutanone Mimics of Penicillins: Effects of Substitution on Conformation and Hemiketal Stability. J. Org. Chem. 2008, 73 (18), 6970–6982. https://doi.org/10.1021/jo801274m.
|
Räber, J. L.; Brun, K. A.; Heimgartner, H. A Novel Heterospirocyclic 2H-Azirin-3-amine as Synthon for 3-Aminothiolane-3-carboxlic Acid. Heterocycles 2007, 74 (1), 397–409. https://doi.org/10.3987/COM-07-S(W)18.
Dolbier, Jr. W. R.; Zheng, Z. Use of 1,3-dipolar reactions for the preparation of SF₅-substituted five-membered ring heterocycles. Pyrroles and thiophenes. J. Fluor. Chem. 2011, 132, 389 – 393. https://doi.org/10.1016/j.jfluchem.2011.03.017" target="_blank" rel="noreferrer noopener" aria-label="Persistent link using digital object identifier" title="Persistent link using digital object identifier">https://doi.org/10.1016/j.jfluchem.2011.03.017.