Ring-Opening Reactions of Donor–Acceptor Cyclopropanes with Some Enolizable Azaheterocyclic Thiones: S- versus N-Attack

Grzegorz Mlostoń; Mateusz Kowalczyk; Małgorzata Celeda; Gwyndaf A. Oliver; Daniel B. Werz

doi:10.1055/s-0043-1773524

Synlett, Table of Contents

Synlett 2025; 36(11): 1548-1552
DOI: 10.1055/s-0043-1773524

letter

Ring-Opening Reactions of Donor–Acceptor Cyclopropanes with Some Enolizable Azaheterocyclic Thiones: S- versus N-Attack

Grzegorz Mlostoń∗

^aDepartment of Organic & Applied Chemistry, University of Łodź, Tamka 12, 91-403 Łodź, Poland

,

Mateusz Kowalczyk

^aDepartment of Organic & Applied Chemistry, University of Łodź, Tamka 12, 91-403 Łodź, Poland

^bThe Bio-Med-Chem Doctoral School of the University of Łodź and Łodź Institutes of the Polish Academy of Sciences, Faculty of Biology and Environmental Protection, University of Łodź, 90237 Łodź, Poland

,

Małgorzata Celeda

^aDepartment of Organic & Applied Chemistry, University of Łodź, Tamka 12, 91-403 Łodź, Poland

,

Gwyndaf A. Oliver

^cInstitute of Organic Chemistry, Albert-Ludwigs-Universität Freiburg, Albertstraße 21, 79104 Freiburg im Breisgau, Germany

,

Daniel B. Werz

^cInstitute of Organic Chemistry, Albert-Ludwigs-Universität Freiburg, Albertstraße 21, 79104 Freiburg im Breisgau, Germany

› Author Affiliations

Abstract

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This work is dedicated to Professor Mieczysław Mąkosza (Warsaw) on the occasion of his 90^th birthday

Abstract

We report ring-opening reactions of donor–acceptor (D–A) cyclopropanes with a variety of five- and six-membered enolizable azaheterocyclic thiones, using Sc(OTf)₃ as catalyst in dichloromethane. The majority of these systems reacted through nucleophilic S-attack at the donor position of the cyclopropane. 5-Mercapto-1,3,4-triazoles were shown to give the products of formal N-attack, and systems bearing two external C-S bonds could react with two equivalents of D–A cyclopropane to generate difunctionalized azaheterocycles.

Key words

azaheterocycles - thiones - donor–acceptor systems - cyclopropanes - ring opening

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References

References and Notes

1a Reissig H.-U, Zimmer R. Chem. Rev. 2003; 103: 1151
1b Yu M, Pagenkopf BL. Tetrahedron 2005; 61: 321
1c Carson CA, Kerr MA. Chem. Soc. Rev. 2009; 38: 3051
1d Cavitt MA, Phun LH, France S. Chem. Soc. Rev. 2014; 43: 804
1e Schneider TF, Kaschel J, Werz DB. Angew. Chem. Int. Ed. 2014; 53: 5504
1f Werz DB, Biju AT. Angew. Chem. Int. Ed. 2020; 59: 3385
1g Singh P, Varshnaya RK, Dey R, Banerjee P. Adv. Synth. Catal. 2020; 362: 1447

2 Gordon MS. J. Am. Chem. Soc. 1980; 102: 7419

3a Sparr C, Gilmour R. Angew. Chem. Int. Ed. 2011; 50: 8391
3b Halskov KS, Kniep F, Lauridsen VH, Iversen EH, Donslund BS, Jørgensen KA. J. Am. Chem. Soc. 2015; 137: 1685
3c Levens A, Ametovski A, Lupton DW. Angew. Chem. Int. Ed. 2016; 55: 16136
3d Sanchez-Diez E, Vesga DL, Reyes E, Uria U, Carrillo L, Vicario JL. Org. Lett. 2016; 18: 1270
3e Wallbaum J, Garve LK. B, Jones PG, Werz DB. Chem. Eur. J. 2016; 22: 18756

4a Blom J, Vidal-Albalat A, Jørgensen J, Barløse CL, Jessen KS, Iversen MV, Jørgensen KA. Angew. Chem. Int. Ed. 2017; 56: 11831
4b McLeod DA, Thøgersen MK, Barløse CL, Skipper ML, Obregón EB, Jørgensen KA. Angew. Chem. Int. Ed. 2022; 61: e202206096

5a Kolb S, Petzold M, Brandt F, Jones PG, Jacob CR, Werz DB. Angew. Chem. Int. Ed. 2021; 60: 15928
5b Kolb S, Ahlburg NL, Werz DB. Org. Lett. 2021; 23: 5549
5c Oliver GA, Kolb S, Werz DB. Synlett 2023; 35: 963

6 Garve LK. B, Barkawitz P, Jones PG, Werz DB. Org. Lett. 2014; 16: 5804

7a Ivanova OA, Budynina EM, Grishin YK, Trushkov IV, Verteletskii PV. Angew. Chem. Int. Ed. 2008; 47: 1107
7b Goldberg AF. G, O’Connor NR, Craig RA. II, Stoltz BM. Org. Lett. 2012; 14: 5314
7c Zhu W, Fang J, Liu Y, Ren J, Wang Z. Angew. Chem. Int. Ed. 2013; 52: 2032
7d Chakrabarty S, Chatterjee I, Wibbeling B, Daniliuc CG, Studer A. Angew. Chem. Int. Ed. 2014; 53: 5964
7e Garve LK. B, Petzold M, Jones PG, Werz DB. Org. Lett. 2016; 18: 564
7f Wang Z.-H, Zhang H.-H, Wang D.-M, Xu P.-F, Luo Y.-C. Chem. Commun. 2017; 53: 8521
7g Xu P.-W, Liu J.-K, Shen L, Cao Z.-Y, Zhao X.-L, Yan J, Zhou J. Nat. Commun. 2017; 8: 1619
7h Chagarovskiy AO, Vasin VS, Kuznetsov VV, Ivanova OA, Rybakov VB, Shumsky AN, Makhova NN, Trushkov IV. Angew. Chem. Int. Ed. 2018; 57: 10338
7i Kreft A, Jones PG, Werz DB. Org. Lett. 2018; 20: 2059
7j Kreft A, Lücht A, Grunenberg J, Jones PG, Werz DB. Angew. Chem. Int. Ed. 2019; 58: 1955
7k Petzold M, Jones PG, Werz DB. Angew. Chem. Int. Ed. 2019; 58: 6225
7l Oliver GA, Loch MN, Augustin AU, Steinbach P, Sharique M, Tambar UK, Jones PG, Bannwarth C, Werz DB. Angew. Chem. Int. Ed. 2021; 60: 25825
7m Jacob A, Barkawitz P, Jones PG, Werz DB. Org. Lett. 2022; 24: 3028
7n Ahlburg NL, Hergert O, Jones PG, Werz DB. Angew. Chem. Int. Ed. 2023; 62: e202214390
7o Borisov DD, Platonov DN, Sokolov NA, Novikov RA, Tomilov YV. Angew. Chem. Int. Ed. 2024; 63: e202410081

8a Schneider TF, Kaschel J, Awan SI, Dittrich B, Werz DB. Chem. Eur. J. 2010; 16: 11276
8b Kaschel J, Schmidt CD, Mumby M, Kratzert D, Stalke D, Werz DB. Chem. Commun. 2013; 49: 4403
8c Sabbatani J, Maulide N. Angew. Chem. Int. Ed. 2016; 55: 6780
8d Ivanova OA, Chagarovskiy AO, Shumsky AN, Krasnobrov VD, Levina II, Trushkov IV. J. Org. Chem. 2018; 83: 543
8e Shim SY, Choi Y, Ryu DH. J. Am. Chem. Soc. 2018; 140: 11184

9a Lifchits O, Charette AB. Org. Lett. 2008; 10: 2809
9b Lifchits O, Alberico D, Zakharian I, Charette AB. J. Org. Chem. 2008; 73: 6838
9c Ivanov KL, Villemson EV, Budynina EM, Ivanova OA, Trushkov IV, Melnikov MY. Chem. Eur. J. 2015; 21: 4975
9d Kaicharla T, Roy T, Thangaraj M, Gonnade RG, Biju AT. Angew. Chem. Int. Ed. 2016; 55: 10061
9e Das S, Daniliuc CG, Studer A. Org. Lett. 2016; 18: 5576
9f Wallbaum J, Garve LK. B, Jones PG, Werz DB. Org. Lett. 2017; 19: 98
9g Konik YA, Elek GZ, Kaabel S, Järving I, Lopp M, Kananovich DG. Org. Biomol. Chem. 2017; 15: 8334
9h Lücht A, Patalag LJ, Augustin AU, Jones PG, Werz DB. Angew. Chem. Int. Ed. 2017; 56: 10587
9i Singh K, Bera T, Jaiswal V, Biswas S, Mondal B, Das D, Saha J. J. Org. Chem. 2019; 84: 710
9j Guin A, Rathod T, Gaykar RN, Roy T, Biju AT. Org. Lett. 2020; 22: 2276
9k Deswal S, Guin A, Biju AT. Org. Lett. 2023; 25: 1643
9l Oliver GA, Werz DB. Org. Lett. 2023; 25: 3568
9m von Köller HF, Jones PG, Werz DB. Chem. Eur. J. 2023; 29: e202203986
9n Harikumar S, Kandy LT. K, Guin A, Biju AT. Org. Biomol. Chem. 2024; 22: 1834
9o Li H, Cheng W, Cunde WangC. J. Org. Chem. 2024; 89: 10333

10 Augustin AU, Werz DB. Acc. Chem. Res. 2021; 54: 1528
11 Budynina EM, Ivanov KL, Sorokin ID, Melnikov MY. Synthesis 2017; 49: 3035

12a Augustin AU, Sensse M, Jones PG, Werz DB. Angew. Chem. Int. Ed. 2017; 56: 14293
12b Augustin AU, Merz JL, Jones PG, Mlostoń G, Werz DB. Org. Lett. 2019; 21: 9405
12c Mlostoń G, Kowalczyk M, Augustin AU, Jones PG, Werz DB. Beilstein J. Org. Chem. 2020; 16: 1288
12d Mlostoń G, Kowalczyk M, Augustin AU, Jones PG, Werz DB. Eur. J. Org. Chem. 2021; 6250
12e Mlostoń G, Kowalczyk M, Palusiak M, Oliver GA, von Köller HF, Werz DB. Eur. J. Org. Chem. 2024; 27: e202301182

13 Mlostoń G, Celeda M, Kowalczyk M, Oliver GA, Werz DB. Eur. J. Org. Chem. 2024; 27: e202400831

14a Comprehensive Heterocyclic Chemistry II . Katritzky AR, Rees CW, Scriven EF. V. Pergamon Press; New York: 1996
14b Comprehensive Heterocyclic Chemistry IV . Black D, Cossy J, Stevens C. Elsevier; Amsterdam: 2022

15 Sinha S, Srivastava AK, Tripathi CM, Pandey OP, Sengupta SK. Bioinorg. Chem. Appl. 2007; 87918

16a Tasaka A, Tamura N, Matsushita Y, Teranishi K, Hayashi R, Okonogi K, Itoh K. Chem. Pharm. Bull. 1993; 41: 1035
16b Zhilitskaya LV, Shainyan BA, Yarosh NO. Molecules 2021; 26: 2190

17a Kazeminejad Z, Marzi M, Shiroudi A, Kouhpayeh SA, Farjam M, Zarenezhad E. Biomed. Res. Int. 2022; 4584846
17b Teixeira MM, Carvalho DT, Sousa E, Pinto E. Pharmaceuticals 2022; 15: 1427

18 Representative Procedure: Dimethyl 2-{2-phenyl-2-[(1,4,5-trimethyl-1H-imidazol-2-yl)thio]ethyl}malonate (7a) To a magnetically stirred mixture of 2a (117 mg, 0.50 mmol) and cat. amounts of Sc(OTf)₃ (ca. 10 mg) in 2 mL of dry CH₂Cl₂ (or CHCl₃), a portion of 2-mercapto 1H-imidazole derivative 4a (78 mg, 0.55 mmol) was added and stirring was continued at r.t. for 20 h. After evaporation of the solvent, the crude product was purified by preparative layer chromatography using glass plates coated with silica and using a mixture of CH₂Cl₂ and MeOH (98:2) as an eluent. Analytically pure product 7a was isolated as a yellowish oil in 87% yield (163 mg). ¹H NMR (600 MHz, CDCl₃): δ = 1.98 (s, 3 H), 2.13 (s, 3 H), 2.54–2.59 (m, 1 H), 2.60–2.66 (m, 1 H), 2.91 (s, 3 H), 3.52 (dd, J = 8.0, 7.4 Hz, 1 H), 3.61 (s, 3 H), 3.69 (s, 3 H), 4.13 (dd, J = 9.0, 7.0 Hz, 1 H), 7.00–7.02 (m, 2 H), 7.17–7.21 (m, 3 H) ppm. ¹³C NMR (151 MHz, CDCl₃): δ = 9.4, 12.7, 30.6 (3 C), 33.6, 49.7, 52.0, 52.57, 52.63 (2 C), 126.1, 127.5, 127.7, 128.5, 134.3, 135.0, 140.1, 169.3, 169.3 (2 C) ppm. IR (neat): ν = 2952, 1718, 1587, 1435, 1386, 1267, 1237, 1203, 1151, 1047, 700 cm^–1. Anal. Calcd for C₁₉H₂₄N₂O₄S (376.47): C, 60.62; H, 6.42; N, 7.44; S 8.52. Found: C, 60.61; H, 6.44; N, 7.42; S, 8.56.

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