Synthesis of 2-Sulfonylthiazoles via Heteroaryl C–H Sulfonylation of Thiazole N-Oxides

Hyun-Suk Um; Woong Sik Shin; Kyu Jin Son; Chulbom Lee

doi:10.1055/a-2059-3168

Synlett, Inhaltsverzeichnis

Synlett 2023; 34(12): 1447-1451
DOI: 10.1055/a-2059-3168

cluster

Special Issue Honoring Masahiro Murakami’s Contributions to Science

Synthesis of 2-Sulfonylthiazoles via Heteroaryl C–H Sulfonylation of Thiazole N-Oxides

Hyun-Suk Um‡

,

Woong Sik Shin‡

,

Kyu Jin Son

,

Chulbom Lee ∗

Abstract

Alle Artikel dieser Rubrik

This paper is dedicated to Professor Masahiro Murakami for his inspiring contributions to chemical science.

Abstract

Described here is an efficient method for the modular synthesis of 2-sulfonylthiazole derivatives via heteroaryl C–H sulfonylation. The protocol is composed of two stages involving O-activation of thiazole N-oxides and nucleophilic addition of a sulfinate, which induces N(3)-deoxygenation and C(2)-sulfonylation. The vicarious substitution is performed most effectively by using 4-methoxybenzoyl chloride for O-acylation while employing sodium [tert-butyl(dimethyl)silyloxy]methanesulfinate (TBSOMS-Na) as the nucleophile. The sulfones thus obtained can be converted to an array of thiazolyl sulfones, sulfonamides, and sulfonyl fluorides by displacing the silyloxymethyl moiety with alkyl, aryl, amino, and fluoro groups. The C–H sulfonylation approach, in combination with a sulfoxylate (SO₂ ^2–) strategy, provides direct access to sulfonylated thiazole scaffolds without recourse to the use of 2-halothiazoles.

Key words

silyloxymethanesulfinate - C–H functionalization - modular synthesis - azole N-oxides - sulfonylazoles

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Referenzen

References and Notes

1a Gupta RR, Kumar M, Gupta V. Heterocyclic Chemistry: Vol. II: Five-Membered Heterocycles . Springer; Berlin: 1999
1b Comprehensive Heterocyclic Chemistry III, Vols. 3–6. Katritzky AR, Ramsden CA, Scriven EF. V, Taylor RJ. K. Elsevier Science; Amsterdam: 2008
1c Gao H, Shreeve JM. Chem. Rev. 2011; 111: 7377
1d Vitaku E, Smith DT, Njardarson JT. J. Med. Chem. 2014; 57: 10257
1e Kaur N. Metals and Non-Metals: Five-Membered N-Heterocycle Synthesis. CRC Press; Boca Raton: 2019

2a Feng M, Tang B, Liang SH, Jiang X. Curr. Top. Med. Chem. 2016; 16: 1200
2b Scott KA, Njardarson JT. Top. Curr. Chem. 2018; 376: 5
2c Zhao C, Rakesh KP, Ravidar L, Fang W.-Y, Qin H.-L. Eur. J. Med. Chem. 2019; 162: 679

3a Julia M, Paris J.-M. Tetrahedron Lett. 1973; 49: 4833
3b Blakemore PR. J. Chem. Soc., Perkin Trans. 1 2002; 2563
3c Sakaine G, Leitis Z, Ločmele R, Smits G. Eur. J. Org. Chem. 2022; e202201217

4a Zhang D, Devarie-Baez NO, Li Q, Lancaster JR. Jr, Xian M. Org. Lett. 2012; 14: 3396
4b Motiwala HF, Kuo Y.-H, Stinger BL, Palfey BA, Martin BR. J. Am. Chem. Soc. 2020; 142: 1801
4c Wang X, Ye W, Kong T, Wang C, Ni C, Hu J. Org. Lett. 2021; 23: 8554
4d Thierry T, Pfund E, Lequeux T. Chem. Eur. J. 2021; 27: 14826

For reviews, see:

5a Shaaban S, Liang S, Liu N.-W, Manolikakes G. Org. Biomol. Chem. 2017; 15: 1947
5b Liang S, Hofman K, Friederich M, Keller J, Manolikakes G. ChemSusChem 2021; 14: 4878

For conventional approaches toward sulfonylazoles, see:

6a Gibbs EM, Robinson FA. J. Chem. Soc. 1945; 925
6b Liang S, Zhang R.-Y, Xi L.-Y, Chen S.-Y, Yu X.-Q. J. Org. Chem. 2013; 78: 11874

For selected examples in cross-coupling settings, see:

6c Emmett EJ, Hayter BR, Willis MC. Angew. Chem. Int. Ed. 2014; 53: 10204
6d Shyam PK, Jang H.-Y. J. Org. Chem. 2017; 82: 1761
6e Liu N.-W, Liang S, Margraf N, Shaaban S, Luciano V, Drost M, Manolikakes G. Eur. J. Org. Chem. 2018; 1208

For challenges and advances of azole halides in cross-coupling reactions, see:

7a Hooper MW, Utsunomiya M, Hartwig JF. J. Org. Chem. 2003; 68: 2861
7b Reichert EC, Feng K, Sather AC, Buchwald SL. J. Am. Chem. Soc. 2023; 145: 3323

8a Um H.-S, Min J, An T, Choi J, Lee C. Org. Chem. Front. 2018; 5: 2158
8b Kim D.-K, Um H.-S, Park H, Kim S, Choi J, Lee C. Chem. Sci. 2020; 11: 13071

9a Yan G, Borah AJ, Yang M. Adv. Synth. Catal. 2014; 356: 2375
9b Wang Y, Zhang L. Synthesis 2015; 47; 289
9c Heterocyclic N-Oxides . Larionov OV. Springer; Cham: 2017
9d Petrosyan A, Hauptmann R, Pospech J. Eur. J. Org. Chem. 2018; 5237
9e Malykhin RS, Sukhorukov AY. Adv. Synth. Catal. 2021; 363: 3170
9f Wang D, Désaubry L, Li G, Huang M, Zheng S. Adv. Synth. Catal. 2021; 363: 2
9g Kaur R, Mandal S, Banerjee D, Yadav AK. ChemistrySelect 2021; 6: 2832
9h Fershtat LL, Teslenko FE. Synthesis 2021; 53: 3673

For general remarks on C–H functionalization, see:

9i Seregin IV, Gevorgyan V. Chem. Soc. Rev. 2007; 36: 1173
9j Metal Free C–H Functionalization of Aromatics: Nucleophilic Displacement of Hydrogen. Charushin V, Chupakhin O. Springer; Cham: 2014
9k Fujiwara Y, Baran PS. In New Horizons of Process Chemistry: Scalable Reactions and Technologies . Tomioka T, Shioiri T, Sajiki H. Springer Nature; Singapore: 2017: 103

For examples of deoxygenative C–H sulfonylation, see:

10a Wang R, Zeng Z, Chen C, Yi N, Jiang J, Cao Z, Deng W, Xiang J. Org. Biomol. Chem. 2016; 14: 5317
10b Peng S, Song Y.-X, He J.-Y, Tang S.-S, Tan J.-X, Cao Z, Lin Y.-W, He W.-M. Chin. Chem. Lett. 2019; 30: 2287
10c Xie L.-Y, Fang T.-G, Tan J.-X, Zhang B, Cao Z, Yang L.-H, He W.-M. Green Chem. 2019; 21: 3858
10d Patel TI, Laha R, Moschitto MJ. J. Org. Chem. 2022; 87: 15679

For an example of C–H sulfonylation without deoxygenation, see:

10e Wu Z, Song H, Cui X, Pi C, Du W, Wu Y. Org. Lett. 2013; 15: 1270

11a Campeau L.-C, Bertrand-Laperle M, Leclerc J.-P, Villemure E, Gorelsky S, Fagnou K. J. Am. Chem. Soc. 2008; 130: 3276
11b Campeau L.-C, Stuart DR, Leclerc J.-P, Bertrand-Laperle M, Villemure E, Sun H.-Y, Lasserre S, Guimond N, Lecavallier M, Fagnou K. J. Am. Chem. Soc. 2009; 131: 3291
11c Peng X, Huang P, Jiang L, Zhu J, Liu L. Tetrahedron Lett. 2016; 57: 5223
11d Golding WA, Phipps RJ. Chem. Sci. 2020; 11: 3022

12a Takamizawa A, Harada H. Chem. Pharm. Bull. 1973; 21: 770
12b Szpunar M, Loska R. Eur. J. Org. Chem. 2015; 2133
12c Ma S, Dang S, Rose JA, Rablen P, Herzon SB. J. Am. Chem. Soc. 2017; 139: 5998
12d Mirabal RA, Vanderzwet L, Abuadas S, Emmett MR, Schipper D. Chem. Eur. J. 2018; 24: 12231
12e Li H, Zhang J, Zhang Y, Wang J, Song G. Tetrahedron Lett. 2019; 60: 150825

13a Begtrup M, Hansen LB. L. Acta Chem. Scand. 1992; 46: 372
13b Zhu J, Kong Y, Lin F, Wang B, Chen Z, Liu L. Eur. J. Org. Chem. 2015; 1507
13c Zhu J, Chen Y, Lin F, Wang B, Chen Z, Liu L. Org. Biomol. Chem. 2015; 13: 3711

14a Thiazole and Its Derivatives . Metzger JV. Wiley; New York: 1979
14b Roy RS, Gehring AM, Milne JC, Belshaw PJ, Walsh CT. Nat. Prod. Rep. 1999; 16: 249
14c Dondoni A, Marra A. Chem. Rev. 2004; 104: 2557
14d Lin Y, Fan H, Li Y, Zhan X. Adv. Mater. 2012; 24: 3087
14e Chhabria MT, Patel S, Modi P, Brahmkshatriya PS. Curr. Top. Med. Chem. 2016; 16: 2841
14f Jin Z. Nat. Prod. Rep. 2016; 33: 1268
14g Sharma PC, Bansal KK, Sharma A, Sharma D, Deep A. Eur. J. Med. Chem. 2020; 188: 112016

The attempted C–H sulfonylation via N-activation of benzothiazole using triflic anhydride led to extensive decomposition (see the Supporting Information for details). For reports on the direct N-activation approach to the C–H sulfonylation of azine-type N-heteroaromatics, see:

15a Friedrich M, Schulz L, Hofman K, Zangl R, Morgner N, Shaaban S, Manolikakes G. Tetrahedron Chem 2022; 1: 100003
15b Friedrich M, Manolikakes G. Eur. J. Org. Chem. 2022; e202200915

16 Further attempts to extend the protocol to other azole systems met with little success (see the Supporting Information).

17a Baskin JM, Wang Z. Tetrahedron Lett. 2002; 43: 8479
17b Day JJ, Neill DL, Xu S, Xian M. Org. Lett. 2017; 19: 3819
17c Zhang W, Luo M. Chem. Commun. 2016; 52: 2980
17d Shavnya A, Coffey SB, Hesp KD, Ross SC, Tsai AS. Org. Lett. 2016; 18: 5848
17e Wang M, Tang B.-C, Wang J.-G, Xiang J.-C, Guan A.-Y, Huang P.-P, Guo W.-Y, Wu Y.-D, Wu A.-X. Chem. Commun. 2018; 54: 7641
17f Alvarez EM, Plutschack MB, Berger F, Ritter T. Org. Lett. 2020; 22: 4593
17g Shavnya A, Hesp KD, Tsai AS. Adv. Synth. Catal. 2018; 360: 1768

18 As with 3f, facile protodesulfonylation was observed in the attempted copper-catalyzed S-arylation of a ketosulfone substrate (Scheme 3, unpublished results from ref. 8b). Also examined were the reaction of 3f with iodobenzene under metallaphotoredox conditions and the S _N Ar reaction employing an iodonium salt, both of which resulted in the formation of the protodesulfonylation product 4f (see the Supporting Information for details).
19 2-[({[tert-Butyl(dimethyl)silyl]oxy}methyl)sulfonyl]-1,3-thiazole; Typical Procedure 4-methoxybenzoyl chloride (1.1 equiv, 0.44 mmol, 60 μL) was added dropwise to a solution of 1,3-thiazole N-oxide (2a; 0.4 mmol) and TBSOMS-Na (1; 1.5 equiv, 0.6 mmol, 0.1394 g) in anhyd DCM (2 mL), and the mixture was stirred at 30 ℃ for 2 h under atmospheric conditions. Organic fractions were gathered with DCM, washed with aq NaHCO₃ and brine, dried (Na₂SO₄), and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel) to afford the desired sulfone product 3f as a colorless liquid, yield: 85.7 mg (73%); R_f = 0.48 (hexane–EtOAc, 5:1). ¹H NMR (500 MHz, CDCl₃): δ = 8.10 (s, 1 H), 7.78 (s, 1 H), 4.95 (s, 2 H), 0.80 (s, 9 H), 0.06 (s, 6 H). ¹³C NMR (126 MHz, CDCl₃): δ = 163.5, 145.4, 127.0, 79.5, 25.5, 18.3, –5.4. IR (neat): 3116, 2931, 2889, 2858, 1471, 1432, 1362, 1340, 1312, 1258, 1172, 1128, 1067, 1007, 939, 833, 784, 764, 728, 668, 544, 527, 463, 404 cm^–1. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₀H₁₉NNaO₃S₂Si: 316.0468; found: 316.0468.

Zusatzmaterial

Supporting Information