Direct α-Trifluoromethylthiolation of Carboxylic Acids 
    Enabled by Boron Catalysis

Kai Sun; Chung-Yang Dennis Huang; Masaya Sawamura; Yohei Shimizu

doi:10.1055/a-2071-4465

Synlett, Table of Contents

Synlett 2023; 34(18): 2210-2214
DOI: 10.1055/a-2071-4465

cluster

Modern Boron Chemistry: 60 Years of the Matteson Reaction

Direct α-Trifluoromethylthiolation of Carboxylic Acids Enabled by Boron Catalysis

Kai Sun

^bDepartment of Chemistry, Faculty of Science, Hokkaido University, Kita 10 Nishi 8, Kita-ku, Sapporo, Hokkaido 060-0810, Japan

,

Chung-Yang Dennis Huang ∗

^aInstitute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Kita 21 Nishi 10, Kita-ku, Sapporo, Hokkaido 001-0021, Japan

,

Masaya Sawamura

^aInstitute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Kita 21 Nishi 10, Kita-ku, Sapporo, Hokkaido 001-0021, Japan

^bDepartment of Chemistry, Faculty of Science, Hokkaido University, Kita 10 Nishi 8, Kita-ku, Sapporo, Hokkaido 060-0810, Japan

,

Yohei Shimizu ∗

^aInstitute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Kita 21 Nishi 10, Kita-ku, Sapporo, Hokkaido 001-0021, Japan

^bDepartment of Chemistry, Faculty of Science, Hokkaido University, Kita 10 Nishi 8, Kita-ku, Sapporo, Hokkaido 060-0810, Japan

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Abstract

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Abstract

A boron-catalyzed direct α-trifluoromethylthiolation of carboxylic acids was developed. Catalytically generated boron enediolates reacts with electrophilic SCF₃ reagent, N-SCF₃-phthalimide, to provide α-SCF₃ carboxylic acids without the need of substrate pre-activation. The method is applicable to direct modification of bioactive carboxylic acids. Data science analyses provided suitable models for substrate classification as well as yield prediction.

Key words

carboxylic acid - boron catalyst - trifluoromethylthiolation - data science - drug modification - fluorine compounds

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References

References and Notes

1a Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
1b Kirik KL. J. Fluorine Chem. 2006; 127: 1013
1c Zhou Y, Wang J, Gu Z, Wang S, Zhu W, Aceña JL, Soloshonok VA, Izawa K, Liu H. Chem. Rev. 2016; 116: 422
1d Gillis EP, Eastman KJ, Hill MD, Donnelly DJ, Meanwell NA. J. Med. Chem. 2015; 58: 8315
1e Zanda M. New J. Chem. 2004; 28: 1401
1f Jeschke P. ChemBioChem 2004; 5: 570

2a Hansch C, Leo A. Substituent Constants for Correlation Analysis in Chemistry and Biology. Wiley; New York: 1979: 339
2b Barata-Vallejo S, Bonesi S, Postigo A. Org. Biomol. Chem. 2016; 14: 7150

3a Rossi S, Puglisi A, Raimondi L, Benaglia M. ChemCatChem 2018; 10: 2717
3b Barthelemy A.-L, Manier E, Dagousset G. Synthesis 2018; 50: 4765
3c Ghiazza C, Billard T. Eur. J. Org. Chem. 2021; 5571

4a Saidalimu I, Yoshioka T, Liang Y, Tokunaga E, Shibata N. Chem. Commun. 2018; 54: 8761
4b Kondo H, Maeno M, Sasaki K, Guo M, Hashimoto M, Shiro M, Shibata N. Org. Lett. 2018; 20: 7044
4c Jin MY, Gu X, Deng M, Wang C, Wang J. Chem. Commun. 2020; 56: 10552

5a Alazet S, Ismalaj E, Glenadel Q, Le Bars D, Billard T. Eur. J. Org. Chem. 2015; 4607
5b Jiang L, Yan Q, Wang R, Ding T, Yi W, Zhang W. Chem. Eur. J. 2018; 24: 18749

6a Capaccio V, Sicignano M, Rodríguez RI, Sala GD, Aléman J. Org. Lett. 2020; 22: 219
6b Franco F, Meninno S, Lattanzi A, Puglisi A, Benaglia M. J. Org. Chem. 2021; 86: 14207
6c Franco F, Meninno S, Benaglia M, Lattanzi A. Chem. Commun. 2020; 56: 3073
6d Zhang H, Shen Q. Tetrahedron 2021; 101: 132508 I Sicignano M., Rodríguez R. I., Capaccio V., Borello F., Cano R., De Riccardis F., Bernardi L., Díaz-Tendero S., Sala G. D., Aléman J.; Org. Biomol. Chem.; 2020, 18: 2914

7a Lübcke M, Yuan W, Szabó KJ. Org. Lett. 2017; 19: 4548
7b Zhang Z, Sheng Z, Yu W, Wu G, Zhang R, Chu W.-D, Zhang Y, Wang J. Nat. Chem. 2017; 9: 970
7c Hu M, Rong J, Miao W, Ni C, Han Y, Hu J. Org. Lett. 2014; 16: 2030
7d Wang X, Zhou YJ, Ji G, Wu G, Li M, Zhang Y, Wang J. Eur. J. Org. Chem. 2014; 3093
7e Lefebvre Q, Fava E, Nikolaienko P, Rueping M. Chem. Commun. 2014; 50: 6617

8a Mizuta S, Kitamura K, Morii Y, Ishihara J, Yamaguchi T, Ishikawa T. J. Org. Chem. 2021; 86: 18017
8b Li SG, Zard SZ. Org. Lett. 2013; 15: 5898

9 Jiang X, Meyer D, Baran D, Cortés MA, Szabó KJ. J. Org. Chem. 2020; 85: 8311

10a Shimizu Y, Kanai M. Chem. Rec. 2023; e202200273
10b Sawamura M, Shimizu Y. Eur. J. Org. Chem. 2023; 26: e202201249
10c Sun K, Ueno M, Imaeda K, Ueno K, Sawamura M, Shimizu Y. ACS Catal. 2021; 11: 9722
10d Morisawa T, Sawamura M, Shimizu Y. Org. Lett. 2019; 21: 7466
10e Fujita T, Yamamoto T, Morita Y, Chen H, Shimizu Y, Kanai M. J. Am. Chem. Soc. 2018; 140: 5899
10f Ishizawa K, Nagai H, Shimizu Y, Kanai M. Chem. Pharm. Bull. 2017; 66: 231
10g Nagai H, Morita Y, Shimizu Y, Kanai M. Org. Lett. 2016; 18: 2076
10h Morita Y, Yamamoto T, Nagai H, Shimizu Y, Kanai MJ. Am. Chem. Soc. 2015; 137: 7075
10i Chen H, Yamaguchi S, Morita Y, Nakao H, Zhai X.-N, Shimizu Y, Mitsunuma H, Kanai M. Cell Rep. Phys. Sci. 2021; 2: 100679
10j Hu H, Wang C, Wu X, Liu Y, Yue G, Su G, Feng J. Org. Chem. Front. 2022; 9: 1315

11a Mack KA, Sigman MS. J. Am. Chem. Soc. 2023; 145: 110
11b Sigman MS, Doyle AG. Science 2021; 374: 301

12 Sigman MS, Davies HM. L. J. Am. Chem. Soc. 2022; 144: 15549
13 The program used for logistic regression can be found here (accessed Mar 13, 2023): DOI: https://github.com/DWs-code-drink/SCF3_Logistic.
14 General Procedure for α-Trifluoromethylthiolation of Carboxylic Acids Carboxylic acid (0.1 mmol, 1.0 equiv) was added to a 4 mL vial and then brought into the glove box. (AcO)₄B₂O (2.7 mg, 0.1 equiv), THF (1 mL), DBU (35.7 μL, 2.4 equiv), and N-(trifluoromethylthio)phthalimide (37.1 mg, 1.5 equiv) were sequentially added. The vial was sealed and removed from the glove box, and the resulting solution was stirred for 2 h at room temperature (23–28 ℃). MeI (37.4 μL, 6.0 equiv) was consequently added, and the reaction mixture was left stirred for another 2 h. Then, the reaction was worked up by adding 2 mL of 2:1:1 solution of brine, water, and 4 M HCl, followed by extraction with EtOAc (3 times). The combined organic layer was dried over Na₂SO₄, filtered, and concentrated in vacuo. To this crude product was added tetrabromoethane (11.6 μL, 0.1 mmol) and hexafluorobenzene (34.6 μL, 0.3 mmol) as the standards for the determination of NMR yield. The residue was then purified by silica gel chromatography on a Biotage Isolera One using a dry-load method.

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