Late-Stage Transformation of Carboxylic Acids to N-Trifluoroethyl­imides with Trifluoromethyl Diazomethane

Xiao-Feng Qiu; De-Yong Liu; Wen-Feng Zhang; Xiang-Guo Hu

doi:10.1055/a-1339-3227

Synthesis, Table of Contents

Synthesis 2021; 53(05): 961-970
DOI: 10.1055/a-1339-3227

paper

Late-Stage Transformation of Carboxylic Acids to N-Trifluoroethylimides with Trifluoromethyl Diazomethane

Xiao-Feng Qiu

^aNational Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang, 330022, P. R. of China

^bKey Laboratory of Small Functional Organic Molecule, Ministry of Education, Jiangxi Normal University, Nanchang, Jiangxi 330022, P. R. of China

,

De-Yong Liu

^aNational Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang, 330022, P. R. of China

,

Wen-Feng Zhang

^aNational Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang, 330022, P. R. of China

,

Xiang-Guo Hu ∗

^aNational Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang, 330022, P. R. of China

^bKey Laboratory of Small Functional Organic Molecule, Ministry of Education, Jiangxi Normal University, Nanchang, Jiangxi 330022, P. R. of China

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Abstract

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Abstract

We report the first systematic evaluation of the reaction of trifluoromethyl diazomethane (2,2,2-trifluorodiazoethane, CF₃CHN₂) with drug-like molecules. We found our previous copper-catalyzed transformation of carboxylic acids to the corresponding N-trifluoroethylimides with CF₃CHN₂ and acetonitrile is well-suited for the late-stage modification of drug and drug-like acids. A procedure that enables the use of solid nitriles and nitriles with high boiling points as viable substrates is also disclosed.

Key words

N-trifluoroethylimides - trifluoromethyl diazomethane - late-stage functionalization - fluoroalkyl - copper - trifluoromethyl - 2,2,2-trifluorodiazoethane

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References

References
1 Cernak T, Dykstra KD, Tyagarajan S, Vachal P, Krska SW. Chem. Soc. Rev. 2016; 45: 546

2a Neumann CN, Ritter T. Angew. Chem. Int. Ed. 2015; 54: 3216
2b Sladojevich F, Arlow SI, Tang P, Ritter T. J. Am. Chem. Soc. 2013; 135: 2470
2c Tang P, Furuya T, Ritter T. J. Am. Chem. Soc. 2010; 132: 12150

3 Xiao H, Liu Z, Shen H, Zhang B, Zhu L, Li C. Chem 2019; 5: 940

4a Gillis EP, Eastman KJ, Hill MD, Donnelly DJ, Meanwell NA. J. Med. Chem. 2015; 58: 8315
4b O’Hagan D. Chem. Soc. Rev. 2008; 37: 308

5 Lopchuk JM. Imide Natural Products . In Developments in Organic Chemistry - Imides, Chap. 7 . Luzzio FA. Elsevier; Amsterdam: 2019: 255-334

6a Mertens L, Koenigs RM. Org. Biomol. Chem. 2016; 14: 10547
6b Mykhailiuk PK. Chem. Rev. 2020; 120: 12718

7a Molander GA, Cavalcanti LN. Org. Lett. 2013; 15: 3166
7b Slobodyanyuk EY, Artamonov OS, Shishkin OV, Mykhailiuk PK. Eur. J. Org. Chem. 2014; 2487
7c Morandi B, Carreira EM. Angew. Chem. Int. Ed. 2010; 49: 938
7d Morandi B, Cheang J, Carreira EM. Org. Lett. 2011; 13: 3080
7e Morandi B, Mariampillai B, Carreira EM. Angew. Chem. Int. Ed. 2011; 50: 1101
7f Zhu CL, Yang LJ, Li S, Zheng Y, Ma JA. Org. Lett. 2015; 17: 3442
7g Chen Z, Zheng Y, Ma JA. Angew. Chem. Int. Ed. 2017; 56: 4569
7h Le Maux P, Juillard S, Simonneaux G. Synthesis 2006; 1701
7i Hock KJ, Mertens L, Metze FK, Schmittmann C, Koenigs RM. Green Chem. 2017; 19: 905

8a Morandi B, Carreira EM. Angew. Chem. Int. Ed. 2010; 49: 4294
8b Liu CB, Meng W, Li F, Wang S, Nie J, Ma JA. Angew. Chem. Int. Ed. 2012; 51: 6227
8c Britton J, Jamison TF. Angew. Chem. Int. Ed. 2017; 56: 8823

9 Zhang FG, Wei Y, Yi YP, Nie J, Ma JA. Org. Lett. 2014; 16: 3122
10 Luo HQ, Wu GJ, Zhang Y, Wang JB. Angew. Chem. Int. Ed. 2015; 54: 14503

11a Pieber B, Kappe CO. Org. Lett. 2016; 18: 1076
11b Morandi B, Carreira EM. Angew. Chem. Int. Ed. 2011; 50: 9085

12 Meese CO. Synthesis 1984; 1041

13a Argintaru OA, Ryu D, Aron I, Molander GA. Angew. Chem. Int. Ed. 2013; 52: 13656
13b Molander GA, Ryu D. Angew. Chem. Int. Ed. 2014; 53: 14181

14 Hyde S, Veliks J, Liegault B, Grassi D, Taillefer M, Gouverneur V. Angew. Chem. Int. Ed. 2016; 55: 3785
15 Arkhipov AV, Arkhipov VV, Cossy J, Kovtunenko VO, Mykhailiuk PK. Org. Lett. 2016; 18: 3406
16 Guo R, Zheng Y, Ma JA. Org. Lett. 2016; 18: 4170
17 Peng SQ, Zhang XW, Zhang L, Hu XG. Org. Lett. 2017; 19: 5689
18 Mykhailiuk PK, Kishko I, Kubyshkin V, Budisa N, Cossy J. Chem. Eur. J. 2017; 23: 13279

19a Koley D, Colon OC, Savinov SN. Org. Lett. 2009; 11: 4172
19b Li Y.-X, Li L.-H, Yang Y.-F, Hua H.-L, Yan X.-B, Zhao L.-B, Zhang J.-B, Ji F.-J, Liang Y.-M. Chem. Commun. 2014; 50: 9936

20 Mykhailiuk PK. Angew. Chem. Int. Ed. 2015; 54: 6558
21 More comments on the in situ generated CF₃CHN₂ (Method A/A′): Although the yields with 20 equiv of valeronitrile in Table 1, entries 5 and 6 are higher than those with a solvent quantity of valeronitrile, we found that other nitriles still need solvent quantities to get high yields. For example, when using 20 equiv of nitrile, low yields were obtained for the synthesis of 3d and 3m, with the NMR yield being 29% and 13%, respectively.
22 Mumm O. Ber. Dtsch. Chem. Ges. 1910; 43: 886
23 CF₃CF₂CHN₂, as a close analogue of CF₃CHN₂, may be applicable using the current method: Mykhailiuk PK. Chem. Eur. J. 2014; 20: 4942

Supplementary Material

Supporting Information

Late-Stage Transformation of Carboxylic Acids to N-Trifluoroethyl­imides with Trifluoromethyl Diazomethane

Late-Stage Transformation of Carboxylic Acids to N-Trifluoroethylimides with Trifluoromethyl Diazomethane