Transition-Metal-Free Synthesis of Trifluoromethylated Furans via a Bu3P-Mediated Tandem Acylation–Wittig Reaction

Maizhan Li; Wei Zhou

doi:10.1055/s-0040-1707263

Synlett, Table of Contents

Synlett 2020; 31(20): 2035-2038
DOI: 10.1055/s-0040-1707263

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Transition-Metal-Free Synthesis of Trifluoromethylated Furans via a Bu₃P-Mediated Tandem Acylation–Wittig Reaction

Maizhan Li

,

Wei Zhou ∗

International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education, College of Pharmacy, Jinan University, No. 601 Huangpu Avenue West, Guangzhou, 510632, P. R. of China Email: weizhou88@jnu.edu.cn

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Abstract

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Abstract

A highly efficient nucleophilic addition–O-acylation–intramolecular Wittig reaction of β-trifluoromethyl α,β-enones is disclosed. This strategy features mild reaction conditions and provides a practical transition-metal-free method to a set of biologically significant trifluoromethylated furans in high yields with diverse functional groups.

Key words

β-trifluoromethyl α,β-enones - Wittig reaction - nucleophilic addition - furans - trifluoromethylated furans

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References

References and Notes

1a Muller K, Faeh C, Diederich F. Science 2007; 317: 1881
1b Meanwell NA. J. Med. Chem. 2011; 54: 2529

2a Hagmann WK. J. Med. Chem. 2008; 51: 4359
2b Barnes-Seeman D, Jain M, Bell L, Ferreira S, Cohen S, Chen X.-H, Amin J, Snodgrass B, Hatsis P. ACS Med. Chem. Lett. 2013; 4: 514

3a Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
3b Nie J, Guo H.-C, Cahard D, Ma J.-A. Chem. Rev. 2011; 111: 455
3c Egami H, Sodeoka M. Angew. Chem. Int. Ed. 2014; 53: 8294
3d Alonso C, Martinez de Marigorta E, Rubiales G, Palacios F. Chem. Rev. 2015; 115: 1847
3e Charpentier J, Fruh N, Togni A. Chem. Rev. 2015; 115: 650
3f Liang T, Neumann CN, Ritter T. Angew. Chem. Int. Ed. 2013; 52: 8214

For selected examples, see:

4a Niedermann K, Früh N, Senn R, Czarniecki B, Verel R, Togni A. Angew. Chem. Int. Ed. 2012; 51: 6511
4b Cheng Y, Yuan X, Ma J, Yu S. Chem. Eur. J. 2015; 23: 8355
4c Li L, Mu X, Liu W, Wang Y, Mi Z, Li C.-J. J. Am. Chem. Soc. 2016; 138: 5809
4d Ye K.-Y, Pombar G, Fu N, Sauer GS, Keresztes I, Lin S. J. Am. Chem. Soc. 2018; 140: 2438

For selected examples, see:

5a Li X.-J, Xiong H.-Y, Hua M.-Q, Nie J, Zheng Y, Ma J.-A. Tetrahedron 2012; 53: 2117
5b Mo J, Yang R, Chen X, Tiwari B, Chi YR. Org. Lett. 2013; 15: 50
5c Lin J, Kang T, Liu Q, He L. Tetrahedron: Asymmetry 2014; 25: 949
5d Fu P, Snapper ML, Hoveyda AH. J. Am. Chem. Soc. 2008; 130: 5530
5e Sun L.-H, Liang Z.-Q, Jia W.-Q, Ye S. Angew. Chem. Int. Ed. 2013; 52: 5803
5f Chen P, Yue Z, Zhang J, Lv X, Wang L, Zhang J. Angew. Chem. Int. Ed. 2016; 55: 13316
5g Chen P, Zhang J. Org. Lett. 2017; 19: 6550

For references on the application of the active trifluoromethylated furan compounds, see:

6a Chen D, Zhou Y, Huang Q, Ji J. Chin. J. Org. Chem. 1994; 14: 49
6b Yamamoto H, Hiyama T, Kanie K, Kusumoto T, Morizawa Y, Shimzu M. Organofluorine Compounds: Chemistry and Application . Springer; Berlin: 2000
6c Kirsch P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications. Wiley-VCH; Weinheim: 2004
6d Borcherding DR, Gross A, Shum PW, Willard N, Freed BS. WO2004100946, 2004
6e Jeschke P. ChemBioChem 2004; 5: 570
6f Sakai N, Imamura S, Miyamoto N, Hirayama T. WO2008016192, 2008
6g Kirk KL. Org. Process Res. Dev. 2008; 12: 305

For a review, see:

7a Petrov VA. Fluorinated Heterocyclic Compounds: Synthesis, Chemistry, and Applications. Wiley; Hoboken: 2009. ; and references cited therein

For selected examples, see:

7b Sawada H, Nakayama M, Yoshida M, Yoshida T, Kamigata N. J. Fluorine Chem. 1990; 46: 423
7c Naumann D, Kischkewitz J. J. Fluorine Chem. 1990; 46: 265
7d Bucci R, Laguzzi G, Pompili ML, Speranza M. J. Am. Chem. Soc. 1991; 113: 4544
7e Linderman RJ, Jamois EA, Tennyson SD. J. Org. Chem. 1994; 59: 957
7f Pang W, Zhu S, Xin Y, Jiang H, Zhu S. Tetrahedron 2010; 66: 1261
7g Zhang D, Yuan C. Eur. J. Org. Chem. 2007; 3916
7h Ye Y, Sanford MS. J. Am. Chem. Soc. 2012; 134: 9034

For recently selected examples, see:

8a Yang G.-J, Du W, Chen Y.-C. J. Org. Chem. 2016; 81: 10056
8b Zhou W, Wang H, Tao M, Zhu C.-Z, Lin T.-Y, Zhang J. Chem. Sci. 2017; 8: 4660
8c Wang H, Zhang L, Tu Y, Xiang R, Guo Y.-L, Zhang J. Angew. Chem. Int. Ed. 2018; 57: 15787
8d Li Y, Wang H, Su Y, Li R, Li C, Liu L, Zhang J. Org. Lett. 2018; 20: 6444
8e Ni H, Wong YL, Wu M, Han Z, Ding K, Lu Y. Org. Lett. 2020; 22: 2460

9 Typical Procedure for the Bu₃P-Mediated Tandem Acylation–Wittig Reaction In a 25 mL dry Schlenk tube equipped with a stirring bar, a solution of acyl chloride 2 (1.1 equiv) and Bu₃P (1.1 equiv) in dry THF (1.0 mL) and a solution of β-trifluoromethyl α,β-enone 1 (0.2 mmol) in dry THF (1.0 mL) was added. Subsequently, Et₃N (1.5 equiv) was added to the above reaction solution. The reaction mixture was stirred for 0.5 h at room temperature, the reaction was monitored by TLC (hexane). Thereafter, the solvent was removed by evaporation in vacuo, and the residue was purified by flash chromatography on silica gel (hexane/EtOAc = 100:0 to 40:1) to furnished the desired trifluoromethyl-functionalized multisubstituted furans 3. Analytical Data for Compound 3aa White solid. ¹H NMR (500 MHz, CDCl₃): δ = 7.79−7.72 (m, 4 H), 7.49−7.41 (m, 5 H), 7.34−7.32 (m, 1 H), 6.89 (s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 153.03, 151.90 (q, J = 5.00 Hz), 129.46, 129.31, 128.90, 128.67, 128.41, 127.15 (q, J = 1.25 Hz), 124.06, 122.91 (q, J = 266.25 Hz), 114.29 (q, J = 37.50 Hz), 105.27 (q, J = 3.75 Hz). ¹⁹F NMR (376 MHz, CDCl₃): δ = –56.41 ppm. HRMS (EI): m/z calcd for C₁₇H₁₁F₃O [M]⁺: 288.0757; found: 288.0753.

For pioneering reports on phosphine-mediated tandem O-acylation–Wittig reactions, see:

10a Kao T.-T, Syu S, Jhang Y.-W, Lin W. Org. Lett. 2010; 12: 3066
10b Wang D.-W, Syu S, Huang Y.-T, Chen P, Lee CJ, Chen K.-W, Chen Y.-J, Lin W. Org. Biomol. Chem. 2011; 9: 363
10c Syu S, Lee Y.-T, Jang Y.-J, Lin W. Org. Lett. 2011; 13: 2970
10d Wang Y, Luo Y.-C, Hu X.-Q, Xu P.-F. Org. Lett. 2011; 13: 5346
10e Lee Y.-T, Jang Y.-J, Syu S, Chou S.-C, Lee C.-J, Lin W. Chem. Commun. 2012; 48: 8135
10f Lee C.-J, Tsai C.-C, Hong S.-H, Chang G.-H, Yang M.-C, Möhlmann L, Lin W. Angew. Chem. Int. Ed. 2015; 54: 8502
10g Lee Y.-T, Lee C.-J, Sheu C.-N, Lin B.-Y, Wang J.-H, Lin W. Org. Biomol. Chem. 2013; 11: 5156
10h Chen Y.-R, Reddy GM, Hong S.-H, Wang Y.-Z, Yu J.-K, Lin W. Angew. Chem. Int. Ed. 2017; 56: 5106
10i Yang S.-M, Wang C.-Y, Lin C.-K, Karanam P, Reddy GM, Tsai Y.-L, Lin W. Angew. Chem. Int. Ed. 2018; 57: 1668
10j Khairnar PV, Lung T.-H, Lin Y.-J, Wu C.-Y, Koppolu SR, Edukondalu A, Karanam P, Lin W. Org. Lett. 2019; 21: 4219

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