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

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

Publikationsverlauf

Eingereicht: 07. Juli 2020

Angenommen nach Revision: 03. August 2020

Artikel online veröffentlicht:
02. September 2020

• 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