Synlett 2019; 30(03): 356-360
DOI: 10.1055/s-0037-1611694
letter
© Georg Thieme Verlag Stuttgart · New York

Lewis Acid-Catalyzed Rearrangement of Fluoroalkylated Propargylic Alcohols: An Alternative Approach to β-Fluoroalkyl-α,β-enones

Manickavasakam Ramasamy
a   School of Pharmacy, China Medical University, Taichung 404, Taiwan
,
Hui-Chang Lin
a   School of Pharmacy, China Medical University, Taichung 404, Taiwan
,
Sheng-Chu Kuo
a   School of Pharmacy, China Medical University, Taichung 404, Taiwan
b   Chinese Medicine Research Center, China Medical University, Taichung 404, Taiwan
c   Research Center for Chinese Herbal Medicine, China Medical University, Taichung 404, Taiwan
,
Min-Tsang Hsieh*
a   School of Pharmacy, China Medical University, Taichung 404, Taiwan
b   Chinese Medicine Research Center, China Medical University, Taichung 404, Taiwan
c   Research Center for Chinese Herbal Medicine, China Medical University, Taichung 404, Taiwan
d   Chinese Medicinal Research and Development Center, China Medical University Hospital, Taichung 404, Taiwan   Email: T21917@mail.cmu.edu.tw
› Author Affiliations
This research project was funded by Ministry of Science and Technology, Taiwan (MOST 105-2113-M-039-004) and “Chinese Medicine Research Center, China Medical University” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan (CMRC-CHM-6).
Further Information

Publication History

Received: 07 November 2018

Accepted after revision: 02 December 2018

Publication Date:
03 January 2019 (online)


Abstract

A practical Lewis acid-catalyzed Meyer–Schuster rearrangement of fluoroalkylated propargylic alcohols, leading to a series of β-fluoroalkyl-α,β-enones, is developed. The methodology reported herein features moderate to high yields and high stereoselectivity in the synthesis of β-alkyl-β-fluoroalkyl-α,β-enones.

Supporting Information

 
  • References and Notes

  • 3 Congmon J, Tius MA. Eur. J. Org. Chem. 2003; 68: 2853
  • 4 Sanz-Marco A, Carcia-Ortiz A, Blay G, Pedro JR. Chem. Commun. 2014; 50: 2275
  • 5 Li Y, Wang H, Su Y, Li R, Li C, Liu L, Zhang J. Org. Lett. 2018; 20: 6444
  • 7 Funabiki K, Matsunaga K, Nojiri M, Hashimoto W, Yamamoto H, Shibata K, Matsui M. J. Org. Chem. 2003; 68: 2853
  • 8 Yamazaki T, Kawasaki-Takasuka T, Furuta A, Sakamoto S. Tetrahedron 2009; 65: 5945
  • 9 Boreux A, Lambion A, Campeau A, Sanita M, Coronel R, Riant O, Gagosz F. Tetrahedron 2018; 74: 5232
  • 10 Bizet V, Pannecoucke X, Renaud J.-L, Cahard D. J. Fluorine Chem. 2013; 152: 56
  • 11 Watanabe Y, Yamazaki T. J. Org. Chem. 2011; 76: 1957
  • 13 Hsieh MT, Lee KH, Kuo SC, Lin HC. Adv. Synth. Catal. 2018; 360: 1605
  • 14 For the preparation of fluorinated alkyl alkynyl ketones, see reference 13 and: Hsieh M.-T, Kuo S.-C, Lin H.-C. Adv. Synth. Catal. 2015; 357: 683
  • 15 Engel DA, Lopez SS, Dudley GB. Tetrahedron 2008; 64: 6988
  • 18 For BF3·OEt2-mediated syn-selective Meyer–Schuster reaction, see: Puri S, Babu MH, Reddy MS. Org. Biomol. Chem. 2016; 14: 7001
  • 19 General Procedure for the Synthesis of Compounds 2ar The general procedure is illustrated immediately below with compound 2a as a specific example. A stirred solution of compound 1a (100 mg, 0.50 mmol) and BF3·OEt2 (36 mg, 0.25 mmol) in dichloroethane (2 mL) was heated at 70 oC under nitrogen for 4 h. Then, water (2 mL) and saturated Na2CO3 solution (1 mL) were added to quench the reaction at 0 °C. The aqueous layer was separated and extracted with CH2Cl2 (3 x 3 mL). The combined organic extracts were washed with brine, dried with MgSO4, filtered, and concentrated to give the crude residue, which was purified by flash chromatography on silica gel with EtOAc/n-hexane (1:19) to afford compound 2a (80 mg, 80% yield) as a yellow oil and compound 3a (5 mg, 4% yield) as colorless oil. (E)-4,4,4-Trifluoro-1-phenylbut-2-en-1-one (2a) The spectroscopic data were in good agreement with the literature data.12b Colorless oil; 1H NMR (CDCl3, 500 MHz): δ 8.00 (d, J = 8.5 Hz, 2 H), 7.69–7.65 (m, 1 H), 7.58–7.54 (m, 3 H), 6.85 (dq, J = 15.5, 6.5 Hz, 1 H); 13C NMR (CDCl3, 125 MHz): δ 188.0, 136.1, 134.1, 131.0, 130.3 (q, J = 35.0 Hz), 129.0, 128.3, 122.5 (q, J = 268.7 Hz); 19F NMR (CDCl3, 470 MHz): δ –65.1; HRMS (ESI): m/z [M + H]+ calcd for C10H8F3O: 201.0527; found: 201.0525. 4,4,4-Trifluoro-3-hydroxy-1-phenylbutan-1-one (3a) The spectroscopic data were in good agreement with the literature data.20 White solid; mp = 76.0–77.0 °C; 1H NMR (CDCl3, 500 MHz): δ 7.95–7.93 (m, 2 H), 7.62–7.58 (m, 1 H), 7.49–7.46 (m, 2 H), 4.69–4.65 (m, 1 H), 3.56–3.55 (m, 1 H), 3.39–3.26 (m, 2 H); 13C NMR (CDCl3, 125 MHz): δ 197.5, 136.0, 134.1, 128.8, 128.4, 124.7 (q, J = 277.0 Hz), 67.0 (q, J = 32.5 Hz), 38.2; 19F NMR (CDCl3, 470 MHz): δ –79.2.
  • 20 Xiong HY, Yang ZY, Chen Z, Zeng JL, Nie J, Ma JA. Chem. Eur. J. 2014; 20: 8325
  • 21 A similar mechanism in syn-selective Meyer–Schuster rearrangement, mediated by BF3·OEt2, was reported. See reference 18.
  • 22 As shown below, the BF3·OEt2-catalyzed reaction of 1s did not proceed and only the starting substrate was recovered.
  • 24 All of the synthetic β-fluoroalkyl-α,β-enones were characterized according to their 1H NMR, 13C NMR, 19F NMR, and mass spectra. The stereochemistry of (E)-β-alkyl-β-fluoroalkyl-α,β-enones was unequivocally determined by comparing their NMR spectra to those of structurally identical or similar compounds.