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Synlett 2018; 29(01): 75-78
DOI: 10.1055/s-0036-1588534
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© Georg Thieme Verlag Stuttgart · New York

Synthetic Studies Towards the Synthesis of 6-Substituted 3-Fluoro-5,6-dihydropyran-2-ones[1]

Samir K. Mandal  *
a   Department of Chemistry, Saldiha College, Saldiha-722173, India   Email: samirmandal2004@gmail.com
,
Apurba Sarkar
a   Department of Chemistry, Saldiha College, Saldiha-722173, India   Email: samirmandal2004@gmail.com
,
Puskin Chakraborty
b   Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur-700032, India
,
Ashoke P. Chattopadhyay
c   Department of Chemistry, University of Kalyani, Kalyani-741235, India
› Author AffiliationsThis research project was funded by DST-SERB, India under the Start-Up Research Grant (Young Scientists)-CHEMICALSCIENCES [S.O #SB/FT/CS-192/2013].
Further Information

Publication History

Received: 26 June 2017

Accepted after revision: 11 July 2017

Publication Date:
17 August 2017 (online)

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Abstract

The synthesis of 6-substituted 3-fluoro-5,6-dihydropyran-2-ones under mild conditions is described. The key step of the synthesis involves a Julia–Kocienski olefination.

Key words

fluorosulfones - lactones - dihydropyranones - Julia–Kocienski olefination

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1588534.
  • Supporting Information
 

  • References and Notes

  • 1 Presented at the NEHU (ETC-2016) and KU (NSCTC-VII-2016) conference: S. K. Mandal and A. P. Chattopadhyay, An Approach for the Synthesis of Fluorinated 6-Substituted 5,6-Dihydropyran-2-one Analogues. Also presented at the VB (RTCR-2017) conference: S. K. Mandal and A. Sarkar, Synthesis of Fluorinated 6-Substituted 5,6-Dihydropyran-2-one Analogues.
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  • 24 3-Hydroxy-3-phenylpropanal (4a); Typical Oxidation Procedure To a solution of 1-phenylbut-3-en-1-ol (5a; 150 mg, 1.01 mmol) in 3:1 1,4-dioxane/H2O (10 mL) at r.t. were successively added 2.5% OsO4 in t-BuOH (0.18 mL; 0.022 mmol) and 2,6-lutidine (0.24 mL, 2.02 mmol). NaIO4 (864 mg, 4.04 mmol) was then added in portions over 30 min, and the mixture was stirred at r.t. for 2 h. The reaction was quenched by addition of H2O (10 mL), and the mixture was diluted with Et2O (20 mL). The layers were separated, and the aqueous layer was extracted with Et2O (2 × 50 mL). The organic layers were combined, washed with H2O (2 × 25 mL) and brine (25 mL), then dried (Na2SO4), filtered, and concentrated in vacuo to give the crude product, which was used directly in the condensation reaction.
  • 25 Ethyl (2E)-2-Fluoro-5-hydroxy-5-phenylpent-2-enoate (2a) and Ethyl (2Z)-2-Fluoro-5-hydroxy-5-phenylpent-2-enoate (IIa); Typical Condensation Procedure Cs2CO3 (780 mg, 2.4 mmol) was added to a stirred solution of the crude 4a and sulfone 3 (366 mg, 1.2 mmol) in CH2Cl2 (10 mL) at r.t., and the mixture was stirred overnight. The solids were removed by filtration, and the solvent was removed in vacuo. The crude product was purified by column chromatography [silica gel (100–200 mesh) EtOAc/PE (4:1)] to give a mixture of 2a and IIa; yield: 147 mg (62%)
  • 26 3-Fluoro-6-phenyl-5,6-dihydro-2H-pyran-2-one (1a): Typical Lactonization Procedure The mixture of 2a and IIa obtained from the condensation reaction was treated with CSA (5 mg, 2 mol%) in CH2Cl2 (10 mL) at r.t. overnight. The resulting mixture was concentrated and purified by column chromatography [silica gel (100–200 mesh), CH2Cl2] to give a white solid; yield: 63 mg (33% overall); mp 82 °C. IR (KBr) 1743, 1674, 1164, 769 cm–1. 1H NMR (400 MHz, CDCl3): δ = 2.66–2.74 (m, 1 H), 2.83–2.93 (m, 1 H), 5.54 (dd, J = 4.0, 12.0 Hz, 1 H), 6.36–6.40 (m, 1 H), 7.36–7.48 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 30.6 (d, 3 J CF = 4.0 Hz), 80.0, 118.0 (d, 2 J CF = 13.0 Hz), 126.1 (2 C), 128.9 (2 C), 129.1, 137.4, 147.6 (d, 1 J CF = 258.0 Hz), 158.9 (d, 2 J CF = 31.0 Hz). HRMS: m/z [M + H] calcd for C11H10FO2: 193.0665; found: 193.0668.