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

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

Department of Chemistry, Saldiha College, Saldiha-722173, India   Email: samirmandal2004@gmail.com
,
Apurba Sarkar
Department of Chemistry, Saldiha College, Saldiha-722173, India   Email: samirmandal2004@gmail.com
,
Puskin Chakraborty
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur-700032, India
,
Ashoke P. Chattopadhyay
Department of Chemistry, University of Kalyani, Kalyani-741235, India
› Author Affiliations
This 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 (eFirst)

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.

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.
    • 2a Cardona W. Quiñones W. Robledo S. Vélez I. Murga J. García-Fortanet J. Carda M. Cardona D. Echeverri F. Tetrahedron 2006; 62: 4086
    • 2b Saeed M. Ilg T. Schick M. Abbas M. Voelter W. Tetrahedron Lett. 2001; 42: 7401
    • 2c Davies-Coleman M. Rivett D. Phytochemistry 1987; 26: 3047
  • 3 Newlands ES. Rustin GJ. S. Brampton MH. Br. J. Cancer 1996; 74: 648
  • 4 Ohkuma H. Naruse N. Nishiyama Y. Tsuno T. Hoshino Y. Sawada Y. Konishi M. Oki T. J. Antibiot. (Tokyo) 1992; 45: 1239
  • 5 Teruya T. Simizu S. Kanoh N. Osada H. FEBS Lett. 2005; 579: 2463
    • 6a Kumar P. Naidu SV. J. Org. Chem. 2006; 71: 3935
    • 6b de Fátima A. Kohn LK. Antonio MA. de Carvalho JE. Pilli RA. Bioorg. Med. Chem. 2006; 14: 622
  • 7 Newman DJ. Cragg GM. J. Nat. Prod. 2004; 67: 1216
  • 8 Kudo N. Wolff B. Sekimoto T. Schreiner EP. Yoneda Y. Yanagida M. Horinouchi S. Yoshida M. Exp. Cell Res. 1998; 242: 540
  • 9 Lin J. Qiu X.-L. Qing F.-L. Beilstein J. Org. Chem. 2010; 6: 37
  • 10 Bonazzi S. Eidam O. Güttinger S. Wach J.-Y. Zemp I. Kutay U. Gademann K. J. Am. Chem. Soc. 2010; 132: 1432
    • 11a Sham HL. Wideburg NE. Spanton SG. Kohlbrenner WE. Betebenner DA. Kempf DJ. Norbeck DW. Plattner JJ. Erickson JW. J. Chem. Soc., Chem. Commun. 1991; 110
    • 11b Thaisrivongs S. Schostarez H. Pals DT. Turner SR. J. Med. Chem. 1987; 30: 1837
    • 13a Smart BE. J. Fluorine Chem. 2001; 109: 3
    • 13b Lemal DM. J. Org. Chem. 2004; 69: 1
    • 13c O’Hagan D. Chem. Soc. Rev. 2008; 37: 308
    • 14a Ono T. Hayakawa H. Yasuda N. Uekusa H. Ohashi Y. In Current Fluoroorganic Chemistry: New Synthetic Directions, Technologies, Materials, and Biological Applications . Soloshonok VA. Mikami K. Yamazaki T. Welch JT. Honek JF. ACS Symposium Series 949; Washington: 2007. Chap. 10 170
    • 14b Bégué J.-P. Bonnet-Delpon D. J. Fluorine Chem. 2006; 127: 992
    • 14c Alonso DA. Fuensanta M. Gómez-Bengoa E. Nájera C. Adv. Synth. Catal. 2008; 350: 1823
    • 14d Chevrie D. Lequeux T. Pommelet J.-C. Tetrahedron 2002; 58: 4759
    • 14e Hara S. Yamamoto K. Yoshida M. Fukuhara T. Yoneda N. Tetrahedron Lett. 1999; 40: 7815
    • 14f Chevrie D. Lequeux T. Demoute JP. Pazenok S. Tetrahedron Lett. 2003; 44: 8127
    • 14g Champagne PA. Desroches J. Hamel J.-D. Vandamme M. Paquin J.-F. Chem. Rev. 2015; 115: 9073
    • 14h Yanai H. Taguchi T. Eur. J. Org. Chem. 2011; 5939
  • 15 Jeschke P. ChemBioChem 2004; 5: 570
  • 16 Bégué J.-P. Bonnet-Delpon D. Bioorganic and Medicinal Chemistry of Fluorine . Wiley; Hoboken: 2008
    • 17a Burton DJ. Yang Z.-Y. Qiu W. Chem. Rev. 1996; 96: 1641
    • 17b Barros ME. S. B. Freitas JC. R. Oliveira JM. da Cruz CH. B. da Silva PB. N. de Araújo LC. C. Militão GC. G. da Silva TG. Oliveira RA. Menezes PH. Eur. J. Med. Chem. 2014; 76: 291
    • 17c Oliveira JM. Freitas JC. R. Comasseto JV. Menezes PH. Tetrahedron 2011; 67: 3003
    • 17d Nokami J. Anthony L. Sumida S.-I. Chem. Eur. J. 2000; 6: 2909
    • 18a Kocienski PJ. Bell A. Blakemore PR. Synlett 2000; 365
    • 18b Zajc B. Kumar R. Synthesis 2010; 1822
    • 18c Baudin JB. Hareau G. Julia SA. Ruel O. Tetrahedron Lett. 1991; 32: 1175
    • 19a Paira M. Banerjee B. Jana S. Mandal SK. Roy SC. Tetrahedron Lett. 2007; 48: 3205
    • 19b Mandal SK. Roy SC. Tetrahedron Lett. 2007; 48: 4131
    • 19c Mandal SK. Roy SC. Tetrahedron 2008; 64: 11050
    • 19d Mandal SK. Paira M. Roy SC. J. Org. Chem. 2008; 73: 3823
    • 19e Saha S. Mandal SK. Roy SC. Tetrahedron Lett. 2011; 52: 3128
    • 20a Li B. Masuda S. Minato D. Zhou D. Sugimoto K. Nemoto H. Matsuya Y. Tetrahedron 2014; 70: 3981
    • 20b Calata C. Pfund E. Lequeux T. Tetrahedron 2011; 67: 1398
    • 20c Ghosh AK. Banerjee S. Sinha S. Kang SB. Zajc B. J. Org. Chem. 2009; 74: 3689
    • 20d Zajc B. Kake S. Org. Lett. 2006; 8: 4457
    • 21a Mandal SK. Ghosh AK. Kumar R. Zajc B. Org. Biomol. Chem. 2012; 10: 3164
    • 21b Chowdhury M. Mandal SK. Banerjee S. Zajc B. Molecules 2014; 19: 4418
    • 21c Ayeni DO. Mandal SK. Zajc B. Tetrahedron Lett. 2013; 54: 6008
  • 22 Yuasa Y. Shibuya S. Yuasa Y. Synth. Commun. 2003; 33: 3947
  • 23 Lee K. Kim H. Hong J. Org. Lett. 2009; 11: 5202
  • 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.