Synlett 2017; 28(17): 2320-2324
DOI: 10.1055/s-0036-1588485
letter
© Georg Thieme Verlag Stuttgart · New York

Ferrier Rearrangement of 1,2-Dihydropyrans with Organozinc Species in Toluene/n-Dibutyl Ether

Pauline Rabet, Simon Wagschal*, Sébastien Lemaire*
This work has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution for the Innovative Medicine Initiative under Grant Agreement No. 115360 (Chemical manufacturing methods for the 21st century pharmaceutical industries, CHEM21).
Further Information

Publication History

Received: 27 May 2017

Accepted: 05 June 2017

Publication Date:
18 July 2017 (eFirst)

Abstract

Herein, we report the catalyst-free addition of organozinc species to glycal derivatives and dihydropyrans in a toluene/n-dibutyl ether solvent mixture via a Ferrier rearrangement at room temperature. This methodology requires only a slight excess of the nucleophile and leads preferentially to the C-glycoside α-anomer. Various 1,2-dihydropyrans were assessed with a range of nucleophiles (aryl, alkynyl, alkyl) yielding the desired C-glycosides in good yield and diastereoselectivity up to 20:1.

 
  • References and Notes

  • 1 New address: School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK.
    • 2a Faul MM. Huff BE. Chem. Rev. 2000; 100: 2407
    • 2b Faulkner DJ. Nat. Prod. Rep. 2000; 17: 7
    • 2c Postema MH. D. Tetrahedron 1992; 48: 8545
    • 3a Ferrier RJ. Overend WG. Ryan AE. J. Chem. Soc. 1962; 3667

    • For recent reviews on the Ferrier type I rearrangement, see:
    • 3b Gómez AM. Lobo F. Uriel C. López JC. Eur. J. Org. Chem. 2013; 7221
    • 3c Ansari AA. Lahiri R. Vankar YD. Arkivoc 2013; (ii): 316

      For selected examples, see:
    • 4a Panarese JD. Waters SP. Org. Lett. 2009; 11: 5086
    • 4b Zeng J. Ma J. Xiang S. Cai S. Liu X.-W. Angew. Chem. Int. Ed. 2013; 125: 5238
    • 5a Bililign T. Griffith BR. Thorson JS. Nat. Prod. Rev. 2005; 22: 742
    • 5b Simons WC. Synthesis 2004; 1533
    • 5c Stanbasky J. Hocek M. Kosovsky P. Chem. Rev. 2009; 109: 6729
  • 6 Steinhuebel D. Fleming JJ. DuBois J. Org. Lett. 2002; 4: 293
  • 7 Xue S. He L. Han KZ. Zheng XQ. Guo Q.-X. Carbohydr. Res. 2005; 340: 303
  • 8 Cook MJ. Fletcher MJ. E. Gray D. Lovell PJ. Ghallager T. Tetrahedron 2004; 60: 5085
  • 9 Lemaire S. Houpis IN. Xiao T. Li J. Digard E. Gozlan C. Liu R. Gavryushin A. Diene C. Wang Y. Farina V. Knochel P. Org. Lett. 2012; 14: 1480
  • 10 Wagschal S. Guilbaud J. Rabet P. Farina V. Lemaire S. J. Org. Chem. 2015; 80: 9328
  • 11 General Procedure for the Synthesis of Dihydropyrans 6a–c, 7a–g, and 8a,b A 25 mL Schlenk tube was equipped with magnetic agitation under inert atmosphere (N2). The corresponding iodo compound (1.1 equiv) was dissolved in toluene (4 L/mol). After cooling the mixture to 0 °C with an ice-bath, n-BuLi (1.15 equiv, 25% w/w in heptane) was added over 5 min. After 20 min, ZnBr2·LiBr (1.15 equiv, 32% w/w in DBE) was added over 5 min at 0 °C. After 20 min, a toluene solution of glycal substrate (1.0 equiv, 1 L/mol) was added at 0 °C. The reaction was stirred at r.t. and followed by TLC until starting material was completely consumed (1–5 h). After completion, the reaction medium was quenched with saturated NH4Cl (aq) (4 L/mol) for 30 min, and phases were separated. The aqueous phase was extracted three times with EtOAc. All organic layers were combined and dried over Na2SO4, filtered, and finally put under reduced pressure to remove volatile materials. The diastereomeric ratio was determined from the crude mixture based on the 1H NMR spectrum analysis. After evaporation, purification on silica gel by flash column chromatography afforded the desired product. (2S,6S)-2-[(Benzyloxy)methyl]-6-[4-(benzyloxy)phenyl]-3,6-dihydro-2H-pyran (6a) 248 mg isolated (69% yield – 0.93 mmol scale); colorless oil. Major Diastereomer Rf = 0.12 (60:40 CH2Cl2/heptane). 1H NMR (360 MHz, CDCl3): δ = 7.48–7.28 (m, 12 H), 7.01–6.94 (m, 2 H), 6.09–6.03 (m, 1 H), 6.03–5.97 (m, 1 H), 5.31–5.26 (m, 1 H), 5.08 (s, 2 H), 4.53 (s, 2 H), 3.87–3.79 (m, 1 H), 3.59–3.45 (m, 2 H), 2.30–3.18 (m, 1 H), 2.08–1.99 (m, 1 H). 13C NMR (90 MHz, CDCl3): δ = 158.4, 138.4, 137.0, 133.4, 129.4, 128.6, 128.3, 127.9, 127.7, 127.6, 127.5, 127.4, 125.3, 114.5, 73.7, 73.2, 72.8, 70.0, 67.6, 27.4. Minor Diastereomer Rf = 0.15 (60:40 CH2Cl2/heptane). 1H NMR (360 MHz, CDCl3): δ = 7.47–7.26 (m, 12 H), 7.00–6.91 (m, 2 H), 5.97–5.90 (m, 1 H), 5.77–5.72 (m, 1 H), 5.21–5.16 (m, 1 H), 5.07 (s, 2 H), 4.67–4.53 (m, 2 H), 4.08–3.49 (m, 1 H), 3.68–3.49 (m, 2 H), 2.25–2.12 (m, 1 H), 2.12–2.00 (m, 1 H). 13C NMR (90 MHz, CDCl3): δ = 158.4, 138.4, 137.1, 133.9, 130.3, 128.6, 128.5, 128.3, 127.9, 127.7, 127.5, 127.4, 124.1, 114.8, 77.1, 73.7, 73.4, 73.3, 70.0, 27.7. HRMS: m/z calcd for C26H27O3 [M + H]+: 387.1954; found: 387.1956.