Synlett 2012; 23(19): 2845-2849
DOI: 10.1055/s-0032-1317491
letter
© Georg Thieme Verlag Stuttgart · New York

Toward a Total Synthesis of Divergolide A; Synthesis of the Amido Hydro- quinone Core and the C10–C15 Fragment

Guanglian Zhao
a  Laboratory of Asymmetric Catalysis and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. of China   Fax: +86(571)87953128   Email: [email protected]
,
Jinlong Wu
a  Laboratory of Asymmetric Catalysis and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. of China   Fax: +86(571)87953128   Email: [email protected]
,
Wei-Min Dai*
a  Laboratory of Asymmetric Catalysis and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. of China   Fax: +86(571)87953128   Email: [email protected]
b  Laboratory of Advanced Catalysis and Synthesis, Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, P. R. of China   Fax: +852(2)3581594   Email: [email protected]
› Author Affiliations
Further Information

Publication History

Received: 20 August 2012

Accepted after revision: 26 September 2012

Publication Date:
09 November 2012 (online)


Abstract

A ring-closing metathesis (RCM) approach was envisioned for installing the E double bond at the C9 and C10 positions of divergolide A, isolated from a mangrove endophyte. Accordingly, the C10–C15 diene diol fragment and the amido hydroquinone core with the requisite functionalities and stereochemistry have been synthesized by using the norephedrine-based syn-selective glycolate aldol and the anti-selective aldol reactions, respectively. CuI-catalyzed amidation was employed to access the anilide intermediate, which was further transformed into the amido hydroquinone core.

Supporting Information

 
  • References and Notes

  • 1 For isolation and structures of divergolide A–D, see: Ding L, Maier A, Fiebig H.-H, Görls H, Lin W.-H, Peschel G, Hertweck C. Angew. Chem. Int. Ed. 2011; 50: 1630
  • 2 Xu Z, Ding L, Hertweck C. Angew. Chem. Int. Ed. 2011; 50: 4667
    • 3a Wilson RM, Danishefsky SJ. J. Org. Chem. 2006; 71: 8329
    • 3b Cragg GM, Grothaus PG, Newman DJ. Chem. Rev. 2009; 109: 3012
    • 3c Szpilman AM, Carreira EM. Angew. Chem. Int. Ed. 2010; 49: 9592
    • 3d Fürstner A. Isr. J. Chem. 2011; 51: 329
    • 3e Nicolaou KC, Hale CR. H, Nilewski C, Ioannidou HA. Chem. Soc. Rev. 2012; 41: 5185
    • 3f See also: Wender PA, Miller BL. Nature 2009; 460: 197
    • 3g Ghosh AK. J. Org. Chem. 2010; 75: 7967
    • 4a Li H, Wu J, Luo J, Dai W.-M. Chem.–Eur. J. 2010; 16: 11530
    • 4b Wu D, Li H, Jin J, Wu J, Dai W.-M. Synlett 2011; 895
    • 4c Sun L, Wu D, Wu J, Dai W.-M. Synlett 2011; 3036
    • 5a Dai W.-M, Chen Y, Jin J, Wu J, Lou J, He Q. Synlett 2008; 1737
    • 5b Jin J, Chen Y, Wu J, Dai W.-M. Org. Lett. 2007; 9: 2585
    • 6a Liu Y, Wang J, Li H, Wu J, Feng G, Dai W.-M. Synlett 2010; 2184
    • 6b Liu Y, Feng G, Wang J, Wu J, Dai W.-M. Synlett 2011; 1774

      For selected reviews on RCM, see:
    • 7a Grubbs RH, Chang S. Tetrahedron 1998; 54: 4413
    • 7b Fürstner A. Angew. Chem. Int. Ed. 2000; 39: 3012
    • 7c Trnka TM, Grubbs RH. Acc. Chem. Res. 2001; 34: 18
    • 7d Schrock RR, Hoveyda AH. Angew. Chem. Int. Ed. 2003; 42: 4592
    • 7e Deiters A, Martin SF. Chem. Rev. 2004; 104: 2199
    • 7f Grubbs RH. Tetrahedron 2004; 60: 7117
    • 7g Nicolaou KC, Bulger PG, Sarlah D. Angew. Chem. Int. Ed. 2005; 44: 4490
    • 7h Gradillas A, Pérez-Castells J. Angew. Chem. Int. Ed. 2006; 45: 6086
    • 7i Schrodi Y, Pederson RL. Aldrichimica Acta 2007; 40: 45
    • 7j Hoveyda AH, Zhugralin AR. Nature 2007; 450: 243
    • 7k Handbook of Metathesis . Vol. 1–3. Grubbs RH. Wiley-VCH; Weinheim: 2003
    • 7l Kotha S, Dipak MK. Tetrahedron 2012; 68: 397
    • 8a Abiko A, Liu J.-F, Masamune S. J. Am. Chem. Soc. 1997; 119: 2586
    • 8b Inoue T, Liu J.-F, Buske D, Abiko A. J. Org. Chem. 2002; 67: 5250
    • 8c Abiko A. Acc. Chem. Res. 2004; 37: 387

      For a review, see:
    • 9a Ley SV, Thomas AW. Angew. Chem. Int. Ed. 2003; 42: 5400
    • 9b See also: Klapars A, Huang X, Buchwald SL. J. Am. Chem. Soc. 2002; 124: 7421
    • 10a Andrus MB, Soma Sekhar BB. V, Turner TM, Meredith EL. Tetrahedron Lett. 2001; 42: 7197
    • 10b Andrus MB, Meredith EL, Simmons BL, Soma Sekhar BB. V, Hicken EJ. Org. Lett. 2002; 4: 3549
  • 11 Corey EJ, Fuchs PL. Tetrahedron Lett. 1972; 13: 3769
    • 12a Dai W.-M, Li Y, Zhang Y, Lai KW, Wu J. Tetrahedron Lett. 2004; 45: 1999
    • 12b Dai W.-M, Zhang Y. Tetrahedron Lett. 2005; 46: 1377
    • 12c Dai W.-M, Li Y, Zhang Y, Yue C, Wu J. Chem.–Eur. J. 2008; 14: 5538
    • 12d Sun L, Dai W.-M. Tetrahedron 2011; 67: 9072
    • 12e See also ref. 5b.
  • 13 For asymmetric Heck reaction using atropisomeric Aphos, see: Dai W.-M, Yeung KK. Y, Wang Y. Tetrahedron 2004; 60: 4425
  • 14 Synthesis of Diene 13 from Ester 12: To a solution of 12 (285.4 mg, 0.75 mmol) in anhydrous CH2Cl2 (8 mL) cooled in a dry ice–acetone bath (–78 °C) under an N2 atmosphere was added slowly a solution of DIBAL-H (1 M in toluene, 1.1 mL, 1.1 mmol). The resultant mixture was stirred for 1.5 h at the same temperature, then MeOH (2 mL) was added to quench the reaction. The reaction mixture was allowed to warm to –40 °C, then a saturated aqueous solution of potassium sodium tartrate was added followed by stirring at r.t. until the mixture became clear. The mixture was extracted with CH2Cl2 (5 × 3 mL) and the combined organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give the crude aldehyde. The latter was dissolved in anhydrous THF (2 mL) for use in the next step without further purification. To a solution of Ph3P+CH(Me)2I (486.3 mg, 1.13 mmol) in anhydrous THF (10 mL) cooled in an ice–water bath (0 °C) under an N2 atmosphere was added n-BuLi (1.5 M in hexane, 0.74 mL, 1.1 mmol) followed by stirring at the same temperature for 30 min. After cooling the resultant solution of the ylide to –78 °C, the above THF solution of the aldehyde was added and the resultant mixture was stirred for 2 h at –78 °C. The reaction was quenched by the addition of saturated aqueous NH4Cl at –78 °C and the reaction mixture was allowed to warm to r.t. and extracted with EtOAc (8 × 3 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (SiO2; EtOAc–petroleum ether, 1:120) to give diene 13 (248.6 mg, 88% yield for 2 steps from 12). Compound 13: Colorless oil; [α]D 20 +3.78 (c 1.20, CHCl3); Rf = 0.40 (EtOAc–petroleum ether, 1%); IR (film): 2954, 2925, 2854, 1614, 1514, 1249, 1064, 1039 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.25 (d, J = 8.8 Hz, 2 H), 6.85 (d, J = 8.8 Hz, 2 H), 5.87 (ddd, J = 16.8, 10.4, 5.2 Hz, 1 H), 5.24 (d, J = 17.2 Hz, 1 H), 5.09 (d, J = 10.0 Hz, 1 H), 5.07 (d, J = 7.6 Hz, 1 H), 4.52 and 4.31 (ABq, J = 11.6 Hz, 2 H), 4.17 (dd, J = 5.6, 5.2 Hz, 1 H), 3.95 (dd, J = 9.6, 6.4 Hz, 1 H), 3.80 (s, 3 H), 1.76 (s, 3 H), 1.59 (s, 3 H), 0.88 (s, 9 H), 0.03 (s, 3 H), 0.02 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 158.8, 137.9, 137.4, 131.2, 129.2 (2×), 122.5, 114.9, 113.5 (2×), 78.4, 75.8, 69.4, 55.2, 26.0, 25.9 (3×), 18.7, 18.3, –4.7, –4.8. HRMS (EI+): m/z [M+] calcd for C22H36O3Si: 376.2434; found: 376.2433.
  • 15 Jeges G, Nagy T, Meszaros T, Kovacs J, Dorman G, Kowalczyk A, Goodnow RA. J. Comb. Chem. 2009; 11: 327

    • Fremy’s salt (potassium nitrosodisulfonate) was not available to us and it was not tested in the oxidation of 23. For recent examples, see:
    • 16a Bouaziz Z, Ghérardi A, Régnier F, Sarciron M.-E, Bertheau X, Fenet B, Walchshofer N, Fillion H. Eur. J. Org. Chem. 2002; 1834
    • 16b Jana CK, Scopelliti R, Gademann K. Chem.–Eur. J. 2010; 16: 7692
    • 16c Jadhav VD, Duerfeldt AS, Blagg BS. J. Bioorg. Med. Chem. Lett. 2009; 19: 6845
    • 17a Tajbakhsh M, Hosseinzadeh R, Sadatshahabi M. Synth. Commun. 2005; 35: 1547
    • 17b Urimi AG, Alinezhad H, Tajbakhsh M. Acta Chim. Slov. 2008; 55: 481
  • 18 Synthesis of Quinone 24 via Oxidation of Phenol 23: To a solution of phenol 23 (257.0 mg, 0.55 mmol) in MeCN (4 mL) at r.t. was quickly added an aqueous solution of 2,6-DCPFC (334 mg in 1.1 mL H2O, 1.1 mmol), prepared according to the literature procedure.17a After stirring for 1 min, the reaction was quenched by addition of saturated aqueous NaHCO3. The reaction mixture was extracted with EtOAc (10 × 3 mL) and the combined organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (SiO2; EtOAc–petroleum ether, 1:40) to give quinone 24 (209.3 mg, 79% yield) as a yellow solid. Mp 80–81 °C (CH2Cl2–pentane); [α]D 20 +53.60 (c 1.10, CHCl3); Rf = 0.40 (EtOAc–petroleum ether, 2.4%). IR (film): 3380, 3296, 2957, 2925, 2854, 1714, 1650, 1606, 1502, 1255, 1099 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.06 (br s, 1 H, NH), 7.50 (d, J = 2.8 Hz, 1 H), 6.70 (dd, J = 2.0, 1.2 Hz, 1 H), 4.73 (d, J = 4.8 Hz, 1 H), 3.57 (dd, J = 10.0, 5.6 Hz, 1 H), 3.44 (dd, J = 10.0, 5.2 Hz, 1 H), 2.22 (s, 3 H), 1.94–1.91 (m, 1 H), 0.90 (s, 9 H), 0.89 (d, J = 6.0 Hz, 3 H), 0.81 (s, 9 H), 0.06 (s, 3 H), –0.05 (s, 3 H), –0.07 (s, 3 H), –0.09 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 188.2, 182.6, 169.1, 148.2, 138.1, 133.3, 114.5, 69.1, 63.5, 42.4, 25.8 (3×), 25.8 (3×), 24.8, 18.3, 18.0, 14.2, –4.6, –5.2, –5.5, –5.6. HRMS (EI+): m/z [M+] calcd for C24H43NO5Si2: 481.2680; found: 481.2682.
  • 19 Synthesis of Hydroquinone 25 via Reduction of 24: To a yellow solution of quinone 24 (144.5 mg, 0.30 mmol) in a mixed solvent of THF–Et2O–H2O (6 mL; v/v/v = 1:1:1) at r.t., was added Na2S2O4 (525 mg, 3 mmol) in portions with vigorous stirring until the yellow color of the mixture disappeared. The reaction mixture was diluted with H2O (5 mL) and extracted with EtOAc (5 × 3 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (SiO2; EtOAc–petroleum ether, 1:3) to give hydroquinone 25 (145.2 mg, 99% yield) as a colorless oil. Rf = 0.50 (EtOAc–PE, 33%). [Note: Hydroquinone 25 was oxidized to quinone in air during acquisition of 13C NMR data. No optical rotation data was taken for this sample]. 1H NMR (400 MHz, CDCl3): δ = 8.19 (s, 1 H, NH), 8.10 (s, 1 H, OH), 7.91 (s, 1 H, OH), 7.55 (s, 1 H), 6.32 (s, 1 H), 4.84 (d, J = 6.0 Hz, 1 H), 3.61 (dd, J = 9.6, 4.4 Hz, 1 H), 3.43 (dd, J = 9.2, 7.2 Hz), 2.34 (s, 3 H), 2.15–2.07 (m, 1 H), 0.94 (s, 9 H), 0.89 (s, 9 H), 0.74 (d, J = 6.8 Hz, 3 H), 0.11 (s, 3 H), 0.9 (s, 6 H), –0.05 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 169.3, 149.7, 137.0, 126.9, 126.0, 109.8, 106.2, 64.7, 60.4, 42.4, 25.9 (4×), 25.7 (3×), 24.8, 18.3, 18.1, –5.1, –5.3 (2×), –5.5. HRMS (EI+): m/z [M+] calcd for C24H45NO5Si2: 483.2836; found: 483.2834.