Synlett 2015; 26(07): 927-930
DOI: 10.1055/s-0034-1380122
letter
© Georg Thieme Verlag Stuttgart · New York

Biomimetic Total Synthesis of 6a,7,8,9,10,10a-Hexahydro-3,6,9-trimethyl-6-(4-methylpent-3-en-1-yl)-1,9-epoxy-6H-dibenzo-[b,d]pyran and Its Diastereoisomer

Huiying Zeng*
The Key Laboratory of Coordination Chemistry of Jiangxi, Province and College of Chemistry and Chemical Engineering, Jinggangshan University, Ji’an, Jiangxi 343009, P. R. of China   Email: zenghuiying2005@163.com
,
Daiping Duan
The Key Laboratory of Coordination Chemistry of Jiangxi, Province and College of Chemistry and Chemical Engineering, Jinggangshan University, Ji’an, Jiangxi 343009, P. R. of China   Email: zenghuiying2005@163.com
,
Boxiao Tang
The Key Laboratory of Coordination Chemistry of Jiangxi, Province and College of Chemistry and Chemical Engineering, Jinggangshan University, Ji’an, Jiangxi 343009, P. R. of China   Email: zenghuiying2005@163.com
› Author Affiliations
Further Information

Publication History

Received: 30 November 2014

Accepted after revision: 27 December 2014

Publication Date:
10 February 2015 (online)


Abstract

The first total synthesis of 6a,7,8,9,10,10a-hexahydro-3,6,9-trimethyl-6-(4-methylpent-3-en-1-yl)-1,9-epoxy-6H-dibenzo[b,d]pyran and its diastereoisomer via tandem pericyclic reactions were achieved in one step. Our biomimetic strategy features a sequential Aldol-type addition, 6π electrocyclization, and hetero-Diels–Alder cycloaddition, where three rings, two C–C bonds, and two C–O bonds were spontaneously constructed in a highly efficient way.

Supporting Information

 
  • References and Notes


    • Selective representive examples, see:
    • 1a Classics in Total Synthesis . Nicolaou KC, Sorensen EJ. VCH; Weinheim: 1996
    • 1b Beaudry CM, Trauner D. Org. Lett. 2002; 4: 2221
    • 1c Moses JE, Baldwin JE, Bruckner S, Eade SJ, Adlington RM. Org. Biomol. Chem. 2003; 1: 3670
    • 1d Parker KA, Lim Y.-H. J. Am. Chem. Soc. 2004; 126: 15968

      Selective representative examples, see:
    • 2a Kurdyumov AV, Hsung RP, Ihlen K, Wang J. Org. Lett. 2003; 5: 3935
    • 2b Paduraru MP, Wilson PD. Org. Lett. 2003; 5: 4911

      Selective representative examples, see:
    • 3a Lee JC, Strobel GA, Lobkovsky E, Clardy J. J. Org. Chem. 1996; 61: 3232
    • 3b Li CM, Johnson RP, Porco JA. Jr. J. Am. Chem. Soc. 2003; 125: 5095
    • 4a Breslow R. Chem. Soc. Rev. 1972; 1: 553
    • 4b Breslow R. Acc. Chem. Res. 1980; 13: 170
    • 5a Snider BB, Lobera M. Tetrahedron Lett. 2004; 45: 5015
    • 5b Zhou J, Lobera M, Neubert-Langille BJ, Snider BB. Tetrahedron 2007; 63: 10018
    • 6a Lee YR, Choi JH, Yoon SH. Tetrahedron Lett. 2005; 46: 7539
    • 6b Lee YR, Wang X, Noh SK, Lyoo WS. Synth. Commun. 2006; 36: 3329
  • 7 Kitanaka S, Iwata N. JP 2002265463 A, 2002
  • 8 Liu L.-Y, Li Z.-H, Ding Z.-H, Dong Z.-J, Li G.-T, Li Y, Liu J.-K. J. Nat. Prod. 2013; 76: 79
  • 9 See ref. 7 and the Supporting Information for the comparison of the natural products and our synthesized compounds.

    • (2E,6E)-Farnesal was oxidized from (2E,6E)-farnesol, see:
    • 10a Corey EJ, Gilman NW, Ganem BE. J. Am. Chem. Soc. 1968; 90: 5616
    • 10b Ishihara K, Ishibashi H, Yamamoto H. J. Am. Chem. Soc. 2002; 124: 3647
  • 11 Diastereoselective Total Synthesis of 3,6,9-Trimethyl-6-(4-methylpent-3-en-1-yl)-1,9-epoxy-6H-dibenzo[b,d]pyran (1) (2E,6E)-Farnesal (440 mg, 2 mmol) and 5-methylbenzene-1,3-diol (372 mg, 3 mmol) were added to pyridine (15 mL) and the mixture was refluxed rigorously at 160 °C for 16 h under argon. The reaction mixture was cooled to r.t., and the solvent was evaporated in vacuo. The residue was purified by column chromatography on silica gel with the appropriate mixture of hexane and EtOAc to give 6a,7,8,9,10,10a-hexahydro-3,6,9-trimethyl-6-(4-methylpent-3-en-1-yl)-1,9-epoxy-6H-dibenzo[b,d]pyran (1, 476 mg, 73%) as pale yellow liquid. IR (film): νmax = 1621, 1067 cm–1. 1H NMR (400 MHz, CDCl3): δ = 6.31 (s, 1 H), 6.27 (s, 1 H), 5.17 (t, J = 7.0 Hz, 1 H), 2.85 (s, 1 H), 2.25 (s, 3 H), 2.21–2.19 (m, 1 H), 2.17 (dd, J = 4.5, 3.3 Hz, 1 H), 2.08 (ddd, J = 11.6, 5.3, 2.9 Hz, 2 H), 1.95–1.85 (m, 1 H), 1.82–1.73 (m, 3 H), 1.71 (s, 3 H), 1.65 (s, 3 H), 1.46–1.38 (m, 1 H), 1.37 (s, 3 H), 0.96 (s, 3 H), 0.87 (dt, J = 6.6, 5.1 Hz, 1 H), 0.63 (ddd, J = 25.0, 13.3, 6.1 Hz, 1 H). 13C NMR (101 MHz, CDCl3): δ = 156.7, 156.5, 137.2, 131.8, 124.3, 114.3, 110.7, 109.6, 85.8, 74.5, 45.3, 42.1, 37.5, 35.3, 29.1, 27.9, 25.7, 22.9, 22.2, 21.7, 20.9, 17.7. HRMS (APCI): m/z calcd for C22H31O2: 327.2319; found: 327.2305 [M + H].