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Synlett 2021; 32(16): 1662-1664
DOI: 10.1055/s-0040-1707188
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Modern Nickel-Catalyzed Reactions

Ni-Catalyzed Intramolecular Reductive 1,2-Dicarbofunctionalization of Alkene: Facile Access to Podophyllum Lignans Core

Jian Xiao
a   School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P. R. of China
,
Ya-Wen Wang
a   School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P. R. of China
,
Zhong-Ping Qiu∗
a   School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P. R. of China
,
Yu Peng  ∗
a   School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P. R. of China
b   State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China
› Author AffiliationsThis work was supported by the National Natural Science Foundation of China (21772078 and 21472075) and the Fundamental Research Funds for the Central Universities (2682019CX70, 2682019CX71, and 2682020CX55). We also thank Science and Technology Department of Sichuan Province (2020JDRC0021).
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In memory of Prof. Xuan Tian

Abstract

The facile access to the tetracyclic skeleton of podophyllotoxin, a medicinally important lignan natural product, was efficiently achieved via a unique intramolecular alkylarylation of the tethered alkene in a dihalide under mild conditions using reductive nickel catalysis.

Key words

nickel - reductive coupling - intramolecular - cyclization - synthesis

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1707188.
  • Supporting Information


Publication History

Received: 17 May 2020

Accepted: 16 June 2020

Article published online:
17 July 2020

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  • References and Notes

  • 2 For a review, see: Ping Y, Kong W. Synthesis 2020; 52: 979
    CrossrefPubMed

      • For selected examples, see:
    • 3a Anthony D, Lin Q, Baudet J, Diao T. Angew. Chem. Int. Ed. 2019; 58: 3198
      CrossrefPubMed
    • 3b Kuang Y, Wang X, Anthony D, Diao T. Chem. Commun. 2018; 54: 2558
      CrossrefPubMed
    • 3c Wang K, Ding Z, Zhou Z, Kong W. J. Am. Chem. Soc. 2018; 140: 12364
      CrossrefPubMed
    • 3d Xu S, Wang K, Kong W. Org. Lett. 2019; 21: 7498
      CrossrefPubMed
    • 3e Jin Y, Wang C. Chem. Sci. 2019; 10: 1780
      CrossrefPubMed
    • 3f Jin Y, Wang C. Angew. Chem. Int. Ed. 2019; 58: 6722
      CrossrefPubMed
    • 3g Qin X, Lee MW. Y, Zhou JS. Angew. Chem. Int. Ed. 2017; 56: 12723
      CrossrefPubMed
  • 4 García-Domínguez A, Li Z, Nevado C. J. Am. Chem. Soc. 2017; 139: 6835
    CrossrefPubMed
    • 5a Yan C.-S, Peng Y, Xu X.-B, Wang Y.-W. Chem. Eur. J. 2012; 18: 6039 ; corrigendum: Chem. Eur. J. 2013, 19, 15438
      CrossrefPubMed
    • 5b Xu X.-B, Liu J, Zhang J.-J, Wang Y.-W, Peng Y. Org. Lett. 2013; 15: 550
      CrossrefPubMed
    • 5c Peng Y, Luo L, Yan C.-S, Zhang J.-J, Wang Y.-W. J. Org. Chem. 2013; 78: 10960
      CrossrefPubMed
    • 5d Peng Y, Xu X.-B, Xiao J, Wang Y.-W. Chem. Commun. 2014; 50: 472
      CrossrefPubMed
    • 5e Luo L, Zhang J.-J, Ling W.-J, Shao Y.-L, Wang Y.-W, Peng Y. Synthesis 2014; 46: 1908
      Article in Thieme Connect
    • 5f Peng Y, Xiao J, Xu X.-B, Duan S.-M, Ren L, Shao Y.-L, Wang Y.-W. Org. Lett. 2016; 18: 5170
      CrossrefPubMed
    • 5g Xiao J, Wang Y.-W, Peng Y. Synthesis 2017; 49: 3576
      Article in Thieme Connect
    • 5h Xiao J, Cong X.-W, Yang G.-Z, Wang Y.-W, Peng Y. Org. Lett. 2018; 20: 1651
      CrossrefPubMed
    • 5i Xiao J, Cong X.-W, Yang G.-Z, Wang Y.-W, Peng Y. Chem. Commun. 2018; 54: 2040
      CrossrefPubMed
    • 5j Luo L, Zhai X.-Y, Wang Y.-W, Peng Y, Gong H. Chem. Eur. J. 2019; 25: 989
      CrossrefPubMed
    • 5k Ouyang Y, Peng Y, Li W.-DZ. Tetrahedron 2019; 75: 4486
      Crossref

      For reviews, see:
    • 6a Peng Y. Lignans, Lignins, and Resveratrols. From Biosynthesis to Total Synthesis: Strategies and Tactics for Natural Products. Zografos AL. John Wiley & Sons; Hoboken: 2016. Chap. 10, 331-379
      CrossrefGoogle Scholar
    • 6b Liu Y.-Q, Yang L, Tian X. Curr. Bioact. Compd. 2007; 3: 37
      Crossref
    • 6c Sellars JD, Steel PG. Eur. J. Org. Chem. 2007; 3815

      • For past syntheses of podophyllotoxin (3), see:
    • 6d Ting CP, Tschanen E, Jang E, Maimone TJ. Tetrahedron 2019; 75: 3299
      Crossref
    • 6e Hajra S, Garai S, Hazra S. Org. Lett. 2017; 19: 6530
      CrossrefPubMed
    • 6f Ting CP, Maimone TJ. Angew. Chem. Int. Ed. 2014; 53: 3115
      CrossrefPubMed
    • 6g Wu Y, Zhao J, Chen J, Pan C, Li L, Zhang H. Org. Lett. 2009; 11: 597
      CrossrefPubMed
    • 6h Stadler D, Bach T. Angew. Chem. Int. Ed. 2008; 47: 7557
      CrossrefPubMed
    • 6i Wu Y, Zhang H, Zhao Y, Zhao J, Chen J, Li L. Org. Lett. 2007; 9: 1199
      CrossrefPubMed
    • 6j Reynolds AJ, Scott AJ, Turner CI, Sherburn MC. J. Am. Chem. Soc. 2003; 125: 12108
      CrossrefPubMed
    • 6k Berkowitz DB, Choi S, Maeng J.-H. J. Org. Chem. 2000; 65: 847
      CrossrefPubMed
    • 6l Hadimani SB, Tanpure RP, Bhat SV. Tetrahedron Lett. 1996; 37: 4791
      Crossref
    • 6m Bush EJ, Jones DW. J. Chem. Soc., Chem. Commun. 1993; 1200
    • 6n Van Speybroeck R, Guo H, Van der Eycken J, Vandewalle M. Tetrahedron 1991; 47: 4675
      Crossref
    • 6o Andrews RC, Teague SJ, Meyers AI. J. Am. Chem. Soc. 1988; 110: 7854
      Crossref
    • 6p Macdonald DI, Durst T. J. Org. Chem. 1986; 51: 4749
      Crossref
    • 6q Gensler WJ, Gatsonis CD. J. Am. Chem. Soc. 1962; 84: 1748 ; see also ref. 5h in this article
      Crossref

      • For chemoenzymatic syntheses of podophyllotoxin (3), see:
    • 6r Li J, Zhang X, Renata H. Angew. Chem. Int. Ed. 2019; 58: 11657
      CrossrefPubMed
    • 6s Lazzarotto M, Hammerer L, Hetmann M, Borg A, Schmermund L, Steiner L, Hartmann P, Belaj F, Kroutil W, Gruber K, Fuchs M. Angew. Chem. Int. Ed. 2019; 58: 8226
      CrossrefPubMed

      • For a synthesis of deoxypodophyllotoxin, see:
    • 6t Kolly-Kovač T, Renaud P. Synthesis 2005; 1459
  • 7 Snyder SA, Wright NE, Pflueger JJ, Breazzano SP. Angew. Chem. Int. Ed. 2011; 50: 8629
    CrossrefPubMed
  • 8 Gibson SE, Guillo N, Middleton RJ, Thuilliez A, Tozer MJ. J. Chem. Soc., Perkin Trans. 1 1997; 447
  • 9 Kato T, Ichinose I, Kamoshida A, Kitahara Y. J. Chem. Soc., Chem. Commun. 1976; 518 ; and references cited therein
  • 10 In a 100 mL round-bottom flask, enol ether 7 (1.50 g, 3.1 mmol) was dissolved in anhydrous CH2Cl2 (35 mL) and cooled to 0 °C. To this solution was added TBCD (97%, 1.57 g, 3.7 mmol, 1.2 equiv) portionwise, and the mixture was stirred for 30 min at 0 °C. A solution of allyl alcohol (3.6 mL, 62 mmol, 20.0 equiv) in CH2Cl2 (5 mL) was then added dropwise, and the resulting mixture was gradually warmed to room temperature and stirred further for 9 h. The reaction was quenched with saturated aqueous NaHCO3 (3 mL), Na2SO3 (3 mL), and stirred further for 30 min. The resulting mixture was extracted with CH2Cl2 (2 × 50 mL), and the combined organic layers were washed with water (2 × 15 mL) and brine (15 mL), respectively, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (petroleum ether/EtOAc = 10:1 → petroleum ether/EtOAc = 4:1) on silica gel to afford 8 (1.519 g, 79% yield) as a yellow oil. Rf = 0.36 (petroleum ether/EtOAc = 2:1). IR (film): νmax = 2930, 2838, 1590, 1504, 1479, 1461, 1422, 1383, 1326, 1265, 1229, 1128, 1037, 929, 845, 792, 736, 701, 685, 582 cm–1. 1H NMR (400 MHz, CDCl3): δ (major isomer) = 7.19 (s, 1 H), 6.99 (s, 1 H), 6.52 (s, 2 H), 5.93 (s, 1 H), 5.89 (s, 1 H), 5.86–5.80 (m, 1 H), 5.35 (dd, J = 17.2, 1.6 Hz, 1 H), 5.13 (dd, J = 10.8, 1.6 Hz, 1 H), 4.76 (d, J = 10.8 Hz, 1 H), 4.55 (dd, J = 11.2, 2.8 Hz, 1 H), 4.26 (dd, J = 13.2, 4.8 Hz, 1 H), 4.00 (d, J = 2.4 Hz, 1 H), 3.88 (dd, J = 12.8, 5.2 Hz, 1 H), 3.76 (s, 6 H), 3.74 (s, 3 H), 3.31 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.3 (2 C), 148.7, 147.3, 137.23, 137.17, 135.6, 133.8, 119.0, 116.7, 107.0, 105.3 (2 C), 102.0, 101.8, 90.5, 69.7, 60.8, 57.7, 57.3, 56.21 (2 C), 56.17 ppm. HRMS (ESI): m/z calcd for C23H26O7 79BrINa+ [M + Na]+: 642.9799; found: 642.9791.
  • 11 Xiao J, Nan G, Wang Y.-W, Peng Y. Molecules 2018; 23: 3037
    CrossrefPubMed