Synlett 2017; 28(20): 2918-2922
DOI: 10.1055/s-0036-1588558
letter
© Georg Thieme Verlag Stuttgart · New York

Biology-Oriented Synthesis of Decahydro-4,8-epoxyazulene Scaffolds

Zhi-Jun Jia
a   Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany   Email: herbert.waldmann@mpi-dortmund.mpg.de
b   Chemical Biology, Faculty of Chemistry and Chemical Biology, Technical University Dortmund, Otto-Hahn-Strasse 4a, 44227 Dortmund, Germany
,
Christian Merten
c   Ruhr-Universität Bochum, Lehrstuhl für Organische Chemie II, Universitätsstrasse 150, 44801 Bochum, Germany
,
Lena Knauer
d   Inorganic Chemistry, Faculty of Chemistry and Chemical Biology,Technical University Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany
,
Sandip Murarka
e   Department of Chemistry, IIT Jodhpur, Old Residency Road, Ratanada, Jodhpur-342011, Rajasthan, India
,
Carsten Strohmann
d   Inorganic Chemistry, Faculty of Chemistry and Chemical Biology,Technical University Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany
,
Herbert Waldmann*
a   Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany   Email: herbert.waldmann@mpi-dortmund.mpg.de
b   Chemical Biology, Faculty of Chemistry and Chemical Biology, Technical University Dortmund, Otto-Hahn-Strasse 4a, 44227 Dortmund, Germany
› Author Affiliations
C.M. thanks the FCI for a Liebig Fellowship and the Deutsche Forschungsgemeinschaft (DFG) for support through the Cluster of Excellence RESOLV (‘Ruhr Explores Solvation’, EXC 1069). This research was supported by the European Research Council under the Seventh Framework Programme of the European Union (FP7/2007–2013; ERC Grant 268309 to H.W.) and by the Max Planck Society.
Further Information

Publication History

Received: 13 June 2017

Accepted after revision: 28 July 2017

Publication Date:
23 August 2017 (online)


Dedicated to Victor Snieckus on the occasion of his 80th birthday

Abstract

Guided by the principle of biology-oriented synthesis, a collection of compounds with decahydro-4,8-epoxyazulene scaffold occurring in bioactive natural products was synthesized by the rhodium(II)-catalyzed 1,3-dipolar cycloaddition reaction of pentafulvenes and carbonyl ylides. The products can be obtained in moderate to high yields, with moderate enantioselectivity and excellent diastereoselectivity and regioselectivity.

Supporting Information

 
  • References and Notes

    • 1a Kumar K. Waldmann H. Angew. Chem. Int. Ed. 2009; 48: 3224
    • 1b Bon RS. Waldmann H. Acc. Chem. Res. 2010; 43: 1103
    • 1c Wetzel S. Bon RS. Kumar K. Waldmann H. Angew. Chem. Int. Ed. 2011; 50: 10800
    • 1d van Hattum H. Waldmann H. J. Am. Chem. Soc. 2014; 136: 11853
    • 2a Willot M. Radtke L. Könning D. Fröhlich R. Gessner VH. Strohmann C. Christmann M. Angew. Chem. Int. Ed. 2009; 48: 9105
    • 2b Nicolaou KC. Kang Q. Ng SY. Chen DY. K. J. Am. Chem. Soc. 2010; 132: 8219
    • 2c Xu J. Caro-Diaz EJ. E. Theodorakis EA. Org. Lett. 2010; 12: 3708
    • 2d Zhou Q. Chen X. Ma D. Angew. Chem. Int. Ed. 2010; 49: 3513
    • 2e Molawi K. Delpont N. Echavarren AM. Angew. Chem. Int. Ed. 2010; 49: 3517
    • 2f Li Z. Nakashige M. Chain WJ. J. Am. Chem. Soc. 2011; 133: 6553
    • 2g Takahashi K. Komine K. Yokoi Y. Ishihara J. Hatakeyama S. J. Org. Chem. 2012; 77: 7364
    • 2h Zahel M. Keßberg A. Metz P. Angew. Chem. Int. Ed. 2013; 52: 5390
    • 2i Wang J. Chen S.-G. Sun B.-F. Lin G.-Q. Shang Y.-J. Chem. Eur. J. 2013; 19: 2539
    • 2j Zhang J. Zheng S. Peng W. Shen Z. Tetrahedron Lett. 2014; 55: 1339
    • 2k Hanari T. Shimada N. Kurosaki Y. Thrimurtulu N. Nambu H. Anada M. Hashimoto S. Chem. Eur. J. 2015; 21: 11671
    • 2l Kusama H. Tazawa A. Ishida K. Iwasawa N. Chem. Asian J. 2016; 11: 64
    • 2m Nelson R. Gulías M. Mascareñas JL. López F. Angew. Chem. Int. Ed. 2016; 55: 14359

      For selected examples of the bioactivity of englerin A, see:
    • 3a Ratnayake R. Covell D. Ransom TT. Gustafson KR. Beutler JA. Org. Lett. 2009; 11: 57
    • 3b Radtke L. Willot M. Sun H. Ziegler S. Sauerland S. Strohmann C. Fröhlich R. Habenberger P. Waldmann H. Christmann M. Angew. Chem. Int. Ed. 2011; 50: 3998
    • 3c Williams RT. Yu AL. Diccianni MB. Theodorakis EA. Batova A. J. Exp. Clin. Cancer Res. 2013; 32: 1
    • 3d Sulzmaier FJ. Li Z. Nakashige ML. Fash DM. Chain WJ. Ramos JW. PLoS One 2012; 7: e48032
    • 3e Sourbier C. Scroggins BT. Ratnayake R. Prince TL. Lee S. Lee MJ. Nagy PL. Lee YH. Trepel JB. Beutler JA. Linehan WM. Neckers L. Cancer Cell 2013; 23: 228
    • 3f Akbulut Y. Gaunt HJ. Muraki K. Ludlow MJ. Amer MS. Bruns A. Vasudev NS. Radtke L. Willot M. Hahn S. Seitz T. Ziegler S. Christmann M. Beech DJ. Waldmann H. Angew. Chem. Int. Ed. 2015; 54: 3787

      For selected reviews including natural products with decahydro-4,8-epoxyazulene scaffolds, see:
    • 4a Fraga BM. Nat. Prod. Rep. 2012; 29: 1334
    • 4b Foley DA. Maguire AR. Tetrahedron 2010; 66: 1131
  • 5 Li X.-S. Zhou X.-J. Zhang X.-J. Su J. Li X.-J. Yan Y.-M. Zheng Y.-T. Li Y. Yang L.-M. Cheng Y.-X. J. Nat. Prod. 2011; 74: 1521
  • 6 Daniewski WM. Gumuҟa M. Pankowska E. Ptaszyńska K. Bөszyk E. Jacobsson U. Norin T. Phytochemistry 1993; 32: 1499
  • 7 Luo D.-Q. Wang F. Bian X.-Y. Liu J.-K. J Antibiot. 2005; 58: 456
  • 8 Xu J. Jin D.-Q. Liu C. Xie C. Guo Y. Fang L. J. Agric. Food Chem. 2012; 60: 8051
    • 9a Ahmed AA. Hegazy M.-EF. Hassan NM. Wojcinska M. Karchesy J. Pare PW. Mabry TJ. Phytochemistry 2006; 67: 1547
    • 9b Ono M. Yamashita M. Mori K. Masuoka C. Eto M. Kinjo J. Ikeda T. Yoshimitsu H. Nohara T. Food Sci. Technol. Res. 2008; 14: 499

      For selected reviews, see:
    • 10a Padwa A. Helv. Chim. Acta 2005; 88: 1357
    • 10b Padwa A. Chem. Soc. Rev. 2009; 38: 3072
    • 10c Padwa A. Tetrahedron 2011; 67: 8057
    • 10d Hodgson DM. Labande AH. Muthusamy S. Org. React. 2013; 80: 133
    • 11a Toyoda J. Ibata T. Tamura H. Ogawa K. Nishino T. Takebayashi M. Bull. Chem. Soc. Jpn. 1985; 58: 2212
    • 11b Hodgson DM. Brückl T. Glen R. Labande AH. Selden DA. Dossetter AG. Redgrave AJ. Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 5450
  • 12 For selected review, see: Preethalayam P. Krishnan KS. Thulasi S. Chand SS. Joseph J. Nair V. Jaroschik F. Radhakrishnan KV. Chem. Rev. 2017; 117: 3930
  • 13 Muthusamy S. Babu SA. Gunanathan C. Suresh E. Dastidar P. Synlett 2001; 1407
  • 14 Dirhodium(II)-Catalyzed 1,3-Dipoar Cycloaddition of Fulvenes 1 and Diazo Derivatives 2 A typical procedure is given for the reaction of fulvene 1a and diazo derivative 2a (Table 1, entry 5). A flame-dried Schlenk tube was charged with Rh2(S-TCPTTL)4 (1.96 mg, 0.001 mmol, 1 mol%) and 4 Å MS (20 mg). Under argon flow, a solution of fulvene 1a (14.62 mg, 0.1 mmol, 1 equiv) in 0.5 mL of α,α,α-trifluorotoluene was added, followed by a solution of the corresponding diazo compound 2a (36.03 mg, 0.15 mmol, 1.5 equiv) in 0.5 mL α,α,α-trifluorotoluene. The reaction mixture was allowed to stir for an additional 1 h. Upon completion monitored by thin-layer chromatography (TLC), the reaction mixture was directly loaded on the silica gel column and was purified by using EtOAc/PE mixture as an eluent to afford the desired compound 3a in 92% yield. 1H NMR (500 MHz, CD2Cl2): δ = 6.59 (dd, J = 5.7, 2.0 Hz, 1 H), 5.72 (dd, J = 5.7, 2.3 Hz, 1 H), 3.73 (d, J = 6.9 Hz, 1 H), 3.47 (d, J = 6.9 Hz, 1 H), 2.72 (ddd, J = 16.5, 11.9, 8.2 Hz, 1 H), 2.45 (dd, J = 16.5, 5.8 Hz, 1 H), 2.42–2.33 (m, 1 H), 2.28 (dd, J = 9.1, 3.2 Hz, 1 H), 2.22–2.12 (m, 2 H), 2.12–1.99 (m, 2 H), 1.68–1.56 (m, 4 H), 1.56–1.43 (m, 11 H), 1.27 (s, 3 H) ppm. 13C NMR (126 MHz, CD2Cl2): δ = 203.38, 166.32, 136.24, 135.29, 134.97, 131.18, 91.02, 84.52, 82.85, 57.77, 49.74, 40.32, 34.31, 33.66, 32.12, 28.44, 28.37, 28.12, 27.10, 22.68 ppm. FT-IR: ν = 2982, 2929, 2855, 2161, 1745, 1722, 1448, 1160 cm–1. HRMS: m/z calcd for [M + Na]+ C22H30O4Na: 381.2036; found: 381.2023. HPLC conditions: CHIRAPAK IC column, (CH2Cl2/EtOH = 100:2)/i-hexane = 30:70, flow rate = 0.5 mL min–1, major enantiomer: t R = 61.3 min; minor enantiomer: t R = 28.2 min, 59% ee.
  • 15 Reaction-conditions screening including adding the diazo substrate by syringe pump over 1 h, temperature, solvents, and the ratio of fulvene and diazo substrate.
  • 16 The structure was confirmed by X-ray crystallographic analysis. CCDC 1552869 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures. Please see the Supporting Information for details.
  • 17 See details in Supporting Information.
    • 18a Padwa A. Snyder JP. Curtis EA. Sheehan SM. Worsencroft KJ. Kappe CO. J. Am. Chem. Soc. 2000; 122: 8155
    • 18b Hodgson DM. Pierard FY. T. M. Stupple PA. Chem. Soc. Rev. 2001; 30: 50
    • 18c Hodgson DM. Brückl T. Glen R. Labande AH. Selden DA. Dossetter AG. Redgrave AJ. Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 5450
    • 18d Hashimoto T. Maruoka K. Chem. Rev. 2015; 115: 5366

      For Rh2(S-TCPTTL)4, see:
    • 19a Lindsay VN. G. Lin W. Charette AB. J. Am. Chem. Soc. 2009; 131: 16383

    • For the other phthalimidoderived catalysts, see:
    • 19b DeAngelis A. Dmitrenko O. Yap GP. A. Fox JM. J. Am. Chem. Soc. 2009; 131: 7230
    • 19c DeAngelis A. Boruta DT. Lubin J.-B. Plampin JN. III. Yap GP. A. Fox JM. Chem. Commun. 2010; 46: 4541
    • 19d Ghanem A. Gardiner MG. Williamson RM. Müller P. Chem. Eur. J. 2010; 16: 3291