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Synlett 2018; 29(15): 1978-1982
DOI: 10.1055/s-0037-1610258
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© Georg Thieme Verlag Stuttgart · New York

Synthesis of Polycyclic Frameworks through Iron-Catalyzed Intramolecular [5+2] Cycloaddition

Yongjiang Liu
Key Laboratory of Green Chemistry &Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, P. R. of China   Email: chembliu@scu.edu.cn   Email: fsm09@aliyun.com
,
Yanhui Zhang
Key Laboratory of Green Chemistry &Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, P. R. of China   Email: chembliu@scu.edu.cn   Email: fsm09@aliyun.com
,
Xiao Wang
Key Laboratory of Green Chemistry &Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, P. R. of China   Email: chembliu@scu.edu.cn   Email: fsm09@aliyun.com
,
Shaomin Fu*
Key Laboratory of Green Chemistry &Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, P. R. of China   Email: chembliu@scu.edu.cn   Email: fsm09@aliyun.com
,
Bo Liu  *
Key Laboratory of Green Chemistry &Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, P. R. of China   Email: chembliu@scu.edu.cn   Email: fsm09@aliyun.com
› Author AffiliationsWe acknowledge financial support from the NSFC (21672153).
Further Information

Publication History

Received: 08 July 2018

Accepted after revision: 26 July 2018

Publication Date:
23 August 2018 (online)

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Abstract

A concise and efficient approach to the core of the C18/C19 diterpenoid alkaloids and phomopsterone B is reported. Both syntheses share the same iron-catalyzed intramolecular [5+2] cycloaddition to assemble the tricyclo[6.3.1.01,6]]dodecane skeleton. The following ­approach to the 6/5/6/7 tetracyclic core scaffold of C18/C19 diterpenoid alkaloids features a regioselective Grignard addition/thermal Claisen rearrangement/RCM cyclization. Meanwhile the synthetic steps to access the spiro 6/5/6 tricyclic subunits of phomopsterone B were characterized as intramolecular aldol reaction, Wacker oxidation, and Criegee ­reaction.

Key words

C18/C19-diterpenoid alkaloids - phomopsterone B - Iron-catalyzed - [5+2] cycloaddition

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1610258.
  • Supporting Information
 

  • References and Notes

  • 1 Wang F.-P. Chen Q.-H. Liang X.-T. In The Alkaloids: Chemistry and Biology . Vol. 67. Cordell GA. Elsevier Science; New York: 2009: 1-78
    Search in Google Scholar
  • 4 Dzhakhangirov FN. Sultankhodzhaev MN. Tashkhodzhaev B. Salimov BT. Chem. Nat. Compd. 1997; 33: 190
    CrossrefSearch in Google Scholar
  • 5 Zhang HQ. Zhu YL. Zhu RH. Acta Bot. Sin. 1982; 24: 259
    Search in Google Scholar
  • 7 Shi Y. Wilmot JT. Nordstrøm LU. Tan DS. Gin DY. J. Am. Chem. Soc. 2013; 135: 14313
    CrossrefPubMedSearch in Google Scholar
  • 14 Matsuo J. Sasaki S. Hoshikawa T. Ishibashi H. Chem. Commun. 2010; 934
    PubMed
  • 15 Rinderhagen H. Mattay J. Chem. Eur. J. 2004; 10: 851
    CrossrefPubMedSearch in Google Scholar
  • 16 Liu Y. Wang X. Chen S. Fu S. Liu B. Org. Lett. 2018; 20: 2934
    CrossrefPubMedSearch in Google Scholar
  • 17 Nicolaou KC. Dong L. Deng L. Talbot AC. Chen DY.-K. Chem. Commun. 2010; 70
    PubMed
  • 19 We also tried to construct the 6/5/6/5 tetracyclic core skeleton of the C18/C19-diterpenoid alkaloids, but failed (Scheme 5).
  • 20 Reduction of compound 10 under LiAlH4 gave two diastereo­isomers, 20-1 and 20-2 in 49% yield and 24% yield, respectively. Compound 20-1 was further transformed into compound 20, the structure of which was confirmed by X-ray crystallography. The stereochemistry of hydroxyl group at C1 in target compound 11 could be identified from X-ray crystallographic analysis of compound 20 (Scheme 6).
  • 21 Shen J. Shi Y. Tian W. Chin. J. Chem. 2015; 33: 683
    CrossrefSearch in Google Scholar
  • 22 Experimental Procedure and Characteristic Data for Ketone (24): Compound 21 (22.3 mg, 0.08 mmol) was added to toluene (0.5 mL) in a sealed tube and stirred at 170 °C overnight. The solvent was then removed in vacuo to afford the crude product, which was used in the next step without further purification. To a solution of Grubbs II (17.5 mg, 0.02 mmol) in CH2Cl2 (8.0 mL) at room temperature was added the above product in CH2Cl2 (2.5 mL) and the mixture was stirred at room temperature for 10 h. The solvent was then removed in vacuo and the crude product was purified by column chromatography (EtOAc/petroleum ether = 1:5) to afford the product 24 (12.1 mg, 60% for two steps) as a white solid; mp 119–121 °C. 1H NMR (400 MHz, CDCl3): δ = 5.65–5.59 (m, 2 H), 3.87 (s, 1 H), 2.88 (t, J = 5.2 Hz, 1 H), 2.73–2.60 (m, 2 H), 2.46 (dd, J = 5.2, 7.2 Hz, 1 H), 2.04–1.98 (m, 2 H), 1.90–1.81 (m, 2 H), 1.70 (dd, J = 5.2, 13.2 Hz, 1 H), 1.66–1.59 (m, 1 H), 1.52–1.47 (m, 1 H), 1.42 (ddd, J = 2.8, 7.6, 14.0 Hz, 1 H), 1.15 (dddd, J = 2.8, 4.0, 12.4, 25.2 Hz, 1 H), 1.03 (ddt, J = 2.8, 12.8, 25.6 Hz, 1 H), 0.72 (ddd, J = 3.2, 13.2, 25.6 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 211.8, 211.0, 132.7, 127.9, 78.9, 60.5, 50.6, 48.5, 35.2, 34.8, 31.6, 30.6, 24.0, 22.7, 20.6. IR (neat): 2925, 2850, 1735, 1448, 1369, 1239, 1141, 1030 cm–1. HRMS (ESI): m/z [M+Na]+ calcd for C15H18NaO3: 269.1154; found: 269.1151.