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Chiral aminophosphines derived from hydroxyproline and their application in allene–imine [4 + 2] annulation

Abstract

A robust synthetic route from l-hydroxyproline (l-Hyp) to phosphines has established an expandable library of six chiral aminophosphines, which were then applied to the phosphine-catalyzed [4 + 2] allene–imine annulation. The enantioinduction in the annulations—induced by a purely steric effect—were moderate (up to 57% ee). A switch of the reaction site from the γ- to the β′-carbon atom of the allenoate was observed during the annulations performed using sterically demanding chiral phosphines.

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References

  1. 1.

    Vitaku E, Smith DT, Njardarson JT. Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals. J Med Chem. 2014;57:10257–74.

    CAS  Article  Google Scholar 

  2. 2.

    Rubiralta M, Giralt E, Diez A. Piperidine. Structure, preparation, reactivity and synthetic applications of piperidine and its derivatives. Elsevier: Amsterdam; 1991.

  3. 3.

    Michael JP. Indolizidine and quinolizidine alkaloids. Nat Prod Rep. 2004;21:625–49.

    CAS  Article  Google Scholar 

  4. 4.

    Michael JP. Simple indolizidine alkaloids. In: Cordell GA, editor. The Alkaloids. Vol. 55. San Diego: Academic Press; 2001.

    Google Scholar 

  5. 5.

    Dewick PM. Medicinal natural products. Chichester: John Wiley and Sons; 1997. Chapter 6.

    Google Scholar 

  6. 6.

    Buffat MGP. Synthesis of piperidines. Tetrahedron. 2004;60:1701–29.

    CAS  Article  Google Scholar 

  7. 7.

    Zhu X-F, Lan J, Kwon O. An expedient phosphine-catalyzed [4+2] annulation: synthesis of highly functionalized tetrahydropyridines. J Am Chem Soc. 2003;125:4716–7.

    CAS  Article  Google Scholar 

  8. 8.

    Lu K, Kwon O. Phosphine-catalyzed [4+2] annulation: synthesis of ethyl 6-phenyl-tosyl-1,2,5,6-tetrahydropyridine-3-carboxylate. Org Synth. 2009;86:212–24.

    CAS  Article  Google Scholar 

  9. 9.

    Wurz RP, Fu GC. Catalytic asymmetric synthesis of piperidine derivatives through the [4+2] annulation of imines with allenes. J Am Chem Soc. 2005;127:12234–5.

    CAS  Article  Google Scholar 

  10. 10.

    Xiao H, et al. Bifunctional N-acyl-aminophosphine-catalyzed asymmetric [4+2] cycloadditions of allenoates and imines. Chem Eur J. 2011;17:10562–5.

    CAS  Article  Google Scholar 

  11. 11.

    Yu H, et al. Phosphine-catalyzed [4+2] cycloaddition of sulfamate-derived cyclic imines with allenoates: synthesis of sulfamate-fused tetrahydropyridines. Tetrahedron. 2014;70:340–8.

    CAS  Article  Google Scholar 

  12. 12.

    Takizawa S, Arteaga FA, Yoshida Y, Suzuki M, Sasai H. Enantioselective organocatalyzed formal [4+2] cycloaddition of ketimines with allenoates: easy access to a tetrahydropyridine framework with a chiral tetrasubstituted stereogenic carbon center. Asian J. Org. Chem. 2014;3:412–5.

    CAS  Article  Google Scholar 

  13. 13.

    Guo H, Fan YC, Sun Z, Wu Y, Kwon O. Phosphine organocatalysis. Chem Rev. 2018;118:10049–293.

    CAS  Article  Google Scholar 

  14. 14.

    Ni H, Chan W-L, Lu Y. Phosphine-catalyzed asymmetric organic reactions. Chem Rev. 2018;118:9344–411.

    CAS  Article  Google Scholar 

  15. 15.

    Fu W, Tang W. Chiral monophosphorus ligands for asymmetric catalytic reactions. ACS Catal. 2016;6:4814–58.

    CAS  Article  Google Scholar 

  16. 16.

    Tang W, Zhang X. New chiral phosphorus ligands for enantioselective hydrogenation. Chem Rev. 2003;103:3029–70.

    CAS  Article  Google Scholar 

  17. 17.

    Henry CE, et al. Hydroxyproline-derived pseudoenantiomeric [2.2.1] bicyclic phosphines: asymmetric synthesis of (+)- and (−)-pyrrolines. J Am Chem Soc. 2014;136:11890–3.

    CAS  Article  Google Scholar 

  18. 18.

    Smaligo AJ, Vardhineedi S, Kwon O. Carvone-derived P-stereogenic phosphines: design, synthesis, and use in allene–imine [3+2] annulation. ACS Catal. 2018;8:5188–92.

    CAS  Article  Google Scholar 

  19. 19.

    Xu Q, et al. Catalytic enantioselective synthesis of guvacine derivatives through [4 + 2] annulations of imines with α‑methylallenoates. Org Lett. 2018;20:6089–93.

    CAS  Article  Google Scholar 

  20. 20.

    Bertelsen S, Jørgensen KA. Organocatalysis: after the gold rush. Chem Soc Rev. 2009;38:2178–89.

    CAS  Article  Google Scholar 

  21. 21.

    Jensen KL, Dickmeiss G, Jiang H, Albrecht Ł, Jørgensen KA. The diarylprolinol silyl ether system: a general organocatalyst. Acc Chem Res. 2012;45:248–64.

    CAS  Article  Google Scholar 

  22. 22.

    Jiang H, Albrecht Ł, Jørgensen KA. Aminocatalytic remote functionalization strategies. Chem Sci. 2013;4:2287–2300.

    CAS  Article  Google Scholar 

  23. 23.

    Burés J, Armstrong A, Blackmond DG. Curtin–Hammett paradigm for stereocontrol in organocatalysis by diarylprolinol ether catalysts. J Am Chem Soc. 2012;134:6741–50.

    Article  Google Scholar 

  24. 24.

    Tran YS, Kwon O. Phosphine-catalyzed [4 + 2] annulation: synthesis of cyclohexenes. J Am Chem Soc. 2007;129:12632–3.

    CAS  Article  Google Scholar 

  25. 25.

    Moriarty KJ, et al. N-heterocyclic inhibitors of TNF-ALPHA expression, US2002/65270 (A1); 2002.

  26. 26.

    Lee K, et al. Melanocortin receptor agonists, US2010120783 (A1); 2010.

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Acknowledgements

Financial support for this study was provided by the NIH (R01GM071779). We thank Dr. Saeed Khan (UCLA) for the crystallographic analyses. C.X. thanks Prof. Neil K. Garg and Sarah Anthony (UCLA) for sharing their SFC instrument.

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Correspondence to Ohyun Kwon.

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Khong, S.N., Xie, C., Wang, X. et al. Chiral aminophosphines derived from hydroxyproline and their application in allene–imine [4 + 2] annulation. J Antibiot 72, 389–396 (2019). https://doi.org/10.1038/s41429-019-0181-0

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