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Modular and regioselective synthesis of all-carbon tetrasubstituted olefins enabled by an alkenyl Catellani reaction

Nature Chemistry volume 11, pages 1106–1112 (2019)Cite this article

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Abstract

All-carbon tetrasubstituted olefins have been found in numerous biologically important compounds and organic materials. However, regio- and stereocontrolled construction of this structural motif still constitutes a significant synthetic challenge. Here, we show that a modular and regioselective synthesis of all-carbon tetrasubstituted olefins can be realized via alkenyl halide- or triflate-mediated palladium/norbornene catalysis, which is enabled by a modified norbornene containing a C2 amide moiety. This new norbornene co-catalyst effectively suppressed undesired cyclopropanation pathways, which have previously been a main obstacle for developing such reactions. Diverse cyclic and acyclic alkenyl bromides or triflates with a wide range of functional groups can be employed as substrates. Various substituents can be introduced at the alkene C1 and C2 positions regioselectively simply by changing the coupling partners. Initial mechanistic studies provide insights on the rate-limiting step as well as the structure of the actual active ligand in this system.

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Fig. 1: Representative natural products containing all-carbon tetrasubstituted olefins.
Fig. 2: Alkenyl Catellani-type reactions.
Fig. 3: NBE effect for the alkenyl Catellani reaction.
Fig. 4: Mechanistic studies and synthetic utility.

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Data availability

The data supporting the findings of this study are available within the paper and its Supplementary Information. Crystallographic data for compound 4e have been deposited at the Cambridge Crystallographic Data Centre (CCDC) under deposition no. CCDC 1908383. These data can be obtained free of charge from the CCDC (http://www.ccdc.cam.ac.uk/data_request/cif).

References

  1. Flynn, A. B. & Ogilvie, W. W. Stereocontrolled synthesis of tetrasubstituted olefins. Chem. Rev. 107, 4698–4745 (2007).

    CAS  PubMed  Google Scholar 

  2. Normant, J. F. & Alexakis, A. Carbometallation (C-metallation) of alkynes – stereospecific synthesis of alkenyl derivatives. Synthesis 1981, 841–870 (1981).

    Google Scholar 

  3. Doyle, M. P. in Comprehensive Organometallic Chemistry II, Vol. 12 (eds. Abel, E. W. et al.) Ch. 5.1, 387–420 (Pergamon, 1995).

  4. Muller, D. S. & Marek, I. Copper mediated carbometalation reactions. Chem. Soc. Rev. 45, 4552–4566 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Negishi, E., Zhang, Y., Cederbaum, F. E. & Webb, M. B. A selective method for the synthesis of stereodefined exocyclic alkenes via allylmetalation of propargyl alcohols. J. Org. Chem. 51, 4080–4082 (1986).

    CAS  Google Scholar 

  6. Itami, K., Kamei, T. & Yoshida, J. Diversity-oriented synthesis of tamoxifen-type tetrasubstituted olefins. J. Am. Chem. Soc. 125, 14670–14671 (2003).

    CAS  PubMed  Google Scholar 

  7. Zhou, C. X. & Larock, R. C. Regio- and stereoselective route to tetrasubstituted olefins by the palladium-catalyzed three-component coupling of aryl iodides, internal alkynes, and arylboronic acids. J. Org. Chem. 70, 3765–3777 (2005).

    CAS  PubMed  Google Scholar 

  8. Zhang, D.-H. & Ready, J. M. Iron-catalyzed carbometalation of propargylic and homopropargylic alcohols. J. Am. Chem. Soc. 128, 15050–15051 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Gericke, K. M., Chai, D. I., Bieler, N. & Lautens, M. The norbornene shuttle: multicomponent domino synthesis of tetrasubstituted helical alkenes through multiple C–H functionalization. Angew. Chem. Int. Ed. 48, 1447–1451 (2009).

    CAS  Google Scholar 

  10. Zhou, Y.-Q., You, W., Smith, K. B. & Brown, M. K. Copper-catalyzed cross-coupling of boronic esters with aryl iodides and application to the carboboration of alkynes and allenes. Angew. Chem. Int. Ed. 53, 3475–3479 (2014).

    CAS  Google Scholar 

  11. Xue, F., Zhao, J., Hor, T. S. A. & Hayashi, T. Nickel-catalyzed three-component domino reactions of aryl grignard reagents, alkynes, and aryl halides producing tetrasubstituted alkenes. J. Am. Chem. Soc. 137, 3189–3192 (2015).

    CAS  PubMed  Google Scholar 

  12. Gampe, C. M. & Carreira, E. M. Arynes and cyclohexyne in natural product synthesis. Angew. Chem. Int. Ed. 51, 3766–3778 (2012).

    CAS  Google Scholar 

  13. Catellani, M., Frignani, F. & Rangoni, A. A complex catalytic cycle leading to a regioselective synthesis of o,o’‐disubstituted vinylarenes. Angew. Chem. Int. Ed. Engl. 36, 119–122 (1997).

    CAS  Google Scholar 

  14. Catellani, M., Motti, E. & Della Ca’, N. Catalytic sequential reactions involving palladacycle-directed aryl coupling steps. Acc. Chem. Res. 41, 1512–1522 (2008).

    CAS  PubMed  Google Scholar 

  15. Martins, A., Mariampillai, B. & Lautens, M. Synthesis in the key of Catellani: norbornene-mediated ortho C–H functionalization. Top. Curr. Chem. 292, 1–33 (2010).

    CAS  PubMed  Google Scholar 

  16. Ye, J. & Lautens, M. Palladium-catalysed norbornene-mediated C–H functionalization of arenes. Nat. Chem. 7, 863–870 (2015).

    CAS  PubMed  Google Scholar 

  17. Della, Ca’,N., Fontana, M., Motti, E. & Catellani, M. Pd/Norbornene: a winning combination for selective aromatic functionalization via C–H bond activation. Acc. Chem. Res. 49, 1389–1400 (2016).

    Google Scholar 

  18. Liu, Z.-S., Gao, Q., Cheng, H.-G. & Zhou, Q. The alkylating reagents employed in catellani-type reactions. Chem. Eur. J. 24, 15461–15476 (2018).

    CAS  PubMed  Google Scholar 

  19. Wang, J. & Dong, G. Palladium/Norbornene cooperative catalysis. Chem. Rev. 119, 7478–7528 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Lautens, M. & Piguel, S. A new route to fused aromatic compounds by using a palladium-catalyzed alkylation–alkenylation sequence. Angew. Chem. Int. Ed. 39, 1045–1046 (2000).

    CAS  Google Scholar 

  21. Catellani, M., Motti, E. & Baratta, S. A novel palladium-catalyzed synthesis of phenanthrenes from ortho-substituted aryl iodides and diphenyl- or alkylphenylacetylenes. Org. Lett. 3, 3611–3614 (2001).

    CAS  PubMed  Google Scholar 

  22. Faccini, F., Motti, E. & Catellani, M. A new reaction sequence involving palladium-catalyzed unsymmetrical aryl coupling. J. Am. Chem. Soc. 126, 78–79 (2004).

    CAS  PubMed  Google Scholar 

  23. Catellani, M. & Chiusoli, G. P. Competitive processes in palladium-catalyzed C–C bond formation. J. Organomet. Chem. 233, C21–C24 (1982).

    CAS  Google Scholar 

  24. Khanna, A., Premachandra, I. D. U. A., Sung, P. D. & Van Vranken, D. L. Palladium-catalyzed Catellani aminocyclopropanation reactions with vinyl halides. Org. Lett. 15, 3158–3161 (2013).

    CAS  PubMed  Google Scholar 

  25. Blaszykowski, C., Aktoudianakis, E., Bressy, C., Alberico, D. & Lautens, M. Preparation of annulated nitrogen-containing heterocycles via a one-pot palladium-catalyzed alkylation/direct arylation sequence. Org. Lett. 8, 2043–2045 (2006).

    CAS  PubMed  Google Scholar 

  26. Yamamoto, Y., Murayama, T., Jiang, J., Yasui, T. & Shibuya, M. The vinylogous Catellani reaction: a combined computational and experimental study. Chem. Sci. 9, 1191–1199 (2018).

    CAS  PubMed  Google Scholar 

  27. Wang, J., Li, R., Dong, Z., Liu, P. & Dong, G. Complementary site-selectivity in arene functionalization enabled by overcoming the ortho constraint in palladium/norbornene catalysis. Nat. Chem. 10, 866–872 (2018).

    CAS  PubMed  Google Scholar 

  28. Blanchot, M., Candito, D. A., Larnaud, F. & Lautens, M. Formal synthesis of nitidine and nk109 via palladium-catalyzed domino direct arylation/n-arylation of aryl triflates. Org. Lett. 13, 1486–1489 (2011).

    CAS  PubMed  Google Scholar 

  29. Dong, Z., Lu, G., Wang, J., Liu, P. & Dong, G. Modular ipso/ortho difunctionalization of aryl bromides via palladium/norbornene cooperative catalysis. J. Am. Chem. Soc. 140, 8551–8562 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhang, H., Chen, P. & Liu, G. Palladium-catalyzed cascade C–H trifluoroethylation of aryl iodides and heck reaction: efficient synthesis of ortho-trifluoroethylstyrenes. Angew. Chem. Int. Ed. 53, 10174–10178 (2014).

    CAS  Google Scholar 

  31. Qureshi, Z., Schlundt, W. & Lautens, M. Introduction of hindered electrophiles via C–H functionalization in a palladium-catalyzed multicomponent domino reaction. Synthesis 47, 2446–2456 (2015).

    CAS  Google Scholar 

  32. Dong, Z., Wang, J., Ren, Z. & Dong, G. Ortho C–H acylation of aryl iodides by palladium/norbornene catalysis. Angew. Chem. Int. Ed. 54, 12664–12668 (2015).

    CAS  Google Scholar 

  33. Shen, P.-X., Wang, X.-C., Wang, P., Zhu, R.-Y. & Yu, J.-Q. Ligand-enabled meta-C–H alkylation and arylation using a modified norbornene. J. Am. Chem. Soc. 137, 11574–11577 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Surry, D. S. & Buchwald, S. L. Biaryl phosphane ligands in palladium-catalyzed amination. Angew. Chem. Int. Ed. 47, 6338–6361 (2008).

    CAS  Google Scholar 

  35. Wang, P. et al. Ligand-promoted meta-C–H arylation of anilines, phenols, and heterocycles. J. Am. Chem. Soc. 138, 9269–9276 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Wang, P. et al. Ligand-accelerated non-directed C–H functionalization of arenes. Nature 551, 489 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Uemura, T., Yamaguchi, M. & Chatani, N. Phenyltrimethylammonium salts as methylation reagents in the nickel-catalyzed methylation of C–H bonds. Angew. Chem. Int. Ed. 55, 3162–3165 (2016).

    CAS  Google Scholar 

  38. Catellani, M., Motti, E. & Minari, M. Symmetrical and unsymmetrical 2,6-dialkyl-1,1’-biaryls by combined catalysis of aromatic alkylation via palladacycles and suzuki-type coupling. Chem. Commun. 157–158 (2000).

  39. Catellani, M. & Fagnola, M. C. Palladacycles as intermediates for selective dialkylation of arenes and subsequent fragmentation. Angew. Chem. Int. Ed. 33, 2421–2422 (1994).

    Google Scholar 

  40. Wilhelm, T. & Lautens, M. Palladium-catalyzed alkylation–hydride reduction sequence: synthesis of meta-substituted arenes. Org. Lett. 7, 4053–4056 (2005).

    CAS  PubMed  Google Scholar 

  41. Martins, A. & Lautens, M. Aromatic ortho-benzylation reveals an unexpected reductant. Org. Lett. 10, 5095–5097 (2008).

    CAS  PubMed  Google Scholar 

  42. Deledda, S., Motti, E. & Catellani, M. Palladium-catalysed synthesis of nonsymmetrically disubstituted-1,1’-biphenyls from o-substituted aryl iodides through aryl coupling and delayed hydrogenolysis. Can. J. Chem. 83, 741–747 (2005).

    CAS  Google Scholar 

  43. Catellani, M. et al. A new catalytic method for the synthesis of selectively substituted biphenyls containing an oxoalkyl chain. J. Organomet. Chem. 687, 473–482 (2003).

    CAS  Google Scholar 

  44. Liu, Z.-S. et al. Palladium/Norbornene cooperative catalysis to access tetrahydronaphthalenes and indanes with a quaternary center. ACS Catal. 8, 4783–4788 (2018).

    CAS  Google Scholar 

  45. Baba, K., Tobisu, M. & Chatani, N. Palladium-catalyzed direct synthesis of phosphole derivatives from triarylphosphines through cleavage of carbon−hydrogen and carbon−phosphorus bonds. Angew. Chem. Int. Ed. 52, 11892–11895 (2013).

    CAS  Google Scholar 

  46. Fourmy, K., Nguyen, D. H., Dechy-Cabaret, O. & Gouygou, M. Phosphole-based ligands in catalysis. Catal. Sci. Technol. 5, 4289–4323 (2015).

    CAS  Google Scholar 

  47. Trost, B. M. & Murayama, E. An approach to the phenanthrene nucleus via thionium ions and epoxyketone cyclizations. Tetrahedron Lett. 23, 1047–1050 (1982).

    CAS  Google Scholar 

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Acknowledgements

Financial support from the University of Chicago and NIGMS (1R01GM124414-01A1) is acknowledged. We thank K.-Y. Yoon for the X-ray crystallography.

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  1. Department of Chemistry, University of Chicago, Chicago, IL, USA

    Jianchun Wang, Zhe Dong, Cheng Yang & Guangbin Dong

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  1. Jianchun Wang
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Contributions

J.W., Z.D. and G.D. conceived and designed the experiments. J.W. performed experiments. C.Y. prepared a few substrates. J.W. and G.D. co-wrote the manuscript.

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Correspondence to Guangbin Dong.

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Supplementary information

Supplementary information

Experimental procedures, product characterization data, and mechanistic studies

Crystallographic data

Crystallographic data for compound 4e; CCDC reference 1908383

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Wang, J., Dong, Z., Yang, C. et al. Modular and regioselective synthesis of all-carbon tetrasubstituted olefins enabled by an alkenyl Catellani reaction. Nat. Chem. 11, 1106–1112 (2019). https://doi.org/10.1038/s41557-019-0358-y

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