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Copper-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with β-trifluoromethyl-substituted alkenyl heteroarenes

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Abstract

Copper-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides and β-trifluoromethyl-substituted alkenyl heteroarenes was developed for the first time. A wide range of enantioenriched pyrrolidines containing both heteroarenes and trifluoromethyl group with multiple stereogenic centers could be readily accessible by this method with good to high yields and excellent levels of both stereo- and regioselectivity (up to 99% yield, >20:1 rr, >20:1 dr, and up to 95% ee). Notably, substrate-controlled umpolung-type dipolar cycloaddition was also disclosed in this protocol to achieve regiodivergent synthesis with α-aryl substituted aldimine esters as the dipole precursors. Systematic DFT studies were conducted to explore the origin of the stereo- and regioselectivity of this 1,3-dipolar cycloaddition, and suggest that copper(II) salt utilized in this catalytic system could be reduced in-situ to the active copper(I) species and might be responsible for the observed high stereo- and regioselectivity.

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References

  1. Enders D, Thiebes C. Pure Appl Chem, 2001, 73: 573–578

    Article  CAS  Google Scholar 

  2. Harwood LM, Vickers RJ. in Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products. Padwa A and Pearson W, eds. Hoboken: John Wiley & Sons, Ltd., 2002

  3. Pyne S, Davis A, Gates N, Hartley J, Lindsay K, Machan T, Tang M. Synlett, 2004, 2004: 2670–2680

    Article  Google Scholar 

  4. Michael JP. Nat Prod Rep, 2008, 25: 139–165

    Article  CAS  PubMed  Google Scholar 

  5. Mukaiyama T, Asami M. Top Curr Chem, 1985, 127: 133–167

    Article  CAS  Google Scholar 

  6. Vicario JL, Badia D, Carrillo L, Ruiz N, Reyes E. Targets Heterocyclic Syst, 2008, 12: 302–327

    CAS  Google Scholar 

  7. Bhat C, Tilve SG. RSC Adv, 2014, 4: 5405–5452

    Article  CAS  Google Scholar 

  8. Sulzer-Mossé S, Alexakis A. Chem Commun, 2007, 30: 3123–3135

    Article  Google Scholar 

  9. Jensen KL, Dickmeiss G, Jiang H, Albrecht Ł, Jørgensen KA. Acc Chem Res, 2012, 45: 248–264

    Article  CAS  PubMed  Google Scholar 

  10. Li X, Li J. Mini-Rev Med Chem, 2010, 10: 794–805

    Article  CAS  PubMed  Google Scholar 

  11. Vega-Peñaloza A, Paria S, Bonchio M, Dell’Amico L, Companyó X. ACS Catal, 2019, 9: 6058–6072

    Article  Google Scholar 

  12. Cossy J, Pardo DG. Targets Heterocyclic Syst, 2002, 6: 1–26

    CAS  Google Scholar 

  13. Chelucci G, Murineddu G, Pinna GA. Tetrahedron-Asymmetry, 2004, 15: 1373–1389

    Article  CAS  Google Scholar 

  14. Liu X, Lin L, Feng X. Org Chem Front, 2014, 1: 298–302

    Article  CAS  Google Scholar 

  15. Daly JW. J Med Chem, 2003, 46: 445–452

    Article  CAS  PubMed  Google Scholar 

  16. Harrity JPA, Provoost O. Org Biomol Chem, 2005, 3: 1349–1358

    Article  CAS  PubMed  Google Scholar 

  17. Escolano C, Amat M, Bosch J. Chem Eur J, 2006, 12: 8198–8207

    Article  CAS  PubMed  Google Scholar 

  18. Vitaku E, Smith DT, Njardarson JT. J Med Chem, 2014, 57: 10257–10274

    Article  CAS  PubMed  Google Scholar 

  19. Jiang W, Li Y, Wang Z. Chem Soc Rev, 2013, 42: 6113–6127

    Article  CAS  PubMed  Google Scholar 

  20. Kukhar VP and Soloshonok VA, ed. Fluorine Containing Amino Acids—Synthesis and Properties. Chichester: Wiley, 1995

    Google Scholar 

  21. Shimizu M, Hiyama T. Angew Chem Int Ed, 2005, 44: 214–231

    Article  CAS  Google Scholar 

  22. Schlosser M. Angew Chem Int Ed, 2006, 45: 5432–5446

    Article  CAS  Google Scholar 

  23. Uneyama K, Katagiri T, Amii H. Acc Chem Res, 2008, 41: 817–829

    Article  CAS  PubMed  Google Scholar 

  24. Smits R, Cadicamo CD, Burger K, Koksch B. Chem Soc Rev, 2008, 37: 1727–1739

    Article  CAS  PubMed  Google Scholar 

  25. Nie J, Guo HC, Cahard D, Ma JA. Chem Rev, 2010, 111: 455–529

    Article  PubMed  Google Scholar 

  26. Merino E, Nevado C. Chem Soc Rev, 2014, 43: 6598–6608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ojima I, Macarthy JR, Welch JT. Biomedical Frontiers of Fluorine Chemistry. New York: American Chemical Society, 1996

    Book  Google Scholar 

  28. Luzina EL, Popov AV. J Fluorine Chem, 2014, 168: 121–127

    Article  CAS  Google Scholar 

  29. Kaur K, Kumar V, Gupta GK. J Fluorine Chem, 2015, 178: 306–326

    Article  CAS  Google Scholar 

  30. Zanda M. New J Chem, 2004, 28: 1401–1411

    Article  CAS  Google Scholar 

  31. Dmowski W. Wiadomosci Chemiczne, 1997, 51: 263–291

    CAS  Google Scholar 

  32. Tredwell M, Gouverneur V. Edited by Carreira EM, Yamamoto H. Fluorine in medicinal chemistry: Importance of chirality. Compre Chiral, 2012, 1: 70–85

    Article  CAS  Google Scholar 

  33. Huisgen R. Angew Chem Int Ed, 1963, 2: 565–598

    Article  Google Scholar 

  34. Padwa A and Pearson WH. Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products. New York: Wiley-VCH, 2002

    Book  Google Scholar 

  35. Hashimoto T, Maruoka K. Chem Rev, 2015, 115: 5366–5412

    Article  CAS  PubMed  Google Scholar 

  36. Adrio J, Carretero JC. Chem Commun, 2019, 55: 11979–11991

    Article  CAS  Google Scholar 

  37. Wei L, Chang X, Wang CJ. Acc Chem Res, 2020, 53: 1084–1100

    Article  CAS  PubMed  Google Scholar 

  38. Zhao P, Li Z, He J, Liu X, Feng X. Sci China Chem, 2021, 64: 1355–1360

    Article  CAS  Google Scholar 

  39. Li YN, Chang X, Xiong Q, Dong XQ, Wang CJ. Chin Chem Lett, 2021, 32: 4029–4032

    Article  CAS  Google Scholar 

  40. Stohler R, Wahl F, Pfaltz A. Synthesis, 2005, 2005: 1431–1436

    Google Scholar 

  41. Chen XH, Wei Q, Luo SW, Xiao H, Gong LZ. J Am Chem Soc, 2009, 131: 13819–13825

    Article  CAS  PubMed  Google Scholar 

  42. Cristóbal C, Gaviña D, Alonso I, Ribagorda M, Carretero JC, del Pozo C, Adrio J. Chem Commun, 2022, 58: 7805–7808

    Article  Google Scholar 

  43. Deng Y, Dong Z, Gao F, Guo Y, Sun M, Li Y, Wang Y, Chen Q, Wang K, Yan W. J Org Chem, 2021, 86: 13011–13024

    Article  CAS  PubMed  Google Scholar 

  44. Feng B, Lu LQ, Chen JR, Feng G, He BQ, Lu B, Xiao WJ. Angew Chem Int Ed, 2018, 57: 5888–5892

    Article  CAS  Google Scholar 

  45. Shen C, Yang Y, Wei L, Dong WW, Chung LW, Wang CJ. iScience, 2019, 11: 146–159

    Article  CAS  PubMed  Google Scholar 

  46. Xu S, Zhang ZM, Xu B, Liu B, Liu Y, Zhang J. J Am Chem Soc, 2018, 140: 2272–2283

    Article  CAS  PubMed  Google Scholar 

  47. Gill M, Das A, Singh VK. Org Lett, 2022, 24: 5629–5634

    Article  CAS  PubMed  Google Scholar 

  48. Li QH, Tong MC, Li J, Tao HY, Wang CJ. Chem Commun, 2011, 47: 11110–11112

    Article  CAS  Google Scholar 

  49. Li QH, Xue ZY, Tao HY, Wang CJ. Tetrahedron Lett, 2012, 53: 3650–3653

    Article  CAS  Google Scholar 

  50. López-Pérez A, Adrio J, Carretero J. Angew Chem Int Ed, 2009, 48: 340–343

    Article  Google Scholar 

  51. Tong MC, Li J, Tao HY, Li YX, Wang CJ. Chem Eur J, 2011, 17: 12922–12927

    Article  CAS  PubMed  Google Scholar 

  52. Chang X, Yang Y, Shen C, Xue KS, Wang ZF, Cong H, Tao HY, Chung LW, Wang CJ. J Am Chem Soc, 2021, 143: 3519–3535

    Article  CAS  PubMed  Google Scholar 

  53. See computational details in the Supplementary Information

  54. Lam Y, Grayson MN, Holland MC, Simon A, Houk KN. Acc Chem Res, 2016, 49: 750–762

    Article  CAS  PubMed  Google Scholar 

  55. Peng Q, Paton RS. Acc Chem Res, 2016, 49: 1042–1051

    Article  CAS  PubMed  Google Scholar 

  56. Tantillo DJ. Acc Chem Res, 2016, 49: 741–749

    Article  CAS  PubMed  Google Scholar 

  57. Ahn S, Hong M, Sundararajan M, Ess DH, Baik MH. Chem Rev, 2019, 119: 6509–6560

    Article  CAS  PubMed  Google Scholar 

  58. Harvey JN, Himo F, Maseras F, Perrin L. ACS Catal, 2019, 9: 6803–6813

    Article  CAS  Google Scholar 

  59. Lan J, Li X, Yang Y, Zhang X, Chung LW. Acc Chem Res, 2022, 55: 1109–1123

    Article  CAS  PubMed  Google Scholar 

  60. Ess DH, Houk KN. J Am Chem Soc, 2008, 130: 10187–10198

    Article  CAS  PubMed  Google Scholar 

  61. Wang M, Wang CJ, Lin Z. Organometallics, 2012, 31: 7870–7876

    Article  CAS  Google Scholar 

  62. Pascual-Escudero A, de Cózar A, Cossío FP, Adrio J, Carretero JC. Angew Chem Int Ed, 2016, 55: 15334–15338

    Article  CAS  Google Scholar 

  63. Domingo LR, Ríos-Gutiérrez M, Pérez P. J Org Chem, 2018, 83: 10959–10973

    Article  CAS  PubMed  Google Scholar 

  64. Cheng F, Kalita SJ, Zhao Z, Yang X, Zhao Y, Schneider U, Shibata N, Huang Y. Angew Chem Int Ed, 2019, 58: 16637–16643

    Article  CAS  Google Scholar 

  65. Xiong Y, Du Z, Chen H, Yang Z, Tan Q, Zhang C, Zhu L, Lan Y, Zhang M. J Am Chem Soc, 2019, 141: 961–971

    Article  CAS  PubMed  Google Scholar 

  66. Li B, Xu H, Dang Y, Houk KN. J Am Chem Soc, 2022, 144: 1971–1985

    Article  CAS  PubMed  Google Scholar 

  67. Chang X, Liu XT, Li F, Yang Y, Chung LW, Wang CJ. Chem Sci, 2023, 14: 5460–5469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Xu L, Chung LW, Wu YD. ACS Catal, 2016, 6: 483–493

    Article  CAS  Google Scholar 

  69. Gao W, Lv H, Zhang T, Yang Y, Chung LW, Wu YD, Zhang X. Chem Sci, 2017, 8: 6419–6422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Lan J, Liao T, Zhang T, Chung LW. Inorg Chem, 2017, 56: 6809–6819

    Article  CAS  PubMed  Google Scholar 

  71. Zhang X, Chung LW. Chem Eur J, 2017, 23: 3623–3630

    Article  CAS  PubMed  Google Scholar 

  72. Wu SB, Zhang T, Chung LW, Wu YD. Org Lett, 2019, 21: 360–364

    Article  CAS  PubMed  Google Scholar 

  73. Yang Y, Zhang X, Zhong LP, Lan J, Li X, Li CC, Chung LW. Nat Commun, 2020, 11: 1850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Du X, Xiao Y, Yang Y, Duan Y, Li F, Hu Q, Chung LW, Chen G, Zhang X. Angew Chem Int Ed, 2021, 60: 11384–11390

    Article  CAS  Google Scholar 

  75. Lan J, Zhang T, Yang Y, Li X, Chung LW. Inorg Chem, 2022, 61: 18019–18032

    Article  CAS  PubMed  Google Scholar 

  76. Morokuma K. Acc Chem Res, 1977, 10: 294–300

    Article  CAS  Google Scholar 

  77. Ess DH, Houk KN. J Am Chem Soc, 2007, 129: 10646–10647

    Article  CAS  PubMed  Google Scholar 

  78. Bickelhaupt FM, Houk KN. Angew Chem Int Ed, 2017, 56: 10070–10086

    Article  CAS  Google Scholar 

  79. Chen C, Zhang Z, Jin S, Fan X, Geng M, Zhou Y, Wen S, Wang X, Chung LW, Dong XQ, Zhang X. Angew Chem Int Ed, 2017, 56: 6808–6812

    Article  CAS  Google Scholar 

  80. Kalita SJ, Zhao Z, Li Z, Cheng F, Zhao Y, Huang Y. Eur J Org Chem, 2021, 2021(40): 5530–5535

    Article  Google Scholar 

  81. Calvo JS, Villones RLE, York NJ, Stefaniak E, Hamilton GE, Stelling AL, Bal W, Pierce BS, Meloni G. J Am Chem Soc, 2022, 144: 709–722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Mooibroek TJ, Aromí G, Quesada M, Roubeau O, Gamez P, DeBeer George S, van Slageren J, Yasin S, Ruiz E, Reedijk J. Inorg Chem, 2009, 48: 10643–10651

    Article  CAS  PubMed  Google Scholar 

  83. Castañeda-Arriaga R, Pérez-González A, Alvarez-Idaboy JR, Galano A. Int J Quantum Chem, 2018, 118: e25527

    Article  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (22071186, 22071187, 22073067, 22101216, 22271226, 21933003, 22193020, 22193023), the National Youth Talent Support Program, the Natural Science Foundation of Hubei Province (2020CFA036 2021CFA069), the Fundamental Research Funds for the Central Universities (2042022kf1180, 2042022kf1040), the Shenzhen Nobel Prize Scientists Laboratory Project (C17783101) and the Guangdong Provincial Key Laboratory of Catalytic Chemistry (2020B121201002). We thank the Center for Computational Science and Engineering at the Southern University of Science and Technology and CHEM HPC at SUSTech for partly supporting this work.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China

    Xiang Cheng, Xin Chang, Zongpeng Zhang, Jing Li, Yipu Li, Wenxiao Zhao, Xiu-Qin Dong & Chun-Jiang Wang

  2. State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Shanghai, 230021, China

    Xiang Cheng, Xin Chang & Chun-Jiang Wang

  3. Shenzhen Grubbs Institute, Department of Chemistry and Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, 518055, China

    Yuhong Yang & Lung Wa Chung

  4. College of Science, Huazhong Agricultural University, Wuhan, 430070, China

    Huailong Teng

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  1. Xiang Cheng
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  2. Xin Chang
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Correspondence to Lung Wa Chung, Huailong Teng, Xiu-Qin Dong or Chun-Jiang Wang.

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11426_2023_1683_MOESM1_ESM.pdf

Copper-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with β-trifluoromethyl-substituted alkenyl heteroarenes

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Cheng, X., Chang, X., Yang, Y. et al. Copper-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with β-trifluoromethyl-substituted alkenyl heteroarenes. Sci. China Chem. 66, 3193–3204 (2023). https://doi.org/10.1007/s11426-023-1683-9

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