Research Progress in the Synthesis of α-Tertiary Amines via Radical Strategies

doi:10.6023/cjoc202406040

Abstract

α-Tertiary amines are a class of amine compounds with a tertiary carbon center at the α-position of the nitrogen atom. The presence of the tertiary carbon center significantly alters the lipid solubility and metabolic stability of α-tertiary amines in biological systems, making them valuable in pharmaceutical development. Traditional methods for the synthesis of α-tertiary amines include nucleophilic addition of ketimines, electrophilic amination of carbonyl compounds, allylic amination of tertiary allyl electrophiles, and rearrangement reactions. Due to the high reactivity, mild reaction conditions, and good functional group tolerance of the radical, radical reactions exhibit unique advantages in the synthesis of α-tertiary amines. Given the importance of α-tertiary amines and the advantages of radical reactions, various methods have been developed, including radical amination/hydroamination of alkenes, radical C-N cross-coupling, radical addition of imines, and C-H bond activation of alkanes. This review summarizes the radical-mediated intermolecular synthesis of α-tertiary amines over the past decade and discusses in detail the characteristics of each method.

Key words: α-tertiary amines, radical, imine

Cite this article

Fang Jiaheng, Tian Runyan, Chen Jijun, Liu Xinyuan. Research Progress in the Synthesis of α-Tertiary Amines via Radical Strategies[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202406040.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] Hager A.; Vrielink N.; Hager D.; Lefranc J.; Trauner D. Nat. Prod. Rep. 2016, 33, 491.
[2] Wanka L.; Iqbal K.; Schreiner P. R. Chem. Rev. 2013, 113, 3516.
[3] Ramos-Gonzalez, N.; Paul, B.; Majumdar, S. Pharmacol. Res. 2023, 197, 106961.
[4] Xu Y.; Wang J.; Deng G.-J.; Shao W. Chem.Commun. 2023, 59, 4099.
[5] Kiyokawa K.; Watanabe T.; Fra L.; Kojima T.; Minakata S. J. Org. Chem. 2017, 82, 11711.
[6] Nakagawa A.; Iwai Y.; Hashimoto H.; Miyazaki N.; Oiwa R.; Takahashi Y.; Hirano A.; Shibukawa N.; Kojima Y.; Omura S. J.Antibiot. 1981, 34, 1408.
[7] Kimura T.; Suga T.; Kameoka M.; Ueno M.; Inahashi Y.; Matsuo H.; Iwatsuki M.; Shigemura K.; Shiomi K.; Takahashi Y.; Omura S.; Nakashima T. J.Antibiot. 2019, 72, 169.
[8] Morgenthaler M.; Schweizer E.; Hoffmann-Röder, A.; Benini, F.; Martin, R. E.; Jaeschke, G.; Wagner, B.; Fischer, H.; Bendels, S.; Zimmerli, D.; Schneider, J.; Diederich, F.; Kansy, M.; Müeller, K. ChemMedChem 2007, 2, 1100.
[9] Shibasaki M.; Kanai M. Chem.Rev. 2008, 108, 2853.
[10] Enders D.; Gottfried K.; Raabe G. Adv. Synth. Catal. 2010, 352, 3147.
[11] Bloch, R. Chem.Rev. 1998, 98, 1407.
[12] Yamada K.-i; Tomioka, K. Chem. Rev. 2008, 108, 2874.
[13] Kobayashi S.; Mori Y.; Fossey J. S.; Salter M. M. Chem. Rev. 2011, 111, 2626.
[14] Curto J. M.; Dickstein J. S.; Berritt S.; Kozlowski M. C. Org. Lett. 2014, 16, 1948.
[15] Wieland L. C.; Vieira E. M.; Snapper M. L.; Hoveyda A. H.J. Am. Chem. Soc. 2008, 131, 570.
[16] Trost B. M.; Tracy J. S.; Lin E. Y. ACS Catal. 2019, 9, 11082.
[17] Ohmatsu K.; Ando Y.; Nakashima T.; Ooi T. Chem 2016, 1, 802.
[18] Guo W.; Cai A.; Xie J.; Kleij, A. W. Angew. Chem., Int. Ed. 2017, 56, 11797.
[19] Cai A.; Guo W.; Martínez-Rodríguez, L.; Kleij, A. W. J. Am. Chem. Soc. 2016, 138, 14194.
[20] Arnold J. S.; Nguyen H. M.J. Am. Chem. Soc. 2012, 134, 8380.
[21] Clayden J.; Donnard M.; Lefranc J.; Tetlow D. J. Chem. Commun. 2011, 47, 4624.
[22] Iosub V.; Haberl A. R.; Leung J.; Tang M.; Vembaiyan K.; Parvez M.; Back T. G.J. Org. Chem. 2010, 75, 1612.
[23] Arnold J. S.; Cizio G. T.; Nguyen H. M. Org. Lett. 2011, 13, 5576.
[24] Romero K. J.; Galliher M. S.; Pratt D. A.; Stephenson C. R.J. Chem. Soc. Rev. 2018, 47, 7851.
[25] Yan M.; Lo J. C.; Edwards J. T.; Baran P. S.J. Am. Chem. Soc. 2016, 138, 12692.
[26] Gu Q.-S.; Li Z.-L.; Liu, X.-Y. Acc. Chem. Res. 2020, 53, 170.
[27] Sibi M. P.; Manyem S.; Zimmerman J. Chem.Rev. 2003, 103, 3263.
[28] Bunescu A.; Ha T. M.; Wang Q.; Zhu J. Angew.Chem., Int. Ed. 2017, 56, 10555.
[29] Bao X.; Yokoe T.; Ha T. M.; Wang Q.; Zhu J. Nat.Commun. 2018, 9, 3725.
[30] Forster D.; Guo W.; Wang Q.; Zhu J. ACS Catal. 2021, 11, 10871.
[31] Carlson A. S.; Topczewski J. J. Org. Biomol. Chem. 2019, 17, 4406.
[32] Lv D.; Sun Q.; Zhou H.; Ge L.; Qu Y.; Li T.; Ma X.; Li Y.; Bao H. Angew.Chem., Int. Ed. 2021, 60, 12455.
[33] Liu W.; Pu M.; He J.; Zhang T.; Dong S.; Liu X.; Wu Y.-D.; Feng X. J. Am. Chem. Soc. 2021, 143, 11856.
[34] Ge L.; Wang H.; Liu Y.; Feng X. J. Am. Chem. Soc. 2024, 146, 13347.
[35] Wu L.; Zhang Z.; Wu D.; Wang F.; Chen P.; Lin Z.; Liu G. Angew.Chem., Int. Ed. 2021, 60, 6997.
[36] Suh S.-E.; Chen, S. -J.; Mandal, M.; Guzei, I. A.; Cramer, C. J.; Stahl, S. S. J. Am. Chem. Soc. 2020, 11388.
[37] Gockel S. N.; Buchanan T. L.; Hull K. L.J. Am. Chem. Soc. 2018, 140, 58.
[38] Nicely A. M.; Popov A. G.; Wendlandt H. C.; Trammel G. L.; Kohler D. G.; Hull K. L. Org. Lett. 2023, 25, 5302.
[39] Gui J.; Pan C.-M.; Jin Y.; Qin T.; Lo J. C.; Lee B. J.; Spergel S. H.; Mertzman M. E.; Pitts W. J.; La Cruz, T. E.; Schmidt, M. A.; Darvatkar, N.; Natarajan, S. R.; Baran, P. S. Science. 2015, 348, 886.
[40] Zhu K.; Shaver M. P.; Thomas S. P. Chem. Sci. 2016, 7, 3031.
[41] Trowbridge A.; Reich D.; Gaunt M. J. Nature 2018, 561, 522.
[42] Henry Blackwell, J.; Harris, G. R.; Smith, M. A.; Gaunt, M. J. J. Am. Chem. Soc. 2021, 143, 15946.
[43] Harris G. R.; Trowbridge A. D.; Gaunt M. J. Org. Lett. 2023, 25, 861.
[44] Ashley M. A.; Yamauchi C.; Chu J. C.K.; Otsuka, S.; Yorimitsu, H.; Rovis, T. Angew. Chem., Int. Ed. 2019, 58, 4002.
[45] Ye J.; Kalvet I.; Schoenebeck F.; Rovis T. Nat.Chem. 2018, 10, 1037.
[46] Ryder A. S.H.; Cunningham, W. B.; Ballantyne, G.; Mules, T.; Kinsella, A. G.; Turner-Dore, J.; Alder, C. M.; Edwards, L. J.; McKay, B. S. J.; Grayson, M. N.; Cresswell, A. J. Angew. Chem., Int. Ed. 2020, 59, 14986.
[47] Askey H. E.; Grayson J. D.; Tibbetts J. D.; Turner-Dore, J. C.; Holmes, J. M.; Kociok-Kohn, G.; Wrigley, G. L.; Cresswell, A. J. J. Am. Chem. Soc. 2021, 143, 15936.
[48] Liu W.-Q.; Lee, B. C.; Song, N.; He, Z.; Shen, Z. -A.; Lu, Y.; Koh, M. J. Angew. Chem., Int. Ed. 2024, 63, e202402140.
[49] Fisher D. J.; Burnett G. L.; Velasco R.; Read de Alaniz, J. J. Am. Chem. Soc. 2015, 137, 11614.
[50] Janey, J. M. Angew. Chem., Int. Ed. 2005, 44, 4292.
[51] Kainz Q. M.; Matier C. D.; Bartoszewicz A.; Zultanski S. L.; Peters J. C.; Fu G. C. Science 2016, 351, 681.
[52] Peacock D. M.; Roos C. B.; Hartwig J. F. ACS Cent. Sci. 2016, 2, 647.
[53] Cho H.; Suematsu H.; Oyala P. H.; Peters J. C.; Fu G. C.J. Am. Chem. Soc. 2022, 144, 4550.
[54] Zhang Y.-F.; Wang J.-H.; Yang N.-Y.; Chen Z.; Wang L.-L.; Gu Q.-S.; Li Z.-L.; Liu, X.-Y. Angew. Chem., Int. Ed. 2023, 62, e202302983.
[55] Chen J.-J.; Zhang J.-Y.; Fang J.-H.; Du X.-Y.; Xia H.-D.; Cheng B.; Li N.; Yu Z.-L.; Bian J.-Q.; Wang F.-L.; Zheng J.-J.; Liu W.-L.; Gu Q.-S.; Li Z.-L.; Liu X.-Y.J. Am. Chem. Soc. 2023, 145, 14686.
[56] Zheng J.-J.; Liu W.-L.; Gu Q.-S.; Li Z.-L.; Chen J.-J.; Liu X.-Y. Precis. Chem. 2023, 1, 576.
[57] Chen J.-J.; Fang J.-H.; Du X.-Y.; Zhang J.-Y.; Bian J.-Q.; Wang F.-L.; Luan C.; Liu W.-L.; Liu J.-R.; Dong X.-Y.; Li Z.-L.; Gu Q.-S.; Dong Z.; Liu X.-Y. Nature 2023, 618, 294.
[58] Du X.-Y.; Fang J.-H.; Chen J.-J.; Shen B.; Liu W.-L.; Zhang J.-Y.; Ye X.-M.; Yang N.-Y.; Gu Q.-S.; Li Z.-L.; Yu P.; Liu X.-Y.J. Am. Chem. Soc. 2024, 146, 9444.
[59] Gong Y.; Zhu Z.; Qian Q.; Tong W.; Gong H. Org.Lett. 2021, 23, 1005.
[60] Duan G.; Qian Q.; Chen Y.Tetrahedron Lett. 2023, 129, 154730.
[61] Jeffrey J. L.; Petronijević F. R.; MacMillan, D. W. C. J. Am. Chem. Soc. 2015, 137, 8404.
[62] Brueckner A. C.; Hancock E. N.; Anders E. J.; Tierney M. M.; Morgan H. R.; Scott K. A.; Lamar A. A. Org. Biomol. Chem. 2016, 14, 4387.
[63] Zhang H.-H.; Yu S. J. Org. Chem. 2017, 82, 9995.
[64] Rong J. W.; Seeberger P. H.; Gilmore K. Org.Lett. 2018, 20, 4081.
[65] Nicastri M. C.; Lehnherr D.; Lam Y.-h.; DiRocco, D. A.; Rovis, T. J. Am. Chem. Soc. 2020, 142, 987.
[66] Li S.; Du H.-W.; Davies P. W.; Shu W. CCS Chem. 2024, 6, 1060.
[67] Tomono R.; Kawasaki T.; Ishida N.; Murakami M. Chem.Lett. 2021, 50, 1972.
[68] Zhao H.; Hu Y.; Zheng S.; Yuan W. Org.Lett. 2023, 25, 6699.
[69] Dickstein J. S.; Kozlowski M. C. Chem. Soc. Rev. 2008, 37, 1166.
[70] Lamas M.-C.; Vaillard S. E.; Wibbeling B.; Studer A. Org.Lett. 2010, 12, 2072.
[71] Li Y.; Zhou K.; Wen Z.; Cao S.; Shen X.; Lei M.; Gong L. J. Am. Chem. Soc. 2018, 140, 15850.
[72] Li Y.; Lei M.; Gong L. Nat.Catal. 2019, 2, 1016.
[73] Blackwell J. H.; Kumar R.; Gaunt M. J.J. Am. Chem. Soc. 2021, 143, 1598.
[74] Phelps J. M.; Kumar R.; Robinson J. D.; Chu J. C.K.; Flodén, N. J.; Beaton, S.; Gaunt, M. J. J. Am. Chem. Soc. 2024, 146, 9045.
[75] Song X.; Zhang Y.; Li Y.; Zhao X.; Yin Y.; Ban X.; Jiang Z. ACS Catal. 2023, 13, 6396.
[76] Wu X.; Xia H.; Gao C.; Luan B.; Wu L.; Zhang C.; Yang D.; Hou L.; Liu N.; Xia T.; Li H.; Qu J.; Chen Y. Nat.Chem. 2023, 16, 398.
[77] Xia T.; Wu Y.; Hu J.; Wu X.; Qu J.; Chen Y. Angew.Chem., Int. Ed. 2024, 63, e202316012.
[78] Xia T.; Wu W.; Wu X.; Qu J.; Chen Y. Angew.Chem., Int. Ed. 2024, 63, e202318991.
[79] Sharma A.; Hartwig J. F. Nature 2015, 517, 600.
[80] Niu L.; Jiang C.; Liang Y.; Liu D.; Bu F.; Shi R.; Chen H.; Chowdhury A. D.; Lei A. J. Am. Chem. Soc. 2020, 142, 17693.
[81] Hu A.; Guo J.-J.; Pan, H.; Tang, H.; Gao, Z.; Zuo, Z. J. Am. Chem. Soc. 2018, 140, 1612.
[82] An Q.; Wang Z.; Chen Y.; Wang X.; Zhang K.; Pan H.; Liu W.; Zuo Z. J. Am. Chem. Soc. 2020, 142, 6216.

自由基介导的α-叔胺合成研究进展