Synthesis 2022; 54(02): 341-354
DOI: 10.1055/a-1625-9095
feature

Native Amine-Directed ortho-C–H Halogenation and Acetoxylation /Condensation of Benzylamines

Pratibha Chand-Thakuri
,
Indunil Alahakoon
,
Daniel Liu
,
Mohit Kapoor
,
John F. Kennedy
,
Kenneth W. Jenkins III
,
Allison M. Rabon
,
This work was supported in part through start-up funds from The University of Toledo, as well as a generous grant from the ACS Herman Frasch Foundation for Chemical Research (830-HF17). J.F.K. was supported by funds from The University of Toledo, Office of Undergraduate Research (Undergraduate Summer Research and Creative Activities Program).


Abstract

Free or unfunctionalized benzylamines are well known to participate in C–H activation in the presence of palladium salts. Despite the ease with which these complexes can be activated, subsequent functionalization of the dimeric cyclometalates can be challenging. We demonstrate herein a free primary amine based C–H activation/functionalization protocol that allows for the ortho-C–H chlorination and bromination of unprotected benzylamines. We also demonstrate how use of fluorine-based oxidants gives rise to a unique acetoxylation/­cyclization owing to the nucleophilicity of the free primary amine directing group.

Supporting Information



Publication History

Received: 24 August 2021

Accepted: 31 August 2021

Publication Date:
31 August 2021 (online)

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

    • 1a Rogge T, Kaplaneris N, Chatani N, Kim J, Chang S, Punji B, Schafer LL, Musaev DG, Wencel-Delord J, Roberts CA, Sarpong R, Wilson ZE, Brimble MA, Johansson MJ, Ackermann L. Nat. Rev. Methods Primers 2021; 1: 43
    • 1b Gensch T, Hopkinson MN, Glorius F, Wencel-Delord J. Chem. Soc. Rev. 2016; 45: 2900
    • 2a Basak S, Biswas JP, Maiti D. Synthesis 2021; 53: 3151
    • 2b Tang Z, Tong Z, Qui R, Yin S.-F, Kambe N. Synthesis 2021; 53: 3193
    • 2c Dong Z, Ren Z, Thompson SJ, Xu Y, Dong G. Chem. Rev. 2017; 117: 9333
  • 3 Aguilera EY, Sanford MS. Angew. Chem. Int. Ed. 2021; 60: 11227
    • 4a Yu J.-Q, Giri R, Chen X. Org. Biomol. Chem. 2006; 4: 4041
    • 4b Jaiswal Y, Kumar A. Catal. Commun. 2019; 131: 105784
    • 4c Liu T, Myers MC, Yu J.-Q. Angew. Chem. Int. Ed. 2017; 56: 306
    • 4d Das R, Kapur M. J. Org. Chem. 2017; 82: 1114
    • 4e Aihara Y, Chatani N. ACS Catal. 2016; 6: 4323
    • 4f Chu L, Xiao K.-J, Yu J.-Q. Science 2014; 346: 451
    • 4g Engle KM, Mei T.-S, Wang X, Yu J.-Q. Angew. Chem. Int. Ed. 2011; 50: 1478
    • 4h Wang X, Mei T.-S, Yu J.-Q. J. Am. Chem. Soc. 2009; 131: 7520
    • 4i Hull K, Anani WQ, Sanford MS. J. Am. Chem. Soc. 2006; 128: 7134
    • 4j Fahey DR. J. Organomet. Chem. 1971; 27: 283
    • 5a Chandrashekar HB, Dolui P, Li B, Mandal A, Guin S, Ge H, Maiti D. Angew. Chem. Int. Ed. 2021; 60: 18194
    • 5b Whitehurst WG, Gaunt MJ. J. Am. Chem. Soc. 2020; 142: 14169
    • 5c Rodrigalvarez J, Nappi M, Azuma H, Flodén NJ, Burns ME, Gaunt MJ. Nat. Chem. 2020; 12: 76
    • 5d Yuan F, Hou Z.-L, Pramanick PK, Yao B. Org. Lett. 2019; 21: 9381
    • 5e Ho DK. H, Calleja J, Gaunt MJ. Synlett 2019; 30: 454
    • 5f Nappi M, Gaunt MJ. Organometallics 2019; 38: 143
    • 5g Kapoor M, Liu D, Young MC. J. Am. Chem. Soc. 2018; 140: 6818
    • 5h Zhang C, Ding Y, Gao Y, Li S, Li G. Org. Lett. 2018; 20: 2595
    • 5i Wu Y, Chen Y.-Q, Liu T, Eastgate MD, Yu J.-Q. J. Am. Chem. Soc. 2016; 138: 14554
    • 5j Xu Y, Young MC, Wang C, Magness DM, Dong G. Angew. Chem. Int. Ed. 2016; 55: 9084
  • 6 Klumpp DA. Electrophilic Aromatic Substitution: Mechanism. In Arene Chemistry. Mortier J. Wiley; Hoboken: 2015: 1
  • 7 Liu Q, Sun B, Liu Z, Kao Y, Dong B.-W, Jiang S.-D, Li F, Liu G, Yang Y, Mo F. Chem. Sci. 2018; 9: 8731
  • 8 Snieckus V. Chem. Rev. 1990; 90: 879
    • 9a Wang R, Ding Y, Li G. Org. Biomol. Chem. 2017; 15: 4966
    • 9b Lu C, Zhang S.-Y, He G, Nack WA, Chen G. Tetrahedron 2014; 70: 4197
    • 10a Jacob C, Maes BU. W, Evano G. Chem. Eur. J. 2021; accepted for publication DOI: 10.1002/chem.202101598.
    • 10b Dalton T, Faber T, Glorius F. ACS Cent. Sci. 2021; 7: 245
    • 10c Yang K, Song M, Liu H, Ge H. Chem. Sci. 2020; 11: 12616
    • 10d Kapoor M, Singh A, Sharma K, Hsu MH. Adv. Synth. Catal. 2020; 362: 4513
    • 10e St John-Campbell S, Bull JA. Org. Biomol. Chem. 2018; 16: 4582
  • 11 Chen Y.-Q, Singh S, Wu Y, Wang Z, Hao W, Verma P, Qiao JX, Sunoj RB, Yu J.-Q. J. Am. Chem. Soc. 2020; 142: 9966
  • 12 Gair JJ, Haines BE, Filatov AS, Musaev DG, Lewis JC. Chem. Sci. 2017; 8: 5746
  • 13 Lazareva A, Daugulis O. Org. Lett. 2006; 8: 5211
  • 14 Kapoor M, Chand-Thakuri P, Young MC. J. Am. Chem. Soc. 2019; 141: 7980
    • 15a Váňa J, Hanusek J, Sedlák M. Dalton Trans. 2018; 47: 1378
    • 15b Vicente J, Saura-Llamas I. Comments Inorg. Chem. 2007; 28: 39
  • 16 Zhang X, He G, Chen G. Org. Biomol. Chem. 2016; 14: 5511
  • 17 Chand-Thakuri P, Landge VG, Kapoor M, Young MC. J. Org. Chem. 2020; 85: 6626
  • 18 Iconomou N, Valkanas G. J. Chromatogr., A 1964; 16: 437
  • 19 Bhattacharya T, Ghosh A, Maiti D. Chem. Sci. 2021; 12: 3857
  • 20 Chen G, Gong W, Zhuang Z, Andra MS, Chen Y.-Q, Hong X, Yang Y.-F, Liu T, Houk KN, Yu J.-Q. Science 2016; 353: 1023
  • 21 Pearson RE, Martin JC. J. Am. Chem. Soc. 1963; 85: 354
  • 22 While we were preparing this manuscript, another paper which was focused on free phenylalanine derivatives showed similar results for a chlorination/bromination/iodination protocol, as well as for the two phenylglycine reactions: Ville A., Annibaletto J., Coufourier S., Hoarau C., Tamion R., Journot G., Schneider C., Brière J.-F.; Chem. Eur. J.; 2021, accepted for publication; DOI: 10.1002/chem.202102411
  • 23 Xu F, Qian X.-Y, Li Y.-J, Xu H.-C. Org. Lett. 2017; 19: 6332
  • 24 Haines BE, Berry JF, Yu J.-Q, Musaev DG. ACS Catal. 2016; 6: 829
  • 25 Luo J, Khusnutdinova JR, Rath NP, Mirica LM. Chem. Commun. 2012; 48: 1532
  • 26 Bercaw JE, Durrell AC, Gray HB, Green JC, Hazari N, Labinger JA, Winkler JR. Inorg. Chem. 2010; 49: 1801
  • 27 CCDC 2106671 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.
  • 28 Fulmer GR, Miller AJ. M, Sherden NH, Gottlieb HE, Nudelman A, Stoltz BM, Bercaw JE, Goldberg KI. Organometallics 2010; 29: 2176
  • 29 Rosenau CP, Jelier BJ, Gossert AD, Togni A. Angew. Chem. Int. Ed. 2018; 57: 9528
  • 30 Wiss J, Fleury C, Heuberger C, Onken U, Glor M. Org. Process Res. Dev. 2007; 11: 1096
  • 31 Conrow RE, Dean WD. Org. Process Res. Dev. 2008; 12: 1285
    • 32a Nikitin KV, Andryukhova NP. Mendeleev Commun. 2000; 10: 31
    • 32b Goswami PP, Suding VP, Carlson AS, Topczewki JJ. Eur. J. Org. Chem. 2016; 4809
  • 33 Gallardo-Macias R, Kumar P, Jaskowski M, Richmann T, Shrestha R, Russo R, Singleton E, Zimmerman MD, Ho HP, Dartois V, Connell N, Alland D, Freundlich JS. Bioorg. Med. Chem. Lett. 2019; 29: 601