Synthesis 2018; 50(14): 2693-2706
DOI: 10.1055/s-0037-1610142
short review
© Georg Thieme Verlag Stuttgart · New York

Regioselective Transition-Metal-Catalyzed C–H Functionalization of Anilines

Jamie A. Leitch*
Department of Chemistry, University of Bath, Claverton Down, Somerset, BA2 7AY, UK   Email: j.leitch@bath.ac.uk   Email: c.g.frost@bath.ac.uk
,
Christopher G. Frost*
Department of Chemistry, University of Bath, Claverton Down, Somerset, BA2 7AY, UK   Email: j.leitch@bath.ac.uk   Email: c.g.frost@bath.ac.uk
› Author Affiliations
Further Information

Publication History

Received: 19 February 2018

Accepted after revision: 06 April 2018

Publication Date:
11 June 2018 (online)


Abstract

Anilines are a vital synthetic core of pharmaceuticals, agrochemicals, natural products and building blocks. Metal-catalyzed C–H functionalization has emerged as a powerful tool to derivatize biologically relevant molecules. To this end, the derivation of anilines via catalytic C–H functionalization has been the subject of important new synthetic methodology. This review focuses on the tactics used to allow regioselective C–H functionalization of anilines.

1 Introduction

2 ortho-Selective C–H Functionalization

2.1 Palladium

2.2 Rhodium

2.3 Ruthenium

2.4 Nickel

3 meta-Selective C–H Functionalization

4 para-Selective C–H Functionalization

5 Conclusion

 
  • References

  • 1 The Chemistry of Anilines . Rappoport Z. John Wiley & Sons; Hoboken: 2007
    • 2a McGrath NA. Brichacek N. Njardarson JT. J. Chem. Educ. 2010; 87: 1348
    • 2b Vitaku E. Smith DT. Njardarson JT. J. Med. Chem. 2014; 57: 10257

      For reading transition-metal-catalyzed C–H activation, see:
    • 3a Ackermann L. Chem. Rev. 2011; 113: 1315
    • 3b Arockiam PB. Bruneau C. Dixneuf P. Chem. Rev. 2012; 112: 5879
    • 3c Chen X. Engle KM. Wang D.-H. Yu J.-Q. Angew. Chem. Int. Ed. 2009; 48: 5094
    • 3d Engle KM. Mei T.-S. Wasa M. Yu J.-Q. Acc. Chem. Res. 2012; 45: 788
    • 3e Davies HM. L. Morton D. J. Org. Chem. 2016; 81: 343

    • For reading on the derivation of biologically relevant molecules, see:
    • 3f Ma W. Dong H. Wang D. Ackermann L. Adv. Synth. Catal. 2017; 359: 966
    • 3g Yamaguchi J. Yamaguchi AD. Itami K. Angew. Chem. Int. Ed. 2012; 51: 8960
    • 3h Brown JA. Cochrane AR. Irvine S. Kerr WJ. Mondal B. Parkinson JA. Paterson LC. Reid M. Tuttle T. Andersson S. Nilsson GN. Adv. Synth. Catal. 2014; 356: 3551
    • 3i Leitch JA. Bhonoah Y. Frost CG. ACS Catal. 2017; 7: 5618
    • 3j Kerr WJ. Lindsay DM. Owens PK. Reid M. Tuttle T. Campos S. ACS Catal. 2017; 7: 7182

      For reading on selectivity in C–H activation, see:
    • 4a Frost CG. Marcé P. Liu PM. In Organometallic Chemistry . Fairlamb IJ. S. Lynam J. Royal Society of Chemistry; Abingdon: 2015: 54-87
    • 4b Dey A. Maity S. Maiti D. Chem. Commun. 2016; 52: 12398
    • 4c Yiang J. Org. Biomol. Chem. 2015; 13: 1930
    • 4d Dey A. Agasti S. Maiti D. Org. Biomol. Chem. 2016; 14: 5440
    • 4e Ping L. Chung DS. Bouffard J. Lee S.-G. Chem. Soc. Rev. 2017; 46: 4299
    • 5a Chen Z. Wang B. Zhang J. Yu W. Liu Z. Zhang Y. Org. Chem. Front. 2015; 2: 1107
    • 5b De Sarkar S. Liu W. Kozhushkov SI. Ackermann L. Adv. Synth. Catal. 2014; 356: 1461
  • 6 Bruckl T. Baxter RD. Ishihara Y. Baran PB. Acc. Chem. Res. 2012; 45: 826
  • 7 Lyons TW. Sanford MS. Chem. Rev. 2010; 110: 1147
  • 8 Kalyani D. Deprez NR. Desai LV. Sanford MS. J. Am. Chem. Soc. 2005; 127: 7330
  • 9 Yeng CS. Zhao Z. Borduas N. Dong VM. Chem. Sci. 2010; 1: 331
  • 10 Yeng CS. Dong VM. Synlett 2011; 7: 974
  • 11 Xu H. Shang M. Dai H.-X. Yu J.-Q. Org. Lett. 2015; 17: 3830
  • 12 Nishikata T. Abela AR. Huang S. Lipshutz BH. J. Am. Chem. Soc. 2010; 132: 4978
  • 13 Chu J.-H. Li P.-S. Lee Y.-M. Shen W.-T. Wu M.-J. Chem. Eur. J. 2011; 17: 13613
  • 14 Chu J.-H. Huang H.-P. Hsu W.-T. Chen S.-T. Wu M.-J. Organometallics 2014; 33: 1190
  • 15 Skubi KL. Blum TR. Yoon TP. Chem. Rev. 2016; 116: 10035
  • 16 Kalyani D. McMurtrey KB. Neufeldt SR. Sanford MS. J. Am. Chem. Soc. 2011; 133: 18566
  • 17 Jiang J. Zhang W.-M. Dai J.-J. Xu J. Xu H.-J. J. Org. Chem. 2017; 82: 3622
  • 18 Desai LV. Malik HA. Sanford MS. Org. Lett. 2006; 8: 1141
  • 19 Jiang T.-S. Wang G.-W. J. Org. Chem. 2012; 77: 9504
  • 20 Wan X. Ma Z. Li B. Zhang K. Cao S. Zhang S. Shi Z. J. Am. Chem. Soc. 2006; 128: 7416
  • 21 Kalyani D. Dick AR. Anani WQ. Sanford MS. Tetrahedron 2006; 62: 11483
  • 22 Bedford RB. Mitchell CJ. Webster RL. Chem. Commun. 2010; 46: 3095
  • 23 Houlden CE. Hutchby M. Bailey CD. Ford JG. Tyler SN. G. Gagné M. Lloyd-Jones GC. Booker-Milburn KI. Angew. Chem. Int. Ed. 2009; 48: 1830
  • 24 Giri R. Lam JK. Yu J.-Q. J. Am. Chem. Soc. 2010; 132: 686
  • 25 Liang D. He Y. Zhu Q. Org. Lett. 2014; 16: 2748
  • 26 Li W. Duan Z. Zhang X. Zhang H. Wang M. Jiang R. Zeng H. Liu C. Lei A. Angew. Chem. Int. Ed. 2015; 54: 1893
  • 27 Wu J. Cui X. Mi X. Li Y. Wu Y. Chem. Commun. 2010; 46: 6771
  • 28 Geng K. Fan Z. Zhang A. Org. Chem. Front. 2016; 3: 349
  • 29 Wu Y. Li B. Mao F. Li X. Kwong FY. Org. Lett. 2011; 13: 3258
  • 30 Neufeldt SR. Seigeran CK. Sanford MS. Org. Lett. 2013; 15: 2302
  • 31 Pawar GG. Brahamanandan A. Kapur M. Org. Lett. 2016; 18: 448
  • 32 Colby DA. Tsai AS. Bergman RG. Ellman JA. Acc. Chem. Res. 2012; 45: 814
  • 33 Stuart DR. Bertrand-Laperle M. Burgess KM. N. Fagnou K. J. Am. Chem. Soc. 2008; 130: 16474
  • 34 Chen J. Song G. Pan C.-L. Li X. Org. Lett. 2010; 12: 5426
  • 35 Liu B. Fan Y. Gao Y. Sun C. Xu C. Zhu J. J. Am. Chem. Soc. 2013; 135: 468
  • 36 Dong J. Wu Z. Liu Z. Liu P. Sun P. J. Org. Chem. 2015; 80: 12588
  • 38 Li D.-D. Cao Y.-X. Wang G.-W. Org. Biomol. Chem. 2015; 13: 6958
  • 39 Wu Y. Sun L. Chen Y. Zhou Q. Huang J.-W. Miao H. Luo HB. J. Org. Chem. 2016; 81: 1244
  • 40 Midya SP. Sahoo MK. Landge VG. Rajamohanan PR. Balaraman E. Nat. Commun. 2015; 6: 8591
  • 41 Padwa A. Chem. Soc. Rev. 2009; 38: 3072
  • 42 Jiang H. Gao S. Xu J. Wu J. Wu X. Lin A. Yao H. Adv. Synth. Catal. 2016; 358: 188
  • 43 Allu S. Ravi M. Swamy KC. K. Eur. J. Org. Chem. 2016; 34: 5697
  • 44 There is also a report of one example of aniline derivatives in ortho-alkylation chemistry via epoxide ring opening, see: Zhou X. Yu S. Qi Z. Kong L. Li X. J. Org. Chem. 2016; 81: 4869
  • 45 Ackermann L. Pospech J. Org. Lett. 2011; 13: 4153
  • 46 Padala K. Jeganmohan M. Org. Lett. 2012; 14: 1134
  • 47 Ackermann L. Wang L. Wolfram R. Lygin AV. Org. Lett. 2012; 14: 728
  • 48 Manikandan R. Jeganmohan M. Org. Lett. 2014; 16: 912
    • 49a Manikandan R. Madasamy P. Jeganmohan M. ACS Catal. 2016; 6: 230
    • 49b Morita T. Satoh T. Miura M. Org. Lett. 2017; 19: 1800
    • 50a Leitch JA. Wilson PB. McMullin CL. Mahon MF. Bhonoah Y. Williams IH. Frost CG. ACS Catal. 2016; 6: 5520
    • 50b Leitch JA. Cook HP. Bhonoah Y. Frost CG. J. Org. Chem. 2016; 81: 10081
  • 51 Hubric J. Himmler T. Rodefeld L. Ackermann L. Adv. Synth. Catal. 2015; 357: 474
  • 52 Yamaguchi J. Muto K. Itami K. Top. Curr. Chem. 2016; 374: 55
  • 53 Song W. Ackermann L. Chem. Commun. 2013; 49: 6638
  • 54 Ruan Z. Lackner S. Ackermann L. Angew. Chem. Int. Ed. 2016; 55: 3153
  • 55 Ruan Z. Ghorai D. Zanoni G. Ackermann L. Chem. Commun. 2017; 53: 9113
  • 56 Ruan Z. Lackner S. Ackermann L. ACS. Catal. 2016; 6: 4690
  • 57 Muller T. Ackermann L. Chem. Eur. J. 2016; 22: 14151
  • 58 Phipps RJ. Gaunt MJ. Science 2009; 323: 1593
  • 59 Leow D. Li G. Mei T.-S. Yu J.-Q. Nature 2012; 486: 518
  • 60 Tang R.-Y. Li G. Yu J.-Q. Nature 2014; 507: 215
    • 61a Yang G. Lindovska P. Zhu D. Kim J. Wang P. Tang R.-Y. Movassaghi M. Yu J.-Q. J. Am. Chem. Soc. 2014; 136: 10807
    • 61b Yang L. Fu L. Li G. Adv. Synth. Catal. 2017; 359: 2235
  • 62 Leitch JA. Frost CG. Chem. Soc. Rev. 2017; 46: 7145
  • 63 Li J. Warratz S. Zell D. De Sarkar S. Ishikawa EE. Ackermann L. J. Am. Chem. Soc. 2015; 137: 13894
  • 64 Catellani M. Frignani F. Rangoni A. Angew. Chem. Int. Ed. 1997; 36: 119
  • 65 Wang P. Farmer ME. Huo X. Jain P. Shen P.-X. Ishoey M. Bradner JE. Wisniewski SR. Eastgate MD. Yu J.-Q. J. Am. Chem. Soc. 2016; 138: 9269
  • 66 Wang P. Li G.-C. Jain P. Farmer ME. He J. Shen P.-X. Yu J.-Q. J. Am. Chem. Soc. 2016; 138: 14092
  • 67 Shi H. Wang P. Suzuki S. Farmer ME. Yu J.-Q. J. Am. Chem. Soc. 2016; 138: 14876
  • 68 Bag S. Patra T. Modak A. Deb A. Maity S. Dutta U. Dey A. Kancherla R. Maji A. Hazra A. Bera M. Maiti D. J. Am. Chem. Soc. 2015; 137: 11888
  • 69 Ciana C.-L. Phipps RJ. Brandt JR. Meyer F.-M. Gaunt MJ. Angew. Chem. Int. Ed. 2011; 50: 458
    • 70a Sun K. Li Y. Xiong T. Zhang J. Zhang Q. J. Am. Chem. Soc. 2011; 133: 1694

    • There are also two reports of one example of para-selective C–H functionalization of anilines, see:
    • 70b Gu L. Neo BS. Zhang Y. Org. Lett. 2011; 13: 1872
    • 70c Cheng C. Hartwig JF. Science 2014; 343: 853
  • 71 Brand JP. Waser J. Org. Lett. 2012; 14: 744
  • 72 Berzina B. Sokolovs I. Suna E. ACS Catal. 2015; 5: 7008
  • 73 Liang S. Bolte M. Manolikakes G. Chem. Eur. J. 2017; 23: 96
  • 74 Li J.-M. Wang Y.-H. Yu Y. Wu R.-B. Weng J. Lu G. ACS Catal. 2017; 7: 2661
  • 75 Ji X. Li D. Zhou X. Huang H. Deng G.-J. Green. Chem. 2017; 19: 619
  • 76 Leitch JA. McMullin CL. Paterson AJ. Mahon MF. Bhonoah Y. Frost CG. Angew. Chem. Int. Ed. 2017; 56: 15131