Synthesis 2021; 53(09): 1556-1569
DOI: 10.1055/a-1344-2074
short review

Transition-Metal-Free Strategies for the Synthesis of C-1 Aryl-Substituted Tetrahydroisoquinolines

Pushpinder Singh
a  Department of Chemistry, DAV University, Jalandhar, Punjab 144012, India
,
Aanchal Batra
b  PG Department of Chemistry, Mehr Chand Mahajan DAV College for Women, Sector 36A, Chandigarh 160036, India
,
Kamal Nain Singh
c  Department of Chemistry, Panjab University, Chandigarh 160014, India
,
Mritunjay Mritunjay
a  Department of Chemistry, DAV University, Jalandhar, Punjab 144012, India
› Author Affiliations
P. Singh is grateful to DAV University, Jalandhar (Grant no. DAVU/2020/DA/104, dated 23/01/2020) for financial support.


Abstract

1-Aryl-1,2,3,4-tetrahydroisoquinolines are important structural motifs and are widely found in bioactive molecules, pharmaceuticals and synthetic drugs. In view of increasing environmental awareness, the development of transition-metal-free strategies for the synthesis of these compounds is highly desirable. Metal-free oxidative coupling and lithiation methodologies have emerged as effective tools in this area as they exclude the use of transition-metal catalysts and help in reducing unwanted and toxic-metal-based chemical waste in the environment. This review highlights recent advances on the direct arylation of tetrahydroisoquinolines for the synthesis of the title compounds in the absence of a metal salt. Also, the emphasis has been placed on mechanistic considerations of these reactions.

1 Introduction

2 Arylation of Tetrahydroisoquinolines via Oxidative Coupling

2.1 Arylation Using Grignard Reagents

2.2 Arylation Using Other Organometallic Reagents

2.3 Arylation Using Aryl Organoboranes or Arenes

3 Arylation of Tetrahydroisoquinolines via Lithiation

3.1 Intermolecular Arylation

3.2 Intramolecular Arylation

4 Conclusion and Outlook



Publication History

Received: 05 November 2020

Accepted after revision: 30 December 2020

Publication Date:
04 January 2021 (online)

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

    • 1a O’Connor SE. Alkaloids . In Comprehensive Natural Products II . Liu H.-W, Mander L. Elsevier; Oxford: 2010: 977
    • 1b Zarranz De Ysern ME, Ordoñez LA. Prog. Neuro-Psychopharmacol. 1981; 5: 343
    • 1c Singh IP, Shah P. Expert Opin. Ther. Pat. 2017; 27: 17
    • 1d Mihoubi M, Micale N, Scala A, Jarraya RM, Bouaziz A, Schirmeister T, Risitano F, Piperno A, Grassi G. Molecules 2015; 20: 14902
    • 2a Katritzky AR, Rachwal S, Rachwal B. Tetrahedron 1996; 52: 15031
    • 2b Gangapuram M, Jean R, Mazzio E, Badisa R, Eyunni S, Goodman CB, Redda KK, Soliman KF. Anticancer Res. 2016; 36: 5043
    • 2c Lundström J. Simple Isoquinoline Alkaloids . In The Alkaloids: Chemistry and Pharmacology, Vol. 21. Brossi A. Academic Press; New York: 1983: 255
    • 3a Awuah E, Capretta A. J. Org. Chem. 2010; 75: 5627
    • 3b Yang R, Ruan Q, Zhang BY, Zheng ZL, Miao F, Zhou L, Geng HL. Molecules 2014; 19: 8051
    • 3c Gangapuram M, Eyunni S, Redda KK. J. Cancer Sci. Ther. 2014; 6: 161
    • 5a Cheng P, Huang N, Jiang ZY, Zhang Q, Zheng YT, Chen JJ, Zhang XM, Ma YB. Bioorg. Med. Chem. Lett. 2008; 18: 2475
    • 5b Capilla AS, Romero M, Pujol MD, Caignard DH, Renard P. Tetrahedron 2001; 57: 8297
    • 5c Hanna JN, Ntie-Kang F, Kaiser M, Brun R, Efange SM. N. RSC Adv. 2014; 4: 22856
    • 5d Letavic MA, Keith JM, Jablonowski JA, Stocking EM, Gomez LA, Ly KS, Miller JM, Barbier AJ, Bonaventure P, Boggs JD, Wilson SJ, Miller KL, Lord B, McAllister HM, Tognarelli DJ, Wu J, Abad MC, Schubert C, Lovenberg TW, Carruthers NI. Bioorg. Med. Chem. Lett. 2007; 17: 1047
    • 6a Alonso F, Bosque I, Chinchilla R, Gonzalez-Gomez JC, Guijarro D. Curr. Green Chem. 2019; 6: 105
    • 6b Gitto R, De Luca L, Ferro S, Agnello S, Russo E, De Sarro G, Chimirri A. Chem. Pharm. Bull. 2010; 58: 1602
  • 7 Babu RA, Reddy NS. S, Reddy BJ. M, Reddy BV. S. Synthesis 2014; 46: 2794
  • 8 Gitto R, Ficarra R, Stancanelli R, Guardo M, De Luca L, Barreca ML, Pagano B, Rotondo A, Bruno G, Russo E, De Sarro G, Chimirri A. Bioorg. Med. Chem. 2007; 15: 5417
  • 9 Von Nussbaum F, Miller B, Wild S, Hilger CS, Schumann S, Zorbas H, Beck W, Steglich W. J. Med. Chem. 1999; 42: 3478
    • 10a Calcaterra A, Mangiardi L, Monache GD, Quaglio D, Balducci S, Berardozzi S, Iazzetti A, Franzini R, Botta B, Ghirga F. Molecules 2020; 25: 414
    • 10b Stöckigt J, Antonchick AP, Wu F, Waldmann H. Angew. Chem. Int. Ed. 2011; 50: 8538
  • 12 Huang CY, Kang H, Li J, Li CJ. J. Org. Chem. 2019; 84: 12705
  • 13 Gandhi S. Org. Biomol. Chem. 2019; 17: 9683
  • 14 Clayden J. Organolithiums: Selectivity for Synthesis. Pergamon; New York: 2002
  • 15 Simon MO, Li CJ. Chem. Soc. Rev. 2012; 41: 1415
  • 16 Modern Arylation Methods. Ackermann L. Wiley-VCH; Weinheim: 2009: 1-543
    • 17a Sun CL, Shi ZJ. Chem. Rev. 2014; 114: 9219
    • 17b Baudoin O. Chem. Soc. Rev. 2011; 40: 4902
    • 17c Sousa e Silva FC, Van NT, Wengryniuk SE. J. Am. Chem. Soc. 2020; 142: 64
    • 18a Jain P, Verma P, Xia G, Yu JQ. Nat. Chem. 2017; 9: 140
    • 18b Campos KR, Klapars A, Waldman JH, Dormer PG, Chen CY. J. Am. Chem. Soc. 2006; 128: 3538
    • 19a Li CJ. Acc. Chem. Res. 2009; 42: 335
    • 19b Girard SA, Knauber T, Li CJ. Angew. Chem. Int. Ed. 2014; 53: 74
    • 20a Li Z, Li CJ. Org. Lett. 2004; 6: 4997
    • 20b Li CJ, Li Z. Pure Appl. Chem. 2006; 78: 935
    • 20c Krylov IB, Vil VA, Terent’ev AO. Beilstein J. Org. Chem. 2015; 11: 92
    • 21a Scheuermann CJ. Chem. Asian J. 2010; 5: 436
    • 21b Batra A, Singh P, Singh KN. Eur. J. Org. Chem. 2016; 4927
    • 22a Batra A, Singh P, Singh KN. Eur. J. Org. Chem. 2017; 3739
    • 22b Phillips AM. F, Guedes da Silva M. deF. C, Pombeiro AJ. L. Catalysts 2020; 10: 529
    • 22c Singh KN, Singh P, Kaur A, Singh P. Synlett 2012; 23: 760
  • 23 Kouznetsov VV, Ortiz-Villamizar MC, Méndez-Vargas LY, Galvis CE. P. Curr. Org. Chem. 2020; 24: 809
  • 24 Batra A, Singh KN. Eur. J. Org. Chem. 2020; 6676
  • 25 Singh KN, Singh P, Singh P, Maheshwary Y, Kessar SV, Batra A. Synlett 2013; 24: 1963
  • 26 Hari DP, Schroll P, König B. J. Am. Chem. Soc. 2012; 134: 2958
  • 27 Muramatsu W, Nakano K, Li CJ. Org. Lett. 2013; 15: 3650
  • 28 Muramatsu W, Nakano K, Li CJ. Org. Biomol. Chem. 2014; 12: 2189
  • 29 Singh KN, Kessar SV, Singh P, Singh P, Kaur M, Batra A. Synthesis 2014; 46: 2644
  • 30 Oss G, De Vos SD, Luc KN. H, Harper JB, Nguyen TV. J. Org. Chem. 2018; 83: 1000
  • 31 Peng Z, Yu Z, Chen DH, Liang S, Zhang L, Zhao D, Song L, Jiang C. Synlett 2017; 28: 1835
  • 32 Gil-Negrete JM, Pérez Sestelo J, Sarandeses LA. J. Org. Chem. 2019; 84: 9778
  • 33 Liu X, Sun S, Meng Z, Lou H, Liu L. Org. Lett. 2015; 17: 2396
  • 34 Xie Z, Liu L, Chen W, Zheng H, Xu Q, Yuan H, Lou H. Angew. Chem. Int. Ed. 2014; 53: 3904
  • 35 Schweitzer-Chaput B, Klussmann M. Eur. J. Org. Chem. 2013; 666
  • 36 Chen W, Zheng H, Pan X, Xie Z, Zan X, Sun B, Liu L, Lou H. Tetrahedron Lett. 2014; 55: 2879
  • 37 Yu H, Kim H, Baek SH, Lee D. Front. Chem. 2020; 8: 1
  • 38 Alagiri K, Devadig P, Prabhu KR. Chem. Eur. J. 2012; 5160
  • 39 Dhineshkumar J, Lamani M, Alagiri K, Prabhu KR. Org. Lett. 2013; 15: 1092
    • 40a Beak P, Basu A, Gallagher DJ, Park YS, Thayumanavan S. Acc. Chem. Res. 1996; 29: 552
    • 40b Beak P, Kerrick ST, Wu S, Chu J. J. Am. Chem. Soc. 1994; 116: 3231
    • 40c Beak P, Lee WK. J. Org. Chem. 1993; 58: 1109
    • 41a Kessar SV, Singh P. Chem. Rev. 1997; 97: 721
    • 41b Kessar SV. Pure Appl. Chem. 1996; 68: 509
    • 41c Kessar SV, Singh P, Singh KN, Venugopalan P, Kaur A, Bharatam PV, Sharma AK. J. Am. Chem. Soc. 2007; 129: 4506
    • 41d Kessar SV, Singh P, Singh KN, Singh SK. Synlett 2001; 517
    • 41e Kessar SV, Singh P, Singh KN, Dutt M. J. Chem. Soc., Chem. Commun. 1991; 570
    • 41f Singh KN, Singh P, Sharma AK, Singh P, Kessar SV. Synth. Commun. 2010; 40: 3716
  • 42 Singh KN, Singh P, Sharma E, Deol YS. Synthesis 2014; 46: 1739
  • 43 Singh KN, Singh P, Kaur M, Sharma E. ChemistrySelect 2017; 2: 2213
  • 44 Li X, Coldham I. J. Am. Chem. Soc. 2014; 136: 5551
  • 45 Kaur M, Sharma E, Singh A, Singh P, Singh KN. Eur. J. Org. Chem. 2016; 4159