Synthesis 2021; 53(17): 2911-2946
DOI: 10.1055/a-1485-5156
special topic
Bond Activation – in Honor of Prof. Shinji Murai

Remote C–H Functionalizations by Ruthenium Catalysis

Korkit Korvorapun
,
,
Torben Rogge
,
Generous support by the DAAD (fellowship to K.K.), the Alexander von Humboldt foundation (fellowship to R.C.S.) and the DFG (SPP1807 and Gottfried-Wilhelm-Leibniz award to L.A.) is gratefully acknowledged.


Dedicated to Prof. Shinji Murai

Abstract

Synthetic transformations of otherwise inert C–H bonds have emerged as a powerful tool for molecular modifications during the last decades, with broad applications towards pharmaceuticals, material sciences, and crop protection. Consistently, a key challenge in C–H activation chemistry is the full control of site-selectivity. In addition to substrate control through steric hindrance or kinetic acidity of C–H bonds, one important approach for the site-selective C–H transformation of arenes is the use of chelation-assistance through directing groups, therefore leading to proximity-induced ortho-C–H metalation. In contrast, more challenging remote C–H activations at the meta- or para-positions continue to be scarce. Within this review, we demonstrate the distinct character of ruthenium catalysis for remote C–H activations until March 2021, highlighting among others late-stage modifications of bio-relevant molecules. Moreover, we discuss important mechanistic insights by experiments and computation, illustrating the key importance of carboxylate-assisted C–H activation with ruthenium(II) complexes.

1 Introduction

2 Stoichiometric Remote C–H Functionalizations

3 meta-C–H Functionalizations

4 para-C–H Functionalizations

5 meta-/ortho-C–H Difunctionalizations

6 Conclusions



Publication History

Received: 24 March 2021

Accepted after revision: 19 April 2021

Accepted Manuscript online:
19 April 2021

Article published online:
20 May 2021

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References


    • For selected reviews on C–H functionalizations, see:
    • 1a Gandeepan P, Müller T, Zell D, Cera G, Warratz S, Ackermann L. Chem. Rev. 2019; 119: 2192
    • 1b Hu Y, Zhou B, Wang C. Acc. Chem. Res. 2018; 51: 816
    • 1c He J, Wasa M, Chan KS. L, Shao Q, Yu J.-Q. Chem. Rev. 2017; 117: 8754
    • 1d Park Y, Kim Y, Chang S. Chem. Rev. 2017; 117: 9247
    • 1e Gensch T, Hopkinson MN, Glorius F, Wencel-Delord J. Chem. Soc. Rev. 2016; 45: 2900
    • 1f Moselage M, Li J, Ackermann L. ACS Catal. 2016; 6: 498
    • 1g Seki M. Org. Process Res. Dev. 2016; 20: 867
    • 1h Ackermann L. Org. Process Res. Dev. 2015; 19: 260
    • 1i Ackermann L. Acc. Chem. Res. 2014; 47: 281
    • 1j Kozhushkov SI, Ackermann L. Chem. Sci. 2013; 4: 886
    • 1k Wencel-Delord J, Glorius F. Nat. Chem. 2013; 5: 369
    • 1l Arockiam PB, Bruneau C, Dixneuf PH. Chem. Rev. 2012; 112: 5879
    • 1m Colby DA, Tsai AS, Bergman RG, Ellman JA. Acc. Chem. Res. 2012; 45: 814
    • 1n Neufeldt SR, Sanford MS. Acc. Chem. Res. 2012; 45: 936
    • 1o Ackermann L. Chem. Rev. 2011; 111: 1315
    • 1p Ackermann L, Vicente R, Kapdi AR. Angew. Chem. Int. Ed. 2009; 48: 9792
    • 1q Bergman RG. Nature 2007; 446: 391

      For selected reviews on remote meta- and para-C–H functionalizations, see:
    • 2a Ghosh M, De Sarkar S. Asian J. Org. Chem. 2018; 7: 1236
    • 2b Mihai MT, Genov GR, Phipps RJ. Chem. Soc. Rev. 2018; 47: 149
    • 2c Li J, De Sarkar S, Ackermann L. Top. Organomet. Chem. 2016; 55: 217

      For selected examples of palladium-catalyzed remote C–H functionalizations, see:
    • 3a Yang T, Kong C, Yang S, Yang Z, Yang S, Ehara M. Chem. Sci. 2020; 11: 113
    • 3b Liu L.-Y, Qiao JX, Yeung K.-S, Ewing WR, Yu J.-Q. J. Am. Chem. Soc. 2019; 141: 14870
    • 3c Xie S, Li S, Ma W, Xu X, Jin Z. Chem. Commun. 2019; 55: 12408
    • 3d Zhao H, Ma G, Xie X, Wang Y, Hao J, Wan W. Chem. Commun. 2019; 55: 3927
    • 3e Farmer ME, Wang P, Shi H, Yu J.-Q. ACS Catal. 2018; 8: 7362
    • 3f Font M, Spencer AR. A, Larrosa I. Chem. Sci. 2018; 9: 7133
    • 3g Shi H, Herron AN, Shao Y, Shao Q, Yu J.-Q. Nature 2018; 558: 581
    • 3h Dong Z, Wang J, Dong G. J. Am. Chem. Soc. 2015; 137: 5887
    • 3i Wang X.-C, Gong W, Fang L.-Z, Zhu R.-Y, Li S, Engle KM, Yu J.-Q. Nature 2015; 519: 334
    • 3j Ye J, Lautens M. Nat. Chem. 2015; 7: 863
    • 3k Zhang Y.-H, Shi B.-F, Yu J.-Q. J. Am. Chem. Soc. 2009; 131: 5072

      For selected examples of iridium-catalyzed remote C–H functionalizations, see:
    • 4a Mihai MT, Williams BD, Phipps RJ. J. Am. Chem. Soc. 2019; 141: 15477
    • 4b Montero Bastidas JR, Oleskey TJ, Miller SL, Smith MR, Maleczka RE. J. Am. Chem. Soc. 2019; 141: 15483
    • 4c Davis HJ, Genov GR, Phipps RJ. Angew. Chem. Int. Ed. 2017; 56: 13351
    • 4d Saito Y, Segawa Y, Itami K. J. Am. Chem. Soc. 2015; 137: 5193
    • 4e Mkhalid IA. I, Barnard JH, Marder TB, Murphy JM, Hartwig JF. Chem. Rev. 2010; 110: 890
    • 4f Cho J.-Y, Tse MK, Holmes D, Maleczka RE, Smith MR. Science 2002; 295: 305
    • 4g Ishiyama T, Takagi J, Ishida K, Miyaura N, Anastasi NR, Hartwig JF. J. Am. Chem. Soc. 2002; 124: 390

      For a recent review on template-assisted C–H functionalizations, see:
    • 5a Dey A, Sinha SK, Achar TK, Maiti D. Angew. Chem. Int. Ed. 2019; 58: 10820

    • For selected examples, see:
    • 5b Brochetta M, Borsari T, Bag S, Jana S, Maiti S, Porta A, Werz DB, Zanoni G, Maiti D. Chem. Eur. J. 2019; 25: 10323
    • 5c Dutta U, Maiti S, Pimparkar S, Maiti S, Gahan LR, Krenske EH, Lupton DW, Maiti D. Chem. Sci. 2019; 10: 7426
    • 5d Xu J, Chen J, Gao F, Xie S, Xu X, Jin Z, Yu J.-Q. J. Am. Chem. Soc. 2019; 141: 1903
    • 5e Xu H.-J, Kang Y.-S, Shi H, Zhang P, Chen Y.-K, Zhang B, Liu Z.-Q, Zhao J, Sun W.-Y, Yu J.-Q, Lu Y. J. Am. Chem. Soc. 2019; 141: 76
    • 5f Bag S, Jayarajan R, Mondal R, Maiti D. Angew. Chem. Int. Ed. 2017; 56: 3182
    • 5g Dutta U, Modak A, Bhaskararao B, Bera M, Bag S, Mondal A, Lupton DW, Sunoj RB, Maiti D. ACS Catal. 2017; 7: 3162
    • 5h 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
    • 5i Bera M, Maji A, Sahoo SK, Maiti D. Angew. Chem. Int. Ed. 2015; 54: 8515
    • 5j Chu L, Shang M, Tanaka K, Chen Q, Pissarnitski N, Streckfuss E, Yu J.-Q. ACS Cent. Sci. 2015; 1: 394
    • 5k Tang R.-Y, Li G, Yu J.-Q. Nature 2014; 507: 215
    • 5l 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
    • 5m Lee S, Lee H, Tan KL. J. Am. Chem. Soc. 2013; 135: 18778
    • 5n Leow D, Li G, Mei T.-S, Yu J.-Q. Nature 2012; 486: 518
  • 6 Kuninobu Y, Ida H, Nishi M, Kanai M. Nat. Chem. 2015; 7: 712

    • For selected examples, see:
    • 7a Koseki Y, Kitazawa K, Miyake M, Kochi T, Kakiuchi F. J. Org. Chem. 2017; 82: 6503
    • 7b Arockiam PB, Fischmeister C, Bruneau C, Dixneuf PH. Green Chem. 2013; 15: 67
    • 7c Aihara Y, Chatani N. Chem. Sci. 2013; 4: 664
    • 7d Ferrer Flegeau E, Bruneau C, Dixneuf PH, Jutand A. J. Am. Chem. Soc. 2011; 133: 10161
    • 7e Oi S, Aizawa E, Ogino Y, Inoue Y. J. Org. Chem. 2005; 70: 3113
    • 7f Kakiuchi F, Kan S, Igi K, Chatani N, Murai S. J. Am. Chem. Soc. 2003; 125: 1698
    • 7g Oi S, Fukita S, Hirata N, Watanuki N, Miyano S, Inoue Y. Org. Lett. 2001; 3: 2579
    • 7h Murai S, Kakiuchi F, Sekine S, Tanaka Y, Kamatani A, Sonoda M, Chatani N. Nature 1993; 366: 529
  • 8 Gagliardo M, Snelders DJ, Chase PA, Klein Gebbink RJ, van Klink GP, van Koten G. Angew. Chem. Int. Ed. 2007; 46: 8558
  • 9 For a review on ruthenium-catalyzed remote meta-C–H functionalizations, see: Leitch JA, Frost CG. Chem. Soc. Rev. 2017; 46: 7145
  • 10 Clark GR, Headford CE. L, Roper WR, Wright LJ, Yap VP. D. Inorg. Chim. Acta 1994; 220: 261
  • 11 Sutter J.-P, Grove DM, Beley M, Collin J.-P, Veldman N, Spek AL, Sauvage J.-P, van Koten G. Angew. Chem., Int. Ed. Engl. 1994; 33: 1282
  • 12 Coudret C, Fraysse S. Chem. Commun. 1998; 663
    • 13a Clark AM, Rickard CE. F, Roper WR, Wright LJ. J. Organomet. Chem. 2000; 598: 262
    • 13b Clark AM, Rickard CE. F, Roper WR, Wright LJ. Organometallics 1999; 18: 2813
  • 14 Ackermann L, Novák P, Vicente R, Hofmann N. Angew. Chem. Int. Ed. 2009; 48: 6045
  • 15 Ackermann L, Hofmann N, Vicente R. Org. Lett. 2011; 13: 1875
  • 16 Hofmann N, Ackermann L. J. Am. Chem. Soc. 2013; 135: 5877
  • 17 Li J, Warratz S, Zell D, De Sarkar S, Ishikawa EE, Ackermann L. J. Am. Chem. Soc. 2015; 137: 13894
  • 18 Paterson AJ, St John-Campbell S, Mahon MF, Press NJ, Frost CG. Chem. Commun. 2015; 51: 12807
  • 19 Li J, Korvorapun K, De Sarkar S, Rogge T, Burns DJ, Warratz S, Ackermann L. Nat. Commun. 2017; 8: 15430
  • 20 Li G, Ma X, Jia C, Han Q, Wang Y, Wang J, Yu L, Yang S. Chem. Commun. 2017; 53: 1261
  • 21 Li G, Gao P, Lv X, Qu C, Yan Q, Wang Y, Yang S, Wang J. Org. Lett. 2017; 19: 2682
    • 22a Zhu Y, Han J, Wang J, Shibata N, Sodeoka M, Soloshonok VA, Coelho JA. S, Toste FD. Chem. Rev. 2018; 118: 3887
    • 22b Wang J, Sánchez-Roselló M, Aceña JL, del Pozo C, Sorochinsky AE, Fustero S, Soloshonok VA, Liu H. Chem. Rev. 2014; 114: 2432
  • 23 Liu X, Xu C, Wang M, Liu Q. Chem. Rev. 2015; 115: 683
  • 24 Ruan Z, Zhang S.-K, Zhu C, Ruth PN, Stalke D, Ackermann L. Angew. Chem. Int. Ed. 2017; 56: 2045
  • 25 Li Z.-Y, Li L, Li Q.-L, Jing K, Xu H, Wang G.-W. Chem. Eur. J. 2017; 23: 3285
  • 26 Paterson AJ, Heron CJ, McMullin CL, Mahon MF, Press NJ, Frost CG. Org. Biomol. Chem. 2017; 15: 5993
  • 27 Korvorapun K, Kaplaneris N, Rogge T, Warratz S, Stückl AC, Ackermann L. ACS Catal. 2018; 8: 886
  • 28 Fumagalli F, Warratz S, Zhang S.-K, Rogge T, Zhu C, Stückl AC, Ackermann L. Chem. Eur. J. 2018; 24: 3984
  • 29 Wang X.-G, Li Y, Liu H.-C, Zhang B.-S, Gou X.-Y, Wang Q, Ma J.-W, Liang Y.-M. J. Am. Chem. Soc. 2019; 141: 13914
  • 30 Gandeepan P, Koeller J, Korvorapun K, Mohr J, Ackermann L. Angew. Chem. Int. Ed. 2019; 58: 9820
  • 31 Sagadevan A, Greaney MF. Angew. Chem. Int. Ed. 2019; 58: 9826
  • 32 Li G, Jia C, Cai X, Zhong L, Zou L, Cui X. Chem. Commun. 2020; 56: 293
  • 33 Jia C, Wang S, Lv X, Li G, Zhong L, Zou L, Cui X. Eur. J. Org. Chem. 2020; 2020: 1992
  • 34 Xu X, Tao N, Fan W.-T, Tu G, Geng J, Zhang J, Zhao Y. J. Org. Chem. 2020; 85: 13868
    • 35a Li G, An J, Jia C, Yan B, Zhong L, Wang J, Yang S. Org. Lett. 2020; 22: 9450
    • 35b Xu H.-B, Chen Y.-J, Chai X.-Y, Yang J.-H, Xu Y.-J, Dong L. Org. Lett. 2021; 23: 2052
    • 35c Zhou Z.-X, Li J.-W, Wang L.-N, Li M, Liu Y.-J, Zeng M.-H. Org. Lett. 2021; 23: 2057
  • 36 Yang S, Yan B, Zhong L, Jia C, Yao D, Yang C, Sun K, Li G. Org. Chem. Front. 2020; 7: 2474
  • 37 Li G, Gao Y, Jia C, Wang S, Yan B, Fang Y, Yang S. Org. Lett. 2020; 22: 8758
  • 38 Choi I, Müller V, Wang Y, Xue K, Kuniyil R, Andreas LB, Karius V, Alauzun JG, Ackermann L. Chem. Eur. J. 2020; 26: 15290
  • 39 Moselage M, Li J, Kramm F, Ackermann L. Angew. Chem. Int. Ed. 2017; 56: 5341
  • 40 Korvorapun K, Moselage M, Struwe J, Rogge T, Messinis AM, Ackermann L. Angew. Chem. Int. Ed. 2020; 59: 18795
  • 41 Ackermann L, Novák P. Org. Lett. 2009; 11: 4966
  • 42 Yang Y, Lan J, You J. Chem. Rev. 2017; 117: 8787
  • 43 Li G, Li D, Zhang J, Shi D.-Q, Zhao Y. ACS Catal. 2017; 7: 4138
  • 44 Li B, Fang S.-L, Huang D.-Y, Shi B.-F. Org. Lett. 2017; 19: 3950
  • 45 Korvorapun K, Kuniyil R, Ackermann L. ACS Catal. 2020; 10: 435

    • For selected reviews on transition-metal-catalyzed carboxylations, see:
    • 46a Fujihara T, Tsuji Y. Beilstein J. Org. Chem. 2018; 14: 2435
    • 46b Tortajada A, Juliá-Hernández F, Börjesson M, Moragas T, Martin R. Angew. Chem. Int. Ed. 2018; 57: 15948

      For selected examples of C–H activations with RuCl3, see:
    • 47a Ackermann L, Althammer A, Born R. Tetrahedron 2008; 64: 6115
    • 47b Ackermann L, Althammer A, Born R. Synlett 2007; 2833
  • 48 Barlow HL, Teskey CJ, Greaney MF. Org. Lett. 2017; 19: 6662
  • 49 Jia C, Wu N, Cai X, Li G, Zhong L, Zou L, Cui X. J. Org. Chem. 2020; 85: 4536
  • 50 Jing K, Li Z.-Y, Wang G.-W. ACS Catal. 2018; 8: 11875

    • For selected reviews on C–X formations, see:
    • 51a Petrone DA, Ye J, Lautens M. Chem. Rev. 2016; 116: 8003
    • 51b Zhao X, Dimitrijević E, Dong VM. J. Am. Chem. Soc. 2009; 131: 3466
    • 51c Hartwig JF. Nature 2008; 455: 314
  • 52 Saidi O, Marafie J, Ledger AE. W, Liu PM, Mahon MF, Kociok-Köhn G, Whittlesey MK, Frost CG. J. Am. Chem. Soc. 2011; 133: 19298
  • 53 Marcé P, Paterson AJ, Mahon MF, Frost CG. Catal. Sci. Technol. 2016; 6: 7068
  • 54 Li G, Lv X, Guo K, Wang Y, Yang S, Yu L, Yu Y, Wang J. Org. Chem. Front. 2017; 4: 1145
  • 55 Wang L, Ackermann L. Chem. Commun. 2014; 50: 1083
  • 56 Teskey CJ, Lui AY. W, Greaney MF. Angew. Chem. Int. Ed. 2015; 54: 11677
  • 57 Yu Q, Hu L, Wang Y, Zheng S, Huang J. Angew. Chem. Int. Ed. 2015; 54: 15284
  • 58 Warratz S, Burns DJ, Zhu C, Korvorapun K, Rogge T, Scholz J, Jooss C, Gelman D, Ackermann L. Angew. Chem. Int. Ed. 2017; 56: 1557
  • 59 Reddy GM, Rao NS, Maheswaran H. Org. Chem. Front. 2018; 5: 1118
  • 60 Fan Z, Lu H, Cheng Z, Zhang A. Chem. Commun. 2018; 54: 6008
    • 61a Nepali K, Lee H.-Y, Liou J.-P. J. Med. Chem. 2019; 62: 2851
    • 61b Ono N. The Nitro Group in Organic Synthesis. 2001. Wiley-VCH; Weinheim:
  • 62 Fan Z, Ni J, Zhang A. J. Am. Chem. Soc. 2016; 138: 8470
  • 63 Liu D, Luo P, Ge J, Jiang Z, Peng Y, Ding Q. J. Org. Chem. 2019; 84: 12784
  • 64 Chen J, Huang T, Gong X, Yu Z.-J, Shi Y, Yan Y.-H, Zheng Y, Liu X, Li G.-B, Wu Y. Adv. Synth. Catal. 2020; 362: 2984
  • 65 Sasmal S, Sinha SK, Lahiri GK, Maiti D. Chem. Commun. 2020; 56: 7100
  • 67 Fan Z, Li J, Lu H, Wang D.-Y, Wang C, Uchiyama M, Zhang A. Org. Lett. 2017; 19: 3199
  • 68 Fan Z, Lu H, Zhang A. J. Org. Chem. 2018; 83: 3245
  • 69 Zhang D, Gao D, Cai J, Wu X, Qin H, Qiao K, Liu C, Fang Z, Guo K. Org. Biomol. Chem. 2019; 17: 9065
  • 70 Guo X, Li C.-J. Org. Lett. 2011; 13: 4977
  • 71 Liu W, Ackermann L. Org. Lett. 2013; 15: 3484
  • 72 Leitch JA, McMullin CL, Paterson AJ, Mahon MF, Bhonoah Y, Frost CG. Angew. Chem. Int. Ed. 2017; 56: 15131
    • 73a Yuan C, Zhu L, Zeng R, Lan Y, Zhao Y. Angew. Chem. Int. Ed. 2018; 57: 1277
    • 73b Yuan C, Zhu L, Chen C, Chen X, Yang Y, Lan Y, Zhao Y. Nat. Commun. 2018; 9: 1189
  • 74 Wang X.-G, Li Y, Zhang L.-L, Zhang B.-S, Wang Q, Ma J.-W, Liang Y.-M. Chem. Commun. 2018; 54: 9541
  • 75 Ackermann L, Vicente R, Potukuchi HK, Pirovano V. Org. Lett. 2010; 12: 5032
  • 76 Cheng Y, He Y, Zheng J, Yang H, Liu J, An G, Li G. Chin. Chem. Lett. 2021; 32: 1437
  • 77 Ramesh B, Jeganmohan M. Org. Lett. 2017; 19: 6000

    • For selected examples of twofold C–H functionalizations, see:
    • 78a Peglow TJ, da Costa GP, Duarte LF. B, Silva MS, Barcellos T, Perin G, Alves D. J. Org. Chem. 2019; 84: 5471
    • 78b Rogge T, Ackermann L. Angew. Chem. Int. Ed. 2019; 58: 15640
    • 78c Zhang W, Baudouin E, Cordier M, Frison G, Nay B. Chem. Eur. J. 2019; 25: 8643
    • 78d Hayashi Y. Chem. Sci. 2016; 7: 866
    • 78e Yu Y.-Q, Xu D.-Z. Synthesis 2015; 47: 1869
    • 78f Li B, Bheeter CB, Darcel C, Dixneuf PH. ACS Catal. 2011; 1: 1221
    • 78g Ackermann L, Born R, Álvarez-Bercedo P. Angew. Chem. Int. Ed. 2007; 46: 6364
  • 79 Li G, Zhu B, Ma X, Jia C, Lv X, Wang J, Zhao F, Lv Y, Yang S. Org. Lett. 2017; 19: 5166
  • 80 Wei W, Yu H, Zangarelli A, Ackermann L. Chem. Sci. 2021; in press DOI: 10.1039/D1SC00986A.