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Transient directing ligands for selective metal-catalysed C–H activation

Nature Reviews Chemistry volume 5, pages 646–659 (2021)Cite this article

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Abstract

C–H activation is a ‘simple-to-complex’ transformation that nature has perfected over millions of years of evolution. Transition-metal-catalysed C–H activation has emerged as an expeditious means to expand the chemical space by introducing diverse functionalities. Notably, among the strategies to selectively cleave a particular C–H bond, the catalytic use of a small molecule as co-catalyst to generate a transient directing group, which provides a balance between step economy and chemical productivity, has gained immense attention in recent years. This allows one to convert a desired C–H bond irrespective of its geometrical or stereochemical configuration. This Review describes the various transient directing groups used in C–H activation and explains their mechanistic significance.

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Fig. 1: Strategies for site-selective C–H functionalization.
Fig. 2: Aromatic amines as transient moderators for C(sp2)–H activation.
Fig. 3: Aliphatic amines as transient moderators for C(sp3)–H activation.
Fig. 4: Amino acids as transient moderators for C(sp3)–H and C(sp2)–H activation.
Fig. 5: Chiral transient moderators for asymmetric synthesis.
Fig. 6: Chiral transient moderators enable asymmetric C–H activation.
Fig. 7: Carbonyls and phosphites as transient moderators.

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References

  1. Crabtree, R. H. & Lei, A. Introduction: CH activation. Chem. Rev. 117, 8481–8482 (2017).

    Article  CAS  PubMed  Google Scholar 

  2. Kapdi, A. R. & Maiti, D. (eds) Strategies for Palladium-Catalyzed Non-Directed and Directed C–H Bond Functionalization (Elsevier, 2017).

  3. Dey, A., Sinha, S. K., Achar, T. K. & Maiti, D. Accessing remote meta- and para-C(sp2)–H bonds with covalently attached directing groups. Angew. Chem. Int. Ed. 58, 10820–10843 (2019).

    Article  CAS  Google Scholar 

  4. Meng, G. et al. Achieving site-selectivity for C–H activation processes based on distance and geometry: a carpenter’s approach. J. Am. Chem. Soc. 142, 10571–10591 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Dutta, U., Maiti, S., Bhattacharya, T. & Maiti, D. Arene diversification through distal C(sp2)–H functionalization. Science 372, eabd5992 (2021).

    Article  CAS  PubMed  Google Scholar 

  6. Goswami, N. & Maiti, D. An update on distal C(sp3)–H functionalization involving 1,5-HAT emerging from nitrogen radicals. Isr. J. Chem. 60, 303–312 (2020).

    Article  CAS  Google Scholar 

  7. Dutta, U. et al. Para-selective arylation of arenes: a direct route to biaryls by norbornene relay palladation. Angew. Chem. Int. Ed. 132, 21017–21022 (2020).

    Article  Google Scholar 

  8. Davis, H. J. & Phipps, R. J. Harnessing non-covalent interactions to exert control over regioselectivity and site-selectivity in catalytic reactions. Chem. Sci. 8, 864–877 (2017).

    Article  CAS  PubMed  Google Scholar 

  9. Gandeepan, P. & Ackermann, L. Transient directing groups for transformative C–H activation by synergistic metal catalysis. Chem 4, 199–222 (2018).

    Article  CAS  Google Scholar 

  10. St John Campbell, S. & Bull, J. A. Transient imines as ‘next generation’ directing groups for the catalytic functionalisation of C–H bonds in a single operation. Org. Biomol. Chem. 16, 4582–4595 (2018).

    Article  Google Scholar 

  11. Bhattacharya, T., Pimparkar, S. & Maiti, D. Combining transition metals and transient directing groups for C–H functionalizations. RSC Adv. 8, 19456–19464 (2018).

    Article  CAS  PubMed Central  Google Scholar 

  12. Niu, B. et al. Transient ligand-enabled transition metal-catalyzed C–H functionalization. ChemSusChem 12, 2955–2969 (2019).

    Article  CAS  PubMed  Google Scholar 

  13. Higham, J. I. et al. Transient imine directing groups for the C–H functionalisation of aldehydes, ketones and amines: an update 2018–2020. Org. Biomol. Chem. 18, 7291–7315 (2020).

    Article  CAS  PubMed  Google Scholar 

  14. Liao, G. et al. Transition metal-catalyzed enantioselective C–H functionalization via chiral transient directing group strategies. Angew. Chem. Int. Ed. 59, 19773–19786 (2020).

    Article  CAS  Google Scholar 

  15. Liang, Y.-F. et al. Ligand-promoted Pd-catalyzed oxime ether directed C–H hydroxylation of arenes. ACS Catal. 5, 6148–6152 (2015).

    Article  CAS  Google Scholar 

  16. Xu, L.-L. et al. Copper mediated C–H amination with oximes: en route to primary anilines. Chem. Sci. 9, 5160–5164 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Engle, K. M., Mei, T.-S., Wasa, M. & Yu, J.-Q. Weak coordination as a powerful means for developing broadly useful C–H functionalization reactions. Acc. Chem. Res. 45, 788–802 (2012).

    Article  CAS  PubMed  Google Scholar 

  18. Jun, C. H., Lee, H. & Hong, J.-B. Hydroacylation of 1-alkene with heteroaromatic aldehyde by Rh(i) and additives. J. Org. Chem. 62, 1200–1201 (1997).

    Article  CAS  Google Scholar 

  19. Jun, C. H., Lee, D.-Y., Lee, H. & Hong, J.-B. A highly active catalyst system for intermolecular hydroacylation. Angew. Chem. Int. Ed. 39, 3070–3072 (2000).

    Article  CAS  Google Scholar 

  20. Vautravers, N. R., Regent, D. D. & Breit, B. Inter- and intramolecular hydroacylation of alkenes employing a bifunctional catalyst system. Chem. Commun. 47, 6635–6637 (2011).

    Article  CAS  Google Scholar 

  21. Beletskiy, E. V., Sudheer, C. & Douglas, C. J. Cooperative catalysis approach to intramolecular hydroacylation. J. Org. Chem. 77, 5884–5893 (2012).

    Article  CAS  PubMed  Google Scholar 

  22. Jun, C.-H. & Hwang, D.-C. Simultaneous hydrogenation and hydroacylation of vinyl groups in polybutadiene by use of a rhodium catalyst. Polymer 39, 7143–7147 (1998).

    Article  CAS  Google Scholar 

  23. Tan, P. W., Juwaini, N. A. B. & Seayad, J. Rhodium(iii)-amine dual catalysis for the oxidative coupling of aldehydes by directed C–H activation: synthesis of phthalides. Org. Lett. 15, 5166–5169 (2013).

    Article  CAS  PubMed  Google Scholar 

  24. Hu, W., Zheng, Q., Sun, S. & Cheng, J. Rh(iii)-catalyzed bilateral cyclization of aldehydes with nitrosos toward unsymmetrical acridines proceeding with C–H functionalization enabled by a transient directing group. Chem. Commun. 53, 6263–6266 (2017).

    Article  CAS  Google Scholar 

  25. Liu, X., Wang, Z., Chen, Q., He, M.-Y. & Wang, L. Rhodium-catalyzed ortho-C–H olefination of aromatic aldehydes employing transient directing strategy. Appl. Organomet. Chem. 32, e4039 (2018).

    Google Scholar 

  26. Wang, X., Song, S. & Jiao, N. Rh-catalyzed transient directing group promoted C–H amidation of benzaldehydes utilizing dioxazolones. Chin. J. Chem. 36, 213–216 (2018).

    Article  CAS  Google Scholar 

  27. Hande, A. K., Ramesh, V. B. & Prabhu, K. R. Rh(iii)-catalyzed ortho-C-(sp2)–H amidation of ketones and aldehydes under synergistic ligand-accelerated catalysis. Chem. Commun. 54, 12113–12116 (2018).

    Article  CAS  Google Scholar 

  28. Shen, J., Liu, X., Wang, L., Chen, Q. & He, M. Rh(iii)-catalyzed synthesis of unsymmetrical acridines from aldehydes and azides using transient directing strategy in biomass-derived γ-valerolactone. Synth. Commun. 48, 1354–1362 (2018).

    Article  CAS  Google Scholar 

  29. Kim, S. et al. Dual role of anthranils as amination and transient directing group sources: synthesis of 2-acyl acridines. Org. Lett. 20, 4010–4014 (2018).

    Article  CAS  PubMed  Google Scholar 

  30. Liu, X.-H. et al. Diverse ortho-C(sp2)–H functionalization of benzaldehydes using transient directing groups. J. Am. Chem. Soc. 139, 888–896 (2017). This paper describes a series of benzaldehyde ortho-functionalization reactions.

    Article  CAS  PubMed  Google Scholar 

  31. Mu, D., Wang, X., Chen, G. & He, G. Iridium-catalyzed ortho-C(sp2)–H amidation of benzaldehydes with organic azides. J. Org. Chem. 82, 4497–4503 (2017).

    Article  CAS  PubMed  Google Scholar 

  32. Li, F. et al. Assembly of diverse spirocyclic pyrrolidines via transient directing group enabled ortho-C(sp2)–H alkylation of benzaldehydes. Org. Lett. 20, 146–149 (2018).

    Article  CAS  PubMed  Google Scholar 

  33. Zheng, Y., Tice, C. M. & Singh, S. B. The use of spirocyclic scaffolds in drug discovery. Bioorg. Med. Chem. Lett. 24, 3673–3682 (2014).

    Article  CAS  PubMed  Google Scholar 

  34. Rasheed, O. & Zhang, F.-L. Ruthenium-catalyzed ortho-C(sp2)–H amidation of benzaldehydes with organic azides. Synlett 29, 1033–1036 (2018).

    Article  CAS  Google Scholar 

  35. Chen, X.-Y., Ozturk, S. & Sorensen, E. J. Synthesis of fluorenones from benzaldehydes and aryl iodides: dual C–H functionalizations using a transient directing group. Org. Lett. 19, 1140–1143 (2017).

    Article  CAS  PubMed  Google Scholar 

  36. Chen, X.-Y., Ozturk, S. & Sorensen, E. J. Pd-catalyzed ortho C–H hydroxylation of benzaldehydes using a transient directing group. Org. Lett. 19, 6280–6283 (2017).

    Article  CAS  PubMed  Google Scholar 

  37. Chen, X.-Y. & Sorensen, E. J. Pd-catalyzed, ortho-C–H methylation and fluorination of benzaldehydes using orthanilic acids as transient directing groups. J. Am. Chem. Soc. 140, 2789–2792 (2018).

    Article  CAS  PubMed  Google Scholar 

  38. Mu, D., He, G. & Chen, G. Palladium-catalyzed ortho-C–H arylation of benzaldehydes using ortho-sulfinyl aniline as transient auxiliary. Chem. Asian J. 13, 2423–2426 (2018).

    Article  CAS  PubMed  Google Scholar 

  39. Ichikawa, Y. et al. Selective ablation of β-galactosidase-expressing cells with a rationally designed activatable photosensitizer. Angew. Chem. Int. Ed. 53, 6772–6775 (2014).

    Article  CAS  Google Scholar 

  40. Qiao, H. et al. Palladium-catalyzed direct ortho-C–H selenylation of benzaldehydes using benzidine as a transient directing group. Org. Lett. 21, 6914–6918 (2019).

    Article  CAS  PubMed  Google Scholar 

  41. Li, F. et al. Monodentate transient directing group enabled Pd-catalyzed ortho-C–H methoxylation and chlorination of benzaldehydes. Org. Lett. 21, 3692–3695 (2019).

    Article  CAS  PubMed  Google Scholar 

  42. Yong, Q., Suna, B. & Zhang, F.-L. Palladium-catalyzed ortho-C(sp2)–H bromination of benzaldehydes via a monodentate transient directing group strategy. Tetrahedron Lett. 60, 151263–151266 (2019).

    Article  CAS  Google Scholar 

  43. Khan, B., Dwivedi, V. & Sundararaju, B. Cp*Co(III)-catalyzed o-amidation of benzaldehydes with dioxazolones using transient directing group strategy. Adv. Synth. Catal. 362, 1195–1200 (2020).

    Article  CAS  Google Scholar 

  44. Huang, J. et al. Cobalt-catalyzed ortho-C(sp2)–H amidation of benzaldehydes with dioxazolones using transient directing groups. Org. Lett. 21, 7342–7345 (2019).

    Article  CAS  PubMed  Google Scholar 

  45. Ma, F., Lei, M. & Hu, L. Acetohydrazone: a transient directing group for arylation of unactivated C(sp3)–H bonds. Org. Lett. 18, 2708–2711 (2016).

    Article  CAS  PubMed  Google Scholar 

  46. Wen, F. & Li, Z. Semicarbazide: a transient directing group for C(sp3)–H arylation of 2-methylbenzaldehydes. Adv. Synth. Catal. 362, 133–138 (2020).

    Article  CAS  Google Scholar 

  47. Huple, D. B., Chen, C. H., Das, A. & Liu, R. S. Silver-catalyzed exo-dig-azacyclization/[3+2] cycloaddition cascades on 1-tosylhydrazon-4-oxy-5-yne substrates: applicability to diverse alkenes. Adv. Synth. Catal. 353, 1877–1882 (2011).

    Article  CAS  Google Scholar 

  48. Paradkar, M. V., Kulkarni, S. A., Joseph, A. R. & Ranade, A. An efficient synthesis of dimethoxyphthalides. J. Chem. Res. 8, 364–366 (2000).

    Article  Google Scholar 

  49. Nicolaou, K. C., Montagnon, T., Vassilikogiannakis, G. & Mathison, C. J. N. The total synthesis of coleophomones B, C, and D. J. Am. Chem. Soc. 127, 8872–8888 (2005).

    Article  CAS  PubMed  Google Scholar 

  50. Chen, J., Bai, C., Tong, X., Liu, D. & Bao, Y.-S. A dual role for acetohydrazide in Pd-catalyzed controlled C(sp3)–H acetoxylation of aldehydes. RSC Adv. 10, 12192–12196 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. St John-Campbell, S., White, A. J. P. & Bull, J. A. Single operation palladium catalysed C(sp3)–H functionalisation of tertiary aldehydes: investigations into transient imine directing groups. Chem. Sci. 8, 4840–4847 (2017).

    Article  Google Scholar 

  52. St John Campbell, S. & Bull, J. A. Intramolecular palladium(ii)/(iv) catalysed C(sp3)–H arylation of tertiary aldehydes using a transient imine directing group. Chem. Commun. 55, 9172–9175 (2019).

    Article  Google Scholar 

  53. Wang, J. et al. Palladium-catalyzed β-C–H arylation of ketones using amino amide as a transient directing group: applications to synthesis of phenanthridinone alkaloids. Adv. Synth. Catal. 360, 3709–3715 (2018).

    Article  CAS  Google Scholar 

  54. St John-Campbell, S., White, A. J. P. & Bull, J. A. Methylene C(sp3)–H β,β′-diarylation of cyclohexanecarbaldehydes promoted by a transient directing group and pyridone ligand. Org. Lett. 22, 1807–1812 (2020).

    Article  CAS  Google Scholar 

  55. Shao, Q., Wu, K., Zhuang, Z., Qian, S. & Yu, J.-Q. From Pd(OAc)2 to chiral catalysts: the discovery and development of bifunctional mono-N-protected amino acid ligands for diverse C–H functionalization reactions. Acc. Chem. Res. 53, 833–851 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zhang, F.-L., Hong, K., Li, T.-J., Park, H. & Yu, J.-Q. Functionalization of C(sp3)–H bonds using a transient directing group. Science 351, 252–256 (2016). This is a pioneering work on C(sp3)–H functionalization using a TDG.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Yang, K., Li, Q., Liu, Y., Li, G. & Ge, H. Catalytic C–H arylation of aliphatic aldehydes enabled by a transient ligand. J. Am. Chem. Soc. 138, 12775–12778 (2016). This work highlights C(sp3)–H arylation of aliphatic aldehydes using a TDG.

    Article  CAS  PubMed  Google Scholar 

  58. Pan, L., Yang, K., Li, G. & Ge, H. Palladium-catalyzed site-selective arylation of aliphatic ketones enabled by a transient ligand. Chem. Commun. 54, 2759–2762 (2018).

    Article  CAS  Google Scholar 

  59. Hong, K., Park, H. & Yu, J.-Q. Methylene C(sp3)–H arylation of aliphatic ketones using a transient directing group. ACS Catal. 7, 6938–6941 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Wu, Y.-J., Yao, Q.-J., Chen, H.-M., Liao, G. & Shi, B.-F. Palladium-catalyzed ortho-C–H silylation of biaryl aldehydes using a transient directing group. Sci. China Chem. 63, 875–880 (2020).

    Article  CAS  Google Scholar 

  61. Zhang, X.-L. et al. Dehydrogenative β-arylation of saturated aldehydes using transient directing groups. Org. Lett. 21, 2731–2735 (2019).

    Article  CAS  PubMed  Google Scholar 

  62. Guan, Z., Chen, S., Huang, Y. & Yao, H. Rhodium(iii)-catalyzed intramolecular olefin hydroarylation of aromatic aldehydes using a transient directing group. Org. Lett. 21, 3959–3962 (2019).

    Article  CAS  PubMed  Google Scholar 

  63. Thrimurtulu, N. et al. Palladium catalyzed regioselective C4-arylation and olefination of indoles and azaindoles. Adv. Synth. Catal. 361, 1441–1446 (2019).

    Article  CAS  Google Scholar 

  64. Xu, J. et al. Pd-catalyzed direct ortho-C–H arylation of aromatic ketones enabled by a transient directing group. Org. Lett. 19, 1562–1565 (2017).

    Article  CAS  PubMed  Google Scholar 

  65. Li, B. et al. Transient ligand enabled ortho-arylation of five-membered heterocyclic carbonyl compounds: facile build-up of mechanochromic materials. Angew. Chem. Int. Ed. 57, 3401–3405 (2018).

    Article  CAS  Google Scholar 

  66. Wang, D.-Y. et al. Direct dehydrogenative arylation of benzaldehydes with arenes using transient directing groups. Org. Lett. 20, 1794–1797 (2018).

    Article  CAS  PubMed  Google Scholar 

  67. Gou, B.-B., Liu, H.-F., Chen, J. & Zhou, L. Palladium-catalyzed site-selective C(sp3)–H arylation of phenylacetaldehydes. Org. Lett. 21, 7084–7088 (2019).

    Article  CAS  PubMed  Google Scholar 

  68. Wang, Z., Dong, W., Sun, B., Yu, Q. & Zhang, F.-L. Cascade reaction for the synthesis of polycyclic aromatic hydrocarbons via transient directing group strategy. Tetrahedron 75, 4031–4041 (2019).

    Article  CAS  Google Scholar 

  69. Park, H., Yoo, K., Jung, B. & Kim, M. Direct synthesis of anthracenes from o-tolualdehydes and aryl iodides through Pd(ii)-catalyzed sp3 C–H arylation and electrophilic aromatic cyclization. Tetrahedron. 74, 2048–2055 (2018).

    Article  CAS  Google Scholar 

  70. Smyth, J. E., Butler, N. M. & Keller, P. A. A twist of nature–the significance of atropisomers in biological systems. Nat. Prod. Rep. 32, 1562–1583 (2015).

    Article  CAS  PubMed  Google Scholar 

  71. Gustafson, J., Lim, D. & Miller, S. J. Dynamic kinetic resolution of biaryl atropisomers via peptide-catalyzed asymmetric bromination. Science 328, 1251–1255 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Newton, C. G., Wang, S.-G., Oliveira, C. C. & Cramer, N. Catalytic enantioselective transformations involving C–H bond cleavage by transition-metal complexes. Chem. Rev. 117, 8908–8976 (2017).

    Article  CAS  PubMed  Google Scholar 

  73. Yao, Q.-J., Zhang, S., Zhan, B.-B. & Shi, B.-F. Atroposelective synthesis of axially chiral biaryls by palladium-catalyzed asymmetric C–H olefination enabled by a transient chiral auxiliary. Angew. Chem. Int. Ed. 56, 6617–6621 (2017). This is the first atroposelective functionalization using a TDG.

    Article  CAS  Google Scholar 

  74. Fan, J. et al. Asymmetric total synthesis of TAN-1085 facilitated by Pd-catalyzed atroposelective C–H olefination. Org. Lett. 21, 3352–3356 (2019).

    Article  CAS  PubMed  Google Scholar 

  75. Ohmori, K. et al. Concise total synthesis and structure assignment of TAN-1085. Angew. Chem. Int. Ed. 43, 3167–3171 (2004).

    Article  CAS  Google Scholar 

  76. Liao, G. et al. Pd-catalyzed atroposelective C–H allylation through β-O elimination: diverse synthesis of axially chiral biaryls. Angew. Chem. Int. Ed. 57, 17151–17155 (2018).

    Article  CAS  Google Scholar 

  77. Liao, G. et al. Scalable, stereocontrolled formal syntheses of (+)-isoschizandrin and (+)-steganone: development and applications of palladium(ii)-catalyzed atroposelective C–H alkynylation. Angew. Chem. Int. Ed. 57, 3661–3665 (2018).

    Article  CAS  Google Scholar 

  78. Liao, G. et al. Synthesis of chiral aldehyde catalysts by Pd-catalyzed atroposelective C–H naphthylation. Angew. Chem. Int. Ed. 58, 11464–11468 (2019).

    Article  CAS  Google Scholar 

  79. Zhang, S. et al. Enantioselective synthesis of atropisomers featuring pentatomic heteroaromatics by Pd-catalyzed C–H alkynylation. ACS Catal. 9, 1956–1961 (2019).

    Article  CAS  Google Scholar 

  80. Chen, H.-M. et al. Pd-catalyzed atroposelective C–H allylation and alkenylation: access to enantioenriched atropisomers featuring pentatomic heteroaromatics. Organometallics 38, 4022–4028 (2019).

    Article  CAS  Google Scholar 

  81. Zhang, J., Xu, Q., Wu, J., Fan, J. & Xie, M. Construction of N–C axial chirality through atroposelective C–H olefination of N-arylindoles by palladium/amino acid cooperative catalysis. Org. Lett. 21, 6361–6365 (2019).

    Article  CAS  PubMed  Google Scholar 

  82. Song, H. et al. Synthesis of axially chiral styrenes via Pd-catalyzed asymmetric C–H olefination enabled by an amino amide transient directing group. Angew. Chem. Int. Ed. 59, 6576–6580 (2020).

    Article  CAS  Google Scholar 

  83. Xu, J., Liu, Y., Zhang, J., Xua, X. & Jin, Z. Palladium-catalyzed enantioselective C(sp2)–H arylation of ferrocenyl ketones enabled by a chiral transient directing group. Chem. Commun. 54, 689–692 (2018).

    Article  CAS  Google Scholar 

  84. Rueda-Becerril, M. et al. Fluorine transfer to alkyl radicals. J. Am. Chem. Soc. 134, 4026–4029 (2012).

    Article  CAS  PubMed  Google Scholar 

  85. Bloom, S. et al. A polycomponent metal-catalyzed aliphatic, allylic, and benzylic fluorination. Angew. Chem. Int. Ed. 51, 10580–10583 (2012).

    Article  CAS  Google Scholar 

  86. Liu, W. et al. Oxidative aliphatic C–H fluorination with fluoride ion catalyzed by a manganese porphyrin. Science 337, 1322–1325 (2012).

    Article  CAS  PubMed  Google Scholar 

  87. Kalow, J. A. & Doyle, A. G. Enantioselective ring opening of epoxides by fluoride anion promoted by a cooperative dual-catalyst system. J. Am. Chem. Soc. 132, 3268–3269 (2010).

    Article  CAS  PubMed  Google Scholar 

  88. Katcher, M. H. & Doyle, A. G. Palladium-catalyzed asymmetric synthesis of allylic fluorides. J. Am. Chem. Soc. 132, 17402–17404 (2010).

    Article  CAS  PubMed  Google Scholar 

  89. Park, H., Verma, P., Hong, K. & Yu, J.-Q. Controlling Pd(iv) reductive elimination pathways enables Pd(ii)-catalysed enantioselective C(sp3)–H fluorination. Nat. Chem. 10, 755–762 (2018). This work highlights Pd(ii)-catalysed enantioselective C(sp3)–H fluorination using a TDG.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Xiao, L.-J. et al. Pd(ii)-catalyzed enantioselective C(sp3)–H arylation of cyclobutyl ketones using a chiral transient directing group. Angew. Chem. Int. Ed. 59, 9594–9600 (2020).

    Article  CAS  Google Scholar 

  91. Song, G., Wang, F. & Li, X. C–C, C–O and C–N bond formation via rhodium(iii)-catalyzed oxidative C–H activation. Chem. Soc. Rev. 41, 3651–3678 (2012).

    Article  CAS  PubMed  Google Scholar 

  92. Ye, B. & Cramer, N. Chiral cyclopentadienyl ligands as stereocontrolling element in asymmetric C–H functionalization. Science 338, 504–506 (2012).

    Article  CAS  PubMed  Google Scholar 

  93. Audic, B., Wodrich, M. D. & Cramer, N. Mild complexation protocol for chiral CpxRh and Ir complexes suitable for in situ catalysis. Chem. Sci. 10, 781–787 (2019).

    Article  CAS  PubMed  Google Scholar 

  94. Li, G., Jiang, J., Xie, H. & Wang, J. Introducing the chiral transient directing group strategy to rhodium(iii)-catalyzed asymmetric C–H activation. Chem. Eur. J. 25, 4688–4694 (2019).

    Article  CAS  PubMed  Google Scholar 

  95. Li, Z.-Y. et al. Ruthenium-catalyzed enantioselective C–H functionalization: a practical access to optically active indoline derivatives. J. Am. Chem. Soc. 141, 15730–15736 (2019).

    Article  CAS  PubMed  Google Scholar 

  96. Li, G., Liu, Q., Vasamsetty, L., Guo, W. & Wang, J. A rare ruthenium(ii)-catalyzed inert C–H bond activation assisted by a chiral transient directing group. Angew. Chem. Int. Ed. 59, 3475–3479 (2020).

    Article  CAS  Google Scholar 

  97. Oxtoby, L. J. et al. A transient-directing-group strategy enables enantioselective reductive Heck hydroarylation of alkenes. Angew. Chem. Int. Ed. 59, 8885–8890 (2020).

    Article  CAS  Google Scholar 

  98. Liu, Y. & Ge, H. Site-selective C–H arylation of primary aliphatic amines enabled by a catalytic transient directing group. Nat. Chem. 9, 26–32 (2017).

    Article  CAS  Google Scholar 

  99. Wu, Y., Chen, Y.-Q., Liu, T., Eastgate, M. D. & Yu, J.-Q. Pd-catalyzed γ-C(sp3)–H arylation of free amines using a transient directing group. J. Am. Chem. Soc. 138, 14554–14557 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Chen, Y.-Q., Wu, Y., Wang, Z., Qiao, J. X. & Yu, J.-Q. Transient directing group enabled Pd-catalyzed γ-C(sp3)–H oxygenation of alkyl amines. ACS Catal. 10, 5657–5662 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Hu, X.-X. et al. The stabilizing effect of the transient imine directing group in the Pd(ii)-catalyzed C(sp3)–H arylation of free primary amines. Org. Chem. Front. 5, 1670–1678 (2018).

    Article  CAS  Google Scholar 

  102. Lin, H., Wang, C., Bannister, T. D. & Kamenecka, T. M. Site-selective γ-C(sp3)–H and γ-C(sp2)–H arylation of free amino esters promoted by a catalytic transient directing group. Chem. Eur. J. 24, 9535–9541 (2018).

    Article  CAS  PubMed  Google Scholar 

  103. Chen, Y.-Q. et al. Overcoming the limitations of γ- and δ-C–H arylation of amines through ligand development. J. Am. Chem. Soc. 140, 17884–17894 (2018).

    Article  CAS  PubMed  Google Scholar 

  104. St John-Campbell, S., Ou, A. K. & Bull, J. A. Palladium-catalyzed C(sp3)–H arylation of primary amines using a catalytic alkyl acetal to form a transient directing group. Chem. Eur. J. 24, 17838–17843 (2018).

    Article  CAS  Google Scholar 

  105. Chen, Y.-Q. et al. Pd-catalyzed γ-C(sp3)–H fluorination of free amines. J. Am. Chem. Soc. 142, 9966–9974 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Bedford, R. B., Coles, S. J., Hursthouse, M. B. & Limmert, M. E. The catalytic intermolecular ortho-arylation of phenols. Angew. Chem. Int. Ed. 42, 112–114 (2003).

    Article  CAS  Google Scholar 

  107. Bedford, R. B. & Limmert, M. E. Catalytic intermolecular ortho-arylation of phenols. J. Org. Chem. 68, 8669–8682 (2003).

    Article  CAS  PubMed  Google Scholar 

  108. Bedford, R. B. et al. Simple rhodium–chlorophosphine pre-catalysts for the ortho-arylation of phenols. Chem. Commun. https://doi.org/10.1039/B718128K (2008).

    Article  Google Scholar 

  109. Oi, S., Watanabe, S.-I., Fukita, S. & Inoue, Y. Rhodium-HMPT-catalyzed direct ortho arylation of phenols with aryl bromides. Tetrahedron Lett. 44, 8665–8668 (2003).

    Article  CAS  Google Scholar 

  110. Guo, R.-T., Zhang, Y.-L., Tian, J.-J., Zhu, K.-Y. & Wang, X.-C. Rhodium-catalyzed ortho-selective carbene C–H insertion of unprotected phenols directed by a transient oxonium ylide intermediate. Org. Lett. 22, 908–913 (2020).

    Article  CAS  PubMed  Google Scholar 

  111. Yang, J.-F. et al. Ligand-accelerated direct C–H arylation of BINOL: a rapid one-step synthesis of racemic 3,3′-diaryl BINOLs. Angew. Chem. Int. Ed. 55, 14116–14120 (2016).

    Article  CAS  Google Scholar 

  112. Lewis, J. C., Wu, J., Bergman, R. G. & Ellman, J. A. Preagostic Rh–H interactions and C–H bond functionalization: a combined experimental and theoretical investigation of rhodium(i) phosphinite complexes. Organometallics 24, 5737–5746 (2005).

    Article  CAS  Google Scholar 

  113. Carrión, M. C. & Cole-Hamilton, D. J. Halide-free ethylation of phenol by multifunctional catalysis using phosphinite ligands. Chem. Commun. https://doi.org/10.1039/B610038D (2006).

    Article  Google Scholar 

  114. Li, D. Y. et al. Cascade reaction of alkynols and 7-oxabenzonorbornadienes involving transient hemiketal group directed C–H activation and synergistic RhIII/ScIII catalysis. Org. Lett. 18, 5134–5137 (2016).

    Article  CAS  PubMed  Google Scholar 

  115. Mohr, Y. et al. Regiospecificity in ligand-free Pd-catalyzed C–H arylation of indoles: LiHMDS as base and transient directing group. ACS Catal. 10, 2713–2719 (2020).

    Article  CAS  Google Scholar 

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Acknowledgements

Financial support was provided by Science and Engineering Research Board (SERB), India (CRG/2018/003951). University Grants Commission of India (UGC India) supported the scholarships to N.G. and T.B.

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  1. Department of Chemistry, IIT Bombay, Powai, Mumbai, India

    Nupur Goswami, Trisha Bhattacharya & Debabrata Maiti

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  1. Nupur Goswami
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  3. Debabrata Maiti
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N.G. researched literature for the article and contributed to discussion of content and writing. T.B. and D.M. contributed to discussion and reviewing/editing the manuscript before submission.

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Correspondence to Debabrata Maiti.

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Goswami, N., Bhattacharya, T. & Maiti, D. Transient directing ligands for selective metal-catalysed C–H activation. Nat Rev Chem 5, 646–659 (2021). https://doi.org/10.1038/s41570-021-00311-3

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