Practical and sustainable preparation of pyrrolo[2,3-b]indoles by Cu/Fe catalyzed intramolecular C(sp²)–H amination

Abstract

A practical, robust and chemoselective approach toward the synthesis of pyrrolo[2,3-b]indoles via direct intramolecular C–H bond amination of α-indolylhydrazones has been achieved. This base- and oxidant-free chemoselective transformation relies on a Cu/Fe co-catalyst system that operates at 50 °C in air with water as the only reaction medium. The easy product isolation together with the recyclable catalyst aqueous system (reused at least five times, maintaining over 50% of its catalytic activity) can provide an effective environmentally benign approach to fused N-heterocycles of remarkable interest in pharmaceutical and medicinal chemistry. The ability of the hydrazone residue to act as a chelating/directing group as well as an aminating agent guarantees the success of this C–H functionalization.

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The formation of carbon–nitrogen bonds for the preparation of nitrogen-containing molecules is a manifestly important transformation in organic chemistry. As a result, considerable efforts have focused on the discovery of sustainable, more efficient, and selective methods to access valuable N-heterocyclic frameworks. Until recently, conventional approaches for C–N bond construction, routinely used in academia and industry, focused on variations of metal-catalyzed Buchwald–Hartwig, Ullmann and Chan–Lam cross-coupling between aryl- or heteroaryl (pseudo)halides with amine nucleophiles.^1–9 Despite the significant progress achieved in the field, including the contributions on the use of bio-based solvents and water,^10,11 these methodologies are viable only on pre-functionalized substrates, such as aryl- or heteroaryl (pseudo)halides which entails extra steps making them inefficient and unattractive. Conversely, the direct C–H functionalization of non-preactivated substrates undoubtedly constitutes an appealing, cost-effective and atom economical C–N bond connection strategy^12–18 (Fig. 1a). A number of amination reactions including the intramolecular variants,^19–33 the first of which reported by pioneering work by Buchwald in 2005,¹⁹ has been successfully realized to date.

Fig. 1 Approaches of intramolecular C–N cross-coupling: synthesis of fused N-heterocycles.

Within this context, noble catalysts (e.g., Pd, Rh, Ir and Ru) along with stoichiometric or excess amount of oxidant (e.g., Cu(OAc)₂, AgOAc, PhI(OAc)₂, CeSO₄, and/or F⁺) and complex/specialized auxiliary ligands and/or additives have been employed predominantly. However, most of the metal catalysts operate at rather high temperature in toxic, polar, aprotic organic solvents (e.g., N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP), and N,N-dimethylacetamide (DMAc)) which meeting with limited success when used in water. Even with the enormous progress made over the past decade in the most emerging areas of photocatalytic^34–36/electrochemical^37–43/photoelectrocatalytic⁴⁴ oxidative cross-coupling, however, there is still a necessity for the development of greener alternative and more efficient applicable methods which do not rely on noble metal catalysts^45–48 (e.g., Cu, Fe, Zn, Mn, Co and Ni), avoid the use of toxic and/or hazardous organic solvents, and circumventing the need for external oxidants.^49,50 Moreover, despite its conceptual simplicity, the intramolecular C–H bond amination of hydrazones^51–56 possessing a “privileged” indole ring to afford value-added N-fused indoles remains elusive. Just recently, we reported a protocol for the synthesis of azacarbolines via PhIO₂-promoted six-membered cycloamination-oxidation of α-indolylhydrazones⁵⁷ (Fig. 1b, previous work). We envisioned that the pendant hydrazone residue in α-indolylhydrazones could be responsible for a five ring-closing C–H amination as result of the potential hydrazone–enamine tautomerization,^58,59 thus providing a distinct approach for the C(2)–H functionalization of indoles and expedient synthesis of pyrroloindoles⁶⁰ (Fig. 1b, this work). To accomplish this, the hydrazonic residue should serve both as a chelating/directing group^61–63 and as an intramolecular nitrogen source^51–57 under the action of the opportune metal.

In designing a complementary and convenient strategy to produce less saturated version of pyrrolo[2,3-b]indole molecules^64–71via C–H bond functionalization, we herein report an unprecedented intramolecular C(sp²)–N bond amination strategy that utilizes a combination of more advantageous Cu^72–75/Fe^76–78 (the most abundant in the Earth's crust) catalyst, at 50 °C in the presence of air as terminal oxidant in aqueous system/medium (Fig. 1b, this work).

Besides remarkable biological activities exemplified by representative compounds such as pyrroindomycins (PYRs) Sirtuins inhibitor, and inibithor of growth of Bacillus subtilis (Fig. 1c), these 1,8-dihydro pyrrolo[2,3-b]indoles exhibit a broad spectrum of applications in optoelectronic materials and fluorescent probes.

We began our studies by testing the conversion of α-indolylhydrazone 1a to 1-amino pyrrolo[2,3-b]indole 2a using simple copper/iron salts (Table 1). After preliminary screening of a variety of conditions including nature of copper source, (co)catalyst loading, solvent, additive and temperature (see Table S1 of the ESI† for more details), we found that a combination^79–87 of catalytic [commercially accessible] Cu(OAc)₂·H₂O (10 mol%) and FeCl₃·6H₂O (5 mol%) in an open flask at room temperature using water as the only reaction medium,^88–91 was beneficial for this transformation, with the compound 2a being formed in 99% yield (entry 1). Reactions that employed other iron cocatalysts such as Fe₂O₃, Fe(NO₃)₃ 9H₂O, Fe(ClO₄)₃, Fe₂(SO₄)₃·H₂O or Fe(acac)₃ led to inferior results in term of reactivity/efficiency (entries 2–6). Reducing the amount of catalyst/co-catalyst did not affect the yield albeit an extended reaction time was required for complete consumption of 1a (entry 7). On the other hand, we found that a mild heating (50 °C) significantly accelerated the reaction, and 1a was produced in almost quantitative yield within 3 h (entry 8).

Table 1 Optimization studies^a

Entry	Catalyst [mol%]	Co-catalyst [mol%]	T [°C]	t [h]	Yield [%]^b
a All reaction were performed on 0.2 mmol scale of 1a in 2 mL of solvent (0.1 M) under air atmospher for the indicate time. b Unless noted, yields are referred to the isolated product after column chromatography. c The unreacted starting material was recovered. d Without column chromatography.
1	Cu(OAc)2·H2O (10)	FeCl3·6H2O (5)	r.t.	24	99^d
2	Cu(OAc)2·H2O (10)	Fe2O3 (5)	r.t.	20	98^d
3	Cu(OAc)2·H2O (10)	Fe(NO3)3 9H2O (5)	r.t.	10	32
4	Cu(OAc)2·H2O (10)	Fe(ClO4)3 (5)	r.t.	48	73
5	Cu(OAc)2·H2O (10)	Fe2(SO4)3·H2O (5)	r.t.	48	Trace^c
6	Cu(OAc)2·H2O (10)	Fe(acac)3 (5)	r.t.	40	99
7	Cu(OAc)2·H2O (5)	FeCl3·6H2O (2.5)	r.t.	40	99^d
8	Cu(OAc)2·H2O (10)	FeCl3·6H2O (5)	50	3	99^d
9	Cu(OAc)2·H2O (10)	—	r.t.	48	Trace^c
10	—	FeCl3·6H2O (10)	r.t.	48	Trace^c

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Control experiments revealed that both Cu(OAc)₂·H₂O and FeCl₃·6H₂O were essential for this transformation as the omission of one of two catalysts resulted in only a trace amount of 2a (Table 1, entries 9 and 10). To our delight, the product 2a was purified simply by extraction with EtOAc, filtration through a plug of silica gel, concentration, and precipitation without the tedious column chromatography.

With these conditions in hand, the generality and scope of this novel intramolecular C–H amination process was explored (Table 2). First, the effect of different O-alkyl groups on the ester moiety of α-indolylhydrazone 1 was investigated. It was found that, in addition to methyl, ethyl, isopropyl, allyl or benzyl substituted substrates also worked well under the standard conditions, producing the desired products 2a–f in good to excellent yields. Incorporation of a phosphonate residue (R³ = PO(OMe)₂) into the product (2g) was tolerated. Notably, the cyclization could also proceed successfully to deliver product 2h when a substrate with an amide N-protective group (R⁵ = NH₂) was used. Compounds 2i,j, which vary in the substitution pattern at the R⁴, resulted in good yields. An evaluation of the substituents on indolic nitrogen revealed that N–H indole is most sensitive for this transformation. Specifically, for compound 2l, a spontaneous conversion to azacarboline 5a⁹² was registered. This observation imply that the substituent attached to the nitrogen of the indole nucleus is crucial in precluding ring expansion.

Table 2 Substrate scope for the intramolecular C(sp²)–H amination of α-Indolylhydrazones^a

a Reaction conditions: 1 (0.2 mmol), Cu(OAc)₂·H₂O (10 mol%) and FeCl₃·6H₂O (5 mol%) in H₂O (2.0 mL) at 50 °C, 3–48 h. b 3.15 mmol scale reaction (0.933 g). c Isolated yields after column chromatography. d 50 °C for 36 h then 70 °C for 24 h. e A spontaneous conversion to azacarboline 5a (vide infra) was observed.

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Then, we examined the substituent (R²) effect on the indole ring. Delightedly, the reaction well tolerated either EDG or EWG groups at 4-, 5-, 6-, or 7-positions of the indole rings affording the corresponding products 2m–s in excellent yields. Finally, pyrrolo[2,3-b]indole 2t incorporating a ring system between the N and C7 atoms of the indole ring was successfully generated.

For the majority of the reactions, purification of products by column chromatography can be avoided. Also, the recovery and reutilization of the aqueous solution containing the Cu/Fe co-catalyst system was tested using the formation of compound 2a as model reaction (see (Fig. 2) and Table S2 of the ESI†). Thus, after the isolation of the latter compound, the recovered aqueous solution was used again to accomplish the same transformation up to five times. As shown in (Fig. 2), it is possible to use the water solution two times with no variation in both the yields and times of conversion of 1a to 2a. However, for the second recycling run, a clear decrease in the yield was observed. Comparable yield with a remarkable increase of the time of conversion resulted for the third run. While modest variations are observed for the fourth run, a more sensible change of both the yield and process time was registered for the subsequent run with the aqueous catalytic system that retains over 50% of its activity after five cycling runs. Interestingly, recycling involves not only the catalytic system but also the aqueous reaction medium itself, differently from most of the methods reported in the literature in which the metal species has to be prior separated from the reaction medium and often reactivated before its reuse.

Fig. 2 Recycling of the aqueous catalytic system.

In addition, this intramolecular C(sp²)–H amination was found to be scalable delivering product 2a in 94% yield (0.933 g) on 3.15 mmol scale.

To further explore the synthetic potential of the developed method, transformations of the thus formed pyrrolo[2,3-b]indoles were conducted (Scheme 1). Pyrroloindoles 3 and 4 can be easily obtained by N–N bond reductive cleavage (Magnus's protocol⁹³) and removal of N-Boc protecting group, respectively. Also, azacarboline 5b can be prepared from compound 4 following our previously reported oxidation procedure.⁵⁷ Alternatively, a Paal–Knorr pyrrole synthesis from 4 generated the N–N indole-pyrrole scaffold 6.⁹⁴ The acetylenic dienophile DMAD also reacted in Diels–Alder reaction with 2 to give 9H-carbazole 7, after N-aminonitrene extrusion.⁹⁵

Scheme 1 Synthetic transformations of 2.

On the basis of literature information and our findings, a tentative mechanism for the transformation of 1a to 2a is illustrated in (Scheme 2). Initial N,O-bidentate coordination of the hydrazone moiety in 1a to the Cu(OAc)₂ species occurs to form the metallacycle complex I with the release of AcOH. Oxidation of the Cu(II) adduct I to intermediate II by Fe(III) would then facilitate the subsequent electrophilic aromatic substitution. Proton abstraction at the 2-position of indole through a six-membered transition state III (or via acetate ligand-assisted concerted C–H activation pathway) may be followed to give endo-metallacycle⁹⁶ intermediate IV. Finally, reductive elimination promoted by CH/NH tautomerization generates product 2a along with the Cu(I) specie. The catalytic cycle is completed by the regeneration of the active Cu(II) catalyst by air oxidation.

Scheme 2 Tentative mechanism and supporting experiments.

Some control experiments to support this mechanistic scenario were carried out. Under the reaction conditions, α-indolylhydrazone 1u bearing a phenyl substitution failed to produce 2u (Scheme 2a), which implies that the electron-withdrawing group (EWG) at the α-position of the hydrazone substrate results indispensable for the reaction to occur. Furthermore, no cycloamination was detected in the case of N-phenyl 1v because the copper complex via a bidentate coordination could not formed during the catalytic cycle, indicating the crucial role of N-carboxyalkyl moiety in directing/assisting the cyclization at 2-position of the indole ring. A pathway in which a hydrogen abstraction promotes the reductive elimination of metallacycle intermediate IV instead of a preliminary CH/NH tautomerization on 1a⁵⁷ (not shown) is also supported by an experiment in which the addition of K₂CO₃ as a base resulted in the dramatically decrease of the product yield of 2a (29% yield).

Our new method is clearly distinguished from reported copper-catalyzed aerobic annulation of (hetero)aromatic hydrazones. With respect to Xiao and Xu protocol,⁵⁶ this method furnishes 1,8-dihydro pyrrolo[2,3-b]indoles (instead of cinnolines) with excellent control of the chemoselectivity and the obvious benefit of providing more sustainable solution with water under mild reaction conditions.

Conclusions

In conclusion, we herein described the first biocompatible Cu/Fe-catalyzed chemoselective intramolecular C–H bond amination of α-indolylhydrazones. Under a cooperative action of iron(III) and copper(II) salts in the absence of an external oxidant or any other additive a variety of substituted pyrrolo[2,3-b]indoles (relevant bioactive pharmacophoric core) has been prepared in excellent yields. Easy products isolation, recyclability of the catalyst system, mild and clean conditions, use of aqueous medium are the main features that demonstrate the potential of this transformation for industrial application. Further new synthetic applications of this green and low-cost C(sp²)–H amination are currently underway in our laboratory.

Author contributions

Matteo Corrieri: conceptualization, investigation, methodology, data curation, formal analysis; Lucia De Crescentini: data curation, formal analysis; Fabio Mantellini: data curation, resources, supervision; Giacomo Mari: investigation, methodology, and validation; Stefania Santeusanio: data curation, formal analysis; Gianfranco Favi: conceptualization, funding acquisition, supervision, project administration, writing – original draft and writing – review & editing.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

We gratefully acknowledge the financial support from the University of Urbino “Carlo Bo”, and the PhD Programs of Ministry of Education of Italy.

References

1. K. Kunz, U. Scholz and D. Ganzer, Synlett, 2003, 2428–2439.
2. S. V. Ley and A. W. Thomas, Angew. Chem., Int. Ed., 2003, 42, 5400–5449.
3. C. Sambiagio, S. P. Marsden, A. J. Blacker and P. C. McGowan, Chem. Soc. Rev., 2014, 43, 3525–3550.
4. K. Okano, H. Tokuyama and T. Fukuyama, Chem. Commun., 2014, 50, 13650–13663.
5. J. M. Honnanayakanavar, O. Obulesu; and S. Suresh, Org. Biomol. Chem., 2022, 20, 2993–3028.
6. M. Carril, R. SanMartin and E. Domínguez, Chem. Soc. Rev., 2008, 37, 639–647.
7. J. F. Hartwig, Acc. Chem. Res., 2008, 41, 1534–1544.
8. D. S. Surry and S. Buchwald, Angew. Chem., Int. Ed., 2008, 47, 6338–6361.
9. C. Fischer and B. Koenig, Belstein J. Org. Chem., 2011, 7, 59–74.
10. A. F. Quivelli, P. Vitale, F. M. Perna and V. Capriati, Front. Chem., 2019, 7, 723.
11. L. Cicco, J. A. Hernández-Fernández, A. Salomone, P. Vitale, M. Ramos-Martín, J. González-Sabín, A. Presa Soto, F. M. Perna, V. Capriati and J. García-Álvarez, Org. Biomol. Chem., 2021, 19, 1773–1779.
12. S. H. Cho, J. Y. Kim, J. Kwak and S. Chang, Chem. Soc. Rev., 2011, 40, 5068–5083.
13. M.-L. Louillat and F. W. Patureau, Chem. Soc. Rev., 2014, 43, 901–910.
14. V. S. Thirunavukkarasu, S. I. Kozhushkov and L. Ackerman, Chem. Commun., 2014, 50, 29–39.
15. J. Jiao, K. Murakami and K. Itami, ACS Catal., 2016, 6, 610–633.
16. Y. Park, Y. Kim and S. Chang, Chem. Rev., 2017, 117, 9247–9301.
17. M. C. Henry, M. A. B. Mostafa and A. Sutherland, Synthesis, 2017, 4586–4598.
18. K. Murakami, G. J. P. Perry and K. Itami, Org. Biomol. Chem., 2017, 15, 6071–6075.
19. W. C. P. Tsang, N. Zheng and S. L. Buchwald, J. Am. Chem. Soc., 2005, 127, 14560–11456.
20. W. C. P. Tsang, R. H. Munday, G. Brasche, N. Zheng and S. L. Buchwald, J. Org. Chem., 2008, 73, 7603–7610.
21. J. A. Jordan-Hore, C. C. C. Johansson, M. Gulias, E. M. Beck and M. J. Gaunt, J. Am. Chem. Soc., 2008, 130, 16184–16186.
22. B.-J. Li, S.-L. Tian, Z. Fang and Z.-J. Shi, Angew. Chem., Int. Ed., 2008, 47, 1115–1118.
23. S. W. Youn, J. H. Bihn and B. S. Kim, Org. Lett., 2011, 13, 3738–3741.
24. S. H. Cho, J. Yoon and S. Chang, J. Am. Chem. Soc., 2011, 133, 5996–6005.
25. K. Takamatsu, K. Hirano, T. Satoh and M. Miura, Org. Lett., 2014, 16, 2892–2859.
26. G. Brasche and S. L. Buchwald, Angew. Chem., Int. Ed., 2008, 47, 1932–1934.
27. Q. Xiao, W.-H. Wang, G. Liu, F.-K. Meng, J.-H. Chen, Z. Yang and Z.-J. Shi, Chem. – Eur. J., 2009, 15, 7292–7296.
28. H. Wang, Y. Wang, C. Peng, J. Zhang and Q. Zhu, J. Am. Chem. Soc., 2010, 132, 13217–13219.
29. K. Inamoto, T. Saito, M. Katsuno, T. Sakamoto and K. Hiroya, Org. Lett., 2007, 9, 2931–2934.
30. T.-S. Mei, X. Wang and J.-Q. Yu, J. Am. Chem. Soc., 2009, 131, 10806–10807.
31. Y. Tan and J. F. Hartwig, J. Am. Chem. Soc., 2010, 132, 3676–3677.
32. S. Yugandar, S. Konda and H. Ila, J. Org. Chem., 2016, 81, 2035–2052.
33. M. Wasa and J.-Q. Yu, J. Am. Chem. Soc., 2008, 130, 14058–14059.
34. L. Niu, H. Yi, S. Wang, T. Liu, J. Liu and A. Lei, Nat. Commun., 2017, 8, 1748.
35. K. A. Mrgrey, A. Levens and D. Nicewicz, Angew. Chem., Int. Ed., 2017, 56, 15644–15648.
36. A. Ruffoni, F. Juliá, T. D. Svejstrup, A. J. McMillan, J.- J. Douglas and D. Leonori, Nat. Chem., 2019, 11, 426–433.
37. T. Morofuji, A. Shimizu and J.-I. Yoshida, J. Am. Chem. Soc., 2013, 135, 5000–5003.
38. T. Morofuji, A. Shimizu and J.-I. Yoshida, J. Am. Chem. Soc., 2014, 136, 4496–4499.
39. T. Morofuji, A. Shimizu and J.-I. Yoshida, J. Am. Chem. Soc., 2015, 137, 9816–9819.
40. T. Morofuji, A. Shimizu and J.-I. Yoshida, Chem. – Eur. J., 2015, 21, 3211–3214.
41. Y. Zhang, Z. Lin and L. Ackermann, Chem. – Eur. J., 2021, 27, 242–246.
42. M. Puthanveedu, V. Khamraev, L. Brieger, C. Strohmann and A. P. Antonchick, Chem. – Eur. J., 2021, 27, 8008–8012.
43. N. Sauermann, T. H. Meyer, Y. Qiu and L. Ackermann, ACS Catal., 2018, 8, 7086–7103.
44. L. Zhang, L. Liarted, J. Luo, D. Ren, M. Grätzel and X. Gu, Nat. Catal., 2019, 2, 366–373.
45. P. Chirik and R. Morris, Acc. Chem. Res., 2015, 48, 2495–2495.
46. M. Beller, Chem. Rev., 2019, 119, 2089–2089.
47. P. Gandeepan, T. Müller, D. Zell, G. Cera, S. Warratz and L. Ackermann, Chem. Rev., 2019, 119, 2192–2452.
48. R. Singh, E. Sathish, A. K. Gupta and S. Goyal, Tetrahedron, 2021, 100, 132474.
49. J. Wencel-Delord, T. Dröge, F. Liu and F. Glorius, Chem. Soc. Rev., 2011, 40, 4740–4761.
50. T. Dalton, T. Faber and F. Glorius, ACS Cent. Sci., 2021, 7, 245–261.
51. Z. Zheng, L. Tang, Y. Fan, X. Qi, Y. Du and D. Zhang-Negrerie, Org. Biomol. Chem., 2011, 9, 3714–3725.
52. T. Zhang and W. Bao, J. Org. Chem., 2013, 78, 1317–1322.
53. M. Kashiwa, M. Sonoda and S. Tanimori, Eur. J. Org. Chem., 2014, 4720–4723.
54. D. Liang and Q. Zhu, Asian J. Org. Chem., 2015, 4, 42–45.
55. X.-Q. Hu, G. Feng, J.-R. Chen, D.-M. Yan, Q.-Q. Zhao, Q. Wei and W.-J. Xiao, Org. Biomol. Chem., 2015, 13, 3457–3461.
56. C. Lan, Z. Tian, X. Liang, M. Gao, W. Liu, Y. An, W. Fu, G. Jiao, J. Xiao and B. Xu, Adv. Synth. Catal., 2017, 359, 3735–3740.
57. M. Corrieri, L. De Crescentini, F. Mantellini, G. Mari, S. Santeusanio and G. Favi, J. Org. Chem., 2021, 86, 17918–17929.
58. Y. Du, R. Liu, G. Linn and K. Zhao, Org. Lett., 2006, 8, 5919–5922.
59. S. Yugandar, S. Konda and H. Ila, J. Org. Chem., 2016, 81, 2035–2052.
60. Only one example of metal-catalyzed cycloamination of hydrazone was reported to obtain pyrrolo[2,3-b]indole scaffold; however a more than stoichiometric amount of FeBr₃ as well as dichloroethane as solvent were employed. See ref. 49.
61. C. Sambiagio, D. Schönbauer, R. Blieck, T. Dao-Huy, G. Pototschnig, P. Schaaf, T. Wiesinger, M. F. Zia, J. Wencel-Delord, T. Besset, B. U. W. Maes and M. Schnürch, Chem. Soc. Rev., 2018, 47, 6603–6743.
62. A. Ros, R. López-Rodríguez, B. Estepa, E. álvarez, R. Fernández and J. M. Lassaletta, J. Am. Chem. Soc., 2012, 134, 4573–4576.
63. Z. Huang, C. Wang and G. Dong, Angew. Chem., Int. Ed., 2016, 55, 5299–5303.
64. The pyrrolo[2,3-b]indole motif occurs in nature at the hexahydro level in alkaloids, but by contrast, the less saturated version such as 1,8-dihydro pyrrolo[2,3-b]indole is little known.
65. B. Prasad, B. Y. Sreenivas, D. Rambabu, G. R. Krishna, C. M. Reddy, K. L. Kumar and M. Pal, Chem. Commun., 2013, 49, 3970–3972.
66. S. P. Nikumbh, A. Raghunadh, V. N. Murthy, R. Jinkala, S. C. Joseph, Y. L. N. Murthy, B. Prasad and M. Pal, RSC Adv., 2015, 5, 74570–74574.
67. S. Badigenchala, V. Rajeshkumar and G. Sekar, Org. Biomol. Chem., 2016, 14, 2297–2305.
68. Z.-Y. Yang, T. Tian, Y.-F. Du, S.-Y. Li, C.-C. Chu, L.-Y. Chen, D. Li, J.-Y. Liu and B. Wang, Chem. Commun., 2017, 53, 8050–8053.
69. W.-B. Shen, Q. Sun, L. Li, X. Liu, B. Zhou, J.-Z. Yan, X. Lu and L.-W. Ye, Nat. Commun., 2017, 8, 1748.
70. T. Liang, L. Gong, H. Zhao, H. Jiang and M. Zhang, Chem. Commun., 2020, 56, 2807–2810.
71. Y. Dong, J. Yang, H. Zhang, X.-Y. Zhan, S. He, Z.-C. Shi, X.-M. Zhang and J.-Y. Wang, Org. Lett., 2020, 22, 5151–5156.
72. G. Evano, N. Blanchard and M. Toumi, Chem. Rev., 2008, 108, 3054–3131.
73. S. E. Allen, R. R. Walvoord, R. Padilla-Salinas and M. C. Kozlowski, Chem. Rev., 2013, 113, 6234–6458.
74. X. Guo, D. Gu, Z. Wu and W. Zhang, Chem. Rev., 2015, 115, 1622–1651.
75. M. A. Afsina, T. Aneeja, M. Neetha and G. Anilkumar, Eur. J. Org. Chem., 2021, 1776–1808.
76. S. Enthaler, K. Junge and M. Beller, Angew. Chem., Int. Ed., 2008, 47, 3317–3321.
77. C. Bolm, Nat. Chem., 2009, 1, 420–420.
78. Y. Li, T. Yo, T.-T. Wan and C.-M. Che, Tetrahedron, 2019, 75, 130607.
79. M. Taillefer, N. Xia and A. Ouali, Angew. Chem., Int. Ed., 2007, 46, 934–936.
80. J. Mao, G. Xie, M. Wu, J. Guo and S. Jia, Adv. Synth. Catal., 2008, 350, 2477–2482.
81. S. Li, W. Jia and N. Jiao, Adv. Synth. Catal., 2009, 351, 569–575.
82. X. Liu and S. Zhang, Synlett, 2011, 268–272.
83. F. Labre, Y. Gimbert, P. Bannwarth, S. Olivero, E. Duñach and P. Y. Chavant, Org. Lett., 2014, 16, 2366–2369.
84. N. Yi, R. Wang, H. Zou, W. He, W. Fu and W. He, J. Org. Chem., 2015, 80, 5023–5029.
85. C. Liu, Q. Zhang, H. Li, S. Guo, B. Xiao, W. Deng, L. Liu and W. He, Chem. – Eur. J., 2016, 22, 6208–6212.
86. Y. Li and X.-F. Wu, Commun Chem., 2018, 1, 1–8.
87. M. C. Henry, H. M. Senn and A. Sutherland, J. Org. Chem., 2019, 84, 346–364.
88. M. A. Ali, X. Yao, H. Sun and H. Lu, Org. Lett., 2015, 17, 1513–1516.
89. M. A. Ali, X. Yao, G. Li and H. Lu, Org. Lett., 2016, 18, 1386–1389.
90. L. Yang, H. Li, H. Zhang and H. Lu, Eur. J. Org. Chem., 2016, 5611–5615.
91. L. Shi and B. Wang, Org. Lett., 2016, 18, 2820–2823.
92. Although compound 2l was isolated in pure form, a conversion to 5a (see structure below) take places both in DMSO-d₆ solution and in neat sample.
    .
93. P. Magnus, N. Garizi, K. A. Seibert and A. Ornholt, Org. Lett., 2009, 11, 5646–5648.
94. K.-W. Chen, Z.-H. Chen, S. Yang, S.-F. Wu, Y.-C. Zhang and F. Shi, Angew. Chem., 2022, 61, e202116829.
95. A. G. Schultz and M. Shen, Tetrahedron Lett., 1979, 20, 2969–2972.
96. S. R. Sahoo, S. Dutta, S. A. Al-Thabaiti, M. Mokhtar and D. Maiti, Chem. Commun., 2021, 57, 11885–11903.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d2gc02340g

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