Azide–acetonitrile “click” reaction triggered by Cs₂CO₃: the atom-economic, high-yielding synthesis of 5-amino-1,2,3-triazoles

Abstract

Medicinally important 5-amino-1,2,3-triazoles were synthesized using a novel Cs₂CO₃-catalyzed azide–acetonitrile[3 + 2]-cycloaddition. Aryl azides and aryl acetonitriles were employed in this transformation resulting in excellent yields with high regioselectivity.

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1,2,3-Triazoles have emerged as important “amide isosteres” with unique chemical/physical properties and are widely used as pharmaceuticals.¹ Many 1,4- or 1,5-disubstituted and the 1,4,5-trisubstituted 1,2,3-triazoles have found wide range applications in biological, medicinal, organic, bio-organic, polymer and material chemistry due to their surrogating behavior with amide bonds.¹ Several recent studies including relative planarity, strong dipole moment (4–5 D), and amphihydrogen-bonding capability of 1,2,3-triazoles indicate their bio-similarity with amide bonds. 1,2,3-Triazoles have become better choice than amide bonds in biological chemistry due to their inertness towards oxidation, hydrolysis and enzymatic degradation.^1c,1d,1h,1l

In a search for new-type of 1,2,3-triazoles, we thought of synthesizing 5-amino-1,2,3-triazoles.² As these compounds posses high dipole moment compared to simple 1,2,3-triazoles, they have shown significant role in pharmaceutical/biological chemistry (Fig. 1).² Although in the literature simple enolizable nitriles or highly activated malononitrile are used as substrates to furnish 5-amino-1,2,3-triazoles through preformed keteniminate-formation with excess amount of strong base and aryl azides, its further development is required due to the utilization of excess amount of base and harsh reaction conditions.³ Herein, we have shown interest to develop a general organocatalytic protocol for their high-yielding regioselective synthesis from less reactive monosubstituted acetonitriles (Scheme 1). Owing to various applications of 1,2,3-triazoles, the last two decades have witnessed the development of novel methods to synthesize functionalized triazoles in a regioselective manner. Especially, copper-catalyzed azide–alkyne [3 + 2]-cycloaddition reaction (eq. a, Scheme 1),⁴ ruthenium- or iridium-catalyzed azide–alkyne [3 + 2]-cycloaddition reaction,⁵ strain-promoted azide–alkyne [3 + 2]-cycloaddition reaction,⁶ organocatalytic enamine- or enolate-mediated azide-carbonyl [3 + 2]-cycloaddition reaction (eq. b and c, Scheme 1),^7,8 copper- or I₂/TBPB-promoted reaction of N-tosylhydrazones with anilines,⁹ iodine-promoted three-component reaction of N-tosylhydrazones, arylketone and anilines,¹⁰ and classical electronically controlled active olefin–azide [3 + 2]-cycloaddition reaction,¹¹ are among those novel reactions. Many of these reactions are suitable to synthesize a variety of 1,2,3-triazoles, except 5-amino-1,2,3-triazoles, because of the existence of active functional group NH₂ at the 5-position of 1,2,3-triazoles.

Fig. 1 Potential applications based on the 5-amino-1,2,3-triazoles.

Scheme 1 Reaction design for the azide–acetonitrile “click” reaction.

In view of this, we have chosen the transition metal-free organocatalytic keteniminate-mediated [3 + 2]-cycloaddition protocol for the regioselective synthesis of 5-amino-1,2,3-triazoles from easily available aryl azides, monosubstituted acetonitriles and catalytic amount of tert-amines or carbonate salts (eq. d, Scheme 1). Herein, we have disclosed a general, rapid, and operationally simple azide–acetonitrile “click” (AANC) reaction for the chemo- and regioselective synthesis of fully decorated 5-amino-1,2,3-triazoles from the aryl azides and monosubstituted acetonitriles (eq. d, Scheme 1).

We undertook the prior optimization of the AANC reaction by screening simple amine and non-amine catalysts for the reaction of phenylacetonitrile 1a with 1.0 to 1.5 equiv. of PhN₃ 2a (Table 1). To our surprise, the reaction of 1a with 1.5 equiv. of 2a in DMSO under 20 mol% of DBU 3a-catalysis at RT for 0.5 h furnished the expected product 4aa as a single regioisomer with 85% yield (Table 1, entry 1). With lesser catalyst 3a loading (10 or 5 mol%), the reaction became inferior with respect to rate and yield (Table 1, entries 2 and 3). There is not much improvement in the above reaction by changing the solvent to DMF (entry 4). The same AANC reaction at RT for 24 h under 20 mol% of DABCO 3b or DMAP 3c-catalysis furnished 4aa in only 0 and 10% yields, respectively (Table 1, entries 5 and 6). After obtaining moderate results with tert-amine catalysts 3a–c through keteniminate-formation, we thought of exploring the same reaction with non-amine bases 3d–f as the catalysts (Table 1, entries 7–16). Intriguingly, the reaction of 1a with 1.5 equiv. of 2a in DMSO under 20 mol% of Cs₂CO₃ 3e-catalysis at 25 °C for within 0.5 h furnished 4aa in 90% yield, but the same reaction under K₂CO₃ 3d-catalysis furnished the product 4aa in only 45% yield with 75% conversion after 0.75 h (Table 1, entries 7 and 8). Amazingly, the same reaction with just 10 mol% of 3e-catalysis also furnished 4aa in 93% yield within 0.75 h (Table 1, entry 9). But the same AANC reaction under 10 mol% of 3e-catalysis with decreased equivalents (1.2 or 1.0 equiv.) of 2a for 0.75 h furnished 4aa in 93% and 87% yields, respectively (Table 1, entries 10 and 11). The AANC reaction of 1a with 1.2 equiv. of 2a in DMSO + H₂O (7 : 3) under 10 mol% of Cs₂CO₃ 3e-catalysis at 25 °C for 0.5 h furnished 4aa in 99% yield, may be due to there is no product 4aa decomposition in an aqueous dimethyl sulfoxide (Table 1, entry 12). We were astonished to find that, there was no reaction in pure water due to the poor solubility and only starting materials were recovered under 10 mol% of 3e-catalysis for 24 h; and the product 4aa was obtained in only 40% yield in DMF solvent (Table 1, entries 13 and 14). The same reaction with 20 or 10 mol% of strong base, tBuOK 3f-catalysis furnished 4aa in 85 or 65% yield, respectively (Table 1, entries 15, 16). Obtaining moderate yields in tBuOK 3f-catalysis may be the decomposition of 1a or 4aa under the strong basic conditions (Table 1, entries 15 and 16). Finally, we envisioned the optimized condition to be 25 °C in DMSO + H₂O (7 : 3) under 10 mol% of Cs₂CO₃ 3e-catalysis to furnish the single isomer of fully decorated 5-amino-1,2,3-traizole 4aa in 99% yield from 1a and 2a (Table 1, entry 12).

Table 1 Reaction optimization^a

Entry	Catalyst 3	Solvent	Time (h)	Yield 4aa^b (%)
a Reactions were carried out in solvent (0.5 M) with 1.5 equiv. of 2a relative to the 1a (0.5 mmol) in the presence of 5–20 mol% of catalyst 3.b Yield refers to the column-purified product.c 1.2 equiv. of 2a was used.d 1.0 equiv. of 2a was used.e DMSO/H2O (7 : 3) was used as solvent.
1	3a (20 mol%)	DMSO	0.5	85
2	3a (10 mol%)	DMSO	0.75	72
3	3a (5 mol%)	DMSO	24	45
4	3a (20 mol%)	DMF	16	45
5	3b (20 mol%)	DMSO	24	—
6	3c (20 mol%)	DMSO	24	10
7	3d (20 mol%)	DMSO	0.75	45
8	3e (20 mol%)	DMSO	0.5	90
9	3e (10 mol%)	DMSO	0.75	93
10^c	3e (10 mol%)	DMSO	0.75	93
11^d	3e (10 mol%)	DMSO	0.75	87
12^c^,^e	3e (10 mol%)	DMSO + H2O	0.5	99
13	3e (10 mol%)	H2O	24	—
14	3e (10 mol%)	DMF	6	40
15	3f (20 mol%)	DMSO	0.5	85
16	3f (10 mol%)	DMSO	0.5	65

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With the best optimized condition in hand, the generality of the keteniminate-mediated AANC reaction was investigated further. For this, various aryl and alkyl azides 2b–q were reacted with phenylacetonitrile 1a catalyzed by 10 mol% of Cs₂CO₃ 3e at 25 °C in DMSO + H₂O (7 : 3; 0.5 M) for 0.5–2 h (Table 2). Fascinatingly, the aryl azides 2b–n containing different functional groups of F, Cl, Br, Me, OMe, CF₃, CN, CO₂Et, CHO, and NO₂ at three different positions furnished the expected fully decorated 5-amino-1,2,3-triazoles 4ab–an in good to excellent yields within 0.5–2 h (Table 2). The AANC reaction of 1a with 4-CO₂EtC₆H₄N₃ 2l and 4-CHOC₆H₄N₃ 2m under 3e-catalysis in DMSO + H₂O furnished the products 4al and 4am in only 46–49% yields due to the decomposition, but the same reaction under the 10 mol% of DBU 3a-catalysis in DMSO furnished 4al in 75% and 4am in 60% yields (Table 2). Surprisingly, Cs₂CO₃ 3e or DBU 3a-catalyzed AANC reaction of 1a with aliphatic azides of benzyl azide 2o and (2-azidoethyl)benzene 2p did not furnish the expected products 4, but the same reaction under 20 mol% of tBuOK 3f-catalysis for 2 h furnished the 5-amino-1,2,3-triazoles 4ao in 95% and 4ap in 92% yields (Table 2). There was no AANC reaction observed between 1a and TsN₃ 2q under all the three different catalytic conditions (Table 2). The structure and the regiochemistry of the AANC products 4ab–ap were confirmed by NMR analysis and also finally confirmed by the X-ray structure analysis on 4al as shown in the Fig. S1 (ESI†).¹²

Table 2 Azide scope with phenylacetonitrile 1a

a DBU (10 mol%)-catalysis at rt for 1–2 h in DMSO.b tBuOK (20 mol%)-catalysis at rt for 2 h in DMSO.

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To develop a further diverse library of fully decorated 5-amino-1,2,3-triazoles 4, and bis-5-amino-1,2,3-triazoles 5, and also to further understand the electronic factors of monosubstituted arylacetonitriles 1 in the AANC reaction, we have chosen different arylacetonitriles 1b–p, and simple aryl azides 2 (Table 3). The AANC reaction of 2-fluorophenylacetonitrile 1b with less reactive PhN₃ 2a under Cs₂CO₃-catalysis at 25 °C for 0.75 h furnished the 5-amino-1,2,3-triazole 4ba in 93% yield (Table 3). In a similar manner, we have also tested five more examples of 3-F, 4-F, 4-Cl, 3-Br and 4-Br phenylacetonitriles 1c–g for the AANC reaction with PhN₃ 2a at 25 °C for 0.75 h, which furnished the 5-amino-1,2,3-triazoles 4ca–ga in 90–93% yields (Table 3). The AANC reaction of 3-Me, 4-Me, 4-OMe, 4-CF₃, 4-CN, and 2-NO₂-substituted phenylacetonitriles 1h–o with 2a under 3e-catalysis at 25 °C for 0.75–1.0 h furnished the fully decorated 5-amino-1,2,3-triazoles 4ha–oa in 80–93% yields, respectively without showing much electronic influence (Table 3). But surprisingly, the AANC reaction of 4-OAc and 4-NHAc substituted phenylacetonitrile 1k/1l with PhN₃ 2a under Cs₂CO₃-catalysis needed a little higher temperature (60 °C) for 3 h and furnished the 5-amino-1,2,3-triazoles 4ka and 4la in only 50% and 40% yields, respectively (Table 3). With applications in mind, we have prepared the bis-5-amino-1,2,3-triazoles 5pa, 5po and 5ar in good yields from the treatment of 2,2′-(1,4-phenylene)diacetonitrile 1p or 1a with aryl azides PhN₃ 2a, BnN₃ 2o, or 1,4-bis(azidomethyl)benzene 2r at 25 °C for 2 h under tBuOK 3f-catalysis (Table 3). Initially, we were disappointed to find that there was no bis-5-amino-1,2,3-triazole 5pa formation from the reaction of 2,2′-(1,4-phenylene)diacetonitrile 1p with 2a under Cs₂CO₃ 3e-catalysis and only mono-triazole 4pa was isolated in 50% yield (Table 3). Later on switching to tBuOK 3f (20 mol%) as catalyst, we successfully synthesised the bis-5-amino-1,2,3-triazoles 5pa, 5po and 5ar in 50%, 60%, and 60% yields, respectively from the AANC reaction (Table 3).

Table 3 Reaction scope with different azides and phenylacetonitriles

a Reaction performed at 60 °C for 3 h.b tBuOK (20 mol%)-catalysis at rt for 2 h in DMSO.

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The utility of the AANC reaction was further represented by synthesizing medicinally useful compounds 6ga, 6ja and 5asg (Scheme 2).² As shown in Scheme 2, analogues of potassium channel activators 6ga and 6ja were synthesized in very good yield from the corresponding 5-amino-1,2,3-triazoles 4ga and 4ja through the modified Dimroth rearrangement conditions.¹³ In contrast, the literature conditions for the Dimroth rearrangement required highly basic solvent, high temperature and long reaction time.¹³ Further, we synthesized the functionally rich double click compound 5asg through the first AANC reaction of phenylacetonitrile 1a with 1-azido-4-(azidomethyl)benzene 2s in DMSO + H₂O at 25 °C for 5 h under 3e-catalysis to furnish 4as in 60% yield, which on tBuOK-catalyzed second AANC reaction with 4-bromophenylacetonitrile 1g at 25 °C for 2 h furnished 5asg in 50% yield. These results clearly show the advantages of the AANC methodology, which enables a high-yielding metal-free synthesis of medicinally important 5-amino-1,2,3-triazoles.

Scheme 2 Application of azide–acetonitrile “click” reaction.

The provisional mechanism for the 3e-catalyzed AANC reaction in DMSO + H₂O (7 : 3; 0.5 M) is illustrated in Scheme 3. Reaction of monosubstituted acetonitriles 1 with catalyst 3e generates the keteniminate 7,¹⁴ which on in situ treatment with Ar–N₃ 2 furnishes selectively the adduct 1,4-diaryl-1H-1,2,3-triazol-5(4H)-imine 8 via concerted or stepwise [3 + 2]-cycloaddition reaction,⁸ which on further rapid isomerisation transforms into the fully decorated 5-amino-1,2,3-triazole 4 at the ambient conditions. In this AANC reaction, the formation rate and the stability of the reactive intermediates 7 and 8 seems to be induced by the presence of limited amount of water molecules in DMSO under the 3e-catalysis.

Scheme 3 Proposed reaction mechanism for AANC reaction.

In conclusion, we have demonstrated the keteniminate-mediated carbonate-catalyzed AANC reaction that generates medicinally important 5-amino-1,2,3-triazoles decorated with useful functional groups. This protocol highlights the metal-free conditions with high rate and selectivity, and easy access to a library of functionalized 5-amino-1,2,3-triazoles. Moreover, many of the reported syntheses have the disadvantage of requiring the strong bases with many equivalents or using highly reactive substrates; therefore, this catalytic protocol is very convenient. Further work is in progress to utilize the keteniminate-mediated AANC reactions in medicinal and material chemistry.

Acknowledgements

We thank DST (New Delhi) for financial support. PMK thank CSIR, New Delhi for his research fellowship.

Notes and references

1. (a) A. C. Tome, Sci. Synth., 2004, 13, 415; (b) L. S. Kallander, et al., J. Med. Chem., 2005, 48, 5644; (c) Y. L. Angell and K. Burgess, Chem. Soc. Rev., 2007, 36, 1674; (d) A. Tam, U. Arnold, M. B. Soellner and R. T. Raines, J. Am. Chem. Soc., 2007, 129, 12670; (e) S. Ito, A. Satoh, Y. Nagatomi, Y. Hirata, G. Suzuki, T. Kimura, A. Satow, S. Maehara, H. Hikichi, M. Hata, H. Kawamoto and H. Ohta, Bioorg. Med. Chem., 2008, 16, 9817; (f) S. Ito, Y. Hirata, Y. Nagatomi, A. Satoh, G. Suzuki, T. Kimura, A. Satow, S. Maehara, H. Hikichi, M. Hata, H. Ohta and H. Kawamoto, Bioorg. Med. Chem. Lett., 2009, 19, 5310; (g) T. Tsuritani, H. Mizuno, N. Nonoyama, S. Kii, A. Akao, K. Sato, N. Yasuda and T. Mase, Org. Process Res. Dev., 2009, 13, 1407; (h) J. M. Holub and K. Kirshenbaum, Chem. Soc. Rev., 2010, 39, 1325; (i) S. G. Agalave, S. R. Maujan and V. S. Pore, Chem.–Asian J., 2011, 6, 2696; (j) See also: Chem.–Asian J., 2011, 6, Issue 10. Special edition devoted to click chemistry; (k) M. Fujinaga, T. Yamasaki, K. Kawamura, K. Kumata, A. Hatori, J. Yui, K. Yanamoto, Y. Yoshida, M. Ogawa, N. Nengaki, J. Maeda, T. Fukumura and M.-R. Zhang, Bioorg. Med. Chem., 2011, 19, 102; (l) I. E. Valverde, A. Bauman, C. A. Kluba, S. Vomstein, M. A. Walter and T. L. Mindt, Angew. Chem., Int. Ed., 2013, 52, 8957; (m) A. Lauria, R. Delisi, F. Mingoia, A. Terenzi, A. Martorana, G. Barone and A. M. Almerico, Eur. J. Org. Chem., 2014, 3289; (n) S. Li and Y. Huang, Curr. Med. Chem., 2014, 21, 113.
2. (a) J. R. E. Hoover and A. R. Day, J. Am. Chem. Soc., 1956, 78, 5832; (b) G. Biagi, V. Calderone, I. Giorgi, O. Livi, V. Scartoni, B. Baragatti and E. Martinotti, Eur. J. Med. Chem., 2000, 35, 715; (c) X. Zhao, B. W. Lu, J. R. Lu, C. W. Xin, J. F. Li and Y. Liu, Chin. Chem. Lett., 2012, 23, 933.
3. (a) E. Lieber, T. S. Chao and C. N. R. Rao, Org. Synth., 1963, 4, 380; (b) G. L'abbe and L. Beenaerts, Tetrahedron, 1989, 45, 149; (c) P. A. S. Smith, J. J. Friar, W. Resemann and A. C. Watson, J. Org. Chem., 1990, 55, 3351; (d) I. F. Cottrell, D. Hands, P. G. Houghton, G. R. Humphrey and S. H. B. Wright, J. Heterocycl. Chem., 1991, 28, 301; (e) A. T. P. C. Gomes, P. R. C. Martins, D. R. Rocha, M. G. P. M. S. Neves, V. F. Ferreira, A. M. S. Silva, J. A. S. Cavaleiro and F. C. da Silva, Synlett, 2013, 24, 41; (f) H. Singh, J. Sindhu and J. M. Khurana, RSC Adv., 2013, 3, 22360; (g) C.-Y. Peng, J.-R. Lu, C.-W. Xin, J.-F. Li, D. Ji and X.-R. Bao, Chem. J. Chin. Univ., 2013, 34, 1394; (h) G. L'abbe and L. Beenaerts, Tetrahedron, 1989, 45, 749.
4. (a) C. W. Tornoe, C. Christensen and M. Meldal, J. Org. Chem., 2002, 67, 3057; (b) V. V. Rostovtsev, L. G. Green, V. V. Fokin and K. B. Sharpless, Angew. Chem., Int. Ed., 2002, 41, 2596; (c) W. H. Binder and C. Kluger, Curr. Org. Chem., 2006, 10, 1791; (d) H. Nandivada, X. Jiang and J. Lahann, Adv. Mater., 2007, 19, 2197; (e) S. Chuprakov, N. Chernyak, A. S. Dudnik and V. Gevorgyan, Org. Lett., 2007, 9, 2333; (f) J.-F. Lutz and Z. Zarafshani, Adv. Drug Delivery Rev., 2008, 60, 958.
5. (a) L. Zhang, X. Chen, P. Xue, H. H. Y. Sun, I. D. Williams, K. B. Sharpless, V. V. Fokin and G. Jia, J. Am. Chem. Soc., 2005, 127, 15998; (b) L. K. Rasmussen, B. C. Boren and V. V. Fokin, Org. Lett., 2007, 9, 5337; (c) B. C. Boren, S. Narayan, L. K. Rasmussen, L. Zhang, H. Zhao, Z. Lin, G. Jia and V. V. Fokin, J. Am. Chem. Soc., 2008, 130, 8923; (d) E. Rasolofonjatovo, S. Theeramunkong, A. Bouriaud, S. Kolodych, M. Chaumontet and F. Taran, Org. Lett., 2013, 15, 4698; (e) S. Ding, G. Jia and J. Sun, Angew. Chem., Int. Ed., 2014, 53, 1877.
6. (a) N. J. Agard, J. A. Preschner and C. R. Bertozzi, J. Am. Chem. Soc., 2004, 126, 15046; (b) N. J. Agard, J. M. Baskin, J. A. Prescher, A. Lo and C. R. Bertozzi, ACS Chem. Biol., 2006, 1, 644; (c) J. M. Baskin and C. R. Bertozzi, QSAR Comb. Sci., 2007, 26, 1211; (d) J. C. Jewett and C. R. Bertozzi, Chem. Soc. Rev., 2010, 39, 1272; (e) B. Gold, G. B. Dudley and I. V. Alabugin, J. Am. Chem. Soc., 2013, 135, 1558.
7. (a) D. B. Ramachary, K. Ramakumar and V. V. Narayana, Chem.–Eur. J., 2008, 14, 9143; (b) M. Belkheira, D. E. Abed, J.-M. Pons and C. Bressy, Chem.–Eur. J., 2011, 17, 12917; (c) L. J. T. Danence, Y. Gao, M. Li, Y. Huang and J. Wang, Chem.–Eur. J., 2011, 17, 3584; (d) L. Wang, S. Peng, L. J. T. Danence, Y. Gao and J. Wang, Chem.–Eur. J., 2012, 18, 6088; (e) N. Seus, L. C. Goncalves, A. M. Deobald, L. Savegnago, D. Alves and M. W. Paixao, Tetrahedron, 2012, 68, 10456; (f) D. B. Ramachary and A. B. Shashank, Chem.–Eur. J., 2013, 19, 13175; (g) W. Li, Q. Jia, Z. Du and J. Wang, Chem. Commun., 2013, 49, 10187; (h) D. K. J. Yeung, T. Gao, J. Huang, S. Sun, H. Guo and J. Wang, Green Chem., 2013, 15, 2384; (i) N. Seus, B. Goldani, E. J. Lenardão, L. Savegnago, M. W. Paixão and D. Alves, Eur. J. Org. Chem., 2014, 1059; (j) W. Li, Z. Du, J. Huang, Q. Jia, K. Zhang and J. Wang, Green Chem., 2014, 16, 3003; (k) W. Li, Z. Du, K. Zhang and J. Wang, Green Chem., 2015, 17, 781.
8. (a) D. B. Ramachary, A. B. Shashank and S. Karthik, Angew. Chem., Int. Ed., 2014, 53, 10420; (b) A. B. Shashank, S. Karthik, R. Madhavachary and D. B. Ramachary, Chem.–Eur. J., 2014, 20, 16877; (c) W. Li and J. Wang, Angew. Chem., Int. Ed., 2014, 53, 14186; (d) For the highlights of OrgACC reactions, see: S. S. V. Ramasastry, Angew. Chem., Int. Ed., 2014, 53, 14310.
9. (a) S. S. van Berkel, S. Brauch, L. Gabriel, M. Henze, S. Stark, D. Vasilev, L. A. Wessjohann, M. Abbas and B. Westermann, Angew. Chem., Int. Ed., 2012, 51, 5343; (b) Z. Chen, Q. Yan, Z. Liu, Y. Xu and Y. Zhang, Angew. Chem., Int. Ed., 2013, 52, 13324; (c) Z.-J. Cai, X.-M. Lu, Y. Zi, C. Yang, L.-J. Shen, J. Li, S.-Y. Wang and S.-J. Ji, Org. Lett., 2014, 16, 5108.
10. Z. Chen, Q. Yan, Z. Liu and Y. Zhang, Chem.–Eur. J., 2014, 20, 17635.
11. (a) J. Thomas, J. John, N. Parekh and W. Dehaen, Angew. Chem., Int. Ed., 2014, 53, 10155; (b) A. Ali, A. G. Corrêa, D. Alves, J. Zukerman-Schpector, B. Westermann, M. A. B. Ferreira and M. W. Paixao, Chem. Commun., 2014, 73, 11926; (c) X.-J. Quan, Z.-H. Ren, Y.-Y. Wang and Z.-H. Guan, Org. Lett., 2014, 16, 5728; (d) G. Cheng, X. Zeng, J. Shen, X. Wang and X. Cui, Angew. Chem., Int. Ed., 2013, 52, 13265.
12. ESI†.
13. (a) E. Lieber, C. N. R. Rao and T. S. Chao, J. Am. Chem. Soc., 1957, 79, 5962; (b) E. Lieber, T. S. Chao and C. N. R. Rao, J. Org. Chem., 1957, 22, 654; (c) E. Lieber, T. S. Chao and C. N. R. Rao, Org. Synth., 1957, 37, 26; (d) Y. Ogata, K. Takagi and E. Hayashi, Bull. Chem. Soc. Jpn., 1977, 50, 2505.
14. L. Becker, M. Haehnel, A. Spannenberg, P. Arndt and U. Rosenthal, Chem.–Eur. J., 2015, 21, 3242.

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Footnote

† Electronic supplementary information (ESI) available: Experimental procedures and analytical data (¹H NMR, ¹³C NMR, and HRMS) for all new compounds. CCDC 1041888. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ra12308a

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