Cobalt-catalyzed amination of triazoles with dioxazol-5-ones through triazole-directed ortho CH activation

Tetrahedron 72 (2016) 8004e8008

Contents lists available at ScienceDirect

Tetrahedron journal homepage: www.elsevier.com/locate/tet

Cobalt-catalyzed amination of triazoles with dioxazol-5-ones through triazole-directed ortho CeH activation Feifei Wu, Yun Zhao, Wanzhi Chen * Department of Chemistry, Zhejiang University, Yuquan Campus, Hangzhou 310013, China

a r t i c l e i n f o

a b s t r a c t

Article history: Received 10 August 2016 Received in revised form 11 October 2016 Accepted 14 October 2016 Available online 17 October 2016

Cobalt-catalyzed reactions of triazoles and dioxazol-5-one involving nitrene transfer were described. A number of amidated 1,2,3-trizole derivatives have been obtained in moderate to excellent yields. Ó 2016 Elsevier Ltd. All rights reserved.

Keywords: CeH activation Cobalt Amination Triazole Nitrene

1. Introduction 1,2,3-Triazole derivatives are important substructures, which can be used as unique ligands for catalysts1 and coordination chemistry.2 Triazole derivatives have found wide applications as photo-active materials,3 medicine,4 chemical sensors,5 and thus synthesis of 1,2,3-trizoles have attracted much attention.6 1,2,3Triazole can be prepared easily via Cu-catalyzed azideealkyne [3þ2] cycloaddition reactions (Eq. 1, Scheme 1).7 The protocol has been widely applied to the synthesis of various triazoles, which is restricted because the commercially available terminal alkynes are limited. Recently, the construction of CeC and CeN bonds through metal-catalyzed CeH bond activation and functionalization has been made great progress.8 We envisioned that the CeH activation strategy would also be applicable to the synthesis of triazoles. Functionalization of triazole through triazole-directed CeH bond activation would be an economic synthetic route for complex triazole derivatives (Eq. 2). 1,4,2-Dioxazol-5-ones is known to be a nitrene precursor, which can generate active N-acyl nitrenes by losing one molecule of CO2 when it was heated or illuminated in the presence of metal. 1,4,2Dioxazol-5-one can be used as a nitrogen source to form CeN bonds by nitrene insertion process.9 We have previously reported rhodium catalyzed annulation of triazoles and internal alkynes. The

* Corresponding author. E-mail address: [email protected] (W. Chen). http://dx.doi.org/10.1016/j.tet.2016.10.032 0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

Scheme 1. Synthesis and functionalization of triazoles.

reaction proceeded via sequential triazole-directed CeH activation, CeC, CeN, and CeO bond formation affording mesoionic triazolo [5,1-a]isoquinoliums.10 In this paper, we report cobalt-catalyzed directed CeH functionalization of 1,2,3-trizaole leading to amidated triazoles in good to excellent yields. 2. Results and discussion The experiment results showed that cobalt complex could catalyze the reaction of 1-benzyl-4-(p-tolyl)-1H-1,2,3-triazole 1a and 3-phenyl-1,4,2-dioxazol-5-one 2a. Initially, the reaction conditions were optimized by using the reaction of 1a and 2a as the model

F. Wu et al. / Tetrahedron 72 (2016) 8004e8008

8005

Table 1 Cobalt-catalyzed amidation of 1,2,3-triazolea

Entry

2a (equiv)

Co (mol %)

Additive

T ( C)

Yield (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

2.0 2.0 2.0 2.0 2.0 2.0 3.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0

10 10 10 10 10 10 10 10 10 15 20 0 20 0 20 20 20

d KOAc NaOAc AgOAc KOAc KOAc KOAc KOAc KOAc KOAc KOAc KOAc KOAc KOAc AgOAc AgOAc d

100 100 100 100 80 120 100 100 100 100 100 100 100 100 100 100 100

64 69 65 42 35 66 60 48b 55c 80 84 NDd Traced NDe NDd NDd,f 73

a

Reaction conditions: 1a (0.20 mmol), AgSbF6 (2 mol %), additives (20 mol %), DCE 2 mL, 100  C 24 h, air; b48 h; c36 h; dNo AgSbF6; e40 mol % AgSbF6; f40 mol % AgOAc.

reaction, and the results were summarized in Table 1. At the loading of 10 mol % [CpCo(CO)I2] and 20 mol % AgSbF6 at 100  C using 1,2dichloroethane as the solvent, the amidation product 3a was obtained in 64% yield (Table 1, entry 1). Further addition of acetate salts such as KOAc and NaOAc can slightly improve the reaction (entries 2 and 3). However, AgOAc showed negative effect (entry 4). When the temperature was lowered to 80  C, the yield of the target product was decreased to 35% (entry 5). Further increase of temperature to 120  C did not show obvious influence on the isolated yield (entry 6). For the triazole-directed amidation reaction, two equivalent of 3-phenyl-1,4,2-dioxazol-5-one 2a is appropriate, and the use of larger amount of 2a did not increase the yield (entry 7). Extension of reaction time did not raise the yield of 3a. Probably longer reaction caused side reactions (entries 8 and 9). When the loading of cobalt catalyst was increased to 15e20 mol %, 3a could be obtained in up to 84% yield (entries 10 and 11). For comparison, in the absence of cobalt complexes, no desired product was observed (entries 12 and 14). In addition, AgSbF6 is also essential (entry 13). Under the same conditions, only trace amount of desired product was observed without using AgSbF6 (entry 14). AgSbF6 could not be replaced by AgOAc (entries 15 and 16). When 20 mol % of cobalt catalyst was used without KOAc, the yield of 3a was decreased 73% (entry 17). After optimization studies, we explored the feasibility of cobaltcatalyzed CeH amidation of other 1,2,3-triazole and dioxazolone derivatives. At the loading of 20 mol % of the cobalt catalyst in 1,2dichloroethane, the amidation reaction of a number of triazoles bearing electron-withdrawing and electron-donating groups at their aromatic rings were studied. The results were summarized in Table 2. The reaction of 1b (R2¼H, R2¼CH2Ph) and 2a afforded 3b in 56% yield. Triazole 1c (R1¼o-CH3, R2¼CH2Ph) having a meta methyl showed lower activity, and the corresponding product was obtained in 64% yield. Fluorine-containing triazole are quite active, and 3d was obtained in 86% yield in the case of 1-benzyl-4-(4fluorophenyl)-1H-1,2,3-triazole, whereas the chlorine-containing triazole showed relatively lower activity. When N-substituent was replaced by an alkyl group, the corresponding triazoles 1f (R1¼H, R2¼oct) and 1g (R1¼p-F, R2¼oct) also reacted with dioxazolone

smoothly, especially in the case of 4-(4-fluorophenyl)-1-octyl-1H1,2,3-triazole 1g (R1¼p-F, R2¼oct), the target product was isolated in nearly quantitative yield. To fully characterize the product, single crystals of 3g were grown by slow diffusion of hexane into the toluene solution of 3g. The structure of 3g determined by X-ray diffraction was given in Fig. 1. The amidation reactions of triazoles having an N-phenylethylsubstituent with dioxazolone were also successful at the loading of 20 mol % of cobalt catalyst at 100  C, and their corresponding amidated products were isolated in 83, 90, 85, 56, and 60% yields, respectively. Finally, we examined the reactivities of dioxazolone bearing different substituents at their aromatic rings. Although the desired amidated products could be successfully obtained, the yields strongly depend on the substituents including methyl, methoxyl, and fluorine. On the basis of the previous reports,10 a plausible catalytic mechanism was proposed and depicted in Fig. 2. The cobalt iodide complexes would generate [Cp*Co(Sol)]þ species I in the presence of AgSbF6 due to halogen abstraction and CO dissociation. Further interaction with a triazole molecule would yield II because of the coordination of triazole. Subsequent CeH metalation with the aid of AcO and reduction of one molecule of HOAc afforded cobaltacyclic complex III. Interaction of 1,4,2-dioxazol-5-one 2 with III generates Co(III) amido species IV with the release of CO2 and following nitrene insertion. Protonation of IV would yield the target product and regenerate the active cobalt species.

3. Conclusion In conclusion, we described cobalt-catalyzed amination of various triazoles by using dioxazolones as the nitrogen source. A number of amidated triazole derivatives have been obtained in good to excellent yields. The reaction was believed to proceed via cobalt catalyzed triazole-directed CeH bond activation and subsequent nitrene insertion. The starting materials are easily available and the catalyst is cheap, thus the protocol offers a new method for the direct functionalization of triazoles.

8006

F. Wu et al. / Tetrahedron 72 (2016) 8004e8008

Table 2 Cobalt-catalyzed amidation of 1,2,3-triazole3

O N

R1

N N N R2

Cp*Co(CO)I2 (20 mol%)

O

N N N R2

AgSbF6 (40 mol%)

O

R1

NH

KOAc (20 mol%) o

DCE, 100 C, 24 h

R3

O

N N N

R3

3

2

1

N N N

Ph

N N N

Me

N N N

Ph

Ph

Ph Me O

O

Ph

3a 84 %

Cl

N oct

F

3e 71 %

Ph

3d 86 % Cl N N N

NH O

Ph

O

O

Ph

N N N oct

NH

Ph

NH

3c 64 %

N N

Ph

NH O

O

Ph

3b 56 %

N N N

F

NH

NH

NH

3f 84 %

NH

Ph O

3g 99 %

Ph 3h 59 %

Me N N N

N N N

N N N

Br

NH O

NH NH

Ph O

N N N

O

MeO

Ph

Me

Me

Ph

NH

N N

Me

O

Ph

3o 60 %

N

N N

Ph Me

NH

N

Ph

NH O

O

Me 3p 90 %

Ph

N

NH O

O Ph 3n 56 %

3m 85 % N N N

Ph

NH

Ph

3l 90 %

N N

N N N

Ph

NH O

3k 83 %

Ph

NH

F

Ph

Ph

3j 50 %

3i 72 %

Cl

O

N N N

Ph

OMe

F

3q 45 %

3r 42 %

4. Experimental section

4.2. General procedure for the amidation of triazoles

4.1. General

1a (0.20 mmol), 2a (0.40 mmol), Cp*Co(CO)I2 (19 mg, 0.04 mmol, 20 mol %), AgSbF6 (27 mg, 0.08 mmol 40 mol %), and KOAc (4.0 mg, 0.04 mmol, 20 mol %) in 1,2-dichloroethane (2 mL) were charged into an oven-diried 2 mL tube sealed with a Teflon screw cap. This sealed tube was heated at 100  C for 24 h under air. The products were purified by flash column chromatography eluting with petroleum ether/ethyl acetate.

All chemicals were of reagent grade quality obtained from commercial sources and used as received. All triazole were synthesized according to the reported methods. 1H and 13C NMR spectra were recorded on a Bruker Avance-400 (400 MHz) spectrometer, 400 MHz for 1H and 100 MHz for 13C. Chemical shift (d) were expressed in ppm downfield to TMS at d¼0 ppm and coupling constants (J) were expressed in Hz. Cobalt catalyst,11 1,2,3triazoles12 and dioxazolones13 were prepared according to reported literatures.

4.2.1. N-(2-(1-Benzyl-1H-1,2,3-triazol-4-yl)-5-methylphenyl)benzamide (3a). Yield: 62.0 mg, 84%. White solid. Mp 117e119  C. 1H NMR (400 MHz, CDCl3): d 12.22 (s, 1H), 8.73 (s, 1H), 8.20e8.18 (m,

F. Wu et al. / Tetrahedron 72 (2016) 8004e8008

8007

128.7, 128.2, 127.6, 127.5, 121.5, 120.6, 117.5, 54.5, 20.8; HRMS (TOF MS EIþ) m/z calcd for C23H20N4O: 368.1637. Found: 368.1634. 4.2.4. N-(2-(1-Benzyl-1H-1,2,3-triazol-4-yl)-5-fluorophenyl)benzamide (3d). Yield: 64 mg, 86%. White solid. Mp 169e171  C. 1H NMR (400 MHz, CDCl3): d 12.35 (s, 1H), 8.65 (dd, J¼12, 2.4 Hz, 2H), 8.10e8.08 (m, 2H), 7.64 (s, 1H), 7.48e7.44 (m, 3H), 7.34e7.18 (m, 6H), 6.70e6.66 (m, 1H), 5.51 (s, 2H); 13C NMR (100 MHz, CDCl3): d 166.0, 164.0, 161.5, 147.6, 138.5, 138.4, 134.8, 134.0, 131.9, 129.4, 129.2, 128.8, 128.3, 128.2, 127.6, 120.4, 113.7, 110.5, 110.2, 108.7, 108.4, 54.6; HRMS (TOF MS EIþ) m/z calcd for C22H17FN4O: 372.1386. Found: 372.1383. Fig. 1. X-ray diffraction structures of 3g.

NN N R2 R1

NH

+ OAc -

O

[Co(III)] R3

3

R1

[Co(III)]=[Cp*Co(OAc)x](2-x)I R2

HOAc

R1

N

N 1

N

R1

O R3

N

H N [Co(III)] R2 N N II

N [Co(III)] N N

R2

IV

OAcR1

CO2

HOAc

[Co(III)] O O N R3

O

4.2.5. N-(2-(1-Benzyl-1H-1,2,3-triazol-4-yl)-5-chlorophenyl)benzamide (3e). Yield: 55 mg, 71%. White solid. Mp 165e167  C. 1H NMR (400 MHz, CDCl3): d 12.27 (s, 1H), 8.87 (d, J¼2.0 Hz, 1H), 8.09e8.06 (m, 2H), 7.66 (s, 1H), 7.47e7.16 (m, 9H), 6.89 (dd, J¼8.4, 2.0 Hz, 1H), 5.49 (s, 2H); 13C NMR (100 MHz, CDCl3): d 165.9, 147.4, 137.7, 134.8, 134.7, 133.9, 132.0, 129.4, 129.2, 128.8, 128.2, 127.8, 127.6, 123.4, 121.2, 120.8, 115.9, 54.6; HRMS (TOF MS EIþ) m/z calcd for C22H17ClN4O: 388.1091. Found 388.1094.

N N N R2 III

2

Fig. 2. Postulated catalytic cycle.

2H), 7.73 (s, 1H), 7.54e7.53 (m, 3H), 7.39e7.38 (m, 3H), 7.32e7.30 (m, 3H), 6.88 (d, J¼8.0 Hz, 1H), 5.57 (s, 2H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3): d 165.9, 148.3, 139.5, 136.7, 135.3, 134.1, 131.6, 129.3, 129.1, 128.7, 128.2, 127.6, 126.9, 124.3, 121.9, 120.4, 115.0, 54.5, 21.7; HRMS (TOF MS EIþ) m/z calcd for C23H20N4O: 368.1637. Found: 368.1641. 4.2.2. N-(2-(1-Benzyl-1H-1,2,3-triazol-4-yl)phenyl)benzamide (3b). Yield: 40 mg, 56%. White solid. Mp 139e141  C. 1H NMR (400 MHz, CDCl3): d 12.18 (s, 1H), 8.79 (d, J¼7.6 Hz, 1H), 8.12e8.09 (m, 2H), 7.69 (s, 1H), 7.46e7.25 (m, 3H), 7.35e7.17 (m, 7H), 6.98 (td, J¼8.0, 0.9 Hz, 1H), 5.50 (s, 2H); 13C NMR (100 MHz, CDCl3): d 165.9, 148.2, 136.9, 135.2, 134.1, 131.7, 129.3, 129.2, 129.1, 128.8, 128.2, 127.6, 127.1, 123.4, 121.5, 120.8, 117.6, 54.5; HRMS (TOF MS EIþ) m/z calcd for C22H18N4O: 354.1481. Found: 354.1481. 4.2.3. N-(2-(1-Benzyl-1H-1,2,3-triazol-4-yl)-4-methylphenyl)benzamide (3c). Yield: 47 mg, 64%. White solid. Mp 152e154  C. 1H NMR (400 MHz, CDCl3): d 12.14 (s, 1H), 8.74 (d, J¼8.4 Hz, 1H), 8.19e8.16 (m, 2H), 7.77 (s, 1H), 7.54e7.52 (m, 3H), 7.40e7.23 (m, 6H), 7.17 (d, J¼8.4 Hz, 1H), 5.59 (s, 2H), 2.30 (s, 3H); 13C NMR (100 MHz, CDCl3): d 165.7, 148.3, 135.3, 134.4, 134.1, 132.9, 131.6, 129.9, 129.3, 129.1,

4.2.6. N-(2-(1-Octyl-1H-1,2,3-triazol-4-yl)phenyl)benzamide (3f). Yield: 63 mg, 84%. White solid. Mp 89e91  C. 1H NMR (400 MHz, CDCl3): d 12.29 (s, 1H), 8.89 (d, J¼8.0 Hz, 1H), 8.17e8.20 (m, 2H), 7.86 (s, 1H), 7.54e7.50 (m, 4H), 7.41e7.37 (m, 1H), 7.14e7.10 (m, 1H), 4.42 (t, J¼7.2 Hz, 2H), 1.97 (m, 2H), 1.31 (m, 10H), 0.87 (m, 3H); 13C NMR (100 MHz, CDCl3): d 165.9, 147.8, 136.9, 135.2, 131.7, 129.1, 128.7, 127.6, 127.0, 123.4, 121.6, 120.6, 117.8, 50.8, 31.7, 30.3, 29.0, 28.9, 26.5, 22.6, 14.1; HRMS (TOF MS EIþ) m/z calcd for C23H28N4O: 376.2263. Found: 376.2268. 4.2.7. N-(5-Fluoro-2-(1-octyl-1H-1,2,3-triazol-4-yl)phenyl)benzamide (3g). Yield: 78 mg, 99%. White solid. Mp 87e90  C. 1H NMR (400 MHz, CDCl3): d 12.48 (s, 1H), 8.74 (dd, J¼12.0, 2.8 Hz, 1H), 8.18e8.16 (m, 2H), 7.82 (s, 1H), 7.55e7.53 (m, 3H), 7.45e7.42 (dd, J¼8.8, 6.4 Hz, 1H), 6.81e6.76 (m, 1H), 4.41 (t, J¼7.2 Hz, 2H), 1.96 (t, J¼6.8 Hz, 2H), 1.34e1.25 (m, 10H), 0.88e0.85 (t, J¼6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 165.0, 162.8, 160.4, 146.1, 137.4, 137.3, 133.7, 130.9, 127.8, 127.2, 127.1, 126.6, 119.3, 112.8, 112.8, 109.4, 109.2, 107.5, 107.3, 49.8, 30.6, 29.2, 28.0, 27.9, 25.5, 21.5, 13.0; HRMS (TOF MS EIþ) m/z calcd for C23H27FN4O: 394.2169. Found: 394.2172. 4.2.8. N-(2-(1-(4-Chlorobenzyl)-1H-1,2,3-triazol-4-yl)phenyl)benzamide (3h). Yield: 46 mg, 59%. White solid. Mp 137e179  C. 1H NMR (400 MHz, CDCl3): d 12.11 (s, 1H), 8.80e8.77 (m, 1H), 8.11e8.08 (m, 2H), 7.70 (s, 1H), 7.47e7.45 (m, 3H), 7.35 (dd, J¼8.0, 1.2 Hz, 1H), 7.31e7.27 (m, 3H), 7.18e7.16 (d, J¼8.0 Hz, 2H), 7.00 (td, J¼7.6, 0.8 Hz, 1H), 5.48 (s, 1H); 13C NMR (100 MHz, CDCl3): d 164.8, 147.3, 135.8, 134.1, 131.5, 130.7, 128.4, 128.2, 127.7, 126.5, 126.1, 122.4, 120.5, 119.6, 116.4, 52.7; HRMS (TOF MS EIþ) m/z calcd for C22H17ClN4O: 388.1091. Found: 388.1087. 4.2.9. N-(2-(1-(2-bromobenzyl)-1H-1,2,3-triazol-4-yl)phenyl)benzamide (3i). Yield: 62 mg, 72%. White solid. Mp 113e115  C. 1H NMR (400 MHz, CDCl3): d 12.14 (s, 1H), 8.79 (d, J¼8.4 Hz, 1H), 8.11e8.09 (m, 2H), 7.81 (s, 1H), 7.56 (d¼8.0 Hz, 1H), 7.46e7.45 (m, 3H),7.39 (d, J¼7.6 Hz, 1H), 7.30e7.24 (m, 2H), 7.20e7.15 (m, 2H), 7.02 (t, J¼7.6 Hz, 1H), 5.66 (s, 1H); 13C NMR (100 MHz, CDCl3): d 165.9, 148.2, 136.9, 135.2, 133.6, 133.4, 131.7, 130.8, 130.5, 129.3, 128.8, 128.4, 127.6, 127.1, 123.7, 123.4, 121.6, 121.0, 117.6, 54.2; HRMS (TOF MS EIþ) m/z calcd for C22H17BrN4O: 432.0586. Found: 432.0587. 4.2.10. N-(2-(1-(3-Methylbenzyl)-1H-1,2,3-triazol-4-yl)phenyl)benzamide (3j). Yield: 37 mg, 50%. White solid. Mp 96e98  C. 1H NMR (400 MHz, CDCl3): d 12.19 (s, 1H), 8.79 (d, J¼8.4 Hz, 1H), 8.11 (m,

8008

F. Wu et al. / Tetrahedron 72 (2016) 8004e8008

2H), 7.69 (s, 1H), 7.46e6.96 (m, 10H), 5.46 (s, 2H), 2.25 (s, 3H); 13C NMR (100 MHz, CDCl3): d 164.8, 147.1, 138.2, 135.8, 134.2, 132.9, 130.6, 128.8, 128.1, 127.8, 127.7, 126.6, 126.0, 124.2, 122.3, 120.4, 119.7, 116.6, 53.5, 20.3; HRMS (TOF MS EIþ) m/z calcd for C23H20N4O: 368.1637. Found: 368.1640. 4.2.11. N-(2-(1-Phenethyl-1H-1,2,3-triazol-4-yl)phenyl)benzamide (3k). Yield: 61 mg, 83%. White solid. Mp 149e151  C. 1H NMR (400 MHz, CDCl3): d 12.21 (s, 1H), 8.86 (d, J¼8.4 Hz, 1H), 8.19e8.16 (m, 2H), 7.55e7.53 (m, 4H), 7.39e7.26 (m, 5H), 7.12e7.07 (m, 3H), 4.67 (t, J¼7.2, 2H), 3.26 (t, J¼7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 165.9, 147.5, 136.8, 136.7, 135.2, 131.7, 129.2, 129.0, 128.8, 128.7, 127.6, 127.4, 127.0, 123.5, 121.6, 121.2, 117.8, 52.1, 36.8; HRMS (TOF MS EIþ) m/z calcd for C23H20N4O: 368.1637. Found: 368.1634. 4.2.12. N-(5-Fluoro-2-(1-phenethyl-1H-1,2,3-triazol-4-yl)phenyl)benzamide (3l). Yield: 69 mg, 89%. White solid. Mp 137e139  C. 1H NMR (400 MHz, CDCl3): d 12.39 (s, 1H), 8.71 (dd, J¼2.8, 2.8 Hz, 1H), 8.16e8.14 (m, 2H), 7.56e7.50 (m, 4H), 7.32e7.26 (m, 4H), 7.10 (d, J¼6.8 Hz, 2H), 6.76 (td, J¼8.4, 2.4 Hz, 1H), 4.66 (t, J¼7.2 Hz, 2H), 3.26 (t, J¼7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 166.0, 163.9, 161.5, 146.9, 138.5, 138.3, 136.7, 134.8, 131.9, 129.0, 128.8, 128.7, 128.2, 128.1, 127.6, 127.4, 120.9, 113.8, 110.5, 110.3, 108.7, 108.4, 52.1, 36.7. HRMS (TOF MS EIþ) m/z calcd for C23H19FN4O: 386.1543. Found: 386.1543. 4.2.13. N-(5-Chloro-2-(1-phenethyl-1H-1,2,3-triazol-4-yl)phenyl)benzamide (3m). Yield: 68 mg, 85%. White solid. Mp 139e141  C. 1H NMR (400 MHz, CDCl3): d 12.24 (s, 1H), 8.88 (d, J¼2.0 Hz, 1H), 8.87 (m, 2H), 7.47e6.92 (m, 11H), 4.58 (t, J¼7.2 Hz, 2H), 3.18 (t, J¼7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 164.9, 145.6, 136.6, 135.5, 133.7, 133.6, 130.9, 127.9, 127.8, 127.6, 126.7, 126.5, 126.3, 125.8, 122.4, 120.2, 115.0, 51.1, 35.7; HRMS (TOF MS EIþ) m/z calcd for C23H19ClN4O: 402.1247. Found: 402.1242. 4.2.14. N-(5-Methoxy-2-(1-phenethyl-1H-1,2,3-triazol-4-yl)phenyl)benzamide (3n). Yield: 45 mg, 56%. White solid. Mp 142e144  C. 1H NMR (400 MHz, CDCl3): d 12.26 (s, 1H), 8.51 (d, J¼2.4 Hz, 1H), 8.09e8.08 (m, 2H), 7.44e7.43 (m, 3H), 7.37 (s, 1H), 7.20e7.12 (m, 4H), 7.00 (d, J¼6.4 Hz, 2H), 6.53 (dt, J¼8.8, 2.4 Hz, 1H), 4.52 (t, J¼7.2 Hz, 2H), 3.77 (s, 3H), 3.12 (t, J¼7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 166.1, 160.1, 147.5, 1382, 136.8, 135.1, 131.8, 128.9, 128.8, 128.7, 127.9, 127.6, 127.3, 120.3, 110.6, 110.5, 105.5, 55.46, 51.97, 36.73; HRMS (TOF MS EIþ) m/z calcd. For C24H22N4O2: 398.1743. Found: 398.1740. 4.2.15. N-(5-Methyl-2-(1-phenethyl-1H-1,2,3-triazol-4-yl)phenyl)benzamide (3o). Yield: 46 mg, 60%. White solid. Mp 121e123  C. 1 H NMR (400 MHz, CDCl3): d 12.18 (d, 1H), 8.72 (s, 1H), 8.19e8.16 (m, 2H), 7.54e7.51 (m, 4H), 7.31e7.22 (m, 4H), 7.10 (d, J¼6.8 Hz, 2H), 6.90 (s, J¼8.0 Hz, 1H), 4.64 (t, J¼7.2 Hz, 2H), 3.25 (t, J¼7.2 Hz, 2H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3): d 165.9, 147.6, 139.4, 136.7, 136.6, 135.3, 131.6, 129.0, 128.7, 128.6, 127.6, 127.3, 126.9, 124.4, 121.9, 120.8, 115.1, 52.0, 36.8, 21.7; HRMS (TOF MS EIþ) m/z calcd for C24H22N4O: 382.1794. Found: 382.1797. 4.2.16. N-(2-(1-Benzyl-1H-1,2,3-triazol-4-yl)-5-methylphenyl)-4methyl-benzamide (3p). Yield: 69 mg, 90%. White solid. Mp 150e152  C. 1H NMR (400 MHz, CDCl3): d 12.16 (d, 1H), 8.72 (s, 1H), 8.08 (d, J¼8.0 Hz, 2H), 7.72 (s, 1H), 7.40e7.29 (m, 8H), 6.88 (d, J¼7.2 Hz, 1H), 5.58 (s, 2H), 2.42 (s, 3H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3): d 165.9, 148.4, 142.0, 139.5, 136.8, 134.2, 132.5, 129.4, 129.3, 128.2, 127.6, 126.9, 124.2, 121.9, 120.3, 114.9, 54.5, 21.7,

21.5; HRMS (TOF MS EIþ) m/z calcd for C24H22N4O: 382.1794. Found: 382.1794. 4.2.17. N-(2-(1-Benzyl-1H-1,2,3-triazol-4-yl)-5-methylphenyl)-4fluorobenzamide (3q). Yield: 35 mg, 45%. White solid. Mp 135e137  C. 1H NMR (400 MHz, CDCl3): d 12.22 (s, 1H), 8.69 (s, 1H), 8.22e8.18 (m, 2H), 7.75 (s, 1H), 7.42e7.39 (m, 3H), 7.34e7.32 (m, 3H), 7.21 (t, J¼8.8 Hz, 2H), 6.91 (dd, J¼8.0, 0.8 Hz, 1H), 5.61 (s, 2H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3): d 166.2, 164.8, 163.7, 148.4, 139.6, 136.6, 134.0, 131.5, 130.0, 129.9, 129.3, 129.1, 128.2, 126.9, 124.4, 121.9, 120.3, 115.9, 115.6, 114.9, 54.6, 21.7; HRMS (TOF MS EIþ) m/z calcd. For C23H19FN4O: 386.1543. Found: 386.1545. 4.2.18. N-(2-(1-Benzyl-1H-1,2,3-triazol-4-yl)-5-methylphenyl)-4methoxybenzamide (3r). Yield: 34 mg, 43%. White solid. Mp 159e161  C. 1H NMR (400 MHz, CDCl3): d 12.12 (s, 1H), 8.71 (s, 1H), 8.17e8.15 (m, 2H), 7.73 (s, 1H), 7.40e7.39 (m, 3H), 7.33e7.30 (m, 3H), 7.03 (t, J¼8.8 Hz, 2H), 6.88 (dd, J¼7.2 Hz, 1H), 5.59 (s, 2H), 3.87 (s, 3H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3): d 165.5, 162.3, 148.4, 139.5, 136.9, 134.1, 129.5, 129.3, 129.1, 128.1, 127.7, 126.9, 124.1, 121.9, 120.3, 114.8, 113.9, 55.4, 54.5, 21.7; HRMS (TOF MS EIþ) m/z calcd for C24H22N4O2: 398.1743. Found: 398.1740. Acknowledgements The authors thank the National Science Foundation of China (21572203 and J1210042) and the Zhejiang Provincial Natural Science Foundation (LZ16B020001) for financial support. Supplementary data Supplementary data associated with this article can be found in the online version, at http://dx.doi.org/10.1016/j.tet.2016.10.032. References and notes 1. (a) Yan, W.; Ye, X.; Akhmedov, N. G.; Petersen, J. L.; Shi, X. Org. Lett. 2012, 14, 2358; (b) Bolje, A.; Kosmrlj, J. Org. Lett. 2013, 15, 5084; (c) Dai, Q.; Gao, W.; Liu, D.; Kapes, L. M.; Zhang, X. J. Org. Chem. 2006, 71, 3928. 2. (a) Urankar, D.; Pinter, B.; Pevec, A.; Proft, F. D.; Turel, I.; Kosmrlj, J. Inorg. Chem. 2010, 49, 4820; (b) Urankar, D.; Pevec, A.; Turel, I.; Kosmrlj, J. Cryst. Growth Des. 2010, 10, 4920; (c) Connell, T. U.; White, J. M.; Smith, T. A.; Donnelly, P. S. Inorg. Chem. 2016, 55, 2776; (d) Fletcher, J. T.; Bumgarner, B. J.; Engels, N. D.; Skoglund, D. A. Organometallics 2008, 27, 5430. 3. Li, Y.-C.; Qi, C.; Li, S.-H.; Zhang, H.-J.; Sun, C.-H.; Yu, Y.-Z.; Pang, S.-P. J. Am. Chem. Soc. 2010, 132, 12172. 4. Lee, T.; Cho, M.; Ko, S.-Y.; Youn, H.-J.; Baek, D. J.; Cho, W.-J.; Kang, C.-Y.; Kim, S. J. Med. Chem. 2007, 50, 585. 5. Lau, Y. H.; Rutledge, P. J.; Watkinson, M.; Todd, M. H. Chem. Soc. Rev. 2011, 40, 2848. 6. (a) Moses, J. E.; Moorhouse, A. D. Chem. Soc. Rev. 2007, 36, 1249; (b) Hein, J. E.; Fokin, V. V. Chem. Soc. Rev. 2010, 39, 1302. 7. (a) Tornoe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057; (b) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596; (c) Raushel, J.; Fokin, V. V. Org. Lett. 2010, 12, 4952. 8. (a) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624; (b) Xiao, B.; Gong, T.-J.; Xu, J.; Liu, Z.-J.; Liu, L. J. Am. Chem. Soc. 2011, 133, 1466; (c) Badiei, Y. M.; Dinescu, A.; Dai, X.; Palomino, R. M.; Heinemann, F. W.; Cundari, T. R.; Warren, T. H. Angew. Chem., Int. Ed. 2008, 47, 9961. 9. (a) Wang, F.; Wang, H.; Wang, Q.; Yu, S.; Li, X. Org. Lett. 2016, 18, 1306; (b) Mei, R.; Loup, J.; Ackermann, L. ACS Catal. 2016, 6, 793; (c) Liang, Y.; Liang, Y.-F.; Tang, C.; Yuan, Y.; Jiao, N. Chem.dEur. J. 2015, 21, 16395; (d) Park, J.; Chang, S. Angew. Chem., Int. Ed. 2015, 54, 14103; (e) Wang, H.; Tang, G.; Li, X. Angew. Chem., Int. Ed. 2015, 54, 13049; (f) Park, Y.; Jee, S.; Kim, J. G.; Chang, S. Org. Process Res. Dev. 2015, 19, 1024; (g) Bizet, V.; Bolm, C. Eur. J. Org. Chem. 2015, 2854; (h) Park, Y.; Park, K. T.; Kim, J. G.; Chang, S. J. Am. Chem. Soc. 2015, 137, 4534; (i) Bizet, V.; Buglioni, L.; Bolm, C. Angew. Chem., Int. Ed. 2014, 53, 5639; (j) Zhong, C. L.; Tang, , P.; Nathel, N. B. Y.; Yin, P.; Chen, Y.; He, L. J. Org. Chem. 2012, 77, 4271; (k) Dube F. F.; Vetelino, M.; Couturier, M.; Aboussafy, C. L.; Pichette, S.; Jorgensen, M. L.; Hardink, M. Org. Lett. 2009, 11, 5622; (l) Darlage, L. J.; Kinstle, T. H.; Mcintosh, C. L. J. Org. Chem. 1971, 56, 1088. 10. Zhao, S.; Yu, R.; Chen, W.; Liu, M.; Wu, H. Org. Lett. 2015, 17, 2828. 11. Sun, B.; Yoshino, T.; Matsunaga, S.; Kanaia, M. Adv. Synth. Catal. 2014, 356, 1491. 12. Raushel, J.; Fokin, V. V. Org. Lett. 2010, 12, 4952. 13. Park, Y.; Park, K. T.; Kim, J. G.; Chang, S. J. Am. Chem. Soc. 2015, 137, 4534.