Highly efficient amination in neat water of benzyl

JOURNAL OF CHEMICAL RESEARCH 2013

RESEARCH PAPER 611

OCTOBER, 611–614

Highly efficient amination in neat water of benzyl chlorides with dialkylformamides catalysed by N-heterocyclic carbene-palladium(II)-1methylimidazole complex Wen-Xin Chen, Cai-Yun Zhang and Jian-Mei Lu College of Chemistry and Materials Engineering, Wenzhou University, Chashan University Town, Wenzhou, Zhejiang Province 325035, P.R. China Dialkylformamides are excellent N-sources in the amination of benzyl chlorides when catalysed by a NHC-Pd(II)-Im complex. In the presence of NaOH and the catalyst, variously substituted benzyl chlorides and five different dialkylformamides reacted smoothly to afford the corresponding N,N-dialkyl-benzylamines in good to almost quantitative yields in eco-friendly solvent water at 50 °C within 3 h. Keywords: N-heterocyclic carbene, palladium complex, benzyl chlorides, amination, water During the past decade, N-heterocyclic carbenes (NHCs)metal complexes have shown efficient catalytic activity in the formation of carbon–carbon and carbon–heteroatom bonds.1–3 In our continuing studies of the synthesis of novel NHC–metal complexes and their applications in organic synthesis, we have developed several new reactions for the formation of carbon–carbon and carbon–nitrogen bonds.4–6 For instance, recently, we have found that amides can be excellent N-sources in the catalysed amination of aryl chlorides by a N-heterocyclic carbene-Pd(II)-1-methylimidazole [NHCPd(II)-Im] complex 1; the corresponding anilines being formed in moderate to almost quantitative yields at room temperature within 6 h (Scheme 1).6 These results prompted us to expand its application to the reaction between benzyl chlorides and amides for the synthesis of benzylamines. Furthermore, compared to toxic, flammable and volatile organic solvents, water, as a non-toxic, non-flammable and the most eco-friendly solvent, has attracted much attention in organic synthesis over the past 15 years.7 Considering our experience in the reactions performed in neat water catalysed by NHC-metal complexes4,5 and to develop an alternative method for the N-benzylation of benzyl halides, we investigated the NHC-Pd(II)-Im-catalysed reactions between benzyl chlorides and amides in neat water.8–12 We now report these results in detail. Results and discussion

Initial investigations were carried out using benzyl chloride 2a (0.8 mmol) and N-formylmorpholine 3a (2.0 equiv) as the substrates in the presence of the NHC-Pd(II)-Im complex 1 (1.0 mol%) in water (1.0 mL) at 25 °C for 12 h to find the best Cl

O +

R

R1

NHC-Pd(II)-Im 1 (1.0 mol%) R N KOtBu, THF or DMF, R1 rt, 6 h R3 Pri N

NHC-Pd(II)-Im 1:

N Pr

i

Pri

N

Cl Pd

Pri

Scheme 1.

* Correspondent. E-mail: [email protected]

JCR1302004_FINAL.indd 611

R2

2

Cl

N

N

R3

Table 1 Evaluation of the base and reaction time for the amination of benzyl chloride with N-formylmorpholine by NHC-Pd(II)-Im complex O H Cl N + 2a

Entrya 1 2 3

O 3a

Base KOH NaOH NaOH

NHC-Pd(II)-Im 1 (1.0 mol%) base, H2O

Temp./°C 25 25 50

N 4a

Time/h 12 12 3

O

Yield/%b 70 83 96

Reaction conditions: 2a (0.8 mmol), 3a (2.0 equiv.), base (3.0 equiv.), NHC-Pd(II)-Im 1 (1.0 mol%), H2O (1.0 mL). b Isolated yields. a

base. As can be seen from Table 1, NaOH (83% yield) was better than KOH (70%) as the base in the formation of the corresponding aminated product 4a (Table 1, entries 1 and 2). In the presence of the weaker bases K 2CO3, Na2CO3, KHCO3 and NaHCO3, no reaction occurred. Further study showed that when the reaction temperature was raised to 50 °C, product 4a can be obtained in 96% yield within 3 h (Table 1, entry 3). So the optimal reaction conditions were established as using NHC-Pd(II)-Im complex 1 (1.0 mol%) as the catalyst, NaOH (3.0 equiv) as the base, with the temperature of 50 °C in neat water (Table 1, entry 3). A similar complex such as NHC-Pd-Py developed by Organ’s group12 was also tested for the reaction between benzyl chloride 2a and N-formylmorpholine 3a, and an inferior result was obtained (80%). With the optimal reaction conditions in hand, we then investigated the reactions of a variety of benzyl chlorides 2b–n with N-formylmorpholine 3a to test the generality of the reaction (Table 2). As can be seen from Table 2, regardless of electron-donating or electron-withdrawing groups substituted benzyl chlorides 2b–f and 2h–m as the substrates, all reactions proceeded smoothly to give the desired products 4 in high to almost quantitative yields in 3 h (Table 2, entries 1–5, 8–13). 1-Chloromethylnaphthalene 2n was also found to be a suitable substrate and 98% yield of product 4n was achieved (Table 2, entry 14). Although 4-tert-butylbenzyl chloride 2g was not a good substrate under the optimal conditions, the corresponding product 4g could be obtained in 98% at elevated temperature (80 °C) (Table 2, entries 6 and 7). Encouraged by these results, we also carried out the amination reactions of various substitutes of benzyl chlorides 2 under optical conditions with five other formamides: N-formylpiperidine 3b, N,N-dimethylformamide 3c, N,N‑diethylformamide 3d, formanilide 3e and

04/10/2013 09:19:10

612 JOURNAL OF CHEMICAL RESEARCH 2013 Table 2 Yields of the amination of a series of benzyl chlorides 2b–n with N-formylmorpholine 3a catalysed by NHC-Pd(II)-Im complex under optimal conditions Cl H O +

NHC-Pd(II)-Im 1 (1.0 mol%) NaOH, H2O,

N O 3a

R1 2

50 oC, 3 h

2 (R1) 2b (4-Me) 2c (3-MeO) 2d (4-MeO) 2e (2-Me) 2f (3-Me) 2g (4- tBu) 2g (4- tBu) 2h (4-Cl) 2i (2-CN) 2j (4-CN) 2k (4-F) 2l (4-NO2) 2m (2-Cl) 2m (2-Cl)

Entrya 1 2 3 4 5 6 7c 8 9 10 11 12 13

N

Yield/% 4b, 98 4c, 99 4e, 99 4e, 99 4f, 99 4g, 61 4g, 94 4h, 98 4i, 98 4j, 98 4k, 95 4l, 97 4m, 98

Cl

2n

14

O

4

1

R

4n, 98

Unless otherwise specified, all reactions were carried out using 2 (0.8 mmol), 3a (2.0 equiv.), NaOH (3.0 equiv.) in H2O (1.0 mL) at 50 °C for 3 h. b Isolated yields. c Temperature was 80 °C. a

N-methylformanilide 3f. For the reactions of benzyl chlorides 2 with N-formylpiperidine 3b, N,N-dimethylformamide 3c, N,Ndiethylformamide 3d, and N-methylformanilide 3f, good to almost quantitative yields of products 4o–4w, 4aa and 4ab were achieved under the optimal reaction conditions (Table 3, entries 1–9, 13 and 14). The electronic effect of the substituents on the benzyl chlorides 2 did not affect the reactions. For example, whether electron-donating groups such as MeO- and Me- or electron-withdrawing group such as F- and CN- were attached on the benzyl chlorides, similar good to almost quantitative yields were achieved. When formanilide 3e was used as the substrate, products 4x–4z were also obtained in high yields (Table 3, entries 10–12). All but one of the 25 N,N-dialkyl-benzylamines that were synthesised were characterised by comparison of melting point (when a solid) and 1H and 13C NMR data with cited literature data. The one new compound, 4i, was additionally characterised by IR and HRMS. In conclusion, we have found that formamides can be used as N-sources in the NHC-Pd(II)-Im 1 complex-catalysed monoamination of benzyl chlorides. The reactions can tolerate a broad scope of substrates. Under the optimal conditions, all reactions performed very well to give the corresponding aminated products in good to almost quantitative yields, providing a convenient alternative method for the amination of benzyl chlorides. It should be also pointed out that the reactions can be performed in neat water under mild conditions, extending their potential applications in industrial processes. Experimental

Table 3 Yields of the amination of a series of benzyl chlorides with a series of dialkylformamides 3b–f catalysed by NHC-Pd(II)-Im complex under optimal conditions Cl NHC-Pd(II)-Im 1 R3 O R3 N (1.0 mol%) + N 2 NaOH, H2O, 2 R H 4 R R1 50 oC, 3 h 3 R1 2 Entry 1 2 3 4

2 (R1) 2a (H) 2b (4-Me) 2k (4-F) 2j (4-CN)

3 3b 3b 3b 3b

b O b H b b

5

2c (3-MeO)

3c

c

2m (2-Cl)

Yield/% 4o, 90 4p, 94 4q, 90 4r, 98

N

O H

N

4s, 90

Cl

6

2n

3c

4t, 95

7c

2b

3d

8 9

2c 2n

3d 3d

10

2a

3e

d O d H d d e O

11

2c

3e

e

12 13 14

2j 2d (4-MeO) 2j

3e 3f 3f

f

H ee O

4u, 93

N

N

Ph

N

H

4v, 98 4w, 99 4x, 90 4y, 90 4z 4aa, 98 4ab, 82

f H Ph Unless otherwise specified, all reactions were carried out using 2 (0.8 mmol), 3 (2.0 equiv.), NaOH (3.0 equiv.) in H2O (1.0 mL) at 50 °C for 3 h. b Isolated yields. c Temperature was 80 °C. a


NMR spectra were obtained on a Bruker Avance-300 or -500 MHz spectrometer (1H NMR at 300 or 500 Hz, 13C NMR at 75 or 125 Hz) in CDCl3 with tetramethylsilane (TMS) as an internal standard; J-values are in Hz. Commercially obtained reagents were used without further purification. Flash column chromatography was carried out using Huanghai 300–400 mesh silica gel at increased pressure. FTIR spectroscopy was performed using a NICOLET iS10 instrument. HRMS was detected on a Bruker Esquire HCT spectrometer, and the mass analyser type was an ion trap (ESI). Amination of benzyl chlorides 2 with dialkylformamides 3 in neat water catalysed by NHC-Pd(II)-Im complex 1; general procedure Under a N2 atmosphere, NaOH (3.0 equiv), NHC-Pd(II)-Im complex 1 (1.0 mol%), water (1.0 mL), benzyl chloride 2a (0.8 mmol), and N-formylmorpholine 3a (2.0 equiv) were successively added into a Schlenk reaction tube. The mixture was stirred at 50 °C for 3 h. After cooling to room temperature, the reaction mixture was extracted with EtOAc, washed with brine, and dried over anhydrous Na2SO4. Then the solvent was removed under reduced pressure and the residue was purified by flash column chromatography on silica gel (eluent: PE / EA = 5:1) to give the pure products 4a. 4-Benzyl-morpholine (4a):13 Colourless liquid; 1H NMR (300 MHz): δ 7.31–7.23 (m, 5H), 3.68 (t, J = 4.5 Hz, 4H), 3.47 (s, 2H), 2.42 (t, J = 4.5 Hz, 4H); 13C NMR (75 MHz): δ 137.6, 129.0, 128.1, 127.0, 66.8, 63.3, 53.5. 4-(4-Methyl-benzyl)-morpholine (4b):14 Yellow solid, m.p. 49–51 °C; 1 H NMR (300 MHz): δ 7.19 (d, J = 8.1 Hz, 2H), 7.10 (d, J = 8.1 Hz, 2H), 3.68 (t, J = 4.5 Hz, 4H), 3.43 (s, 2H), 2.41 (t, J = 4.5 Hz, 4H), 2.32 (s, 3H); 13 C NMR (75 MHz): δ 136.5, 134.5, 129.0, 128.8, 66.8, 63.0, 53.4, 20.9. 4-(3-Methoxy-benzyl)-morpholine (4c):15 Yellow liquid; 1H NMR (300 MHz): δ 7.21 (t, J = 7.8 Hz, 1H), 6.91–6.80 (m, 2H), 6.77 (dd, J = 0.9, 2.4 Hz, 1H), 3.79 (s, 3H), 3.70 (t, J = 4.5 Hz, 4H), 3.46 (s, 2H), 2.43 (t, J = 4.5 Hz, 4H); 13C NMR (75 MHz): δ 159.5, 139.4, 129.1, 121.3, 114.5, 112.4, 66.9, 63.2, 55.0, 53.5.

04/10/2013 09:19:12

JOURNAL OF CHEMICAL RESEARCH 2013 613 4-(4-Methoxy-benzyl)-morpholine (4d):14 Colourless liquid; 1H NMR (300 MHz): δ 7.22 (d, J = 8.4 Hz, 2H), 6.84 (d, J = 8.4 Hz, 2H), 3.78 (s, 3H), 3.68 (t, J = 4.5 Hz, 4H), 3.42 (s, 2H), 2.41 (t, J = 4.5 Hz, 4H); 13C NMR (75 MHz): δ 158.7, 130.2, 129.6, 113.5, 66.8, 62.7, 55.1, 53.4. 4-(2-Methyl-benzyl)-morpholine (4e):16 Colourless liquid; 1H NMR (300 MHz): δ 7.23 (d, J = 6.6 Hz, 1H), 7.18–7.107 (m, 3H), 3.66 (t, J = 4.5 Hz, 4H), 3.43 (s, 2H), 2.41 (t, J = 4.5 Hz, 4H), 2.36 (s, 3H); 13C NMR (75 MHz): δ 137.4, 135.8, 130.2, 129.8, 127.0, 125.3, 67.0, 61.2, 53.6, 19.1. 4-(3-Methyl-benzyl)-morpholine 4-(2-Methyl-benzyl)-morpholine (4f):17 Colourless liquid; 1H NMR (300 MHz): δ 7.21–7.03 (m, 4H), 3.68 (t, J = 4.5 Hz, 4H), 3.43 (s, 2H), 2.41 (t, J = 4.5 Hz, 4H), 2.33 (s, 3H); 13C NMR (75 MHz): δ 137.6, 137.5, 129.7, 128.0, 127.7, 126.1, 66.8, 63.3, 53.5, 21.2. 4-(4-t-Butyl-benzyl)-morpholine (4g):18 Colourless liquid; 1H NMR (300 MHz): δ 7.32 (d, J = 8.1 Hz, 2H), 7.23 (d, J = 8.1 Hz, 2H), 3.68 (t, J = 4.5 Hz, 4H), 3.45 (s, 2H), 2.42 (t, J = 4.5 Hz, 4H), 1.31 (s, 9H); 13C NMR (75 MHz): δ 149.8, 134.5, 128.8, 125.0, 66.8, 63.0, 53.5, 34.3, 31.3. 4-(4-Chloro-benzyl)-morpholine (4h):16 Colourless liquid; 1H NMR (300 MHz): δ 7.32–7.24 (m, 4H), 3.70 (t, J = 4.5 Hz, 4H), 3.45 (s, 2H), 2.42 (t, J = 4.5 Hz, 4H); 13C NMR (125 MHz): δ 136.0, 132.8, 130.3, 128.3, 66.8, 62.5, 53.4. 2-Morpholin-4-ylmethyl-benzonitrile (4i): Colourless liquid; IR (neat): ν 2160, 1454, 1351, 1267, 1115, 1008, 913, 865, 763, 740, 701 cm–1; 1H NMR (300 MHz): δ 7.65 (d, J = 7.5 Hz, 1H), 7.57–7.53 (m, 2H), 7.39–7.28 (m, 1H), 3.71 (t, J = 4.5 Hz, 4H), 3.69 (s, 2H), 2.51 (t, J = 4.5 Hz, 4H); 13C NMR (75 MHz): δ 141.9, 132.9, 132.5, 130.0, 127.6, 117.7, 113.0, 66.8, 60.8, 53.3; MS (ESI): 203 [M + H]+; HRMS (ESI): calcd. for C12H15N2O [M + H]+: 203.1179; found: 203.1169. 4-Morpholin-4-ylmethyl-benzonitrile (4j):19 Yellow solid, m.p. 78– 81 °C; 1H NMR (300 MHz): δ 7.51 (d, J = 8.1 Hz, 2H), 7.38 (d, J = 8.1 Hz, 2H), 3.61 (t, J = 4.5 Hz, 4H), 3.46 (s, 2H), 2.35 (t, J = 4.5 Hz, 4H); 13C NMR (75 MHz): δ 143.6, 131.8, 129.2, 118.6, 110.6, 66.6, 62.4, 53.3. 4-(4-Fluoro-benzyl)-morpholine (4k):16 Yellow liquid; 1H NMR (300 MHz): δ 7.30–7.25 (m, 2H), 7.02–6.96 (m, 2H), 3.69 (t, J = 4.5 Hz, 4H), 3.44 (s, 2H), 2.41 (t, J = 4.5 Hz, 4H); 13C NMR (75 MHz): δ 161.6 (d, J = 243.8 Hz), 133.4 (d, J = 3.2 Hz), 130.5 (d, J = 7.9 Hz), 114.9 (d, J = 21.0 Hz), 66.8, 62.5, 53.4. 4-(4-Nitro-benzyl)-morpholine (4l):16 Yellow solid, m.p. 76–78 °C; 1 H NMR (500 MHz): δ 8.17 (d, J = 8.5 Hz, 2H), 7.55 (d, J = 8.5 Hz, 2H), 3.73 (t, J = 4.5 Hz, 4H), 3.62 (s, 2H), 2.48 (t, J = 4.5 Hz, 4H); 13C NMR (125 MHz): δ 147.0, 145.7, 129.4, 123.3, 66.7, 62.2, 53.4. 4-(2-Chloro-benzyl)-morpholine (4m):20 Yellow liquid; 1H NMR (500 MHz): δ 7.47 (dd, J = 1.0, 7.5 Hz, 1H), 7.33 (dd, J = 1.5, 8.0 Hz, 1H), 7.22 (td, J = 7.5, 1.5 Hz, 1H), 7.17 (td, J = 7.5, 2.0 Hz, 1H), 3.71 (t, J = 4.5 Hz, 4H), 3.61 (s, 2H), 2.50 (t, J = 4.5 Hz, 4H); 13C NMR (125 MHz): δ 135.3, 134.3, 130.6, 129.3, 128.1, 126.4, 66.9, 59.5, 53.5. 4-Naphthalen-1-yl-methyl-morpholine (4n):18 Colourless liquid; 1H NMR (300 MHz): δ 8.26 (d, J = 7.8 Hz, 1H), 7.79–7.76 (m, 1H), 7.71 (dd, J = 2.7, 6.9 Hz, 1H), 7.47–7.33 (m, 4H), 3.81 (s, 2H), 3.62 (t, J = 4.8 Hz, 4H), 2.42 (t, J = 4.8 Hz, 4H); 13C NMR (75 MHz): δ 133.7, 133.4, 132.4, 128.2, 127.9, 127.3, 125.6, 125.5, 124.9, 124.6, 66.9, 61.4, 53.6. 1-Benzyl-piperidine (4o):15 Colourless liquid; 1H NMR (300 MHz): δ 7.31–7.21 (m, 5H), 3.47 (s, 2H), 2.35 (t, J = 4.8 Hz, 4H), 1.57 (pent, J = 5.4 Hz, 4H), 1.46–1.40 (m, 2H); 13C NMR (75 MHz): δ 138.6, 129.2, 128.1, 126.8, 63.9, 54.5, 25.9, 24.4. 1-(4-Methyl-benzyl)-piperidine (4p):14 Colourless liquid; 1H NMR (500 MHz): δ 7.19 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 3.43 (s, 2H), 2.36 (t, J = 4.8 Hz, 4H), 2.32 (s, 3H), 1.56 (pent, J = 5.5 Hz, 4H), 1.42–1.41 (m, 2H); 13C NMR (125 MHz): δ 136.3, 135.3, 129.2, 128.7, 63.5, 54.3, 25.9, 24.3, 21.0. 1-(4-Fluoro-benzyl)-piperidine (4q):21 Colourless liquid; 1H NMR (300 MHz): δ 7.27 (dd, J = 5.7, 8.7 Hz, 2H), 6.98 (t, J = 8.7 Hz, 2H), 3.42 (s, 2H), 2.35 (t, J = 4.5 Hz, 4H), 1.60–1.52 (m, 4H), 1.46–1.38 (m, 2H); 13C NMR (75 MHz): δ 161.8 (d, J = 243.0 Hz), 134.3 (d, J = 3.1 Hz), 130.6 (d,


J = 7.8 Hz), 114.8 (d, J = 21.0 Hz), 63.0, 54.3, 25.9, 24.3. 4-Piperidin-1-yl-methyl-benzonitrile (4r):22 Colourless liquid; 1H NMR (300 MHz): δ 7.59 (d, J = 8.1 Hz, 2H), 7.45 (d, J = 8.1 Hz, 2H), 3.50 (s, 2H), 2.37 (t, J = 4.5 Hz, 4H), 1.61–1.54 (m, 4H), 1.48–1.44 (m, 2H); 13C NMR (75 MHz): δ 144.7, 131.9. 129.5, 119.0, 110.5, 63.2, 54.5, 25.9, 24.1. 3-Methoxy-benzyl)-dimethyl-amine (4s):23 Colourless liquid; 1H NMR (500 MHz): δ 7.22 (t, J = 7.5 Hz, 1H), 6.89 (d, J = 7.5 Hz, 2H), 6.81–6.79 (m, 1H), 3.80 (s, 3H), 3.43 (s, 2H), 2.26 (s, 6H); 13C NMR (125 MHz): δ 159.6, 139.9, 129.1, 121.4, 114.3, 112.8, 64.1, 55.1, 45.1. Dimethyl-naphthalen-1-yl-methyl-amine (4t):24 Colourless liquid; 1H NMR (300 MHz): δ 8.24 (d, J = 7.8 Hz, 1H), 7.83–7.75 (m, 2H), 7.51–7.36 (m, 4H), 3.79 (s, 2H), 2.27 (s, 6H); 13C NMR (75 MHz): δ 134.6, 133.8, 132.4, 128.4, 127.9, 127.4, 125.9, 125.5, 125.0, 124.4, 62.4, 45.6. Diethyl-(4-methyl-benzyl)-amine (4u):25 Colourless liquid; 1H NMR (500 MHz): δ 7.21 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 3.53 (s, 2H), 2.51 (q, J = 7.0 Hz, 4H), 2.32 (s, 3H), 1.04 (t, J = 7.0 Hz, 6H); 13C NMR (125 MHz): δ 136.6, 136.1, 128.84, 128.75, 57.1, 46.6, 21.0, 11.6. Diethyl-(3-methoxy-benzyl)-amine (4v):26 colourless liquid; 1H NMR (300 MHz): δ 7.20 (t, J = 7.5 Hz, 1H), 6.92–6.89 (m, 2H), 6.78–6.75 (m, 1H), 3.78 (s, 3H), 3.53 (s, 2H), 2.51 (q, J = 7.2 Hz, 4H), 1.03 (t, J = 7.2 Hz, 6H); 13C NMR (75 MHz): δ 159.5, 141.6, 128.9, 121.1, 114.2, 112.1, 57.4, 55.0, 46.6, 11.6. Diethyl-naphthalen-1-yl-methyl-amine (4w):27 Colourless liquid; 1H NMR (300 MHz): δ 8.46–8.42 (m, 1H), 7.94–7.83 (m, 2H), 7.60–7.48 (m, 4H), 4.07 (s, 2H), 2.69 (q, J = 6.9 Hz, 4H), 1.17 (t, J = 6.9 Hz, 6H); 13C NMR (75 MHz): δ 135.6, 133.8, 132.5, 128.3, 127.5, 127.0, 125.6, 125.4, 125.2, 124.6, 56.0, 46.9, 11.5. Benzyl-phenylamine (4x):14 Colourless liquid; 1H NMR (500 MHz): δ 7.36-7.30 (m, 4H), 7.25 (t, J = 7.0 Hz, 1H), 7.16 (dd, J = 7.5, 8.5 Hz, 2H), 6.72 (t, J = 7.5 Hz, 1H), 6.63 (d, J = 8.0 Hz, 2H), 4.30 (s, 2H); 13C NMR (125 MHz): δ 147.7, 139.1, 129.2, 128.6, 127.6, 127.2, 117.8, 113.1, 48.5. 3-Methoxy-benzyl)-phenylamine (4y):28 Colourless liquid; 1H NMR (500 MHz): δ 7.24 (t, J = 7.5 Hz, 1H), 7.17 (dd, J = 7.0, 8.5 Hz, 2H), 6.95– 6.92 (m, 2H), 6.80 (dd, J = 2.0, 8.5 Hz, 1H), 6.73 (t, J = 7.0 Hz, 1H), 6.65 (d, J = 7.5 Hz, 2H), 4.29 (s, 2H), 3.78 (s, 3H); 13C NMR (125 MHz): δ 159.8, 147.6, 140.7, 129.6, 129.2, 119.8, 118.0, 113.2, 113.1, 112.7, 55.2, 48.5. 2-Phenylaminomethyl-benzonitrile (4z):29 Colourless liquid; 1H NMR (500 MHz): δ 7.56 (d, J = 8.5 Hz, 2H), 7.44 (d, J = 8.5 Hz, 2H), 7.15 (t, J = 7.5 Hz, 2H), 6.72 (t, J = 7.5 Hz, 1H), 6.56 (d, J = 7.5 Hz, 2H), 4.39 (s, 2H), 4.15 (br, 1H); 13C NMR (125 MHz): δ 147.3, 145.3, 132.3, 129.2, 127.6, 118.8, 118.0, 112.8, 110.7, 47.6. 4-Methoxy-benzyl)-methyl-phenylamine (4aa):30 Colourless liquid; 1H NMR (500 MHz): δ 7.18 (t, J = 8.0 Hz, 2H), 7.11 (d, J = 8.5 Hz, 2H), 6.81 (d, J = 8.5 Hz, 2H), 6.73 (d, J = 8.0 Hz, 2H), 6.68 (t, J = 8.0 Hz, 1H), 4.41 (s, 2H), 3.71 (s, 3H), 2.92 (s, 3H); 13C NMR (125 MHz): δ 158.5, 149.7, 130.8, 129.1, 127.9, 116.5, 113.9, 112.5, 55.9, 55.1, 38.2. 4-[(Methyl-phenylamino)-methyl]-benzonitrile (4ab):31 Colourless liquid; 1H NMR (500 MHz): δ 7.59 (d, J = 8.5 Hz, 2H), 7.34 (d, J = 8.5 Hz, 2H), 7.23 (dd, J = 7.5, 9.0 Hz, 2H), 6.76 (t, J = 7.5 Hz, 1H), 6.71 (d, J = 9.0 Hz, 2H), 4.57 (s, 2H), 3.04 (s, 3H); 13C NMR (125 MHz): δ 148.9, 144.7, 132.4, 129.3, 127.4, 118.8, 117.6, 112.6, 110.8, 56.8, 39.0.

Financial support from the National Natural Science Foundation of China (No. 21002072) is greatly appreciated. Received 10 June 2013; accepted 27 July 2013 Paper 1302004 doi:10.3184/174751913X13787959859344 Published online: 7 October 2013 References 1 S. Würtz and F. Glorius, Acc. Chem. Res., 2008, 41, 1523. 2 G.C. Fortman and S.P. Nolan, Chem. Soc. Rev., 2011, 40, 5151. 3 C. Valente, S. Çalimsiz, K.H. Hoi, D. Mallik, M. Sayah and M.G. Organ, Angew. Chem. Int. Ed., 2012, 51, 3314. 4 X.-X. Zhou and L.-X. Shao, Synthesis, 2011, 3138.

04/10/2013 09:19:12

614 JOURNAL OF CHEMICAL RESEARCH 2013 5 X.-F. Lin, Y. Li, S.-Y. Li, Z.-K. Xiao and J.-M. Lu, Tetrahedron, 2012, 68, 5806. 6 W.-X. Chen and L.-X. Shao, J. Org. Chem., 2012, 77, 9236. 7 R.N. Butler and A.G. Coyne, Chem. Rev., 2010, 110, 6302. 8 S. Meiries, K. Speck, D.B. Cordes, M.Z. Slawin and S.P. Nolan, Organometallics, 2013, 32, 330. 9 W.-W. Fang, J. Jiang, Y. Xu, J.-F. Zhou and T. Tu, Tetrahedron, 2013, 69, 673. 10 A. Chartoire, X. Frogneux, A. Boreux, A.M.Z. Slawin and S.P. Nolan, Organometallics, 2012, 31, 6947. 11 S. Meiries, A. Chartoire, A.M.Z. Slawin and S.P. Nolan, Organometallics, 2012, 31, 3402. 12 K.H. Hoi, S. Calimsiz, R.D.J. Froese, A.C. Hopkinson and M.G. Organ, Chem. Eur. J., 2011, 17, 3086. 13 P. Rattanaburi, B. Khumraksa and M. Pattarawarapan, Tetrahedron Lett., 2012, 53, 2689. 14 P. Srinivasa Reddy, S. Kanjilal, S. Sunitha and R.B.N. Prasad, Tetrahedron Lett., 2007, 48, 8807. 15 A.F. Abdel-Magid, K.G. Carson, B.D. Harris, C.A. Maryanoff and R.D. Shah, J. Org. Chem., 1996, 61, 3849. 16 T.R. Long, P.K. Maity, T.B. Samarakoon and P.R. Hanson, Org. Lett., 2010, 12, 2904. 17 S.D. Tella and A. Marie, Eur. J. Med. Chem., 1984, 19, 131. 18 M.-J. Zhang, J.D. Moore, D.L. Flynn and P.R. Hanson, Org. Lett., 2004, 6, 2657.


19 S.C. Leung, P. Gibbons, R. Amewu, G.L. Nixon, C. Pidathala, W. Hong, B. Pacorel, N.G. Berry, R. Sharma, P.A. Stocks, A. Srivastava, A.E. Shone, S. Charoensutthivarakul, L. Taylor, O. Berger, A. Mbekeani, A. Hill, N.E. Fisher, A.J. Warman, G.A. Biagini, S.A. Ward and P.M. O’Neill, J. Med. Chem., 2012, 55, 1844. 20 C.N. Kapanda, G.G. Muccioli, G. Labar, N. Draoui, D.M. Lambert and J.H. Poupaert, Med. Chem. Res., 2009, 18, 243. 21 S. Das, D. Addis, K. Junge and M. Beller, Chem. Eur. J., 2011, 17, 12186. 22 G.A. Molander, P.E. Gormisky and D.L. Sandrock, J. Org. Chem., 2008, 73, 2052. 23 J.M. Pereira, R.P. Severino, P.C. Vieira, J.B. Fernandes, M.F.G.F. da Silva, A. Zottis, A.D. Andricopulo, G. Oliva and A.G. Corrêa, Bioorg. Med. Chem., 2008, 16, 8889. 24 M.B. Skaddan, C.M. Yung and R.G. Bergman, Org. Lett., 2004, 6, 11. 25 A. Heydari, S. Khaksar, J. Akbari, M. Esfandya, M. Pourayoubi and M. Tajbakhsh, Tetrahedron Lett., 2007, 48, 1135. 26 K.P. Bhabak and G. Mugesh, Chem. Eur. J., 2008, 14, 8640. 27 N. Singh, N. Kaur, J. Dunn, M. Mackay and J.F. Callan, Tetrahedron Lett., 2009, 50, 953. 28 A. Kumar, S. Sharma and R.A. Maurya, Adv. Synth. Catal., 2010, 352, 2227. 29 B.T. Cho and S.K. Kang, Tetrahedron, 2005, 61, 5725. 30 V. Kumar, U. Sharma, P.K. Verma, N. Kumar and B. Singh, Adv. Synth. Catal., 2012, 354, 870. 31 A. McNally, C.K. Prier and D.W.C. MacMillan, Science, 2011, 334, 1114.

04/10/2013 09:19:12