DOI: 10.1002/chem.201403144
Full Paper
& Tertiary Amide Synthesis
Copper-Catalyzed Aerobic Oxidative Inert C C and C N Bond Cleavage: A New Strategy for the Synthesis of Tertiary Amides Xiuling Chen, Tieqiao Chen, Qiang Li, Yongbo Zhou, Li-Biao Han, and Shuang-Feng Yin*[a]
Abstract: A copper-catalyzed aerobic oxidative amidation reaction of inert C C bonds with tertiary amines has been developed for the synthesis of tertiary amides, which are significant units in many natural products, pharmaceuticals, and
Introduction Transition-metal-catalyzed selective unstrained C C bond cleavage, which enables the possibility of direct utilization of inert starting materials, has attracted much attention.[1, 2] In recent years, numerous efficient catalytic systems,[3, 4] such as arylation with halobenzenes,[5] amidation with formamide or amines (primary and secondary amines),[6] esterification with alcohols,[7] and others,[8] have been developed for the functionalization of inert C C bonds, which have contributed greatly to modern organic synthesis. The oxidative cleavage of C N bonds represents an important biochemical reaction and offers a major means for the detoxification of xenobiotics,[9] and is also of significant synthetic interest since such bonds are common in numerous molecules. Given that tertiary amines contain three C N bonds and are easily prepared, efficient activation of these C N bonds and further application in organic synthesis is very attractive. Herein, we disclose a novel coppercatalyzed aerobic oxidative amidation reaction of inert C C bonds with tertiary amines through selective C C/C N activation and C H oxygenation with dioxygen [Eq. (1)]. This method accomplishes C C bond activation, C N bond cleavage, and C H bond oxygenation with dioxygen in one pot.
fine chemicals. This method combines C C bond activation, C N bond cleavage, and C H bond oxygenation in a onepot protocol, using molecular oxygen as the sole oxidant without any additional ligands.
The present protocol also provides a facile and efficient approach for the preparation of tertiary amides,[10] which have wide applications in the synthesis of many natural products, pharmaceuticals, and fine chemicals.[11]
Results and Discussion Initially, the reaction of 2-phenylacetonitrile (1 a) with triethylamine (2 a) catalyzed by copper salts was selected as a model reaction for optimization of the reaction conditions, and the obtained results are compiled in Table 1 (for further details, see the Supporting Information). Using CuCl2/pyridine as the catalyst, the reaction of 2-phenylacetonitrile (1 a) with triethylamine (2 a) proceeded smoothly under dioxygen atmosphere and the corresponding product diethylbenzamide (3 a) was produced
1 2 3 4 5 6 7 8[c] 9[d] 10[e]
[a] X. Chen,+ Dr. T. Chen,+ Q. Li, Dr. Y. Zhou, Prof. L.-B. Han, Prof. S.-F. Yin State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering, Hunan University Changsha 410081 (P. R. China) Fax: (+ 86) 731-88821171 E-mail: [email protected]
[Cu]
Ligand
Solvent
Yield[b] [%]
CuCl2 CuCl2 CuCl2 CuCl2 – CuCl CuCl2 CuCl2 CuCl2 CuCl2
pyridine 1,10-phenanthroline 2,2-bipyridine – – – – – – –
toluene toluene toluene toluene toluene toluene DMF toluene toluene toluene
84 72 28 92 – 80 9 18 – –
[a] Reaction conditions: 1 a (0.2 mmol), 2 a (0.24 mmol), catalyst (0.01 mmol, 5 mol %), ligand (0.02 mmol, 10 mol %), O2 (1 atm) in a Schlenk tube (25 mL) at 110 8C, 48 h. [b] GC yields based on 1 a using dodecane as an internal standard. [c] Under air (1 atm). [d] 0.5 mmol H2O2 was employed as oxidant under N2 atmosphere (1 atm). [e] 0.5 mmol tert-butyl hydroperoxide (TBHP) was used as oxidant under N2 atmosphere (1 atm).
[+] These authors contributed equally to this work. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201403144. Chem. Eur. J. 2014, 20, 12234 – 12238
Table 1. Optimization of the reaction conditions.[a]
12234
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper in 84 % yield (Table 1, entry 1). It is worth noting that when stronger bidentate ligands such as 1,10-phenanthroline or 2,2bipyridine were used instead, the catalyst showed low efficiency (Table 1, entries 2 and 3). Thus, it was deduced that an external amine ligand was not necessary and the starting tertiary amine perhaps had sufficient intrinsic ligating ability. Indeed, the present catalytic system showed higher efficiency and diethylbenzamide (3 a) was obtained in 92 % yield without the addition of an external ligand under similar reaction conditions (Table 1, entry 4). Among the copper salts investigated, CuCl2 exhibited the highest catalytic efficiency (Table 1, entries 4 and 6; Supporting Information). It should be noted that a copper salt was essential for this C C/C N bond activation reaction, since it did not proceed at all in the absence of a copper catalyst (Table 1, entry 5). As regards the solvents investigated, toluene proved to be the best choice (Table 1, entry 7; Supporting Information). This amidation reaction was also dependent on the pressure of dioxygen; for example, when it was performed under air atmosphere, 3 a was obtained in only 18 % yield (Table 1, entry 8). Finally, the addition of external oxidants such as H2O2 and TBHP under nitrogen atmosphere did not improve the efficiency of this transformation (Table 1, entries 9 and 10). The substrate scope of the present copper-catalyzed aerobic oxidative amidation reaction through C C/C N bond cleavage was further investigated under the optimal conditions described above. As shown in Table 2, 2-phenylacetonitrile (1 a) reacted readily with both symmetrical and asymmetrical aliphatic tertiary amines through C C and C N bond activation, giving the corresponding tertiary amides in high yields. For symmetrical tertiary amines, only one of the three C N bonds was cleaved to give the product, and the reactivity was independent of the alkyl chain length (Table 2, entries 1–3 and 9). For asymmetrical tertiary amines, high selectivity in the C N bond cleavage was observed with the present catalytic system. For example, under catalysis by 5 mol % CuCl2, N,N-dimethylcyclohexylamine (2 d) underwent selective N-Me cleavage, and the aerobic oxidative amidation with 2-phenylacetonitrile (1 a) yielded 3 d highly efficiently (Table 2, entry 4). High selectivity in the C N bond cleavage was also observed with cyclic amines such as piperidine-derived tertiary amines (2 e-1, 2 e-2), morpholine-derived tertiary amine 2 f, and 1-methylpyrrolidine 2 g (Table 2, entries 5–8). Aromatic tertiary amines 2 i and 2 j also served as efficient substrates under the current catalytic reaction conditions and could be selectively converted to the corresponding amides 3 i and 3 j in yields of 73 % and 79 %, respectively (Table 3, entries 10 and 11). However, when N-methylpyrrole (2 k) and N-methylpyrrolidone (2 l) were used as substrates, none of the expected products were detected. This may have been due to the lone pair of electrons on the N atom participating in the conjugating system and hindering the C N bond activation (Table 2, entries 12 and 13). The present copper-catalyzed aerobic oxidative amidation reaction through selective C C/C N bond cleavage proved to be facile and efficient for the synthesis of asymmetrical tertiary amides compared with those involving asymmetrical secondary amines, which are expensive and difficult to prepare.[10] Chem. Eur. J. 2014, 20, 12234 – 12238
www.chemeurj.org
Table 2. Cu-catalyzed aerobic oxidative amidation of 2-phenylacetonitrile (1 a) with tertiary amines 2.[a]
Amine 2 a–2 l
Product
Yield[b] [%]
1
81
2
86
3
85
4
90
5
92
6
3e
89
7
91
8
90
9[c]
92
10
73
11
79
12
–
–
13[d]
–
–
[a] Reaction conditions: 1 a (0.2 mmol), tertiary amine (0.24 mmol), CuCl2 (0.01 mmol, 5 mol %), toluene (1 mL), O2 (1 atm) in a Schlenk tube (25 mL) at 110 8C, 48 h. [b] Isolated yield. [c] 24 h. [d] 2 l (1 mL).
As compiled in Table 3, under the optimized conditions, 2phenylacetonitriles bearing both electron-rich and electron-deficient groups underwent selective C C bond cleavage and were amidated by the tertiary amines, giving the corresponding amide products in high yields (Table 3, entries 1–7). For example, the reactions of 2-(4-methylphenyl)acetonitrile (1 b) with triethylamine and tribenzylamine proceeded smoothly to produce amides 3 k and 3 l in yields of 87 % and 89 %, respec-
12235
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper Table 3. Cu-catalyzed aerobic oxidative amidation of 2-phenylacetonitrile derivatives 1 with tertiary amines 2.[a]
Substrate 1 b–1 f
1
Amine
Product
2a
Table 4. Cu-catalyzed aerobic oxidative amidation of substrate 1 with tertiary amine 2.[a]
Substrate 1 g–1 j
Yield[b] [%] 1[c]
87
2[c] 3[c] 2[c]
1b
2h
1g 1g
2a
5
91
1h
6 4[c]
1c
2h
7
87
8 [c]
5
2h
Yield[b] [%]
2a
3a
60
2h 2i
3h 3i
63 55
2a
3a
75
2i
3i
70
2a
3a
24
1i
2i
3i
37
2a
–
–
85
6
2a
90
7[c]
2h
89
[a] Reaction conditions: 1 g–1 j (0.2 mmol), tertiary amine (0.24 mmol), CuCl2 (0.01 mmol, 5 mol %), toluene (1 mL), O2 (1 atm) in a Schlenk tube (25 mL) at 110 8C, 24 h. [b] GC yields based on 1 using dodecane as an internal standard. [c] 2 (0.5 mmol).
[a] Reaction conditions: substrate 1 b–1 f (0.2 mmol), tertiary amine (0.24 mmol), CuCl2 (0.01 mmol, 5 mol %), toluene (1 mL), O2 (1 atm) in a Schlenk tube (25 mL) at 110 8C, 48 h. [b] Isolated yield. [c] CuCl2 (0.01 mmol, 5 mol %), 24 h.
tively (Table 3, entries 1 and 2). Excellent yields were observed when the reactions of 2-(4-bromophenyl)acetonitrile (1 c) with triethylamine and tribenzylamine were carried out under the present catalytic conditions (Table 3, entries 3 and 4). 2-(4-Nitrophenyl)acetonitrile (1 d), a substrate bearing a strongly electron-deficient group, also reacted with 2 h to provide the desired product 3 o in 85 % yield (Table 3, entry 5). To our delight, the heteroaryl-substituted amide 3 p was obtained from the reaction of 2-(thiophen-2-yl)acetonitrile with 2 a using the present copper-catalyzed aerobic oxidative amidation, indicating that this method offers an efficient approach for introducing an aromatic heterocycle into functional molecules (Table 3, entry 6). 2-(Naphthalen-2-yl)acetonitrile (1 f) also served as an efficient substrate and reacted with 2 h to furnish the amide 3 q in 89 % yield through selective C C/C N activation catalyzed by 5 mol % CuCl2 under dioxygen atmosphere (Table 3, entry 7). Besides acetonitriles substituted with aromatic groups, other toluene derivatives bearing electron-withdrawing groups could also be amidated by tertiary amines, giving the expected amides through selective C C/C N bond activation under the optimal reaction conditions, as shown in Table 4. In the presChem. Eur. J. 2014, 20, 12234 – 12238
Product
89 4
3
Amine
www.chemeurj.org
ence of 5 mol % CuCl2, the C C s-bond of 1,3-diphenylpropan2-one (1 g) was selectively cleaved, allowing smooth reaction with tertiary amines 2 a, 2 h, and 2 i to give the desired amide products in moderate yields (Table 4, entries 1–3).[12] With the current catalytic system, the C C s-bond of 2-phenylacetaldehyde (1 h) was cleaved, allowing reactions with 2 a and 2 i to proceed readily to provide amides 3 a and 3 i in yields of 75 % and 70 %, respectively (Table 2, entries 4 and 5). Amides 3 a and 3 i could also be obtained from the reactions of 2-phenylacetic acid (1 i) with 2 a and 2 i under the optimal reaction conditions, albeit in relatively low yields (Table 2, entries 4 and 5). This may have been due to the acidity of 2-phenylacetic acid (1 i) preventing coordination between the amine and copper salt. However, when methyl 2-phenylacetate (1 j) and 2 a were used as substrates, C C and C N bond activation was not observed under the present reaction conditions (Table 4, entry 8). It is worth noting that high selectivity for C-Me bond cleavage was also observed for the reactions of toluene derivatives bearing electron-withdrawing groups with N,N-dimethylaniline (2 i) (Table 4, entries 3, 5, and 7). To gain some insight into the reaction mechanism, several control experiments were carried out as shown above. In the absence of amines, benzoyl cyanide (1 k) was generated in 35 % yield under the present reaction conditions [Eq. (2)]. The resulting benzoyl cyanide (1 k) reacted rapidly with tri-n-propylamine (2 b) to afford a 90 % yield of 3 b in only 6 h under similar conditions [Eq. (3)]. These results indicated that benzoyl cyanide (1 k) may have been an effective intermediate for this transformation.[8a] The reaction of 1 a and 2 b in the presence
12236
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper of 18O2 (1 atm) generated the 18O-labeled product [18O]-3 ba in 80 % yield [Eq. (4)], as determined by MS and HRMS (see the Supporting Information). However, with the addition of 0.2 mmol H218O, only [16O]-3 b was obtained in 82 % yield and no 18O-labeled product was detected under the optimal conditions [Eq. (5)]. Thus, the oxygen atoms of the product amides are derived from molecular dioxygen. Besides, the addition of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) did not result in a decrease in the yield of 3 b, ruling out the involvement of a free radical process in the present reaction [Eq. (6)].
oxygen to form [LmCun + 1] composed of the copper salt, amine ligand, and molecular oxygen, and this is followed by autoxidation of the amine ligand to give the iminium-type intermediate I2a, which is then hydrolyzed and oxidized to the key intermediate I2b by elimination of aldehyde.[13] I2b further reacts with benzoyl compound I1a derived from the oxidation of 1 with oxygen in the presence of a copper catalyst to give the corresponding amide 3 with regeneration of the copper catalyst.[8a]
Conclusion In conclusion, a novel and efficient copper-catalyzed aerobic oxidative amidation through C C/C N bond cleavage has been developed. This method successfully combines C C bond activation, C N bond cleavage, and C H bond oxygenation with dioxygen. This protocol also provides a practical, neutral, and mild synthetic approach to tertiary amides, which are important units in biologically active molecules.
Experimental Section General procedure: A 25 mL Schlenk-type tube equipped with a magnetic stir bar was charged with substrate amine 1 (1 a–1 k) (0.2 mmol) and CuCl2 (0.0013 g, 5 mol %). The reaction tube was evacuated and back-filled with O2. Tertiary amines 2 (2 a–2 l) (0.24 mmol) and toluene (1 mL) were added at room temperature under O2 atmosphere, and the reaction mixture was stirred at 110 8C for 24–36 h. The reaction was monitored by GC or GC-MS. After completion of the reaction, the resulting solution was cooled to room temperature and neutralized with a saturated aqueous solution of NH4Cl. The product was extracted with EtOAc or CHCl3, and the extracts were dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel to give the desired product.
According to relevant literature reports[8a, 13] and the above experimental results, a possible catalytic cycle for the coppercatalyzed aerobic oxidative amidation of compounds 1 with tertiary amines through C C/C N bond activation is proposed as shown in Scheme 1. The copper catalyst is first oxidized by
Acknowledgements This work was supported by the NSFC (U1162109, 21172062, 21373080), the Program for Changjiang Scholars and Innovative Research Team in University (IRT1238), the Program for New Century Excellent Talents in Universities (NCET-10–0371), and the Fundamental Research Funds for the Central Universities (Hunan University). Keywords: aerobic oxidation · amidation · amides · C C activation · C N cleavage
Scheme 1. A possible mechanism for the amidation reaction. Chem. Eur. J. 2014, 20, 12234 – 12238
www.chemeurj.org
[1] For reviews on C C bond activation, see: a) Y. J. Park, J. W. Park, C. H. Jun, Acc. Chem. Res. 2008, 41, 222 – 234; b) M. Tobisu, N. Chatani, Chem. Soc. Rev. 2008, 37, 300 – 307; c) M. Rubin, M. Rubina, V. Gevorgyan, Chem. Rev. 2007, 107, 3117 – 3179; d) C. H. Jun, Chem. Soc. Rev. 2004, 33, 610 – 618; e) A. de Meijere, Chem. Rev. 2003, 103, 931 – 932. [2] “Cleavage of Carbon-Carbon Single Bonds by Transition Metals”: M. Murakami, Y. Ito, in Activation of Unreactive Bonds and Organic Synthesis—Topics in Organometallic Chemistry Series, Vol. 3, (Ed.: S. Murai), Springer, Berlin, New York, 1999, pp. 97 – 129. [3] Traditional metal-catalyzed methods for C C bond cleavage: for the use of Rh catalysts, see: a) H. Li, Y. Li, X. S. Zhang, K. Chen, X. Wang, Z.
12237
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper
[4]
[5]
[6]
[7] [8]
[9]
[10]
Shi, J. Am. Chem. Soc. 2011, 133, 15244 – 15247; b) M. Tobisu, H. Kinuta, Y. Kita, E. Rmond, N. Chatani, J. Am. Chem. Soc. 2012, 134, 115 – 118; c) Q. Shuai, L. Yang, X. Guo, O. Basl, C. J. Li, J. Am. Chem. Soc. 2010, 132, 12212 – 12213; for the use of Ru catalysts, see: d) J. Liu, Q. Liu, H. Yi, C. Qin, R. Bai, X. Qi, Y. Lan, A. Lei, Angew. Chem. 2014, 126, 512 – 516; Angew. Chem. Int. Ed. 2014, 53, 502 – 506; for the use of Pd catalysts, see: e) P. Hu, M. Zhang, X. Jie, W. Su, Angew. Chem. 2012, 124, 231 – 235; Angew. Chem. Int. Ed. 2012, 51, 227 – 231; f) Y. Hirata, A. Yada, E. Morita, Y. Nakao, T. Hiyama, M. Ohashi, S. Ogoshi, J. Am. Chem. Soc. 2010, 132, 10070 – 10077; g) S. I. Murahashi, T. Naota, N. Nakajima, J. Org. Chem. 1986, 51, 898 – 901; for the use of Au catalysts, see: h) N. Asao, T. Nogami, S. Lee, Y. Yamamoto, J. Am. Chem. Soc. 2003, 125, 10921 – 10925; for the use of Ni catalysts, see: i) T. Patra, S. Agasti, A. Modak, D. Maiti, Chem. Commun. 2013, 49, 8362 – 8364; j) T. Patra, S. Agasti, Akanksha, D. Maiti, Chem. Commun. 2013, 49, 69 – 71; k) Y. Nakao, Y. Hirata, T. Hiyama, J. Am. Chem. Soc. 2006, 128, 7420 – 7421; l) Y. Hirata, T. Inui, Y. Nakao, T. Hiyama, J. Am. Chem. Soc. 2009, 131, 6624 – 6631; m) Y. Nakao, A. Yada, S. Ebata, T. Hiyama, J. Am. Chem. Soc. 2007, 129, 2428 – 2429; n) M. P. Watson, E. N. Jacobsen, J. Am. Chem. Soc. 2008, 130, 12594 – 12595; o) K. Nakai, T. Kurahashi, S. Matsubara, J. Am. Chem. Soc. 2011, 133, 11066 – 11068; for other methods, see: p) X. Zhang, M. Wang, Y. Zhang, L. Wang, RSC Adv. 2013, 3, 1311 – 1316; q) J. Mecinovic´, R. B. Hamed, C. J. Schofield, Angew. Chem. 2009, 121, 2834 – 2838; Angew. Chem. Int. Ed. 2009, 48, 2796 – 2800; r) H. Li, W. Li, W. Liu, Z. He, Z. Li, Angew. Chem. 2011, 123, 3031 – 3034; Angew. Chem. Int. Ed. 2011, 50, 2975 – 2978; s) X. Kou, J. Fan, X. Tong, Z. Shen, Chin. J. Org. Chem. 2013, 33, 1407 – 1422 and references therein. For a review on aerobic copper-catalyzed C C bond cleavage, see: S. E. Allen, R. R. Walvoord, R. Padilla-Salinas, M. C. Kozlowski, Chem. Rev. 2013, 113, 6234 – 6458. a) C. He, S. Guo, L. Huang, A. Lei, J. Am. Chem. Soc. 2010, 132, 8273 – 8275; b) R. Shang, Y. Fu, J. B. Li, S. Zhang, Q. Guo, L. Liu, J. Am. Chem. Soc. 2009, 131, 5738 – 5739. a) C. Zhang, Z. Xu, T. Shen, G. Wu, L. Zhang, N. Jiao, Org. Lett. 2012, 14, 2362 – 2365; b) Q. Zhao, H. Lia, L. Wang, Org. Biomol. Chem. 2013, 11, 6772 – 6779; c) X. Sun, M. Wang, P. Li, X. Zhang, L. Wang, Green Chem. 2013, 15, 3289 – 3294. C. Zhang, P. Feng, N. Jiao, J. Am. Chem. Soc. 2013, 135, 15257 – 15262. a) J. Jin, Q. Wen, P. Lu, Y. Wang, Chem. Commun. 2012, 48, 9933 – 9935; b) Q. Song, Q. Feng, K. Yang, Org. Lett. 2014, 16, 624 – 627; c) E. J. Park, S. Lee, S. Chang, J. Org. Chem. 2010, 75, 2760 – 2762. a) B. Meunier, S. P. de Visser, S. Shaik, Chem. Rev. 2004, 104, 3947 – 3980; b) I. G. Denisov, T. M. Makris, S. G. Sligar, I. Schlichting, Chem. Rev. 2005, 105, 2253 – 2277. For some selected examples of transformations from aldehyde to amide, see: a) Z. Liu, J. Zhang, S. Chen, Angew. Chem. 2012, 124, 3285 –
Chem. Eur. J. 2014, 20, 12234 – 12238
www.chemeurj.org
3289; Angew. Chem. Int. Ed. 2012, 51, 3231 – 3235; b) V. Prasad, R. R. Kale, B. B. Mishra, D. Kumar, V. K. Tiwari, Org. Lett. 2012, 14, 2936 – 2939; c) L. Colombeau, T. Traor, P. Compain, O. R. Martin, J. Org. Chem. 2008, 73, 8647 – 8650; d) S. C. Ghosh, J. S. Y. Ngiam, C. L. L. Chai, A. M. Seayad, T. T. Dang, A. Q. Chen, Adv. Synth. Catal. 2012, 354, 1407 – 1412; e) S. C. Ghosh, J. S. Y. Ngiam, A. M. Seayad, D. T. Tuan, C. L. L. Chai, A. Q. Chen, J. Org. Chem. 2012, 77, 8007 – 8015; f) C. Zhang, Z. Xu, L. R. Zhang, N. Jiao, Angew. Chem. 2011, 123, 11284 – 11288; Angew. Chem. Int. Ed. 2011, 50, 11088 – 11092; g) M. W. Zhu, K. Fujita, R. Yamaguchi, J. Org. Chem. 2012, 77, 9102 – 9109; h) R. Cadoni, A. Porcheddu, G. Giacomelli, L. D. Luca, Org. Lett. 2012, 14, 5014; i) J. W. W. Chang, T. M. U. Ton, S. Tania, P. C. Taylor, P. W. H. Chan, Chem. Commun. 2010, 46, 922 – 924; j) G.-L. Li, K. K. Y. Kung, M. K. Wong, Chem. Commun. 2012, 48, 4112 – 4114; k) L. Zhang, S. Wang, S. Zhou, G. Yang, E. Sheng, J. Org. Chem. 2006, 71, 3149 – 3153; l) S. Y. Seo, T. J. Marks, Org. Lett. 2008, 10, 317 – 319; m) J. Li, F. Xu, Y. Zhang, Q. Shen, J. Org. Chem. 2009, 74, 2575; for examples of transformations from alcohols to amides, see: n) K. Xu, Y. Hu, S. Zhang, Z. Zha, Z. Wang, Chem. Eur. J. 2012, 18, 9793 – 9797; o) L. U. Nordstrøm, H. Vogt, R. Madsen, J. Am. Chem. Soc. 2008, 130, 17672 – 17673; p) F. Xiao, Y. Liu, C. Tang, G. Deng, Org. Lett. 2012, 14, 984 – 987; for examples of transformations from alkyne to amide, see: q) W. K. Chan, C. M. Ho, M. K. Wong, C. M. Che, J. Am. Chem. Soc. 2006, 128, 14796 – 14797; r) W. Wei, X. Hu, X. Yan, Q. Zhang, M. Cheng, J. Ji, Chem. Commun. 2012, 48, 305 – 307; for an example of transformation from an a-bromo nitroalkane to an amide, see: s) B. Shen, D. M. Makley, J. N. Johnston, Nature 2010, 465, 1027 – 1032; for other methods furnishing amides, see: t) R. J. Carroll, H. Leisch, E. Scocchera, T. Hudlicky, D. P. Cox, Adv. Synth. Catal. 2008, 350, 2984 – 2992; u) C. Vila, M. Rueping, Green Chem. 2013, 15, 2056 – 2059; v) D. N. Sawant, Y. S. Wagh, K. D. Bhatte, B. M. Bhanage, J. Org. Chem. 2011, 76, 5489 – 5494; w) C. Hu, X. Yan, X. Zhou, Z. Li, Org. Biomol. Chem. 2013, 11, 8179 – 8182; x) W. Mai, G. Song, J. Yuan, L. Yang, G. Sun, Y. Xiao, P. Mao, L. Qu, RSC Adv. 2013, 3, 3869 – 3872; y) Y. Li, L. Ma, F. Jia, Z. Li, J. Org. Chem. 2013, 78, 5638; z) Y. Li, F. Jia, Z. Li, Chem. Eur. J. 2013, 19, 82 – 86. [11] a) J. M. Humphrey, A. R. Chamberl, Chem. Rev. 1997, 97, 2243 – 2266; b) C. L. Allen, J. M. J. Williams, Chem. Soc. Rev. 2011, 40, 3405 – 3415. [12] It is noteworthy that N,N-diethyl-2-phenylacetamide was produced in 30 % yield in this case, which demonstrates that the remaining 1,3-diphenylpropan-2-one underwent the coupling process with amine substrate 2 a to produce the corresponding amide. [13] S. Guo, B. Qian, Y. Xie, C. Xia, H. Huang, Org. Lett. 2011, 13, 522 – 525.
Received: April 17, 2014 Revised: June 20, 2014 Published online on August 5, 2014
12238
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper
& Tertiary Amide Synthesis
Copper-Catalyzed Aerobic Oxidative Inert C C and C N Bond Cleavage: A New Strategy for the Synthesis of Tertiary Amides Xiuling Chen, Tieqiao Chen, Qiang Li, Yongbo Zhou, Li-Biao Han, and Shuang-Feng Yin*[a]
Abstract: A copper-catalyzed aerobic oxidative amidation reaction of inert C C bonds with tertiary amines has been developed for the synthesis of tertiary amides, which are significant units in many natural products, pharmaceuticals, and
Introduction Transition-metal-catalyzed selective unstrained C C bond cleavage, which enables the possibility of direct utilization of inert starting materials, has attracted much attention.[1, 2] In recent years, numerous efficient catalytic systems,[3, 4] such as arylation with halobenzenes,[5] amidation with formamide or amines (primary and secondary amines),[6] esterification with alcohols,[7] and others,[8] have been developed for the functionalization of inert C C bonds, which have contributed greatly to modern organic synthesis. The oxidative cleavage of C N bonds represents an important biochemical reaction and offers a major means for the detoxification of xenobiotics,[9] and is also of significant synthetic interest since such bonds are common in numerous molecules. Given that tertiary amines contain three C N bonds and are easily prepared, efficient activation of these C N bonds and further application in organic synthesis is very attractive. Herein, we disclose a novel coppercatalyzed aerobic oxidative amidation reaction of inert C C bonds with tertiary amines through selective C C/C N activation and C H oxygenation with dioxygen [Eq. (1)]. This method accomplishes C C bond activation, C N bond cleavage, and C H bond oxygenation with dioxygen in one pot.
fine chemicals. This method combines C C bond activation, C N bond cleavage, and C H bond oxygenation in a onepot protocol, using molecular oxygen as the sole oxidant without any additional ligands.
The present protocol also provides a facile and efficient approach for the preparation of tertiary amides,[10] which have wide applications in the synthesis of many natural products, pharmaceuticals, and fine chemicals.[11]
Results and Discussion Initially, the reaction of 2-phenylacetonitrile (1 a) with triethylamine (2 a) catalyzed by copper salts was selected as a model reaction for optimization of the reaction conditions, and the obtained results are compiled in Table 1 (for further details, see the Supporting Information). Using CuCl2/pyridine as the catalyst, the reaction of 2-phenylacetonitrile (1 a) with triethylamine (2 a) proceeded smoothly under dioxygen atmosphere and the corresponding product diethylbenzamide (3 a) was produced
1 2 3 4 5 6 7 8[c] 9[d] 10[e]
[a] X. Chen,+ Dr. T. Chen,+ Q. Li, Dr. Y. Zhou, Prof. L.-B. Han, Prof. S.-F. Yin State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering, Hunan University Changsha 410081 (P. R. China) Fax: (+ 86) 731-88821171 E-mail: [email protected]
[Cu]
Ligand
Solvent
Yield[b] [%]
CuCl2 CuCl2 CuCl2 CuCl2 – CuCl CuCl2 CuCl2 CuCl2 CuCl2
pyridine 1,10-phenanthroline 2,2-bipyridine – – – – – – –
toluene toluene toluene toluene toluene toluene DMF toluene toluene toluene
84 72 28 92 – 80 9 18 – –
[a] Reaction conditions: 1 a (0.2 mmol), 2 a (0.24 mmol), catalyst (0.01 mmol, 5 mol %), ligand (0.02 mmol, 10 mol %), O2 (1 atm) in a Schlenk tube (25 mL) at 110 8C, 48 h. [b] GC yields based on 1 a using dodecane as an internal standard. [c] Under air (1 atm). [d] 0.5 mmol H2O2 was employed as oxidant under N2 atmosphere (1 atm). [e] 0.5 mmol tert-butyl hydroperoxide (TBHP) was used as oxidant under N2 atmosphere (1 atm).
[+] These authors contributed equally to this work. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201403144. Chem. Eur. J. 2014, 20, 12234 – 12238
Table 1. Optimization of the reaction conditions.[a]
12234
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper in 84 % yield (Table 1, entry 1). It is worth noting that when stronger bidentate ligands such as 1,10-phenanthroline or 2,2bipyridine were used instead, the catalyst showed low efficiency (Table 1, entries 2 and 3). Thus, it was deduced that an external amine ligand was not necessary and the starting tertiary amine perhaps had sufficient intrinsic ligating ability. Indeed, the present catalytic system showed higher efficiency and diethylbenzamide (3 a) was obtained in 92 % yield without the addition of an external ligand under similar reaction conditions (Table 1, entry 4). Among the copper salts investigated, CuCl2 exhibited the highest catalytic efficiency (Table 1, entries 4 and 6; Supporting Information). It should be noted that a copper salt was essential for this C C/C N bond activation reaction, since it did not proceed at all in the absence of a copper catalyst (Table 1, entry 5). As regards the solvents investigated, toluene proved to be the best choice (Table 1, entry 7; Supporting Information). This amidation reaction was also dependent on the pressure of dioxygen; for example, when it was performed under air atmosphere, 3 a was obtained in only 18 % yield (Table 1, entry 8). Finally, the addition of external oxidants such as H2O2 and TBHP under nitrogen atmosphere did not improve the efficiency of this transformation (Table 1, entries 9 and 10). The substrate scope of the present copper-catalyzed aerobic oxidative amidation reaction through C C/C N bond cleavage was further investigated under the optimal conditions described above. As shown in Table 2, 2-phenylacetonitrile (1 a) reacted readily with both symmetrical and asymmetrical aliphatic tertiary amines through C C and C N bond activation, giving the corresponding tertiary amides in high yields. For symmetrical tertiary amines, only one of the three C N bonds was cleaved to give the product, and the reactivity was independent of the alkyl chain length (Table 2, entries 1–3 and 9). For asymmetrical tertiary amines, high selectivity in the C N bond cleavage was observed with the present catalytic system. For example, under catalysis by 5 mol % CuCl2, N,N-dimethylcyclohexylamine (2 d) underwent selective N-Me cleavage, and the aerobic oxidative amidation with 2-phenylacetonitrile (1 a) yielded 3 d highly efficiently (Table 2, entry 4). High selectivity in the C N bond cleavage was also observed with cyclic amines such as piperidine-derived tertiary amines (2 e-1, 2 e-2), morpholine-derived tertiary amine 2 f, and 1-methylpyrrolidine 2 g (Table 2, entries 5–8). Aromatic tertiary amines 2 i and 2 j also served as efficient substrates under the current catalytic reaction conditions and could be selectively converted to the corresponding amides 3 i and 3 j in yields of 73 % and 79 %, respectively (Table 3, entries 10 and 11). However, when N-methylpyrrole (2 k) and N-methylpyrrolidone (2 l) were used as substrates, none of the expected products were detected. This may have been due to the lone pair of electrons on the N atom participating in the conjugating system and hindering the C N bond activation (Table 2, entries 12 and 13). The present copper-catalyzed aerobic oxidative amidation reaction through selective C C/C N bond cleavage proved to be facile and efficient for the synthesis of asymmetrical tertiary amides compared with those involving asymmetrical secondary amines, which are expensive and difficult to prepare.[10] Chem. Eur. J. 2014, 20, 12234 – 12238
www.chemeurj.org
Table 2. Cu-catalyzed aerobic oxidative amidation of 2-phenylacetonitrile (1 a) with tertiary amines 2.[a]
Amine 2 a–2 l
Product
Yield[b] [%]
1
81
2
86
3
85
4
90
5
92
6
3e
89
7
91
8
90
9[c]
92
10
73
11
79
12
–
–
13[d]
–
–
[a] Reaction conditions: 1 a (0.2 mmol), tertiary amine (0.24 mmol), CuCl2 (0.01 mmol, 5 mol %), toluene (1 mL), O2 (1 atm) in a Schlenk tube (25 mL) at 110 8C, 48 h. [b] Isolated yield. [c] 24 h. [d] 2 l (1 mL).
As compiled in Table 3, under the optimized conditions, 2phenylacetonitriles bearing both electron-rich and electron-deficient groups underwent selective C C bond cleavage and were amidated by the tertiary amines, giving the corresponding amide products in high yields (Table 3, entries 1–7). For example, the reactions of 2-(4-methylphenyl)acetonitrile (1 b) with triethylamine and tribenzylamine proceeded smoothly to produce amides 3 k and 3 l in yields of 87 % and 89 %, respec-
12235
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper Table 3. Cu-catalyzed aerobic oxidative amidation of 2-phenylacetonitrile derivatives 1 with tertiary amines 2.[a]
Substrate 1 b–1 f
1
Amine
Product
2a
Table 4. Cu-catalyzed aerobic oxidative amidation of substrate 1 with tertiary amine 2.[a]
Substrate 1 g–1 j
Yield[b] [%] 1[c]
87
2[c] 3[c] 2[c]
1b
2h
1g 1g
2a
5
91
1h
6 4[c]
1c
2h
7
87
8 [c]
5
2h
Yield[b] [%]
2a
3a
60
2h 2i
3h 3i
63 55
2a
3a
75
2i
3i
70
2a
3a
24
1i
2i
3i
37
2a
–
–
85
6
2a
90
7[c]
2h
89
[a] Reaction conditions: 1 g–1 j (0.2 mmol), tertiary amine (0.24 mmol), CuCl2 (0.01 mmol, 5 mol %), toluene (1 mL), O2 (1 atm) in a Schlenk tube (25 mL) at 110 8C, 24 h. [b] GC yields based on 1 using dodecane as an internal standard. [c] 2 (0.5 mmol).
[a] Reaction conditions: substrate 1 b–1 f (0.2 mmol), tertiary amine (0.24 mmol), CuCl2 (0.01 mmol, 5 mol %), toluene (1 mL), O2 (1 atm) in a Schlenk tube (25 mL) at 110 8C, 48 h. [b] Isolated yield. [c] CuCl2 (0.01 mmol, 5 mol %), 24 h.
tively (Table 3, entries 1 and 2). Excellent yields were observed when the reactions of 2-(4-bromophenyl)acetonitrile (1 c) with triethylamine and tribenzylamine were carried out under the present catalytic conditions (Table 3, entries 3 and 4). 2-(4-Nitrophenyl)acetonitrile (1 d), a substrate bearing a strongly electron-deficient group, also reacted with 2 h to provide the desired product 3 o in 85 % yield (Table 3, entry 5). To our delight, the heteroaryl-substituted amide 3 p was obtained from the reaction of 2-(thiophen-2-yl)acetonitrile with 2 a using the present copper-catalyzed aerobic oxidative amidation, indicating that this method offers an efficient approach for introducing an aromatic heterocycle into functional molecules (Table 3, entry 6). 2-(Naphthalen-2-yl)acetonitrile (1 f) also served as an efficient substrate and reacted with 2 h to furnish the amide 3 q in 89 % yield through selective C C/C N activation catalyzed by 5 mol % CuCl2 under dioxygen atmosphere (Table 3, entry 7). Besides acetonitriles substituted with aromatic groups, other toluene derivatives bearing electron-withdrawing groups could also be amidated by tertiary amines, giving the expected amides through selective C C/C N bond activation under the optimal reaction conditions, as shown in Table 4. In the presChem. Eur. J. 2014, 20, 12234 – 12238
Product
89 4
3
Amine
www.chemeurj.org
ence of 5 mol % CuCl2, the C C s-bond of 1,3-diphenylpropan2-one (1 g) was selectively cleaved, allowing smooth reaction with tertiary amines 2 a, 2 h, and 2 i to give the desired amide products in moderate yields (Table 4, entries 1–3).[12] With the current catalytic system, the C C s-bond of 2-phenylacetaldehyde (1 h) was cleaved, allowing reactions with 2 a and 2 i to proceed readily to provide amides 3 a and 3 i in yields of 75 % and 70 %, respectively (Table 2, entries 4 and 5). Amides 3 a and 3 i could also be obtained from the reactions of 2-phenylacetic acid (1 i) with 2 a and 2 i under the optimal reaction conditions, albeit in relatively low yields (Table 2, entries 4 and 5). This may have been due to the acidity of 2-phenylacetic acid (1 i) preventing coordination between the amine and copper salt. However, when methyl 2-phenylacetate (1 j) and 2 a were used as substrates, C C and C N bond activation was not observed under the present reaction conditions (Table 4, entry 8). It is worth noting that high selectivity for C-Me bond cleavage was also observed for the reactions of toluene derivatives bearing electron-withdrawing groups with N,N-dimethylaniline (2 i) (Table 4, entries 3, 5, and 7). To gain some insight into the reaction mechanism, several control experiments were carried out as shown above. In the absence of amines, benzoyl cyanide (1 k) was generated in 35 % yield under the present reaction conditions [Eq. (2)]. The resulting benzoyl cyanide (1 k) reacted rapidly with tri-n-propylamine (2 b) to afford a 90 % yield of 3 b in only 6 h under similar conditions [Eq. (3)]. These results indicated that benzoyl cyanide (1 k) may have been an effective intermediate for this transformation.[8a] The reaction of 1 a and 2 b in the presence
12236
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper of 18O2 (1 atm) generated the 18O-labeled product [18O]-3 ba in 80 % yield [Eq. (4)], as determined by MS and HRMS (see the Supporting Information). However, with the addition of 0.2 mmol H218O, only [16O]-3 b was obtained in 82 % yield and no 18O-labeled product was detected under the optimal conditions [Eq. (5)]. Thus, the oxygen atoms of the product amides are derived from molecular dioxygen. Besides, the addition of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) did not result in a decrease in the yield of 3 b, ruling out the involvement of a free radical process in the present reaction [Eq. (6)].
oxygen to form [LmCun + 1] composed of the copper salt, amine ligand, and molecular oxygen, and this is followed by autoxidation of the amine ligand to give the iminium-type intermediate I2a, which is then hydrolyzed and oxidized to the key intermediate I2b by elimination of aldehyde.[13] I2b further reacts with benzoyl compound I1a derived from the oxidation of 1 with oxygen in the presence of a copper catalyst to give the corresponding amide 3 with regeneration of the copper catalyst.[8a]
Conclusion In conclusion, a novel and efficient copper-catalyzed aerobic oxidative amidation through C C/C N bond cleavage has been developed. This method successfully combines C C bond activation, C N bond cleavage, and C H bond oxygenation with dioxygen. This protocol also provides a practical, neutral, and mild synthetic approach to tertiary amides, which are important units in biologically active molecules.
Experimental Section General procedure: A 25 mL Schlenk-type tube equipped with a magnetic stir bar was charged with substrate amine 1 (1 a–1 k) (0.2 mmol) and CuCl2 (0.0013 g, 5 mol %). The reaction tube was evacuated and back-filled with O2. Tertiary amines 2 (2 a–2 l) (0.24 mmol) and toluene (1 mL) were added at room temperature under O2 atmosphere, and the reaction mixture was stirred at 110 8C for 24–36 h. The reaction was monitored by GC or GC-MS. After completion of the reaction, the resulting solution was cooled to room temperature and neutralized with a saturated aqueous solution of NH4Cl. The product was extracted with EtOAc or CHCl3, and the extracts were dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel to give the desired product.
According to relevant literature reports[8a, 13] and the above experimental results, a possible catalytic cycle for the coppercatalyzed aerobic oxidative amidation of compounds 1 with tertiary amines through C C/C N bond activation is proposed as shown in Scheme 1. The copper catalyst is first oxidized by
Acknowledgements This work was supported by the NSFC (U1162109, 21172062, 21373080), the Program for Changjiang Scholars and Innovative Research Team in University (IRT1238), the Program for New Century Excellent Talents in Universities (NCET-10–0371), and the Fundamental Research Funds for the Central Universities (Hunan University). Keywords: aerobic oxidation · amidation · amides · C C activation · C N cleavage
Scheme 1. A possible mechanism for the amidation reaction. Chem. Eur. J. 2014, 20, 12234 – 12238
www.chemeurj.org
[1] For reviews on C C bond activation, see: a) Y. J. Park, J. W. Park, C. H. Jun, Acc. Chem. Res. 2008, 41, 222 – 234; b) M. Tobisu, N. Chatani, Chem. Soc. Rev. 2008, 37, 300 – 307; c) M. Rubin, M. Rubina, V. Gevorgyan, Chem. Rev. 2007, 107, 3117 – 3179; d) C. H. Jun, Chem. Soc. Rev. 2004, 33, 610 – 618; e) A. de Meijere, Chem. Rev. 2003, 103, 931 – 932. [2] “Cleavage of Carbon-Carbon Single Bonds by Transition Metals”: M. Murakami, Y. Ito, in Activation of Unreactive Bonds and Organic Synthesis—Topics in Organometallic Chemistry Series, Vol. 3, (Ed.: S. Murai), Springer, Berlin, New York, 1999, pp. 97 – 129. [3] Traditional metal-catalyzed methods for C C bond cleavage: for the use of Rh catalysts, see: a) H. Li, Y. Li, X. S. Zhang, K. Chen, X. Wang, Z.
12237
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper
[4]
[5]
[6]
[7] [8]
[9]
[10]
Shi, J. Am. Chem. Soc. 2011, 133, 15244 – 15247; b) M. Tobisu, H. Kinuta, Y. Kita, E. Rmond, N. Chatani, J. Am. Chem. Soc. 2012, 134, 115 – 118; c) Q. Shuai, L. Yang, X. Guo, O. Basl, C. J. Li, J. Am. Chem. Soc. 2010, 132, 12212 – 12213; for the use of Ru catalysts, see: d) J. Liu, Q. Liu, H. Yi, C. Qin, R. Bai, X. Qi, Y. Lan, A. Lei, Angew. Chem. 2014, 126, 512 – 516; Angew. Chem. Int. Ed. 2014, 53, 502 – 506; for the use of Pd catalysts, see: e) P. Hu, M. Zhang, X. Jie, W. Su, Angew. Chem. 2012, 124, 231 – 235; Angew. Chem. Int. Ed. 2012, 51, 227 – 231; f) Y. Hirata, A. Yada, E. Morita, Y. Nakao, T. Hiyama, M. Ohashi, S. Ogoshi, J. Am. Chem. Soc. 2010, 132, 10070 – 10077; g) S. I. Murahashi, T. Naota, N. Nakajima, J. Org. Chem. 1986, 51, 898 – 901; for the use of Au catalysts, see: h) N. Asao, T. Nogami, S. Lee, Y. Yamamoto, J. Am. Chem. Soc. 2003, 125, 10921 – 10925; for the use of Ni catalysts, see: i) T. Patra, S. Agasti, A. Modak, D. Maiti, Chem. Commun. 2013, 49, 8362 – 8364; j) T. Patra, S. Agasti, Akanksha, D. Maiti, Chem. Commun. 2013, 49, 69 – 71; k) Y. Nakao, Y. Hirata, T. Hiyama, J. Am. Chem. Soc. 2006, 128, 7420 – 7421; l) Y. Hirata, T. Inui, Y. Nakao, T. Hiyama, J. Am. Chem. Soc. 2009, 131, 6624 – 6631; m) Y. Nakao, A. Yada, S. Ebata, T. Hiyama, J. Am. Chem. Soc. 2007, 129, 2428 – 2429; n) M. P. Watson, E. N. Jacobsen, J. Am. Chem. Soc. 2008, 130, 12594 – 12595; o) K. Nakai, T. Kurahashi, S. Matsubara, J. Am. Chem. Soc. 2011, 133, 11066 – 11068; for other methods, see: p) X. Zhang, M. Wang, Y. Zhang, L. Wang, RSC Adv. 2013, 3, 1311 – 1316; q) J. Mecinovic´, R. B. Hamed, C. J. Schofield, Angew. Chem. 2009, 121, 2834 – 2838; Angew. Chem. Int. Ed. 2009, 48, 2796 – 2800; r) H. Li, W. Li, W. Liu, Z. He, Z. Li, Angew. Chem. 2011, 123, 3031 – 3034; Angew. Chem. Int. Ed. 2011, 50, 2975 – 2978; s) X. Kou, J. Fan, X. Tong, Z. Shen, Chin. J. Org. Chem. 2013, 33, 1407 – 1422 and references therein. For a review on aerobic copper-catalyzed C C bond cleavage, see: S. E. Allen, R. R. Walvoord, R. Padilla-Salinas, M. C. Kozlowski, Chem. Rev. 2013, 113, 6234 – 6458. a) C. He, S. Guo, L. Huang, A. Lei, J. Am. Chem. Soc. 2010, 132, 8273 – 8275; b) R. Shang, Y. Fu, J. B. Li, S. Zhang, Q. Guo, L. Liu, J. Am. Chem. Soc. 2009, 131, 5738 – 5739. a) C. Zhang, Z. Xu, T. Shen, G. Wu, L. Zhang, N. Jiao, Org. Lett. 2012, 14, 2362 – 2365; b) Q. Zhao, H. Lia, L. Wang, Org. Biomol. Chem. 2013, 11, 6772 – 6779; c) X. Sun, M. Wang, P. Li, X. Zhang, L. Wang, Green Chem. 2013, 15, 3289 – 3294. C. Zhang, P. Feng, N. Jiao, J. Am. Chem. Soc. 2013, 135, 15257 – 15262. a) J. Jin, Q. Wen, P. Lu, Y. Wang, Chem. Commun. 2012, 48, 9933 – 9935; b) Q. Song, Q. Feng, K. Yang, Org. Lett. 2014, 16, 624 – 627; c) E. J. Park, S. Lee, S. Chang, J. Org. Chem. 2010, 75, 2760 – 2762. a) B. Meunier, S. P. de Visser, S. Shaik, Chem. Rev. 2004, 104, 3947 – 3980; b) I. G. Denisov, T. M. Makris, S. G. Sligar, I. Schlichting, Chem. Rev. 2005, 105, 2253 – 2277. For some selected examples of transformations from aldehyde to amide, see: a) Z. Liu, J. Zhang, S. Chen, Angew. Chem. 2012, 124, 3285 –
Chem. Eur. J. 2014, 20, 12234 – 12238
www.chemeurj.org
3289; Angew. Chem. Int. Ed. 2012, 51, 3231 – 3235; b) V. Prasad, R. R. Kale, B. B. Mishra, D. Kumar, V. K. Tiwari, Org. Lett. 2012, 14, 2936 – 2939; c) L. Colombeau, T. Traor, P. Compain, O. R. Martin, J. Org. Chem. 2008, 73, 8647 – 8650; d) S. C. Ghosh, J. S. Y. Ngiam, C. L. L. Chai, A. M. Seayad, T. T. Dang, A. Q. Chen, Adv. Synth. Catal. 2012, 354, 1407 – 1412; e) S. C. Ghosh, J. S. Y. Ngiam, A. M. Seayad, D. T. Tuan, C. L. L. Chai, A. Q. Chen, J. Org. Chem. 2012, 77, 8007 – 8015; f) C. Zhang, Z. Xu, L. R. Zhang, N. Jiao, Angew. Chem. 2011, 123, 11284 – 11288; Angew. Chem. Int. Ed. 2011, 50, 11088 – 11092; g) M. W. Zhu, K. Fujita, R. Yamaguchi, J. Org. Chem. 2012, 77, 9102 – 9109; h) R. Cadoni, A. Porcheddu, G. Giacomelli, L. D. Luca, Org. Lett. 2012, 14, 5014; i) J. W. W. Chang, T. M. U. Ton, S. Tania, P. C. Taylor, P. W. H. Chan, Chem. Commun. 2010, 46, 922 – 924; j) G.-L. Li, K. K. Y. Kung, M. K. Wong, Chem. Commun. 2012, 48, 4112 – 4114; k) L. Zhang, S. Wang, S. Zhou, G. Yang, E. Sheng, J. Org. Chem. 2006, 71, 3149 – 3153; l) S. Y. Seo, T. J. Marks, Org. Lett. 2008, 10, 317 – 319; m) J. Li, F. Xu, Y. Zhang, Q. Shen, J. Org. Chem. 2009, 74, 2575; for examples of transformations from alcohols to amides, see: n) K. Xu, Y. Hu, S. Zhang, Z. Zha, Z. Wang, Chem. Eur. J. 2012, 18, 9793 – 9797; o) L. U. Nordstrøm, H. Vogt, R. Madsen, J. Am. Chem. Soc. 2008, 130, 17672 – 17673; p) F. Xiao, Y. Liu, C. Tang, G. Deng, Org. Lett. 2012, 14, 984 – 987; for examples of transformations from alkyne to amide, see: q) W. K. Chan, C. M. Ho, M. K. Wong, C. M. Che, J. Am. Chem. Soc. 2006, 128, 14796 – 14797; r) W. Wei, X. Hu, X. Yan, Q. Zhang, M. Cheng, J. Ji, Chem. Commun. 2012, 48, 305 – 307; for an example of transformation from an a-bromo nitroalkane to an amide, see: s) B. Shen, D. M. Makley, J. N. Johnston, Nature 2010, 465, 1027 – 1032; for other methods furnishing amides, see: t) R. J. Carroll, H. Leisch, E. Scocchera, T. Hudlicky, D. P. Cox, Adv. Synth. Catal. 2008, 350, 2984 – 2992; u) C. Vila, M. Rueping, Green Chem. 2013, 15, 2056 – 2059; v) D. N. Sawant, Y. S. Wagh, K. D. Bhatte, B. M. Bhanage, J. Org. Chem. 2011, 76, 5489 – 5494; w) C. Hu, X. Yan, X. Zhou, Z. Li, Org. Biomol. Chem. 2013, 11, 8179 – 8182; x) W. Mai, G. Song, J. Yuan, L. Yang, G. Sun, Y. Xiao, P. Mao, L. Qu, RSC Adv. 2013, 3, 3869 – 3872; y) Y. Li, L. Ma, F. Jia, Z. Li, J. Org. Chem. 2013, 78, 5638; z) Y. Li, F. Jia, Z. Li, Chem. Eur. J. 2013, 19, 82 – 86. [11] a) J. M. Humphrey, A. R. Chamberl, Chem. Rev. 1997, 97, 2243 – 2266; b) C. L. Allen, J. M. J. Williams, Chem. Soc. Rev. 2011, 40, 3405 – 3415. [12] It is noteworthy that N,N-diethyl-2-phenylacetamide was produced in 30 % yield in this case, which demonstrates that the remaining 1,3-diphenylpropan-2-one underwent the coupling process with amine substrate 2 a to produce the corresponding amide. [13] S. Guo, B. Qian, Y. Xie, C. Xia, H. Huang, Org. Lett. 2011, 13, 522 – 525.
Received: April 17, 2014 Revised: June 20, 2014 Published online on August 5, 2014
12238
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
