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CuSO4-mediated decarboxylative C–N cross-coupling of aromatic carboxylic acids with amides and anilines
Accepted Manuscript CuSO4-mediated Decarboxylative C-N Cross-Coupling of Aromatic Carboxylic Acids with Amides and Anilines Wei-Jian Sheng, Qing Ye, Wu-Bin Yu, Ren-Rong Liu, Meng Xu, Jian-Rong Gao, Yi-Xia Jia PII: DOI: Reference:
S0040-4039(14)02151-0 http://dx.doi.org/10.1016/j.tetlet.2014.12.085 TETL 45609
To appear in:
Tetrahedron Letters
Received Date: Revised Date: Accepted Date:
10 September 2014 10 December 2014 15 December 2014
Please cite this article as: Sheng, W-J., Ye, Q., Yu, W-B., Liu, R-R., Xu, M., Gao, J-R., Jia, Y-X., CuSO4-mediated Decarboxylative C-N Cross-Coupling of Aromatic Carboxylic Acids with Amides and Anilines, Tetrahedron Letters (2014), doi: http://dx.doi.org/10.1016/j.tetlet.2014.12.085
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CuSO4-mediated Decarboxylative C-N Cross-Coupling of Aromatic Carboxylic Acids with Amides and Amines
Wei-Jian Sheng, Qing Ye, Wu-Bin Yu, Ren-Rong Liu, Meng Xu, Jian-Rong Gao, and Yi-Xia Jia* O R OK
+ R
H 1 N
CuSO4 R2
R
R1 N
R2
NMP, additive 28 examples 35-93% yields
1
Tetrahedron Letters j o ur n al h om e p a g e : w w w . e l s e v i er . c o m
CuSO4-mediated Decarboxylative C-N Cross-Coupling of Aromatic Carboxylic Acids with Amides and Anilines Wei-Jian Shenga, Qing Yea, Wu-Bin Yua, Ren-Rong Liu a, Meng Xu a, Jian-Rong Gaoa, and Yi-Xia Jia a,∗ a
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China
A R T IC LE IN F O
A B S TR A C T
Article history: Received Received in revised form Accepted Available online
CuSO 4-mediated decarboxylative C-N cross-coupling of aromatic carboxylic acid with amide has been developed, leading to N-arylamides in modest to excellent yields. Anilines bearing electron-withdrawing substituents could also couple efficiently with aromatic carboxylic acids to give diarylamines in good to excellent yields. 2009 Elsevier Ltd. All rights reserved.
Keywords: decarboxylation cross-coupling carboxylic acid amide aniline
Transition-metal mediated carbon-nitrogen (C-N) bond formation via the cross-coupling of NH-containing fragments and aryl moieties has emerged as a powerful access to aromatic amines, which are important structural motifs in natural products and biologically active molecules. Conventional methods relied on the employment of aryl (pseudo)halides, aryl boronic acids, and arenes as coupling partners, which enabled the developments of efficient and elegant transformations including BuchwaldHartwig amination1, Ullmann-type C-N coupling2, Chan-LamEvans coupling3, and the C-H amination of arenes.4 However, the high demand of ligand system in Pd-catalysis, the use of expensive aryl iodide and boronic acid substrates in Cu-catalysis, and the limitation of directing group in the C-H amination remained the major issues. Recently, the decarboxylative carbon-carbon cross-coupling reactions have been intensely studied.5 In contrast, the process to from carbon-heteroatom bonds was less exploited and only a few examples were reported so far to build C-S,6 C-Cl(Br),7 C-P, 8 and C-O bonds.9 The decarboxylative cross-coupling of aromatic carboxylic acids with amines or amides would be an important complement to the conventional C-N forming strategies. In this context, two examples have been documented for Calkyne -N and CAr-N formations through couplings of amides with propiolic acid10 and arenecarboxylic acid11, respectively. However, amide was the only nitrogen partner in these two reports and phenanthroline was needed as a ligand in the latter case. Herein, we report a decarboxylative C-N cross-coupling reaction of aromatic carboxylic acids with amides and anilines, using inexpensive CuSO4 as mediator to afford aniline derivatives in good to excellent yields (Scheme 1). ———
Scheme 1
At the outset, we chose potassium 2-nitrobenzoate (1a) and benzamide (2a) as model substrates to study the decarboxylative C-N cross-coupling reaction. A range of copper salts were screened. CuSO4 was found to be the best choice as a mediator, yielding the desired product N-(2-nitrophenyl)benzamide (3a) in 39% of GC yield at 140 oC in NMP (N-methyl pyrrolidone) solvent (Table 1, entries 1-4). However, only nitrobenzene was formed through protodecarboxylation reaction when CuI, CuBr, Cu2O, and CuO were used. The yield of 3a was slightly improved to 54% by adding 4Å molecular sieves (entry 5). To our delight, the introduction of silver salt efficiently suppressed the protodecarboxylation reaction. 9 Thus, 3a was isolated in 91% yield in the presence of 1.0 eq. Ag2 CO3 and 1.0 eq. CuSO4 (entry 6). Ag2O showed the equal efficacy (entry 7), while inferior results were given by AgNO3 and AgOAc. The next solvent experiments revealed NMP was the best choice (entries 8-10). Lowering the reaction temperature decreased the product yields (entries 11 and 12). And the introduction of bidentate ligands at 100 oC did not gave positive results (27% for 1,10phenanthroline, 42% for 2,2'-bipyridine, and 14% for TMEDA or DMEDA). Reducing the amount of CuSO4 and Ag2CO3 both decreased the product yields (entries 13-15); and only trace amount of the product was observed without the addition of CuSO4, implying copper salt was crucial for this reaction (entry
∗ Corresponding author. Tel.: +86-571-8832-0890; fax: +85-571-8832-0544; e-mail: [email protected]
2
Tetrahedron
17). When 1.3 eq. of benzamide was used, slightly lower yield (86%) was obtained for this reaction (entry 17).
Table 1. Optimization of the decarboxylative C-N couplinga O O OK
+
Ph
NO2 1a
NHCOPh
[Cu]/[Ag] NH2
Solvent 140 oC
NO2
2a
3a
Entry
Copper salt
Silver salt
Solvent
Yield [%]b
1c
Cu(OAc)2
--
NMP
15
2
Cu(OTf)2
--
NMP
17
3c
CuCl2
--
NMP
27
4c
CuSO4
--
NMP
39
5
CuSO4
--
NMP
54
6
CuSO4
Ag2 CO3
NMP
94(91)
7
CuSO4
Ag2 O
NMP
90
8
CuSO4
Ag2 CO3
DMF
86
9
CuSO4
Ag2 CO3
DMSO
75
c
cyclic secondary amide, gave the desired product 3j in good yield. Aromatic carboxylic acids without ortho-nitro group were also investigated. Only trace amount of the products were detected under the established reaction conditions. Again, by improving the dosage of benzamide and increasing the reaction temperature, the desired products 3q-3s bearing ortho-OMe and ortho-F were isolated in 33-38% yields. The para-MeO benzoic acid also coupled successfully with benzamide to afford the desired products 3t in 41% yield. Unfortunately, the metasubstituted benzoic acids and picolinic acid are failed to give the desired product in acceptable yields. 12
Table 2. Decarboxylative C-N cross-coupling of arene carboxylic acids with amidesa
CuSO4
Ag2 CO3
Xylene
52
11
d
CuSO4
Ag2 CO3
NMP
86
12e
CuSO4
Ag2 CO3
NMP
57
13f
CuSO4
Ag2 CO3
NMP
35
O
CuSO4
Ag2 CO3
NMP
33
3g, 85%
3h, 83%
NO2
NO2
14
f,g
15
g,h
CuSO4
Ag2 CO3
NMP
58
16i
CuSO4
Ag2 CO3
NMP
(84)
17
--
Ag2 CO3
NMP
<5
NO2
b
GC yield (4-nitrotoluene as internal standard), isolated yield for parenthesis.
c
no 4Å molecular sieves.
at 100 C. 20 mol% CuSO4 was used.
g
O2 balloon.
h
40 mol% Ag2 CO3
i
1.3 eq. benzamide was used.
Once the optimal reaction conditions were established, substrate scope of this reaction was explored. As shown in Table 2, a range of benzamides bearing either electron-donating or electron-withdrawing substituents on the phenyl ring coupled smoothly with potassium 2-nitrobenzoate to afford the desired products 3a-3g in good to excellent yields. Notably, halide groups were well tolerated in the reactions though lower yields were obtained for 3e and 3f. The same trend was also observed for the reactions of substituted 2-nitrobenzoic acids. Therefore, 3m, 3n, and 3p containing Cl or Br substituents were isolated in poor to modest yields. However, modest to good yields were obtained for these products containing halides by increasing the amount of the corresponding amides (the data shown in the parenthesis). Other types of amide were then evaluated. Acetamide reacted smoothly with potassium 2-nitrobenzoate to produce N-(2-nitrophenyl)acetamide 3h in 83% yield, while poor yields (3i and 3k) were obtained for trifluoroacetamide and paratoluenesulfonamide. Noteworthy, the reaction of oxazolidinone, a
H N
OMe
3f, 57% (79%) NO2
H N
CF3
N
O O
O 3i, 34% (58%) NO2
H N
Cl O
O
Ph
3j, 84% H N
Ph
NHBz
O
X
3n, X = Br, 40% (69%) 3o, X = NO2, 39% (50%) 3p, X = Cl, 67% (79%)
X 3l, X = OMe, 74% 3m, X = Cl, 45% (65%) F
OMe
F
NHBz
NHBz
NHBz F
3q, 33%b
H N
Ts
3k, 44% (51%)
at 120 C.
f
H N
NO2
O
o
o
NO2
H N
NO2
3a, R = H, 84% (91%) 3b, R = Me, 87% 3c, R = OMe, 79% 3d, R = NO2, 55% (89%) 3e, R = Br, 51% (68%)
10
reactions conditions: potassium 2-nitrobenzoate 0.4 mmol, 2.0 eq. benzamide, 1.0 eq. CuSO4, 1.0 eq. silver salt, and 160 mg 4Å molecular sieves in 2.0 mL solvent at 140 oC for 12 h, NMP = N-methyl pyrrolidone, DMSO = methylsulfinylmethane, DMF = N,N-dimethylformamide.
e
H N O
a
d
R
NO2
3r, 35%b
F F 3s, 38%b
MeO 3t, 41%b
Reaction conditions: potassium 2-nitrobenzoates 0.4 mmol, 1.3 eq. amide, 1.0 eq. CuSO4 , 1.0 eq. Ag2CO3 , and 160 mg 4Å molecular sieves in 2.0 mL NMP at 140 o C for 12h. The data in parenthesis were obtained with 2.0 eq. benzamides. a
b
potassium benzoate 0.4 mmol, 4.0 eq. benzamide, 1.0 eq. CuSO4 , 1.0 eq. Ag2CO3, and 160 mg 4Å molecular sieves in 2.0 mL NMP at 180 o C for 10 min.
Table 3. Decarboxylative C-N cross-coupling of potassium 2nitrobenzoate with anilinesa
3 Reaction conditions: anilines 0.4 mmol, potassium 2-nitrobenzoates 1.0 mmol, CuSO4 1.0 mmol, and 160 mg 4Å molecular sieves in 1.2 mL NMP at 140 oC for 12h. a
We then moved our attention to the decarboxylative C-N cross-coupling of anilines, which is undocumented since aniline is normally sensitive to oxidants. However, unsatisfied yields were given under the optimized reaction conditions for the coupling of benzamides showed in Table 2. Fortunately, the modified reaction conditions led to the desired products in modest to excellent yields (Table 3). Electron-withdrawing substituents on the aniline ring (NO2, CN and halides) were well tolerated to give the desired products in satisfied yields. Lower yield was observed for the reaction of aniline and only trace amount of products were detected for anilines bearing electrondonating groups as the decomposition of anilines, showing the limitation of the reaction. A simple proposed mechanism was presented in Scheme 2. As suggested by Goossen and co-workers,9 silver salts assisted the decarboxylation of potassium 2-nitrobenzoate. Subsequent transmetalation led to the arylcopper species I. Followed ligand exchange gave intermediate II, which afforded the final product via reductive elimination.
Scheme 2
In summary, we have developed an efficient CuSO4-mediated decarboxylative C-N cross-coupling of aromatic carboxylic acids with amides or anilines to afford aniline derivatives in modest to excellent yields. It provides a good complement to the wellestablished C-N cross-coupling reactions. Further extension of this methodology for synthetic application is on progress in the laboratory.
Acknowledgments We are grateful to the financial supports of National Natural Science Foundation of P. R. China (21372202), New Century Excellent Talents in University (NCET-12-1086) and Zhejiang Natural Science Fund for Distinguished Young Scholars (R14B020005). References and notes 1.
2.
3.
(a) Paul, F.; Patt, J.; Hartwig, J. F. J. Am. Chem. Soc. 1994, 116, 5969–5970. (b) Guram, A. S.; Buchwald, S. L. J. Am. Chem. Soc. 1994, 116, 7901–7902. (c) Louie, J.; Hartwig, J. F. Tetrahedron Lett. 1995, 36, 3609–3612. (d) Guram, A. S.; Rennels, R. A.; Buchwald, S. L. Angew. Chem., Int. Ed. 1995, 34, 1348–1350. (e) Wolfe, J. P.; Wagaw, S.; Macroux, J. F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805–818. (f) Hartwig, J. F. Angew. Chem., Int. Ed. 1998, 37, 2046–2067. (g) Muci, A. R.; Buchwald, S. L. Top. Curr. Chem. 2002, 219, 131–209. (a) Ullmann, F. Chem. Ber. 1903, 36, 2382–2384. (b) Son, S. U.; Park, I. K.; Park J.; Hyeon, T. Chem. Commun. 2004, 40, 778–779. (c) Audisio, D.; Messaoudi, S.; Peyrat, J. F.; Brion, J. D.; Alami, M. J. Org. Chem. 2011, 76, 4995–5005. (d) Ma, D.; Cai, Q.; Zhang, H. Org. Lett. 2003, 5, 2453–2455. (e) Ma, D.; Cai, Q. Acc. Chem. Res. 2008, 41, 1450–1460. (f) Sambiagio, C.; Marsden, S. P.; Blacker, A. J.; McGowan, P. C. Chem. Soc. Rev. 2014, 43, 3525–3550. (a) Chan, D. M. T.; Mnaco, K. L.; Wang, R. P.; Winters, M. P. Tetrahedron Lett. 1998, 39, 2933–2936. (b) Lam, P. Y. S.; Clark, C. G.; Saubern, S.; Adams, J.; Winters, M. P.; Chan, D. M. T.; Combs, A. Tetrahedron Lett. 1998, 39, 2941–2944. (c) Lam, P. Y. S.; Clark, C. G.; Saubern, S.; Adams, J.; Averill, K. M.; Chan, D.
M. T.; Combs, A. Synlett 2000, 674–676. (d) Quach, T. D.; Batey, R. A. Org. Lett. 2003, 5, 4397–4400. (e) Kantam, M. L.; Venkanna, G. T.; Sridhar, C.; Sreedhar, B.; Choudary, B. M. J. Org. Chem. 2006, 71, 9522–9524. 4. For a review, see: (a) Louillat, M.-L.; Patureau, F. W. Chem. Soc. Rev. 2014, 43, 901–910. 5. For reviews, see: (a) N. Rodriguez; Goossen, L. J. Chem. Soc. Rev. 2011, 40, 5030–5048. (b) Weaver, J. D.; Recio, A; Grenning, III, A. J.; Tunge, J. A. Chem. Rev. 2011, 111, 1846–1913. (c) Shang, R.; Liu, L. Sci. China Chem. 2011, 54, 1670–1687. 6. (a) Liu, X. G.; Ranjit, S.; Duan, Z. Y.; Zhang, P. F. Org. Lett. 2010, 12, 4134–4136. (b) Liu, X. G.; Duan, Z. Y.; Ranjit, S.; Zhang, P. F. Chem. Eur. J. 2009, 15, 3666–3669. (c) Becht, J. M.; Drian, C. L. J. Org. Chem. 2011, 76, 6327–6330. 7. Luo, Y.; Pan, X. L.; Wu, J. Tetrahedron Lett. 2010, 51, 6646– 6648. 8. Hu, J.; Zhao N.; Yang, B.; Wang, G.; Guo, L.-N.; Liang, Y.-M.; Yang, S.-D. Chem. Eur. J. 2011, 17, 5516–5521. 9. Bhadra, S.; Dzik, W. I.; Goossen, L. J. J. Am. Chem. Soc. 2012, 134, 9938–9941. 10. Jiao, N.; Jia, W. Org. Lett. 2010, 12, 2000–2003. 11. Zhang, Y.; Patel, S.; Mainolfi, N. Chem. Sci. 2012, 3, 3196–3199. 12. Poor yields were observed for the reactions of benzamide with meta-substituted benzoic acids or picolinic acid.
S0040-4039(14)02151-0 http://dx.doi.org/10.1016/j.tetlet.2014.12.085 TETL 45609
To appear in:
Tetrahedron Letters
Received Date: Revised Date: Accepted Date:
10 September 2014 10 December 2014 15 December 2014
Please cite this article as: Sheng, W-J., Ye, Q., Yu, W-B., Liu, R-R., Xu, M., Gao, J-R., Jia, Y-X., CuSO4-mediated Decarboxylative C-N Cross-Coupling of Aromatic Carboxylic Acids with Amides and Anilines, Tetrahedron Letters (2014), doi: http://dx.doi.org/10.1016/j.tetlet.2014.12.085
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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CuSO4-mediated Decarboxylative C-N Cross-Coupling of Aromatic Carboxylic Acids with Amides and Amines
Wei-Jian Sheng, Qing Ye, Wu-Bin Yu, Ren-Rong Liu, Meng Xu, Jian-Rong Gao, and Yi-Xia Jia* O R OK
+ R
H 1 N
CuSO4 R2
R
R1 N
R2
NMP, additive 28 examples 35-93% yields
1
Tetrahedron Letters j o ur n al h om e p a g e : w w w . e l s e v i er . c o m
CuSO4-mediated Decarboxylative C-N Cross-Coupling of Aromatic Carboxylic Acids with Amides and Anilines Wei-Jian Shenga, Qing Yea, Wu-Bin Yua, Ren-Rong Liu a, Meng Xu a, Jian-Rong Gaoa, and Yi-Xia Jia a,∗ a
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China
A R T IC LE IN F O
A B S TR A C T
Article history: Received Received in revised form Accepted Available online
CuSO 4-mediated decarboxylative C-N cross-coupling of aromatic carboxylic acid with amide has been developed, leading to N-arylamides in modest to excellent yields. Anilines bearing electron-withdrawing substituents could also couple efficiently with aromatic carboxylic acids to give diarylamines in good to excellent yields. 2009 Elsevier Ltd. All rights reserved.
Keywords: decarboxylation cross-coupling carboxylic acid amide aniline
Transition-metal mediated carbon-nitrogen (C-N) bond formation via the cross-coupling of NH-containing fragments and aryl moieties has emerged as a powerful access to aromatic amines, which are important structural motifs in natural products and biologically active molecules. Conventional methods relied on the employment of aryl (pseudo)halides, aryl boronic acids, and arenes as coupling partners, which enabled the developments of efficient and elegant transformations including BuchwaldHartwig amination1, Ullmann-type C-N coupling2, Chan-LamEvans coupling3, and the C-H amination of arenes.4 However, the high demand of ligand system in Pd-catalysis, the use of expensive aryl iodide and boronic acid substrates in Cu-catalysis, and the limitation of directing group in the C-H amination remained the major issues. Recently, the decarboxylative carbon-carbon cross-coupling reactions have been intensely studied.5 In contrast, the process to from carbon-heteroatom bonds was less exploited and only a few examples were reported so far to build C-S,6 C-Cl(Br),7 C-P, 8 and C-O bonds.9 The decarboxylative cross-coupling of aromatic carboxylic acids with amines or amides would be an important complement to the conventional C-N forming strategies. In this context, two examples have been documented for Calkyne -N and CAr-N formations through couplings of amides with propiolic acid10 and arenecarboxylic acid11, respectively. However, amide was the only nitrogen partner in these two reports and phenanthroline was needed as a ligand in the latter case. Herein, we report a decarboxylative C-N cross-coupling reaction of aromatic carboxylic acids with amides and anilines, using inexpensive CuSO4 as mediator to afford aniline derivatives in good to excellent yields (Scheme 1). ———
Scheme 1
At the outset, we chose potassium 2-nitrobenzoate (1a) and benzamide (2a) as model substrates to study the decarboxylative C-N cross-coupling reaction. A range of copper salts were screened. CuSO4 was found to be the best choice as a mediator, yielding the desired product N-(2-nitrophenyl)benzamide (3a) in 39% of GC yield at 140 oC in NMP (N-methyl pyrrolidone) solvent (Table 1, entries 1-4). However, only nitrobenzene was formed through protodecarboxylation reaction when CuI, CuBr, Cu2O, and CuO were used. The yield of 3a was slightly improved to 54% by adding 4Å molecular sieves (entry 5). To our delight, the introduction of silver salt efficiently suppressed the protodecarboxylation reaction. 9 Thus, 3a was isolated in 91% yield in the presence of 1.0 eq. Ag2 CO3 and 1.0 eq. CuSO4 (entry 6). Ag2O showed the equal efficacy (entry 7), while inferior results were given by AgNO3 and AgOAc. The next solvent experiments revealed NMP was the best choice (entries 8-10). Lowering the reaction temperature decreased the product yields (entries 11 and 12). And the introduction of bidentate ligands at 100 oC did not gave positive results (27% for 1,10phenanthroline, 42% for 2,2'-bipyridine, and 14% for TMEDA or DMEDA). Reducing the amount of CuSO4 and Ag2CO3 both decreased the product yields (entries 13-15); and only trace amount of the product was observed without the addition of CuSO4, implying copper salt was crucial for this reaction (entry
∗ Corresponding author. Tel.: +86-571-8832-0890; fax: +85-571-8832-0544; e-mail: [email protected]
2
Tetrahedron
17). When 1.3 eq. of benzamide was used, slightly lower yield (86%) was obtained for this reaction (entry 17).
Table 1. Optimization of the decarboxylative C-N couplinga O O OK
+
Ph
NO2 1a
NHCOPh
[Cu]/[Ag] NH2
Solvent 140 oC
NO2
2a
3a
Entry
Copper salt
Silver salt
Solvent
Yield [%]b
1c
Cu(OAc)2
--
NMP
15
2
Cu(OTf)2
--
NMP
17
3c
CuCl2
--
NMP
27
4c
CuSO4
--
NMP
39
5
CuSO4
--
NMP
54
6
CuSO4
Ag2 CO3
NMP
94(91)
7
CuSO4
Ag2 O
NMP
90
8
CuSO4
Ag2 CO3
DMF
86
9
CuSO4
Ag2 CO3
DMSO
75
c
cyclic secondary amide, gave the desired product 3j in good yield. Aromatic carboxylic acids without ortho-nitro group were also investigated. Only trace amount of the products were detected under the established reaction conditions. Again, by improving the dosage of benzamide and increasing the reaction temperature, the desired products 3q-3s bearing ortho-OMe and ortho-F were isolated in 33-38% yields. The para-MeO benzoic acid also coupled successfully with benzamide to afford the desired products 3t in 41% yield. Unfortunately, the metasubstituted benzoic acids and picolinic acid are failed to give the desired product in acceptable yields. 12
Table 2. Decarboxylative C-N cross-coupling of arene carboxylic acids with amidesa
CuSO4
Ag2 CO3
Xylene
52
11
d
CuSO4
Ag2 CO3
NMP
86
12e
CuSO4
Ag2 CO3
NMP
57
13f
CuSO4
Ag2 CO3
NMP
35
O
CuSO4
Ag2 CO3
NMP
33
3g, 85%
3h, 83%
NO2
NO2
14
f,g
15
g,h
CuSO4
Ag2 CO3
NMP
58
16i
CuSO4
Ag2 CO3
NMP
(84)
17
--
Ag2 CO3
NMP
<5
NO2
b
GC yield (4-nitrotoluene as internal standard), isolated yield for parenthesis.
c
no 4Å molecular sieves.
at 100 C. 20 mol% CuSO4 was used.
g
O2 balloon.
h
40 mol% Ag2 CO3
i
1.3 eq. benzamide was used.
Once the optimal reaction conditions were established, substrate scope of this reaction was explored. As shown in Table 2, a range of benzamides bearing either electron-donating or electron-withdrawing substituents on the phenyl ring coupled smoothly with potassium 2-nitrobenzoate to afford the desired products 3a-3g in good to excellent yields. Notably, halide groups were well tolerated in the reactions though lower yields were obtained for 3e and 3f. The same trend was also observed for the reactions of substituted 2-nitrobenzoic acids. Therefore, 3m, 3n, and 3p containing Cl or Br substituents were isolated in poor to modest yields. However, modest to good yields were obtained for these products containing halides by increasing the amount of the corresponding amides (the data shown in the parenthesis). Other types of amide were then evaluated. Acetamide reacted smoothly with potassium 2-nitrobenzoate to produce N-(2-nitrophenyl)acetamide 3h in 83% yield, while poor yields (3i and 3k) were obtained for trifluoroacetamide and paratoluenesulfonamide. Noteworthy, the reaction of oxazolidinone, a
H N
OMe
3f, 57% (79%) NO2
H N
CF3
N
O O
O 3i, 34% (58%) NO2
H N
Cl O
O
Ph
3j, 84% H N
Ph
NHBz
O
X
3n, X = Br, 40% (69%) 3o, X = NO2, 39% (50%) 3p, X = Cl, 67% (79%)
X 3l, X = OMe, 74% 3m, X = Cl, 45% (65%) F
OMe
F
NHBz
NHBz
NHBz F
3q, 33%b
H N
Ts
3k, 44% (51%)
at 120 C.
f
H N
NO2
O
o
o
NO2
H N
NO2
3a, R = H, 84% (91%) 3b, R = Me, 87% 3c, R = OMe, 79% 3d, R = NO2, 55% (89%) 3e, R = Br, 51% (68%)
10
reactions conditions: potassium 2-nitrobenzoate 0.4 mmol, 2.0 eq. benzamide, 1.0 eq. CuSO4, 1.0 eq. silver salt, and 160 mg 4Å molecular sieves in 2.0 mL solvent at 140 oC for 12 h, NMP = N-methyl pyrrolidone, DMSO = methylsulfinylmethane, DMF = N,N-dimethylformamide.
e
H N O
a
d
R
NO2
3r, 35%b
F F 3s, 38%b
MeO 3t, 41%b
Reaction conditions: potassium 2-nitrobenzoates 0.4 mmol, 1.3 eq. amide, 1.0 eq. CuSO4 , 1.0 eq. Ag2CO3 , and 160 mg 4Å molecular sieves in 2.0 mL NMP at 140 o C for 12h. The data in parenthesis were obtained with 2.0 eq. benzamides. a
b
potassium benzoate 0.4 mmol, 4.0 eq. benzamide, 1.0 eq. CuSO4 , 1.0 eq. Ag2CO3, and 160 mg 4Å molecular sieves in 2.0 mL NMP at 180 o C for 10 min.
Table 3. Decarboxylative C-N cross-coupling of potassium 2nitrobenzoate with anilinesa
3 Reaction conditions: anilines 0.4 mmol, potassium 2-nitrobenzoates 1.0 mmol, CuSO4 1.0 mmol, and 160 mg 4Å molecular sieves in 1.2 mL NMP at 140 oC for 12h. a
We then moved our attention to the decarboxylative C-N cross-coupling of anilines, which is undocumented since aniline is normally sensitive to oxidants. However, unsatisfied yields were given under the optimized reaction conditions for the coupling of benzamides showed in Table 2. Fortunately, the modified reaction conditions led to the desired products in modest to excellent yields (Table 3). Electron-withdrawing substituents on the aniline ring (NO2, CN and halides) were well tolerated to give the desired products in satisfied yields. Lower yield was observed for the reaction of aniline and only trace amount of products were detected for anilines bearing electrondonating groups as the decomposition of anilines, showing the limitation of the reaction. A simple proposed mechanism was presented in Scheme 2. As suggested by Goossen and co-workers,9 silver salts assisted the decarboxylation of potassium 2-nitrobenzoate. Subsequent transmetalation led to the arylcopper species I. Followed ligand exchange gave intermediate II, which afforded the final product via reductive elimination.
Scheme 2
In summary, we have developed an efficient CuSO4-mediated decarboxylative C-N cross-coupling of aromatic carboxylic acids with amides or anilines to afford aniline derivatives in modest to excellent yields. It provides a good complement to the wellestablished C-N cross-coupling reactions. Further extension of this methodology for synthetic application is on progress in the laboratory.
Acknowledgments We are grateful to the financial supports of National Natural Science Foundation of P. R. China (21372202), New Century Excellent Talents in University (NCET-12-1086) and Zhejiang Natural Science Fund for Distinguished Young Scholars (R14B020005). References and notes 1.
2.
3.
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