3
a
Reaction conditions: anilines 0.4 mmol, potassium 2-nitrobenzoates 1.0
M. T.; Combs, A. Synlett 2000, 674–676. (d) Quach, T. D.;
mmol, CuSO4 1.0 mmol, and 160 mg 4Å molecular sieves in 1.2 mL NMP at
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.
140 oC for 12h.
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 electron-
donating groups as the decomposition of anilines, showing the
limitation of the reaction.
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.
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.
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.
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 well-
established 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. (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.
2. (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.
3. (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.