Table 1. Optimization of the Reaction Conditiona
Scheme 1. Palladium-Catalyzed Carbonylative Couplings of
Aryl Diazonium Salts
promoter
(equiv)
2a
yield
(%)b
entry
(equiv)
solvent
1
Pd(OAc)2 (0.05)
none
2
2
2
2
2
2
2
2
2
2
2
2
3
3
5
acetone/H2O
acetone/H2O
acetone/H2O
acetone/H2O
acetone/H2O
acetone/H2O
acetone/H2O
acetone/H2O
acetone/H2O
CH3CN/H2O
DMSO/H2O
DMF/H2O
9
2
16
61
67
42
65
65
12
65
36
36
40
73
80
83
3
K2CO3 (1.1)
Cs2CO3 (1.1)
NaOAc (1.1)
t-BuOK (1.1)
Cp2Fe (0.1)
FeCl2 (0.1)
4
reactions using isocyanides as isoelectronic equivalents of
carbon monooxide in palladium-catalyzed isocyanide in-
sertion have grown rapidly in recent years.15 Based on our
continuing interest on isocyanide chemistry,16 we anticipate
that aryl diazonium salts could be used as electrophiles
in palladium-catalyzed isocyanide insertion, affording
arylcarboxyamide.17 Research following this hypothesis
revealed that aryl diazonium tetrafluoroborates can react
with isocyanides in the absence of palladium. This formal
aminocarbonylation process occurs in the absence of CO
and amines or anilines in aqueous media at 0 °C.18 Mecha-
nistic studies suggest that radical intermediates are involved
in the process.
In an initial attempt, p-nitrophenyl diazonium tetra-
fluoroborate 1a and tert-butyl isocyanide 2a were used as
model substrates in the presence of Pd(OAc)2 (5 mol %) in
acetone/H2O (2.5:1) at 0 °C (entry 1, Table 1). As we
expected, the corresponding N-(tert-butyl)-4-nitrobenz-
amide 3a was isolated in 9% yield. However, a control
reaction without a palladium catalyst also produces 3a in
16% yield, indicating that 1a could react with 2a through a
different mechanism as we anticipated. Addition of base
significantly improves the yield of 3a (entries 3À6). In the
case of using cesium carbonate (1.1 equiv) as a base, the
5
6
7
8
9c
10
11
12
13
14d
15d
Cs2CO3 (1.1)
Cs2CO3 (1.1)
Cs2CO3 (1.1)
Cs2CO3 (1.1)
Cs2CO3 (1.1)
Cs2CO3 (1.1)
Cs2CO3 (1.1)
acetone/H2O
acetone/H2O
acetone/H2O
a Reaction conditions: All reactions were performed with 1a
(0.2 mmol) and 2a (2À5 equiv), in 0.4 mL of H2O and 1.0 mL of organic
solvent at 0 °C, in air, for 20 min. b Isolated yields of 3a. c The reaction
was carried out in darkness. d The reaction was carried out in argon.
desired product 3a was obtained in 67% yield. Interest-
ingly, ferrocene (10 mol %) is also a good catalyst in
promoting this transformation, which suggests that this
reaction might proceed through a radical mechanism
(entry 7).19 When the reaction was carried out in darkness,
a similar yield of 65% was obtained, ruling out the
possibility that the reaction was initiated by light induced
decomposition of aryl diazonium salt (entry 9).20 In addi-
tion, it was observed that the reaction was less efficient in
other organic solvents with water as a cosolvent (entries
10À12). Finally, the yield of 3a was improved to 80%
under the optimized reaction conditions involving 1.1
equiv of Cs2CO3 and 3 equiv of tert-butyl isocyanide 2a
in argon (entry 14). Notably, this palladium-free carboxy-
amidation of aryl diazonium tetrafluoroborate occurrs
rapidly at low temperature, providing a formal aminocar-
bonylation reaction of aryl diazonium salts in the absence
of CO and amines or anilines.
(13) For recent developments of the Passerini and Ugi reactions, see
€
selected reviews: (a) Domling, A.; Ugi, I. Angew. Chem., Int. Ed. 2000,
€
39, 3168. (b) Zhu, J. Eur. J. Org. Chem. 2003, 1133. (c) Domling, A.
Chem. Rev. 2006, 106, 17. (d) Lygin, A. V.; de Meijere, A. Angew. Chem.,
Int. Ed. 2010, 49, 9094. (e) Ruijter, E.; Scheffelaar, R.; Orru, R. V. A.
Angew. Chem., Int. Ed. 2011, 50, 6234.
(14) (a) Camaggi, C. M.; Leardini, R.; Nanni, D.; Zanardi, G.
Tetrahedron 1998, 54, 5587. (b) Lenoir, I.; Smith, M. L. J. Chem. Soc.,
Perkin Trans. 1 2000, 641. (c) Masui, H.; Fuse, S.; Takahashi, T. Org.
Lett. 2012, 14, 4090. (d) Tobisu, M.; Koh, K.; Furukawa, T.; Chatani, N.
Angew. Chem., Int. Ed. 2012, 51, 11363.
(15) (a) Qiu, G.; Ding, Q.; Wu, J. Chem. Soc. Rev. 2013, 42, 5257.
(b) Lang, S. Chem. Soc. Rev. 2013, 42, 4867.
A series of substituted aryl diazonium tetrafluorobo-
rates were reacted with isocyanide 2a under the optimized
reaction conditions (Figure 1). Aryl diazonium tetrafluo-
roborates bearing electron-withdrawing groups in the para
(16) (a) Liu, L.; Wang, Y.; Wang, H.; Peng, C.; Zhao, J.; Zhu, Q.
Tetrahedron Lett. 2009, 50, 6715. (b) Zhao, J.; Peng, C.; Liu, L.; Wang,
Y.; Zhu, Q. J. Org. Chem. 2010, 75, 7502. (c) Wang, Y.; Wang, H.; Peng,
J.; Zhu, Q. Org. Lett. 2011, 13, 4604. (d) Peng, J.; Liu, L.; Hu, Z.; Huang,
J.; Zhu, Q. Chem. Commun. 2012, 48, 3772. (e) Wang, Y.; Zhu, Q. Adv.
Synth. Catal. 2012, 354, 1902. (f) Hu, Z.; Liang, D.; Zhao, J.; Huang, J.;
Zhu, Q. Chem. Commun. 2012, 48, 7371. (g) Peng, J.; Zhao, J.; Hu, Z.;
Liang, D.; Huang, J.; Zhu, Q. Org. Lett. 2012, 14, 4966.
(17) Palladium-catalyzed carboxyamidation of aryl bromides or
vinyl bromides with isocyanides was reported by Jiang’s group; see:
Jiang, H.; Liu, B.; Li, Y.; Wang, A.; Huang, H. Org. Lett. 2011, 13, 1028.
(18) While this manuscript was under preparation, a similar reaction
wss published; see: Basavanag, U. M. V.; Dos Santos, A.; El Kaim, L.;
(19) (a) Chernyak, N.; Buchwald, S. L. J. Am. Chem. Soc. 2012, 134,
12466. (b) Connelly, N. G.; Geiger, W. E. Chem. Rev. 1996, 96, 877. (b)
Beckwith, A. L. J.; Jackson, R. A.; Longmore, R. W. Aust. J. Chem.
1992, 45, 857. (c) Freidlina, R. K.; Kandror, I. I.; Gasanov, R. G.;
Kopylova, B. V.; Bragina, I. O.; Yashkina, L. V. Russ. Chem. Bull. 1984,
33, 758. (d) Kochi, J. K. J. Am. Chem. Soc. 1955, 77, 5090. (e) Kochi,
J. K. J. Am. Chem. Soc. 1955, 77, 5274.
(20) (a) Fagnoni, M.; Albini, A. Acc. Chem. Res. 2005, 38, 713. (b)
Ando, W. In The Chemistry of Diazonium and Diazo Groups; Patai, S.,
Ed.; Wiley: New York, 1978; Part 1, Chapter 9, p 341.
ꢀ
~
Gamez-Montano, R.; Grimaud, L. Angew. Chem., Int. Ed. 2013, 52,
7194.
B
Org. Lett., Vol. XX, No. XX, XXXX