A general and efficient copper catalyst for the double carbonylation reaction

Article abstract of DOI:10.1021/ol9001027

The use of (NHC)Cul complex in combination with a N-heterocyclic carbene precursor as catalyst for the double carbonylation of aryl Iodides and secondary amines solves the problem of using the precious metal Pd and phosphine ligands. The new protocol requ

Full text of DOI:10.1021/ol9001027

ORGANIC
LETTERS
2009
Vol. 11, No. 6
1321-1324
A General and Efficient Copper Catalyst
for the Double Carbonylation Reaction
Jianming Liu,†,‡ Rongzhao Zhang,†,‡ Shoufeng Wang,† Wei Sun,*,† and
Chungu Xia*,†
State Key Laboratory for Oxo Synthesis and SelectiVe Oxidation, Lanzhou Institute of
Chemical Physics, Chinese Academy of Sciences, Lanzhou, 730000, P. R. China, and
Graduate School of the Chinese Academy of Sciences, Beijing, 100039, P. R. China
wsun@lzb.ac.cn; cgxia@lzb.ac.cn
Received January 17, 2009
ABSTRACT
The use of (NHC)CuI complex in combination with a N-heterocyclic carbene precursor as catalyst for the double carbonylation of aryl Iodides
and secondary amines solves the problem of using the precious metal Pd and phosphine ligands. The new protocol requires a nonprecious
metal catalyst and has greater generality than those previously reported.
The transition metal-catalyzed carbonylation reaction is a
widely used transformation that has been applied to the
synthesis of complex organic molecules and commodity
chemicals.1 Among the carbonylation reactions, a double
carbonylation reaction can produce R-keto amides, esters and
acids depending on the nucleophiles employed.2 These
compounds are an important unit in several biologically
important natural products or versatile intermediates for
synthesis of R-hydroxy acids, R-amino acids and others.3,4
The traditional protocols for the double carbonylation reac-
tion require the precious metal palladium as the catalyst.5-8
Air-sensitive phosphine ligands are usually required to
promote the selectivity of double carbonylation. The use of
phosphine ligands is a major problem associated with the
double carbonylation reaction. Developing a novel catalytic
system that is not dependent on phosphine ligands or precious
metals to efficiently mediate this reaction is required. Since
the first stable N-heterocyclic carbene (NHC) isolated by
(5) (a) Ozawa, F.; Soyama, H.; Yamamoto, T.; Yamamoto, A. Tetra-
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(c) Ozawa, F.; Sugimoto, T.; Yuasa, Y.; Santra, M.; Yamamoto, T.;
Yamamoto, A. Organometallics 1984, 3, 683. (d) Ozawa, F.; Soyama, H.;
Yanagihara, H.; Aoyama, I.; Takino, H.; Izawa, K.; Yamamoto, T.;
Yamamoto, A. J. Am. Chem. Soc. 1985, 107, 3235. (e) Son, T.; Yanagihara,
H.; Ozawa, F.; Yamamoto, A. Bull. Chem. Soc. Jpn. 1988, 61, 1251. (f)
Murphy, E. R.; Martinelli, J.; Zaborenko, N.; Buchwald, S. L.; Jensen, K. F.
Angew. Chem., Int. Ed. 2007, 46, 1734.
† Lanzhou Institute of Chemical Physics.
‡ Graduate School.
(7) (a) Urata, H.; Ishii, Y.; Fuchikami, T. Tetrahedron Lett. 1989, 30,
4407. (b) Bonnoarie, S. C.; Carpentier, J.; Castanet, Y.; Mortreux, A.
Tetrahedron Lett. 1999, 40, 3717. (c) Ozawa, F.; Kawasaki, N.; Yamatomo,
T.; Yamatoto, A. Chem. Lett. 1985, 567. (d) Ozawa, F.; Kawasaki, N.;
Okamoto, H.; Yamatomo, T.; Yamatomo, A. Organometallics 1987, 6, 1640.
(e) Sakakura, T.; Yamashita, H.; Kobayashi, T.; Hayashi, T.; Tanaka, M.
J. Org. Chem. 1987, 52, 5733. (f) Tanaka, M.; Kobayashi, T.; Sakakura, T.
J. Chem. Soc., Chem. Commun. 1985, 837.
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Goto, T.; Hashimoto, M.; Taga, T. J. Am. Chem. Soc. 1987, 109, 5031. (b)
Fusetani, N.; Matsunaga, S.; Matsumoto, H.; Takebayashi, Y. J. Am. Chem.
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10.1021/ol9001027 CCC: $40.75
Published on Web 02/16/2009
2009 American Chemical Society

Arduengo et al. in 1991, NHCs have emerged as a class of
ligands in metal-mediated reactions due to their strong
σ-donor properties compared with phosphine ligands, thereby
enhancing the stability of NHC complexes toward heat and
moisture.9 This characteristic property is suitable for main-
taining efficient activity in the carbonylation because it is
always carried out under rigorous conditions. Various
catalytic applications for NHC complexes have been involved
recently, including several Pd- or Rh NHC-complex mediated
carbonylation reactions,10-13 but very few nonprecious metal
NHC complexes have been reported for carbonylation
reactions.10f,12,13 We developed an excellent process for the
synthesis of 2-oxazolidinone with good yields and selectivi-
ties catalyzed by a [(NHC)CuI] complex.13 (NHC)Cu
complexes now serve as outstanding catalysts for several
homogeneous reactions and sometimes show unique perfor-
mance.14-17 As a part of our ongoing interest in the
construction of N-containing carbonyl compounds with
carbonylation methods,12,13,18 we report herein a [(NHC)-
CuX]-based (X ) Cl, Br, I) catalytic system together with
imidazolium salts for the double carbonylation of aryl iodides
with secondary amines.
Table 1. Double Carbonylation of Iodobenzene and Morpholine
under Different Conditionsa
entry
catalystb
base
solvent
yieldc
1
2
3
4
5
6
7
8
A
B
C
D
E
F
G
H
E
E
E
E
E
E
E
E
E
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
K3PO4
DABCO
DBU
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
THF
0
57
52
2
93
86
89
71
9
60
10
11
12
13
14
15
16e
17f
49 (16d)
NR
46
86
81
68
41
toluene
CH3CN
1,4-dioxane
1,4-dioxane
82
Iodobenzene and morpholine were chosen as model
substrates in our initial study. Some selected screening results
are summarized in Table 1 with the catalyst and correspond-
ing ligand structures depicted in Figure 1. In general, the
a Reactions were carried out in 5.0 mL of solvent under 3.0-MPa pressure
of CO for 10 h with 1.0 mmol iodobenzene, 4.0 mmol morpholine, 2.0
mmol base, 0.01 mmol IPrCuX with or without 0.02 mmol ligand (for CuI:
b
0.01 mmol CuI and 0.03 mmol ligand). A: CuI; B: CuI + L1; C: CuI +
L2; D: IPrCuI; E: IPrCuI + L1; F: IPrCuI + L2; G: IPrCuCl + L1; H:
IPrCuBr + L1. c Isolated yield. d GC yield of single carbonylation product.
e 80 °C. f 2 MPa of CO.
(9) Arduengo, A. J.; Harlow, R. L.; Kline, M. J. Am. Chem. Soc. 1991,
113, 361.
(10) Reviews and books: (a) Trnka, T. M.; Grubbs, R. H. Acc. Chem.
Res. 2001, 34, 18. (b) Arduengo, A. J. Acc. Chem. Res. 1999, 32, 913. (c)
Herrmann, W. A.; Kocher, C. Angew. Chem., Int. Ed. 1997, 36, 2162. (d)
Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290. (e) D´ıez-Gonza´lez,
S.; Nolan, S. P. Annu. Rep. Prog. Chem., Sect. B 2005, 101, 171. (f)
Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G. Angew Chem., Int. Ed.
2007, 46, 2768. (g) N-Heterocyclic Carbenes in Synthesis; NolanS. P., Ed.;
Wiley-VCH: Weinheim, Germany, 2006. (h) N-Heterocyclic Carbenes in
Transition Metal Catalysis; GloriusF., Ed.; Springer-Verlag: Berlin Heil-
dergerg, Germany, 2007. (i) Veige, A. S. Polyhedron 2008, 27, 3177
.
(11) (a) Okuyama, K.; Sugiyama, J.; Ngahata, R.; Asai, M.; Ueda, M.;
Takeuchi, K. J. Mol. Catal. A: Chem. 2003, 203, 21. (b) Okuyama, K.;
Sugiyama, J.; Ngahata, R.; Asai, M.; Ueda, M.; Takeuchi, K. Green Chem.
2003, 5, 563. (c) Bortenschlager, M.; Schutz, J.; Preysing, D. V.; Nuyken,
O.; Herrmann, W. A.; Weberskirch, R. J. Organomet. Chem. 2005, 690,
6233. (d) Chen, A. C.; Decken, R. L.; Crudden, C. M. Organometallics
2000, 19, 3459. (e) Poyatos, M.; Uriz, P.; Mata, J.; Claver, C.; Fernandez,
Figure 1
the study.
. (NHC)Cu-X complexes and carbene precursors used in
E.; Peris, E. Organometallics 2002, 22, 44
.
(12) (a) Zheng, S. Z.; Peng, X. G.; Liu, J. M.; Sun, W.; Xia, C. G.
use of CuI as the sole catalyst showed no catalytic activity.
Only 2% yield was observed when IPrCuI [IPr ) N,N′-
bis(2,6-diisopropyl-phenyl)imidazol-2-ylidene] was used
as the catalyst. IPrCuI and the NHC precursor IPr·HCl
(ligand L1) made an elegant combination in the double
carbonylation, affording the double carbonylation product
in a 93% yield. The NHC precursor IMes·HCl also
exhibited considerable enhancement, which gave an 86%
yield of double carbonylation product in combination with
IPrCuI complex under identical conditions. The influence
of halogen anions on the (NHC)Cu-X (X ) Cl, Br, I)
complex was further examined in the preparation of
1-morpholino-2-phenyl-ethane-1,2-dione. IPrCuCl and IP-
rCuBr showed less reactivity than that of IPrCuI, giving
the product in 89 and 71% yields, respectively. We also
surveyed the effect of various bases and solvents on the
copper-catalyzed double carbonylation reaction. The choice
Chin. J. Chem. 2007, 25, 1065. (b) Zheng, S. Z.; Peng, X. G.; Liu, J. M.;
Sun, W.; Xia, C. G. HelV. Chim. Acta 2007, 90, 1471
.
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2007, 48, 5883
.
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5, 2417. (b) Laitar, D. S.; Tsui, E. Y.; Sadighi, J. P. J. Am. Chem. Soc.
2006, 128, 11036. (c) Dubinina, G. G.; Furutachi, H.; Vicic, D. A. J. Am.
Chem. Soc. 2008, 130, 8600
.
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2008, 4747. (b) Fructos, M. R.; Belderrain, T. R.; Nicasio, M. C.; Nolan,
S. P.; Kaur, H.; Díaz-Requejo, M. M.; Pe´rez, J. P. J. Am. Chem. Soc. 2004,
126, 10846. (c) Kaur, H.; Zinn, F. K.; Stevens, E. D.; Nolan, S. P.
Organometallics 2004, 23, 1157
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47, 8881. (c) Díez-Gonza´lez, S.; Stevens, E. D.; Scott, N. M.; Petersen,
J. L.; Nolan, S. P. Chem.-Eur. J. 2008, 14, 158. (d) Díez-Gonza´lez, S.;
Scott, N. M.; Nolan, S. P. Organometallics 2006, 25, 2355
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2158. (b) Díez-Gonza´lez, S.; Nolan, S. P. Aldrichim. Acta 2008, 41, 43. (c)
Díez-Gonza´lez, S.; Nolan, S. P. Acc. Chem. Res. 2008, 41, 349
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Lett. 2008, 10, 3933. (b) Liu, J. M.; Peng, X. G.; Liu, J. H.; Zheng, S. Z.;
Sun, W.; Xia, C. G. Tetrahedron Lett. 2007, 48, 929
.
1322
Org. Lett., Vol. 11, No. 6, 2009

The scope of the copper-catalyzed double carbonylation
reaction was explored using 1-2 mol % of IPrCuI, 2-4 mol
% of IPr·HCl ligand, and Cs2CO3 as the base. The reaction of
various aryl iodides and amines are summarized in Table 2.
The scope of the amine components was initially investigated.
The double carbonylation of iodobenzene with morpholine
gave the desired product in high yield, and the reaction with
piperidine, pyrrolidine and diethylamine gave the corresponding
R-keto amides with slightly reduced yields (Table 2, entries
1-4). Aryl iodides possessing an electron-donating group in
the para and ortho positions, such as a methyl and methoxyl
group, gave the double carbonyl products in high yields. When
4-methoxy-1-iodobenzene, 2-methy-1-iodobenzene and 4-ethyl-
1-iodobenzene were employed in the reaction with morpholine
(2a), the desired products were also isolated in reduced yields.
Aryl iodides bearing an electron-withdrawing group such as
chloro, bromo and nitro were well tolerated (Table 2, entries
10, 11, 13). The reaction of 4-acetyl-1-iodobenzene and
morpholine (2a) also afforded the corresponding product in
satisfactory yield (Table 2, entry 12).
Table 2. Scope of NHC-Cu Catalyzed Double Carbonylationa
We were also interested in the possible influence of the
additional NHC precursor on the double carbonylation
reaction. Based on reported work, a bis-carbene copper
complex would be formed if an additional NHC precursor
was introduced to the reaction system.16 The reaction also
occurred with [Cu(IPr)2]BF4 as the sole catalyst; 42% yield
of double carbonylation product was isolated (Figure 2).16
Figure 2. [Cu(IPr)2]BF4 complex.
When the [Cu(IPr)2]BF4 and NaI were employed as catalysts,
the double carbonylation reaction proceeded uneventfully
with nearly quantitative transformation.19 The bis-carbene
copper complex would therefore be the active species.
In conclusion, we developed a highly efficient NHC-Cu-X
based catalyst system for the double carbonylation reaction
of aryl iodides and secondary amines. The new protocol
requires a nonprecious metal, and has greater generality than
those previously reported.
a Reactions were carried out in 5.0 mL of solvent under 3.0-MPa pressure
of CO at 100 °C for 10 h with 1.0 mmol aryl iodides, 4.0 mmol amine, 2.0
mmol Cs2CO3, IPrCuI 0.01 mmol, and IPr·HCl 0.02 mmol. b Isolated yield.
c 130 °C for 10 h. d IPrCuI 0.02 mmol and IPr·HCl 0.04 mmol was used as
catalyst.
This methodology represents a valuable and environmen-
tally benign alternative to the use of toxic phosphine ligands
of base had a more important role than nature of the
catalyst; double carbonylation proceeded best with Cs2CO3
as the base (Table 1, entries 5, 9-12). When K3PO4 was
selected as the base, a single carbonylation product was
formed in a 16% yield (Table 1, entry 10). Among the
solvents tested, 1,4-dioxane was the best choice for the
double carbonylation reaction.
(19) When 1 mol % of [Cu(IPr)2]BF4 was applied to the double
carbonylation of iodobenzene with morpholine, 42% isolated yield of
1-morpholino-2-phenylethane-1,2-dione was obtained. Desired double
carbonylation product was isolated in 93% yield with the use of 10 mol
% of NaI and 1 mol % of [Cu(IPr)2]BF4 as catalyst. (See Supporting
Information).
Org. Lett., Vol. 11, No. 6, 2009
1323

and precious metal palladium catalysts. Further investigations
on the reaction mechanism and utilization of other aryl
halides as substrates are ongoing.
Supporting Information Available: Experimental pro-
cedures for catalyst synthesis and double carbonylation
reaction, spectroscopic data for catalysts and products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. We are grateful for financial support
from the Chinese Academy of Sciences and National Natural
Science Foundation of China (20625308, 20873166).
OL9001027
1324
Org. Lett., Vol. 11, No. 6, 2009