Palladium-catalyzed cross-coupling of aryl or vinyl iodides with ethyl diazoacetate

Article abstract of DOI:10.1021/ja073010+

Pd(PPh₃)₄-catalyzed reaction between aryl or vinyl iodides and ethyl diazoacetate (EDA) leads to the formation of cross-coupling products in good yields. Copyright

Full text of DOI:10.1021/ja073010+

Published on Web 06/23/2007
Palladium-Catalyzed Cross-Coupling of Aryl or Vinyl Iodides with Ethyl
Diazoacetate
Cheng Peng, Jiajia Cheng, and Jianbo Wang*
Beijing National Laboratory of Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and
Molecular Engineering of Ministry of Education, College of Chemistry, Peking UniVersity, Beijing 100871, China
Received April 30, 2007; E-mail: wangjb@pku.edu.cn
Palladium catalyzed cross-coupling reaction has been developed
into one of the most powerful methods for the formation of C-C
bonds.1 Recently, remarkable progress has been made in the Pd-
catalyzed cross-coupling reactions with carbon nucleophiles derived
from active methylene compounds,1d ketones,2 esters,3 amides,4 and
nitriles.5 Hydrazones have also been applied in this type of reactions
as acyl anion nucleophiles.6 In connection with our interest in the
chemistry of diazo compounds as nucleophiles,7 we have conceived
that R-diazocarbonyl compounds, which are commonly used as
carbene precursors,8 may be utilized as carbon nucleophiles in Pd-
catalyzed coupling reactions. Diazo carbon bears a partial negative
charge and thus has considerable nucleophilicity;9 however, to the
best of our knowledge, diazo compounds have not been directly
used as partners in Pd-catalyzed cross-coupling reactions.10 This
may be attributed to the general belief that diazo decomposition
should occur readily upon complexation with transition metals.8,11
Herein we report that ethyl diazoacetate (EDA) undergoes efficient
Pd-catalyzed cross-coupling with aryl or vinyl iodides. Moreover,
carbonylation occurs prior to the coupling if the reaction is carried
out under an atmosphere of CO.
Table 1. Pd-Catalyzed Cross-Coupling of Iodide 1a with EDA
entry
catalyst (mol %)
solvent
base
yield (%)a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16d
17
18
Pd(OAc)2 (2.5)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MeCN
DMF
Me2C)O Et3N
Et2O
MeOH
DMSO
MeCN
MeCN
MeCN
Et3N
b
b
Pd2(dba)3 (2.5)
PdCl2(PPh3)2 (2.5)
Pd(PPh3)4 (2.5)
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
27
41
62
70
66
79
47
40
40
26
c
Et3N
Et3N
Et3N
Cs2CO3
K2CO3
DBU
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
c
Pd(PPh3)4 (5)/n-Bu4NBr
Pd2(dba)3 (2.5)/dppb (5)/n-Bu4NBr
Me2C)O Et3N
Me2C)O Et3N
86
11
trace
c
Pd2(dba)3 (2.5)/tBu3P (5)/n-Bu4NBr Me2C)O Et3N
n-Bu4NBre
Me2C)O Et3N
An initial attempt to couple EDA with ethyl (Z)-3-iodopropenoate
(1a) using Et3N as base and Pd(OAc)2 as catalyst in CH2Cl2 resulted
in rapid diazo decomposition (Table 1, entry 1). Pd2(dba)3 also
decomposed EDA (entry 2). To our delight, with PdCl2(PPh3)2 the
reaction afforded cross-coupling product, albeit in low yield (entry
3). The yield could be slightly improved by Pd(PPh3)4 (entry 4).
Other reaction parameters were then screened with this catalyst.
Increasing the catalyst loading could further improve the yield (entry
5). The reaction seemed more favored in polar solvents such as
MeCN, DMF, and acetone, but MeOH and DMSO resulted in
diminished yields (entries 10, 11). Inorganic bases of Cs2CO3, K2-
CO3 were found unsuitable in this reaction (entries 12, 13). The
introduction of 1 equiv of n-Bu4NBr as additive significantly
improved the reaction (entry 15).12 However, Pd(0) catalyst
containing more electron-rich phosphine ligands were found not
effective in this reaction (entries 16, 17).
a Isolated yield. b Diazo decomposition occurred rapidly to give a
complex mixture. c 2a was not detected. d dppb ) 1,4-bis(diphenylphos-
phino)butane. e No Pd catalyst.
Table 2. Pd(PPh3)4-Catalyzed Cross-Coupling of Vinyl Iodides
1a-f with EDAa
Moreover, it was noteworthy that without Pd(0) catalyst no
coupling product could be observed (entry 18). This experiment
rules out the possibility of a conjugate addition-elimination
mechanism for the formation of 2a.13
A series of vinyl iodides were then subjected to the optimized
reaction conditions (Table 1, entry 15). The reaction gave cross-
coupling products in moderate to good yields (Table 2). The strong
electron-withdrawing substituent at the double bond was found
necessary for this reaction since the reaction with â-iodo styrene
gave no cross-coupling product. Besides, it was noted that the
reaction proceeded with retention of configuration at the double
bond.
a Reaction conditions: 1 (1 equiv), EDA (2.5 equiv), Et3N (1.5 equiv),
n-Bu4NBr (1equiv), Pd(PPh3)4 (5 mol %), in acetone at 35 °C. b Isolated
yield after column chromatography.
Next we conceived to extend the coupling reaction to aryl halides.
However, when the above reaction conditions were applied to
iodobenzene, the expected cross-coupling product was not obtained.
After screening the reaction conditions, we found that by replacing
Et3N with DBU, the above optimized conditions could be success-
fully applied to the coupling reaction with aryl iodides (Table 3).
9
8708
J. AM. CHEM. SOC. 2007, 129, 8708-8709
10.1021/ja073010+ CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Table 3. Pd(PPh3)4-Catalyzed Cross-Coupling Reaction of Aryl
Scheme 1. Mechanistic Rationale
Halides with EDA
entry
halide (3, ArX)
reacn time (h)
4, yield (%)a
1
2
3
4
5
3a, C6H5I
12
14
11
5
5
8
13
8
17
72
72
24
10
4a, 80
4b, 77
4c, 75
4d, 74
4e, 80
4f, 75
4g, 76
4h, 96
4i, 39
4j, trace
4k, trace
4a, trace
4h, 19
3b, p-CH3C6H4I
3c, m-CH3C6H4I
3d, p-ClC6H4I
3e, p-BrC6H4I
6
3f, 3,5-Br2C6H3I
3g, p-CH3O2CC6H4I
3h, p-NO2C6H4I
3i, p-CH3OC6H4I
3j, o-ClC6H4I
3k, o-BrC6H4,I
3l, C6H5Br
7
8b
9
which is a very facile process for transition metal-complexed diazo
compounds,8,11 does not occur from complex B. Finally reductive
elimination of the intermediate C gives the cross-coupling product
and regenerates the catalyst. In the presence of CO, prior to the
reaction with EDA the CO insertion occurs from intermediate A
to afford D, from which reaction with EDA/Et3N followed by
reductive elimination leads to â-keto R-diazocarbonyl compounds
(path c).
10
11
12
13b
3m, p-NO2C6H4Br
a Isolated yield after column chromatography. b Reaction run using 5 mol
% Pd(PPh3)4 and 1.5 equiv of Et3N.
In summary, R-diazocarbonyl compound has been utilized for
the first time as cross-coupling partner in Pd-catalyzed reaction.
The reaction provides a novel approach to introduce diazo
functionality to organic compounds.
Table 4. Pd(PPh3)4-Catalyzed Carbonylation of CO with Iodides
and EDA
Acknowledgment. The project is generously supported by
NSFC (No. 20225205, 20390050) and the Ministry of Education
of China (Cheung Kong Scholars Program).
entry
iodide (3, Ar)
reacn time (h)
5, yield (%)a
Supporting Information Available: Experiment procedure and
characterization data for all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
1
2
3
4
5
6
7
3a, C6H5
11
12
12
13
24
11
11
5a, 62
5b, 66
5c, 43
5d, 51
5e, trace
5f, 60
3b, p-CH3C6H4
3c, m-CH3C6H4
3e, p-BrC6H4
3j, o-ClC6H4
3n, 1-naphthyl
3o, trans-PhCH)CH
References
5g, 59
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a Isolated yield after column chromatography.
The reaction occurred smoothly with meta and para substituted aryl
iodides to afford the corresponding aryl diazoacetate. The contrast-
ing results obtained with p-NO2 and p-MeO substituted substrates
indicated significant influence of electronic effects on the reaction
(entries 8, 9). On the other hand, the reactions with ortho substituted
aryl iodides failed to afford the corresponding coupling products,
which revealed that the reaction was also affected by steric
hindrance (entries 10, 11). It was also noted that aryl bromides
were less reactive in this reaction (entries 12, 13).
(2) (a) Palucki, M.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 11108.
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Encouraged by the results with vinyl and aryl iodides, we further
investigated the carbonylation with CO in this cross-coupling
process. After optimizing the reaction conditions, we found that
Et3N was the suitable base for this purpose. Typical results are
summarized in Table 4. The carbonylation followed by cross-
coupling afforded â-keto R-diazocarbonyl compounds in moderate
yields. The slightly diminished yields as compared with direct
coupling reaction were attributed to the decreased reactivity of the
catalyst under this condition, which resulted in long reaction time
and incomplete reaction. Again, ortho substituted aryl iodide
afforded only trace amount of coupling product (entry 5).
The reaction mechanism for this reaction is shown in Scheme
1. Oxidative addition of Pd(0)Ln with aryl or vinyl iodide affords
the Pd(II) intermediate A. Substitution of the iodo by diazo anion,
which is derived from deprotonation of EDA, provides the
intermediate C (path a). Alternatively, EDA coordinates to Pd(II)
intermediate A to form complex B, from which proton is removed
by base to afford C (path b).14 Remarkably, nitrogen extrusion,
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