Palladium-catalyzed reaction of allyl halides with α-diazocarbonyl compounds

Article abstract of DOI:10.1039/b806970k

The Pd(OAc)₂-catalyzed reaction between α-diazocarbonyl compounds and allyl bromides or chlorides leads to the formation of 1,3-diene derivatives. The Royal Society of Chemistry.

Full text of DOI:10.1039/b806970k

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Palladium-catalyzed reaction of allyl halides with a-diazocarbonyl
compoundsw
Shufeng Chen and Jianbo Wang*
Received (in Cambridge, UK) 24th April 2008, Accepted 20th May 2008
First published as an Advance Article on the web 4th July 2008
DOI: 10.1039/b806970k
The Pd(OAc)2-catalyzed reaction between a-diazocarbonyl
compounds and allyl bromides or chlorides leads to the forma-
tion of 1,3-diene derivatives.
next examined. Bases such as K2CO3, Cs2CO3 and KOAc also
led to the formation of diene 2a in moderate yields (entries
11–13). However, no diene 2a was detected when the organic
base DBU was used (entry 14). The reaction under this
condition resulted in a complex mixture. Finally, in the
absence of base, no reaction occurred and the starting material
was recovered unchanged (entry 15).
p-Allylic palladium complexes are important intermediates in
palladium-catalyzed reactions.1 The p-allylic palladium com-
plexes are electrophilic in character and react with various
nucleophiles, such as amines, alcohols, and carbon nucleo-
philes. These Pd-catalyzed allylation reactions have found
wide applications in organic synthesis. In particular, the
reactions with carbon nucleophiles have developed into a
valuable method for the formation of C–C bonds. The com-
mon carbon nucleophiles used in Pd-catalyzed allylation in-
clude anions or enolates derived from carbonyl compounds
such as ketones, esters, and 1,3-dicarbonyl compounds.2 In
connection to our recent interest in the palladium-catalyzed
reaction of diazo compounds,3,4 we have conceived that it may
be possible to use a-diazocarbonyl compounds as nucleophiles
in the reaction of p-allylic palladium complexes. In this
communication we report the palladium-catalyzed reaction
of allylic halides with aryldiazoacetates and aryldiazoacetones,
in which carbon double bonds are generated to afford
1,3-diene products (Scheme 1).
The optimized reaction conditions were then applied to a
range of aryldiazoacetates and aryldiazoacetones 1a–n
(Table 2). Various substitutions on the aromatic ring could
be tolerated, and moderate to good yields of the products 2a–n
were obtained. The stereoselectivity of the products was gen-
erally high. Moreover, it was noted that the ester moiety of the
diazo compounds did not affect the reaction (entries 13, 14). It
was also observed that diazo compounds other than aryldia-
zoacetates or aryldiazoacetones afforded the diene products in
rather lower yields. The reaction with ethyl diazoacetate under
identical conditions resulted in complex mixture.
Next, we examined the scope of allyl substrates. When the
substituted allyl bromide was subjected to the above reaction
with methyl phenyldiazoacetate 1a, the reaction led to a low
yield of the expected diene products. However, we were de-
lighted to find that when the substituted allyl chloride was used,
the reaction proceeded smoothly under the identical reaction
conditions. As shown in Table 3, for a series of substituted allyl
chlorides 3a–h, the reaction gave the 1,3-diene products in
moderate to good yields. It was noted that the allyl chlorides
worked well with either alkyl or aryl substituents.
At the outset of this investigation, various Pd(0) and Pd(II)
complexes were examined as the catalysts in the reaction of allyl
bromide with methyl phenyldiazoacetate 1a (Table 1). Two
Pd(0) catalysts, Ph(PPh3)4 and Pd2(dba)3, were examined with
Et3N as base and MeCN as solvent. Ph(PPh3)4 was found to be
not effective and the starting materials remained unchanged at
25 1C (entry 1). Pd2(dba)3 led to the formation of 1,3-diene 2a in
45% yield (entry 2). Among four Pd(II) catalysts examined,
Pd(PPh3)2Cl2 was found to be not effective, while PdCl2,
Pd(PhCN)2Cl2 and Pd(OAc)2 all gave 2a in low to moderate
yields (entries 3–6). The highest yield, of 77%, was obtained
with Pd(OAc)2 (entry 6). Rh2(OAc)4, CuOTf and CuI were
examined under the similar reaction conditions and the reac-
tions were found to lead to a complex mixture (entries 7–9).
For comparison, the reaction was carried out in the absence
of transition metal catalyst. No reaction occurred under such
conditions (entry 10). After Pd(OAc)2 was identified as the
most efficient catalyst, the effect of base on this reaction was
It should be mentioned that the formation of 4a–k can not be
attributed to ylide [2,3]-sigmatropic rearrangement–elimination
mechanism.5 Moreover, the same 1,3-diene product 2a can be
obtained under the identical conditions from the reaction of allyl
carbonate 5 or allyl acetate 6 with methyl phenyldiazoacetate 1a,
albeit in low yields (Scheme 2).
Three plausible reaction pathways to account for the forma-
tion of dienes are considered as shown in Scheme 3. In all cases,
the reaction is initiated by the reduction of Pd(II) to Pd(0) by the
diazo compound, followed by the formation of p-allylpalladium
complex A. In path a, the diazo substrate attacks the allyl ligand
Beijing National Laboratory of Molecular Sciences (BNLMS) and
Key Laboratory of Bioorganic Chemistry and Molecular Engineering
of Ministry of Education, College of Chemistry, Peking University,
Beijing100871, China
w Electronic supplementary information (ESI) available: Experimen-
tal. See DOI: 10.1039/b806970k
Scheme 1 Pd-catalyzed reaction of allyl halides with diazo compounds.
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Table 1 Transition metal-catalyzed reaction of allyl bromide with
methyl phenyldiazoacetate 1aa
Table 2 Pd(OAc)2-catalyzed reaction of allyl bromide with diazo
compounds 1a–n
Entry
Cat. (mol%)
Base
Time/h
Yield (%)b
Entry 1, Ar, R
Time/h 2, Yield (%)a E : Z
1
2
3
4
5
6
7
8
Pd(PPh3)4 (5)
Pd2(dba)3 (5)
PdCl2(PPh3)2 (5)
PdCl2 (5)
Pd(PhCN)2Cl2 (5)
Pd(OAc)2 (5)
Rh2(OAc)4 (0.5)
CuOTf (10)
CuI (10)
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
K2CO3
Cs2CO3
KOAc
DBU
None
12
24
24
19
20
12
11
24
24
24
12
1
0 (38)c
45
1
1a, C6H5, OMe
12
12
4
17
7
12
22
8
20
4
2a, 77
2b, 77
2c, 53
2d, 71
2e, 61
2f, 73
2g, 50
2h, 55
2i, 68
2j, 70
2k, 63
2l, 60
2m, 77
2n, 69
420 : 1
5 : 1
420 : 1
5 : 1
10 : 1
0 (54)c
32
55
2
3
4
5
1b, p-CH3C6H4, OMe
1c, p-CH3OC6H4, OMe
1d, m-CH3OC6H4, OMe
1e, o-ClC6H4, OMe
1f, p-ClC6H4, OMe
1g, m, p-Cl2C6H3, OMe
1h, C6H5, Me
77
0d
6
10 : 1
10 : 1
0d
7
8c
9c
420 : 1
420 : 1
420 : 1
420 : 1
420 : 1
420 : 1
420 : 1
9
0d
N.R.e
61
1i, p-ClC6H4, Me
10
11
12
13
14
15
None
10cd 1j, m-ClC6H4, Me
11cd 1k, p-BrC6H4, Me
12cd 1l, m,p-Cl2C6H3, Me
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
48f
55
4
4
4
5
9
24
24
13
14
a
1m, C6H5, O(C6H4o-O-allyl)
1n, C6H5, O(C6H5)2CH
0
N.R.e
b
a
Yield of isolated product after chromatography. Ratio was
Reactions were carried out with 0.3 mmol of allyl bromide,
b
0.42 mmol of 1a, and 0.9 mmol of Et3N. Yield of the isolated
determined by GC-MS and 1H NMR of the crude product. Reac-
tion run with 1 eq. of diazo compound and 3 eq. of allyl bromide.
c
c
d
product after chromatography. The reaction was run at 50 1C. The
reaction gave a complex mixture. N.R.: no reaction, starting materi-
f
als were recovered. Starting materials disappeared after 1 h.
d
e
Reaction was carried out at 60 1C.
the a-diazocarbonyl compounds are categorized as ‘‘soft’’
nucleophiles, which will attack the allyl ligand. However, since
the strong coordination ability of the diazo group toward
transition metals, nucleophilic attack of the diazo substrate to
palladium can not be strictly ruled out. In such case, inter-
mediate C is generated, followed by reductive elimination to
offer diazonium intermediate B and to regenerate Pd(0) catalyst
(path b). The third possible pathway is the generation of a
palladium carbene species D from C (path c). Z3–Z1 Interconver-
sion leads to the Z1-allylpalladium complex E, from which
migratory insertion3b,6 occurs to afford intermediate F.
b-Hydride elimination from F gives the diene product. Further
extensive investigations will be required to distinguish these
possible pathways.
to afford intermediate B with the regeneration of Pd(0). Sub-
sequent deprotonation and dinitrogen extrusion led to the
formation of the 1,3-diene product. In the chemistry of the
p-allylpalladium complex, it has been suggested that ‘‘soft’’
carbon centered nucleophiles, defined as those derived from
conjugate acids whose pKa o 25, usually attack the allyl ligand.
On the contrary, ‘‘hard’’ carbon-centered nucleophiles, defined
as those derived from conjugate acids whose pKa 4 25, attach
themselves to the metal center of the p-allyl palladium complex,
and the substitution occurs through subsequent transmetalla-
tion and reductive elimination.1d The pKa values of the con-
jugate acids of diazoesters and diazoketones have been
estimated to be between À5 and À2, respectively.4a Therefore,
Table 3 Pd(OAc)2-catalyzed reaction of allyl chlorides 3a–h with phenyldiazoacetates 1a, m–p
Entry
3, R1, R2
1, R
Time/h
Yield (%)a
E : Zb
1
2
3
4
5
6
7
8
3a, H, H
3b, CH3, H
3c, CH3, CH3
1a, Me
1a, Me
1a, Me
1a, Me
1a, Me
1a, Me
1a, Me
1a, Me
12
11
1
2
4
14
3
15
16
16
7
2a, 74
4a, 63
4b, 72
4c, 71
4d, 66
4e, 57
4f, 65
4g, 65
4h, 70
4i, 60
4j, 58
4k, 51
420 : 1
10 : 1
420 : 1
420 : 1
420 : 1
420 : 1
420 : 1
420 : 1
420 : 1
420 : 1
420 : 1
420 : 1
3d, –C5H10
–
3e, C6H5, H
3f, p-CH3C6H4,H
3g, p-ClC6H4, H
3h, C6H5, C6H5
3e, C6H5, H
3e, C6H5, H
3e, C6H5, H
3e, C6H5, H
b
9
1m, o-Allyl-O-C6H4
1n, (C6H5)2CH
1o, trans-C6H5CHQCHCH2
1p, CH2QCHCH2
10
11
12
a
3
1
Yield of isolated product. The ratio of E and Z isomers was estimated by GC-MS and H NMR (300 MHz) of the crude product.
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Notes and references
1 (a) For reviews, see: J. Tsuji, Palladium Reagents and Catalysts,
John Wiley & Sons, Chichester, 1995, pp. 290–422; (b) B. M. Trost
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Trost and M. L. Crawley, Chem. Rev., 2003, 103, 2921–2944; (d) J.
Tsuji, Palladium Reagents and Catalysts, New Perspectives for the
21st Century, 2nd edn, John Wiley & Sons, Chichester, 2004; (e) Y.
Nishibayashi and S. Uemura, in Comprehensive Organometallic
Chemistry III, ed. R. H. Crabtree and D. M. Mingos, Elsevier Ltd.,
Oxford, 2007, pp. 75–116.
Scheme 2 The reaction of allyl carbonate 5 and acetate 6 with methyl
phenyldiazoacetate 1a.
2 For recent examples of reaction of carbon nucleophile with p-
allylic palladium complex, see: (a) B. M. Trost and J. Xu, J. Am.
Chem. Soc., 2005, 127, 17180–17181; (b) B. M. Trost, R. N. Bream
and J. Xu, Angew. Chem., Int. Ed., 2006, 45, 3109–3112; (c) P.
Fristrup, T. Jensen, J. Hoppe and P.-O. Norrby, Chem.–Eur. J.,
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Tremblay and J.-F. Paquin, J. Am. Chem. Soc., 2007, 129,
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Reichle, J. Am. Chem. Soc., 2007, 129, 282–283; (i) W.-H. Zheng,
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4 For comprehensive reviews, see: (a) M. P. Doyle, M. A. McKervey
and T. Ye, Modern Catalytic Methods for Organic Synthesis with
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Scheme 3 Possible reaction pathways.
In conclusion, a novel CQC double bond forming reaction
between allyl halides and a-diazocarbonyl compounds was
developed by using Pd(OAc)2 as the catalyst under mild
conditions. Further investigation on related Pd-catalyzed re-
actions of diazo compounds are ongoing in our laboratory.
The project is supported by NSFC (Grant No. 20572002,
20521202, 20772003) and the MOE of China (Cheung Kong
Scholars Program).
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4200 | Chem. Commun., 2008, 4198–4200