Palladium-catalyzed tandem allylation of 1,2-phenylenediamines with cis-1,4-diacetoxy-2-butene

Article abstract of DOI:10.1016/j.tetlet.2004.04.140

The activation of C-O bonds in cis-1,4-diacetoxy-2-butene has been accelerated by carrying out the reactions in the presence of palladium complexes associated with ligands. Palladium-catalyzed tandem allylation of 1,2-phenylenediamines with cis-1,4-diacet

Full text of DOI:10.1016/j.tetlet.2004.04.140

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 4951–4954
Palladium-catalyzed tandem allylation of 1,2-phenylenediamines
with cis-1,4-diacetoxy-2-butene
Shyh-Chyun Yang,* Pei-Chin Liu and Wei-Hao Feng
Graduate Institute of Pharmaceutical Sciences, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, ROC
Received 2 December 2003; revised 15 April 2004; accepted 16 April 2004
Available online 18 May 2004
Abstract—The activation of C–O bonds in cis-1,4-diacetoxy-2-butene has been accelerated by carrying out the reactions in the
presence of palladium complexes associated with ligands. Palladium-catalyzed tandem allylation of 1,2-phenylenediamines with cis-
1,4-diacetoxy-2-butene leads to 1,2,3,4-tetrahydro-2-vinylquinoxalines in good yields.
Ó 2004 Elsevier Ltd. All rights reserved.
Piperazine derivatives have aroused increasing interest
due to their presence in a large number of therapeuti-
cally and biologically active compounds.1 Numerous
quinoxaline derivatives have been prepared to get bio-
logically active compounds, and the research continues
to synthesize new compounds having unusual skele-
tons.2 Transition metal g3-allyl complexes, as well as
transition metal r-alkyl complexes, play important roles
as active species and key intermediates in many reac-
tions catalyzed by transition metal complexes.3 The
palladium-catalyzed allylation of nucleophiles is an
established, efficient, and highly stereo- and chemo-
selective method, which has been widely applied to
organic chemistry.4 The catalytic cycle requires the for-
mation of the cationic g3-allylpalladium(II) complex, an
intermediate that is generated by oxidative addition of
allylic compounds including allylic halides,5 acetates,6
and carbonates7 to a Pd(0) complex and which can be
attacked by nucleophiles at both termini of the allylic
system. We have used palladium catalyzed for the N-
allylation of aminonaphthalenes8a and for regiospecific
tandem allylation of 2-aminophenols into 3,4-dihydro-2-
vinyl-2H-1,4-benzoxazines.8b The reactions should be
promoted in the presence of titanium reagent. However,
there are few reports on palladium(0)-catalyzed reaction
of bifunctional allylic diacetates and dicarbonates with
nucleophiles featuring their bifunctionality.9 It was
reported by Massacret that (Z)-1,4-bis(methoxycarb-
onyloxy)but-2-ene reacted with unprotected 1,2-phenyl-
enediamine in the presence of a palladium catalyst could
not give 1,2,3,4-tetrahydro-2-vinylquinoxaline directly.10
We now study the tandem allylation of 1,2-phenylene-
diamines with cis-1,4-diacetoxy-2-butene for the con-
struction of 1,2,3,4-tetrahydro-2-vinylquinoxalines. This
is, to our knowledge, the first example of palladium-
catalyzed tandem allylation of 1,2-phenylenediamines
by the use of cis-1,4-diacetoxy-2-butene.
The palladium-catalyzed cyclization of 1,2-phenylene-
diamines with cis-1,4-diacetoxy-2-butene was investi-
gated under various conditions (Scheme 1). When a
mixture of 1,2-phenylenediamine (1a, 2 mmol) and cis-
1,4-diacetoxy-2-butene (2, 1.6 mmol) was heated in the
presence of catalytic amounts of PdCl2(MeCN)2
(0.1 mmol), and PPh3 (0.4 mmol) in benzene (5 mL)
under nitrogen at 50 °C for 3 h, 1,2,3,4-tetrahydro-2-vin-
ylquinoxaline (3a) was formed in 69% yield (entry 1 in
1
Table 1). The H and 13C NMR of NCH appear at d
3.85 and 53.0 ppm for 3a. In the reaction under reflux
for 3 h, the yield of product 3a was increased to 99%
(entry 2).11 The reaction did not occur in the absence of
OAc
H
NH2
NH2
R
R
N
R
R
Pd catalyst
+
N
H
OAc
2
1a, R=H
3a, R=H
b, R=Me
c, R=Cl
b, R=Me
c, R=Cl
* Corresponding author. Fax: +886-7-3210683; e-mail: scyang@
kmu.edu.tw
Scheme 1.
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.04.140

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S.-C. Yang et al. / Tetrahedron Letters 45 (2004) 4951–4954
Table 1. Reaction of 1,2-phenylenediamines (1) with cis-1,4-diacetoxy-2-butene (2)a
Entry
1
Palladium catalyst
Solvent
Yield (%)b of 3
1
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
PdCl2(MeCN)2–PPh3
PdCl2(MeCN)2–PPh3
PdCl2(MeCN)2
Benzenec
Benzene
Benzene
Benzene
Dioxane
Toluene
CH2Cl2
THF
69
99
0
2
3
4
PPh3
0
5
PdCl2(MeCN)2–PPh3
PdCl2(MeCN)2–PPh3
PdCl2(MeCN)2–PPh3
PdCl2(MeCN)2–PPh3
PdCl2(MeCN)2–PPh3
PdCl2(MeCN)2–PPh3
PdCl2(MeCN)2–PPh3
Pd(OAc)2–PPh3
86
83
81
79
68
40
26
88
76
79
78
97
85
95
72
62
87
23
20
98
92
82
88
65
99
67
9
6
7
8
9
MeCN
DMF
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
HMPA
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Pd(OCOCF3)2–PPh3
Pd(acac)2–PPh3
Pd2(dba)3–PPh3
PdCl2–PPh3
PdF6(acac)2–PPh3
PdCl2(PhCN)2–PPh3
Pd(propionate)2–PPh3
Pd(PPh3)4
Pd(PPh3)4–PPh3
PdCl2(MeCN)2–Bu3P
PdCl2(MeCN)2–(2-MePh)3P
PdCl2(MeCN)2–(2-furyl)3P
PdCl2(MeCN)2–(2-pyridyl)Ph2P
PdCl2(MeCN)2–(3-MePh)3P
PdCl2(MeCN)2–(4-MePh)3P
PdCl2(MeCN)2–(4-MeOPh)3P
PdCl2(MeCN)2–(4-FPh)3P
PdCl2(MeCN)2–(4-ClPh)3P
PdCl2(MeCN)2–dppmd
PdCl2(MeCN)2–dppee
PdCl2(MeCN)2–dpppf
PdCl2(MeCN)2–dppbg
PdCl2(MeCN)2–dpphh
PdCl2(MeCN)2–PPh3
PdCl2(MeCN)2–PPh3
18
61
88
90
97
73
a Reaction conditions: 1 (2 mmol), 2 (1.6 mmol), Pd catalyst (0.1 mmol), and ligand (0.4 mmol) in a solvent (5 mL) were refluxed for 3 h.
b Isolated yield was based on 2.
c Stirred at 50 °C.
d Bis(diphenylphosphino)methane.
e 1,2-Bis(diphenylphosphino)ethane.
f 1,3-Bis(diphenylphosphino)propane.
g 1,4-Bis(diphenylphosphino)butane.
h 1,6-Bis(diphenylphosphino)hexane.
the phosphine ligand (entry 3) or palladium catalyst
(entry 4). Eight solvents were investigated, HMPA,
DMF, and MeCN gave worst results while benzene gave
the best results (entries 2 and 5–11). The yield of 3a
decreased as the polarity of the solvent increased. Ten
palladium catalysts were investigated, PdCl2(MeCN)2
(entry 2), Pd(OAc)2 (entry 12), Pd(OCOCF3)2 (entry
13), Pd(acac)2 (entry 14), Pd2(dba)3 (entry 15), PdCl2
(entry 16), PdF6(acac)2 (entry 17), PdCl2(PhCN)2 (entry
18), Pd(propionate)2 (entry 19), and Pd(PPh3)4 (entry
20), with PdCl2(MeCN)2, PdCl2, and PdCl2(PhCN)2
showed the best catalytic activity. Using Pd(PPh3)4 with
extra PPh3 as catalyst increased the yield of products
(entry 21). In the presence of various monodentate
ligands including PPh3 (entry 2), Bu3P (entry 22), (2-
MePh)3P (entry 23), (2-furyl)3P (entry 24), (2-pyr-
idyl)Ph2P (entry 25), (3-MePh)3P (entry 26), (4-MePh)3P
(entry 27), (4-MeOPh)3P (entry 28), (4-FPh)3P (entry
29), and (4-ClPh)3P (entry 30) showed that PPh3, (2-
furyl)3P, (2-pyridyl)Ph2P, and (4-FPh)3P were the most
effective ligands. The bidentate ligand including dppm
(entry 31), dppe (entry 32), and dppp (entry 33)
decreased the yield of products. Dppb (entry 34), and
dpph (entry 35) gave high yields of 3a. Compound 1b
was treated with PdCl2(MeCN)2–PPh3 to give the
cyclized product 3b in 97% yield (entry 36). Similarly,
compound 1c gave 3c in a yield of 73% (entry 37).
We studied the extension of this reaction for the con-
struction of benzo[g]quinoxaline. When a mixture of
2,3-diaminonaphthalene (4, 2 mmol) and cis-1,4-diacet-
oxy-2-butene (2, 1.6 mmol) was refluxed in the presence
of catalytic amounts of PdCl2(MeCN)2 (0.1 mmol) and
PPh3 (0.4 mmol) in benzene (5 mL) under nitrogen for
3 h, 1,2,3,4-tetrahydro-2-vinylbenzo[g]quinoxaline 5 was
1
formed in 96% yield (Scheme 2). The H and 13C NMR

S.-C. Yang et al. / Tetrahedron Letters 45 (2004) 4951–4954
4953
References and notes
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Scheme 3.
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ꢁ
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generated by the reaction of cis-1,4-diacetoxy-2-butene
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In summary, we have prepared 1,2,3,4-tetrahydro-2-vin-
ylquinoxalines in high yields in the presence of a palla-
dium catalyst. This cyclization proceeds through tandem
allylic substitution reaction between 1,2-phenylenedi-
amines and cis-1,4-diacetoxy-2-butene via p-allylpalla-
dium intermediates. The reaction did not occur in the
absence of the phosphine ligand or palladium catalyst.
The yield of products decreased as the polarity of the
solvent increased.
Acknowledgements
We gratefully acknowledge the National Science
Council of the Republic of China for financial support.

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S.-C. Yang et al. / Tetrahedron Letters 45 (2004) 4951–4954
Hayashi, T.; Yamamoto, A.; Ito, Y. Tetrahedron Lett. 1987,
2-butene: A mixture of 1a (162 mg, 2 mmol), 2a (206 mg,
1.6 mmol), PdCl2(MeCN)2 (19 mg, 0.1 mmol), and PPh3
(79 mg, 0.4 mmol) in refluxing benzene (5 mL) under
nitrogen for 3 h. After cooling, the reaction mixture was
filtered through Celite and the solvent was distilled under
reduced pressure. The residue was purified by chromato-
graphy on silica gel (n-hexane/EtOAc, 3:1) to give the
cyclized product 3a.
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allylation of 1,2-phenylenediamines with cis-1,4-diacetoxy-