Ring-opening bis(alkoxycarbonylation) reaction of methylenecyclopropanes catalyzed by palladium in the presence of copper(I) salt

Article abstract of DOI:10.1246/cl.2009.46

A palladium-catalyzed ring-opening bis(alkoxycarbonylation) reaction of methylenecyclopropanes in the presence of copper(I) salt was achieved under normal pressure of carbon monoxide and oxygen to give the corresponding α-methyleneglutarates. Copyright

Full text of DOI:10.1246/cl.2009.46

46
Chemistry Letters Vol.38, No.1 (2009)
Ring-opening Bis(alkoxycarbonylation) Reaction of Methylenecyclopropanes
Catalyzed by Palladium in the Presence of Copper(I) Salt
Takahiro Aratani, Yutaka Ukaji,Ã and Katsuhiko InomataÃ
Division of Material Sciences, Graduate School of Natural Science and Technology,
Kanazawa University, Kakuma, Kanazawa 920-1192
(Received September 29, 2008; CL-080931; E-mail: inomata@cacheibm.s.kanazawa-u.ac.jp)
A palladium-catalyzed ring-opening bis(alkoxycarbonyla-
Table 1. Bis(alkoxycarbonylation) reaction of 1a
tion) reaction of methylenecyclopropanes in the presence of cop-
per(I) salt was achieved under normal pressure of carbon monox-
ide and oxygen to give the corresponding ꢀ-methylenegluta-
rates.
PdCl (0.02 equiv)
2
Cu salt (m equiv)
CO Me
2
CO Me
CO/O (ca. 1/1)
2
in THF/MeOH (n/1, v/v)
2
1a
2a
Temp, t h
Entry
Cu salt
m
n
Temp t/h Yield/% E/Za
Carbonylation is an important reaction in organic synthesis
to provide efficient entries to a variety of useful homologated
carbonyl compounds.1 We have reported the selective mono-
and bis(alkoxycarbonylation) reactions of terminal olefins cata-
lyzed by palladium in the presence of copper salts under normal
pressure of carbon monoxide and oxygen. Furthermore, ꢁ-buty-
rolactones and ꢁ-butyrolactams were prepared from homoallylic
alcohols and amine derivatives under the similar conditions, re-
spectively.2,3 Bis(alkoxycarbonylation) reaction of olefins gen-
erally affords succinate derivatives.2–5 In order to prepare gluta-
rate derivatives via a direct introduction of two carbonyl groups,
the bis(alkoxycarbonylation) reaction2 of cyclopropylbenzene
was carried out. However, the desired glutarate derivatives were
not detected. Among the cyclopropane derivatives, methylene-
cyclopropanes are versatile building blocks in organic synthesis
due to unique chemical reactivity derived from ring strain to un-
dergo a variety of ring-opening reactions. Further attractive fea-
ture of them is their surprising stability.6 Herein we describe a
ring-opening bis(alkoxycarbonylation) reaction of methylene-
cyclopropanes catalyzed by palladium in the presence of CuCl
under remarkably mild conditions to afford the corresponding
ꢀ-methyleneglutarates.7
1
2b
3
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
—
1.5
1.5
1.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.1
0.05
—
0
0
0
0
0
0
0
1
1
2
2
5
0
0
0
0
0
0
rt
rt
rt
rt
rt
rt
2
24
2
2
14
14
61
ndc
62
60
75
72
48
78
68
71
43
34
52
24
ndc
11
5
85/15
—
85/15
86/14
86/14
84/16
90/10
89/11
93/7
91/9
93/7
91/9
85/15
86/14
—
85/15
84/16
85/15
4
5
6d
7
0 ꢀC 48
8
9
rt
0 ꢀC 48
rt 24
0 ꢀC 48
rt
rt
rt
rt
rt
rt
rt
14
10
11
12
13
14
15
16
17
48
14
36
24
18
48
20
CuBr
CuI
1.5
1.5
18 CuOTf(C6H6)0:5 0.5
72
aThe ratios were determined by 400 MHz 1H NMR spectra. bThe
reaction was carried out without PdCl2. cThe signal of product 2a
was not detected in the 1H NMR spectrum of a mixture of the
crude products. dEtOH was used instead of MeOH and the ethyl
ester corresponding to 2a was obtained.
First, the bis(alkoxycarbonylation) reaction of benzylidene-
cyclopropane (1a) was carried out in the presence of a 0.02 equiv
of PdCl2 and 1.5 equiv of CuCl under normal pressure of carbon
monoxide and oxygen in MeOH at rt; the desired carbonylated
product, a 85/15 mixture of dimethyl (E)- and (Z)-ꢀ-benzyli-
deneglutarate (2a), was obtained in 61% yield (Table 1, Entry 1).
It was confirmed that in the absence of PdCl2 or CuCl, the glu-
tarate 2a was not formed, respectively (Entries 2 and 15). Other
copper salts CuBr and CuI were less effective than CuCl (Entries
1, 16, and 17), and CuOTf(C6H6)0:5 showed similar reactivity
(Entries 5 and 18). The reaction proceeded smoothly even when
the amount of CuCl was reduced, especially with 0.5 equiv of
CuCl (Entries 1, 3–5, 13, and 14). Bis(ethoxycarbonylation) re-
action also proceeded when EtOH was used as a solvent instead
of MeOH (Entry 6). By addition of THF as a cosolvent (Entries
5, 8, 10, and 12) and/or lowering the reaction temperature
(Entries 7, 9, and 11), E/Z ratio was slightly enhanced although
the reaction was retarded. When the reaction was carried out at
0 ꢀC in THF/MeOH (1/1, v/v), (E)-glutarate 2a was selectively
obtained in 68% yield with the E/Z ratio of 93/7 (Entry 9).
Various methylenecyclopropanes 1 were subjected to bis(al-
koxycarbonylation) reaction in MeOH at rt (Conditions A) or in
THF/MeOH (1/1, v/v) at 0 ꢀC (Conditions B). As shown in
Table 2, the corresponding two carbon-homologated glutarates
2 were obtained in good chemical yields.8–10 Benzylidenecyclo-
propanes 1a–1d furnished (E)-ꢀ-benzylideneglutarates 2a–2d
selectively (Entries 1–6). Alkylidenecyclopropanes 1e and 1f
afforded the ꢀ-alkylideneglutarates in good chemical yields
(Entries 7–9). In the reaction of (cyclohexylmethylidene)cyclo-
propane (1f), (Z)-2f was mainly produced. When the carbonyla-
tion was carried out in THF/MeOH at 0 ꢀC, production of (E)-2f
was slightly increased. Bis(alkoxycarbonylation) reaction of
tetrasubstituted olefinic substrates 1g–1k also proceeded to give
tetrasubstituted olefins 2g–2k in good chemical yields (Entries
10–15). In contrast to 1a, (ꢀ-methylbenzylidene)cyclopropane
(1g) gave (Z)-2g preferentially (Entries 1 and 10, 2 and 11).
Although the precise mechanism of the present ring-opening
bis(alkoxycarbonylation) reaction is still an open question, two
possible pathways are shown in Scheme 1. The carbopalladation
of a double bond in 1 with (methoxycarbonyl)palladium inter-
Copyright Ó 2009 The Chemical Society of Japan

Chemistry Letters Vol.38, No.1 (2009)
47
Table 2. Bis(alkoxycarbonylation) reaction of 1
As described above, bis(alkoxycarbonylation) reaction to-
ward methylenecyclopropanes was realized by utilizing palladi-
um and copper salt under remarkably mild conditions to afford
the corresponding ꢀ-methyleneglutarates in good yields. It is
noteworthy that (E)-olefins 2a–2d were selectively produced
by the reaction of mono-aromatic-substituted substrates 1a–1d,
whereas (Z)-olefins 2g–2i were obtained from tetrasubstituted
olefinic substrates 1g–1i. Further studies are now in progress
in our laboratory.
2
2
R
R
PdCl (0.02 equiv)
2
CO Me
CuCl (0.5 equiv)
2
1
1
R
R
CO/O (ca. 1/1), t h
2
CO Me
2
1
2
Conditions A; in MeOH, rt
Conditions B; in THF/MeOH (1/1, v/v), 0 °C
Entry
1
Conditions t/h Yield/% E/Za
1
2
A
B
14
48
75
68
86/14
93/7
a
The present work was financially supported in part by a
Grant-in-Aid for Scientific Research on Priority Areas ‘‘Ad-
vanced Molecular Transformations of Carbon Resources’’ from
The Ministry of Education, Culture, Sports, Science and Tech-
nology (MEXT).
3
4
b
c
A
A
14
14
94
80
80/20
89/11
O N
2
MeO
References and Notes
1
H. M. Colquhoun, D. J. Thompson, M. V. Twigg, Carbonylation, Plenum
Press, New York, 1991; Catalytic Carbonylation Reactions, ed. by M.
Beller, Springer, Berlin, 2006.
5
6
A
B
34
72
95
29
90/10
92/8
d
n
2
K. Inomata, S. Toda, H. Kinoshita, Chem. Lett. 1990, 1567; S. Toda, M.
Miyamoto, H. Kinoshita, K. Inomata, Bull. Chem. Soc. Jpn. 1991, 64,
3600; T. Mizutani, Y. Ukaji, K. Inomata, Bull. Chem. Soc. Jpn. 2003, 76,
1251.
Enantioselective version of the bis(alkoxycarbonylation) reaction: Y. Ukaji,
M. Miyamoto, M. Mikuni, S. Takeuchi, K. Inomata, Bull. Chem. Soc. Jpn.
1996, 69, 735; S. Takeuchi, Y. Ukaji, K. Inomata, Bull. Chem. Soc. Jpn.
2001, 74, 955; T. Aratani, K. Tahara, S. Takeuchi, Y. Ukaji, K. Inomata,
Chem. Lett. 2007, 36, 1328.
a) D. E. James, J. K. Stille, J. Am. Chem. Soc. 1976, 98, 1810. b) Y. Tamaru,
M. Hojo, Z. Yoshida, J. Org. Chem. 1991, 56, 1099. c) T. Yokota, S.
Sakaguchi, Y. Ishii, J. Org. Chem. 2002, 67, 5005.
Bis(alkoxycarbonylation) reaction of 2-methyl-1-alkenes was reported to
produce glutarates in low yield: see ref. 4a.
a) A. Brandi, A. Goti, Chem. Rev. 1998, 98, 589. b) I. Nakamura, Y.
Yamamoto, Adv. Synth. Catal. 2002, 344, 111. c) A. Brandi, S. Cicchi,
F. M. Cordero, A. Goti, Chem. Rev. 2003, 103, 1213. d) M. Rubin, M.
Rubina, V. Gevorgyan, Chem. Rev. 2007, 107, 3117. e) N. Hayashi, Y.
Hirokawa, I. Shibata, M. Yasuda, A. Baba, J. Am. Chem. Soc. 2008, 130,
2912.
C
H
11 23
7
e
f
A
14
75
48/52
8
9
A
B
20
48
78
55
12/88
37/63
3
4
A
B
14
48
88
57
17/83
14/86
10
11
g
12
h
A
14
91
17/83
5
6
n
C H
13
14
i
A
A
14
14
91
73
16/84
6
13
j

7
8
Palladium-catalyzed ring-opening copolymerization of methylenecyclopro-
panes with CO was recently reported: S. Kim, D. Takeuchi, K. Osakada,
J. Am. Chem. Soc. 2002, 124, 762; D. Takeuchi, A. Yasuda, T. Okada, J.
Kuwabara, K. Osakada, K. Tomooka, Helv. Chim. Acta 2006, 89, 1574.
A representative procedure for the bis(alkoxycarbonylation) reaction of 1a
(Table 2, Entry 2): Under an Ar atmosphere, PdCl2 (1.90 mg, 0.011 mmol),
CuCl (25 mg, 0.25 mmol) was placed in a flask and a MeOH (2 mL) solution
of 1a (64 mg, 0.49 mmol) and THF (2 mL) were added. The Ar atmosphere
was replaced with CO/O2 (ca. 1/1, v/v) and the reaction mixture was stirred
for 48 h at 0 ꢀC. A saturated aqueous solution of NaHCO3 was added and the
insoluble substance was filtered off. After the filtrate was extracted with eth-
yl acetate, the combined extracts were washed with water and brine, dried
over Na2SO4, and condensed in vacuo. The residue was purified by TLC
on silica gel to give 2a (83 mg, 68%, E/Z = 93/7).
15
k
A
72
55

aThe ratios were determined by 400 MHz H NMR spectra.
1
2
2
2
XPd
R
R
R
1
1
R
R
1
CO Me
2
R
CO Me
2
1
2
R
9
The stereochemistry of double bond in 2 was determined by NOE measure-
ment. Representative data were shown below:
XPd
R
XPd
or
6
4
R
CO Me
1
2
XPd
2
2
R
CO Me
3
2
2a; 2.9%
2e; 3.2%
2f; 3.2%
PdX
CO Me
2
H
CH
HH
3
HH
1
1
R
R
or
2
2g; 4.1%
2i; 4.3%
(E = CO Me)
CO Me
PdX
2
5
6
R
R
E
E
E
E
2
Scheme 1.
10 Methylenecyclopropanes with less sterically hindered trisubstituted olefinic
moiety were not stable enough under the reaction conditions. For example in
the case of 1a, the small amount of unidentified by-products were observed
in the crude 1H NMR spectrum. However, a succinate derivative derived
from direct carbonyl insertion of 4a and a product such as methyl 5-phen-
yl-3,4-pentadienoate or methyl 3-phenyl-2-vinylacrylate, which could be
generated from 5a or 6a via ꢂ-hydrogen elimination, were not detected at
least.
11 The palladium-catalyzed reaction mechanism via addition–elimination vs.
the direct cleavage of cyclopropane C–C bond was discussed. See: M.
Suginome, T. Matsuda, Y. Ito, J. Am. Chem. Soc. 2000, 122, 11015 and
ref. 6b.
mediate 3, formed in the presence of CuCl, gives 4,2 which un-
dergoes ring-opening cis- or trans-ꢂ-carbon elimination fol-
lowed by the second carbonylation.7 Another pathway via a
cleavage of proximal cyclopropane C–C bond, probably through
oxidative addition of 3, giving intermediate 5 or 6 could not be
ruled out. The stereochemistry of the double bonds in the prod-
ucts 2, however, could not be elucidated well yet even by both
mechanisms.11
Published on the web (Advance View) December 6, 2008; doi:10.1246/cl.2009.46