A nBuLi-mediated, expeditious and stereoselective ring-opening rearrangement of (arylmethylene)cyclopropane-1,1-dicarboxylates

Article abstract of DOI:10.1002/ejoc.200901165

We report herein an nBuLi-mediated, expeditious, ring-opening rearrangement of (arylmethylene)cyclopropane 1,1-diesters to prepare 1,3-diene derivatives with good stereo-selectivity. The reaction mechanism has also been discussed.

Full text of DOI:10.1002/ejoc.200901165

FULL PAPER
DOI: 10.1002/ejoc.200901165
A nBuLi-Mediated, Expeditious and Stereoselective Ring-Opening
Rearrangement of (Arylmethylene)cyclopropane-1,1-dicarboxylates
Bao Hu,[a] Linan Jiang,[a] Jun Ren,[a] and Zhongwen Wang*[a]
Keywords: Small ring systems / Strained molecules / Rearrangement / Ring opening / 1,3-Dienes / Methylenecyclopropane
We report herein an nBuLi-mediated, expeditious, ring-
opening rearrangement of (arylmethylene)cyclopropane 1,1-
diesters to prepare 1,3-diene derivatives with good stereo-
selectivity. The reaction mechanism has also been discussed.
The most commonly used methods for functionalization of
MCPs at C-3 are reactions of MCPs and various electro-
Introduction
Methylenecyclopropanes (MCPs), a group of highly philes with nBuLi as the base (Scheme 2).[4]
strained molecules, have received much attention due to
their ready availability[1] and good reactivity.[2] Recently, we
reported a hetero [3+3] cycloaddition[3a] and a tandem ring-
opening/intramolecular Friedel–Crafts reaction of MCP
1,1-diesters under the catalysis of Lewis acids
(Scheme 1).[3b] It has been shown that being further acti-
vated by two geminal ester groups on the sp3-hybridized
carbon of the strained three-membered carbocycle, acti-
vated MCPs displayed different chemistry from that of non-
activated MCPs. In order to continue our investigations, we
needed C3-functionalized analogues of MCP 1,1-diesters.
Scheme 2. Functionalization of the sp3-hybridized MCP carbon
atom by carbolithiation.
When we applied this method on phenyl MCP 1,1-diester
1a, instead of the anticipated C3-functionalized product, we
observed a ring-opening rearrangement leading to 1,3-diene
2a (Scheme 3). In this paper, we wish to report our recent
results.
Scheme 3. Ring-opening rearrangement of phenyl MCP 1,1-diester
1a leading to 1,3-diene 2a.
Results and Discussion
Scheme 1. Hetero [3+3] cycloaddition and tandem ring-opening/
intramolecular Friedel–Crafts reaction of MCP 1,1-diesters.
Initially, we treated a solution of MCP 1a in THF with
nBuLi (0.5 equiv.) at –90 °C, and obtained the ring-opening
product 2a in 22% yield together with nucleophilic substitu-
tion product 3a (12% yield, Table 1, Entry 1). We note that
the stereoselectivity of the ring-opening rearrangement was
excellent, and (4Z)-1,3-diene isomer 2a formed exclusively.
[a] State Key Laboratory of Elemento-Organic Chemistry, Institute
of Elemento-Organic Chemistry, Nankai University,
Tianjin 300071, P. R. China
E-mail: wzwrj@nankai.edu.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200901165.
We established the structure of 2a by H and 13C NMR
1
1358
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 1358–1363

Ring-Opening Rearrangement of (Arylmethylene)cyclopropanes
spectroscopy and HRMS. We prepared (4E)-1,3-diene iso- that other solvents gave inferior yields (Table 1, Entries 15
mer 2aЈ by the reported method[5] for further confirmation and 16). We conducted the reaction in hexane at room tem-
of the structure of 2a. We then optimized the reaction con- perature due to the poor solubility of MCP 1a in hexane
ditions. The results in Table 1 show that the reaction pro- below 25 °C (Table 1, Entry 16). Finally, we selected THF
ceeded rapidly to afford 2a in 69% yield after being treated for further investigation.
with 1.5 equiv. of 1.72  nBuLi (Table 1, Entry 8). We fur-
With the optimized reaction conditions in hand, we next
ther improved the yield to 72% when we used 2.1  nBuLi probed the scope of the ring-opening rearrangement using
(Table 1, Entry 9). We note that the concentration of the a variety of MCP 1,1-diesters (Table 2). All of the MCP
reaction had a dramatic effect on the yield of 2a (Table 1, 1,1-diesters were (E) isomers except 1c, 1l and 1m. We ob-
Entries 8, 11 and 12). When we submitted a 0.06  solution served no obvious relationship between the (E/Z) ratios of
of 1a to identical conditions, we only obtained product 2a the starting material and the product (Table 2, Entry 3).
in 22% yield together with 3a (18%) and small amounts of The reactions of halogenated, phenyl-substituted MCP 1,1-
several other unidentified side products (Table 1, Entry 11), diesters (Table 2, Entries 2–6) afforded 2 in moderate yields.
which probably resulted from the increased ratio of con- The reaction of p-tolyl-substituted MCP 1,1-diester
taminants in solvent to the reactants. A higher concentra- (Table 2, Entry 7) also succeeded; however, p-MeO-phenyl-
tion of 1a slightly decreased the yield of 2a (59%, Table 1, substituted MCP 1,1-diester 1h (Table 2, Entry 8) gave a
Entry 12). Subsequently, we examined the effect of various complex result. We hypothesize that the reactivity was re-
strong bases (Table 1, Entries 2, 3 and 17–20) and found lated to the regioselectivity of carbolithiation (Scheme 5).
that, except lithium diisopropylamide (LDA, Table 1, Entry We note that the halogen-lithium exchange occurred in the
19), other bases such as tBuOK, NaH, sBuLi, tBuLi and reaction of MCP 1b (13%, Table 2, Entry 2).[6] In all suc-
LiHMDS were ineffective. Further investigation indicated cessful cases, the (4Z) selectivities for the formation of 1,3-
Table 1. Optimization of conditions for the ring-opening rearrangement of MCP 1,1-diester 1a.[a]
Entry
Base
Solvent
T [°C]
Time [h]
Conversion [%][b] Yield of 2a [%][c,m]
1
2
3
4
5
6
7
8
nBuLi (0.5 equiv.)
tBuOK (1.4 equiv.)
NaH (1.0 equiv.)
nBuLi (0.3 equiv.)
nBuLi (0.8 equiv.)
nBuLi (1.0 equiv.)
nBuLi (1.2 equiv.)
nBuLi (1.5 equiv.)
nBuLi (1.5 equiv.)
nBuLi (1.8 equiv.)
nBuLi (1.5 equiv.)
nBuLi (1.5 equiv.)
nBuLi (1.5 equiv.)
nBuLi (1.5 equiv.)
nBuLi (1.5 equiv.)
nBuLi (1.5 equiv.)
sBuLi (1.5 equiv.)
tBuLi (1.5 equiv.)
LDA (1.5 equiv.)
LiHMDS (1.5 equiv.)
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
Et2O
hexane
THF
THF
THF
THF
–90
66
66
–90
–90
–90
–90
–90
–90
–90
–90
–90
–90
–90
–90
1
26
2
61
10
0
22
0
NR[d]
16
0.05
0.25
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.25
0.05
12
29
100
100
100
100
100
100
100
100
100
100
100
100
84
28
27
36
69
72
63
22
59
68
27
24
trace
Ͻ10
9
61
0
9[e]
10
11[f]
12[g]
13[h]
14[i]
15
16
17[j]
18[k]
19[h]
20[l]
room temp.
–90 to room temp.
–90
–90
0
0.05
0.10
4
24
100
30
[a] Reaction conditions: 1a (0.10  solution in the indicated solvent, 0.50 mmol) was added to nBuLi (1.72  in hexane) in 2.0 mL of the
same solvent over 15 min under a N2 atmosphere. [b] Determined by 1H NMR after purification. [c] Isolated yield. [d] No reaction
occurred. [e] nBuLi (2.10  in hexane). [f] 0.06  solution of 1a in THF. [g] 0.25  solution of 1a in THF. [h] 1a was added to the indicated
base. [i] 100 mg of molecular sieves (3 Å) were added. [j] sBuLi (1.3  in hexane). [k] tBuLi (1.7  in pentane). [l] LiHMDS (1.0  in
hexane). [m] When nBuLi was used as the base, 3a was also observed as a byproduct in most cases.
Eur. J. Org. Chem. 2010, 1358–1363
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1359

B. Hu, L. Jiang, J. Ren, Z. Wang
FULL PAPER
Table 2. nBuLi-mediated, ring-opening rearrangement of MCP 1,1-diesters 1.[a]
Entry
MCP 1
R1
R2
(E/Z) ratio of 1[c]
Product 2
Yield [%][b]
(Z/E) ratio of 2[c]
1
1a
1b
1c
1d
1e
1f
Me
Me
Me
Me
Me
Me
Me
Me
Et
iPr
Bn
Me
Me
C6H5
100:0
100:0
65:35
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
67:33
70:30
2a
72
44
Ͼ20:1
Ͼ20:1
77:23
Ͼ20:1
81:19
93:7
88:12
–
87:13
88:12
Ͼ20:1
–
2[d,e]
3[d]
4[d]
5[d]
6[d]
7
4-BrC6H4
2-BrC6H4
4-ClC6H4
3-ClC6H4
4-FC6H4
4-MeC6H4
4-MeOC6H4
C6H5
C6H5
C6H5
Bn
n-C7H15
2b
2c/2cЈ
2d
2e/2eЈ
2f
2g/2gЈ
2h
35[f]
58
44[f]
59[f]
46[f]
complex
29[f]
60[f]
53
1g
1h
1i
8
9
10
11
12
13
2i/2iЈ
2j
1j
1k
1l
2k
2l
Ͻ5
0
1m
2m
–
[a] Reaction conditions: 1a (0.10  solution in THF, 0.50 mmol) was added to nBuLi (2.10  in hexane) in 2.0 mL of THF under a N2
1
atmosphere. [b] Isolated yield after silica gel chromatography. [c] The (E/Z) [or (Z/E)] ratio was determined on the basis of the H NMR
spectroscopic data. [d] 0.30 mmol scale. [e] 2a was also obtained in 13% yield. [f] The total yield is given for a mixture of two diastereomers.
dienes were good to excellent [(Z/E) = 77:23 to Ͼ20:1]. The (E)-DЈ. The selective formation of (4Z) isomer 2 could be
reactions of alkyl-substituted MCP 1,1-diesters 1l and 1m explained by the more favorable electrophilic attack of lith-
failed (Table 2, Entries 12 and 13).
ium from the direction of less steric hindrance. This stereo-
In contrast to the MCP 1,1-diesters, when we treated chemistry is also well in accordance with the results from
MCP 1,1-keto ester 1n with nBuLi for 1 h under the above allenes reported by Xu and coworkers[8a] and Ma and co-
conditions, instead of the rearrangement process, a ring- workers.[8b] Attempts to trap the anionic intermediates (A,
opening cycloisomerization happened, from which we ob- B, C, D or DЈ) with aldehydes[9a] or deuterated reagents
tained furan 4 in 35% yield (Scheme 4).
(DCl, CF3CO2D or D2O)[9b] failed, probably due to the ra-
pidity of the reaction,[9b] to afford the active vinyl anion,
which was then protonated either by the intermolecular
shift of the allylic hydrogen in MCP 1 or by other proton
sources in the reaction mixture (e.g. contaminants in the
solvent and reagent) prior to the addition of the electro-
philes. At present, we do not have enough experimental evi-
dence to prove if the reaction proceeds in a catalytic manner
or not. The treatment of MCP 1,1-keto ester 1n with nBuLi
afforded enolate F, which then cycloisomerized to interme-
diate G. We obtained furan 4 after isomerization and pro-
tonation. A similar process promoted by PdCl2/NaI was re-
ported by Ma and coworkers.[10] Further investigations on
the mechanism are still needed.
Scheme 4. nBuLi-promoted, ring-opening/cycloisomerization of
MCP 1,1-keto ester 1n.
A plausible mechanism for the formation of 1,3-diene 2,
2Ј and furan 4 is illustrated in Scheme 5. Initially, cyclopro-
pyl carbanion A was generated upon deprotonation of
MCP 1 with nBuLi. Due to the electron-withdrawing acti-
vation of the two germinal ester groups, proximal bond
cleavage of the three-membered ring via an allylic anion (A
Conclusions
In conclusion, we have disclosed an nBuLi-mediated, ex-
or B) afforded allenoate anion C. Shi and coworkers re- peditious and stereoselective reaction of aryl-MCP 1,1-dies-
ported a similar result on vinylidenecyclopropane.[7] A 1,5- ters. This provides a protocol for the synthesis of 1,3-dienes,
shift of lithium afforded a vinyl anion existing as (Z)-D or although the yields are moderate.
1360
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 1358–1363

Ring-Opening Rearrangement of (Arylmethylene)cyclopropanes
Scheme 5. A plausible mechanism for the formation of 1,3-dienes 2 and 2Ј and furan 4.
ArCH=C), 3.77 (s, 3.89 H, OCH3), 3.73 (s, 2.11 H OCH3), 2.51 (d,
Experimental Section
J = 2.8 Hz, 1.30 H, CH2, cyclopropane), 2.29 (t, J = 2.8 Hz, 0.70
H, CH2, cyclopropane) ppm. 13C NMR (CDCl3, 100 MHz): δ =
168.0, 167.6, 134.9, 134.2, 133.2, 133.0, 129.5, 127.9, 127.8, 127.7,
127.4, 125.0, 124.2, 123.9, 119.1, 119.0, 53.0, 41.1, 32.7, 31.2, 19.1,
General Remarks: MCPs 1 were prepared according to the litera-
ture procedure.[3,11] All NMR spectra were recorded with a spec-
trometer at 400 MHz (1H NMR) and 100 MHz (13C NMR) in
CDCl3. The chemical shifts are reported in ppm referenced to
CDCl3 (δ = 7.26 ppm) for 1H NMR and relative to the central
CDCl3 resonance (δ = 77.0 ppm) for 13C NMR spectroscopy. Col-
umn chromatography was performed on silica gel (100–200 or 200–
300 mesh) using petroleum ether and EtOAc as eluent. Thin layer
chromatography (TLC) was performed on Merck silica gel GF254
plates and visualized by UV light (254 nm). Melting points were
uncorrected. All solvents were purified and dried using standard
procedures.
16.7 ppm. IR (KBr): ν = 2953, 2927, 1732, 1436, 1310, 1282, 1257,
˜
1107, 1024, 756 cm–1. HRMS (ESI): calcd. for C14H13BrO4Na [M
+ Na]+ 346.9889; found 346.9889.
(E)-Dimethyl 2-(3-Chlorobenzylidene)cyclopropane-1,1-dicarboxyl-
ate (1e): Yield 2.69 g, 48%, a single (E) isomer, pale yellow solid,
m.p. 43–45 °C. 1H NMR (CDCl3, 400 MHz): δ = 7.49 (s, 1 H, Ar),
7.36 (d, J = 7.2 Hz, 1 H, Ar), 7.32–7.23 (m, 2 H, Ar), 6.88 (t, J =
2.4 Hz, 1 H, ArCH=C), 3.76 (s, 6 H, 2 OCH3), 2.51 (d, J = 2.4 Hz,
2 H, CH2, cyclopropane) ppm. 13C NMR (CDCl3, 100 MHz): δ =
167.9, 137.4, 134.6, 129.9, 128.1, 127.1, 125.7, 124.0, 119.1, 52.9,
30.1, 19.2 ppm. IR (KBr): ν˜ = 3062, 3003, 2954, 2846, 1735, 1435,
1311, 1265, 1107, 888, 786, 683 cm–1. HRMS (ESI): calcd. for
A Typical Experimental Procedure for the Formation of (4Z)-1,3-
Diene (2a): Under a N2 atmosphere, to MCP 1a (123 mg,
0.50 mmol) in THF (5.0 mL) was slowly added nBuLi (0.36 mL,
0.75 mmol, 2.1  in hexane) in THF (2.0 mL) at –90 °C over ap- C14H13ClO4Na [M + Na]+ 303.0395; found 303.0394.
proximately 15 min, and the mixture was stirred at the same tem-
(E)-Dibenzyl 2-Benzylidenecyclopropane-1,1-dicarboxylate (1k):
Yield 2.07 g, 26%, a single (E) isomer, yellow liquid. 1H NMR
(CDCl3, 400 MHz): δ = 7.53 (d, J = 7.0 Hz, 2 H, Ar), 7.36–7.32
(m, 13 H, Ar), 6.99 (t, J = 2.4 Hz, 1 H, PhCH=C), 5.22 (s, 2 H,
OCH2Ph), 5.21 (s, 2 H, OCH2Ph), 2.57 (d, J = 2.4 Hz, 2 H, CH2,
cyclopropane) ppm. 13C NMR (CDCl3, 100 MHz): δ = 167.6,
135.5, 128.7, 128.5, 128.4, 128.3, 128.0, 127.5, 126.2, 122.5, 120.6,
perature for a further 3 min. The reaction was then quenched by
the addition of aqueous ammonium chloride and warmed to room
temperature. The solution was extracted with Et2O (3ϫ10 mL),
and the combined organic layers were washed with water and dried
with anhydrous MgSO4. The solvent was removed under reduced
pressure, and the residue was purified by column chromatography
(EtOAc/petroleum ether, 1:20) to give 2a [89 mg, 72% yield, single
(Z) isomer] as a yellow liquid. 1H NMR (CDCl3, 400 MHz): δ =
7.83 (d, J = 12.0 Hz, 1 H, PhCH=CHCH), 7.45–7.28 (m, 5 H, Ar),
7.03 (d, J = 11.2 Hz, 1 H, PhCH=CH), 6.65 (t, J = 12.0 Hz, 1 H,
PhCH=CHCH), 3.89 (s, 3 H, OCH3), 3.79 (s, 3 H, OCH3) ppm.
13C NMR (CDCl3, 100 MHz): δ = 165.8, 165.0, 141.9, 140.8, 135.7,
67.4, 30.5, 19.4 ppm. IR (thin film): ν = 3064, 3033, 2956, 1732,
˜
1455, 1294, 1266, 1101, 750, 696 cm–1. HRMS (ESI): calcd. for
C26H22O4Na [M + Na]+ 421.1410; found 421.1416.
(E)-Dimethyl 2-(3-Phenylallylidene)malonate (2aЈ):[5,12] Yield 1.28 g,
52%, yellow solid, m.p. 63–64 (lit. 66–68 °C). 1H NMR (CDCl3,
400 MHz): δ = 7.57 (d, J = 11.6 Hz, 1 H, PhCH=CHCH), 7.54–
7.47 (m, 2 H, Ar), 7.42–7.32 (m, 3 H, Ar), 7.27 (dd, J = 11.6,
15.2 Hz, 1 H, PhCH=CHCH), 7.06 (d, J = 15.2 Hz, 1 H,
PhCH=CH), 3.09 (s, 3 H, OCH3), 3.82 (s, 3 H, OCH3) ppm. 13C
129.6, 128.8, 128.6, 126.6, 124.0, 52.5, 52.4 ppm. IR (thin film): ν
˜
= 2953, 1720, 1618, 1436, 1251, 1220, 1104, 1057 cm–1. HRMS
(ESI): calcd. for C14H14O4Na [M + Na]+ 269.0784; found 269.0791.
Dimethyl
2-(2-Bromobenzylidene)cyclopropane-1,1-dicarboxylate NMR (CDCl3, 100 MHz): δ = 165.7, 165.2, 146.2, 145.2, 135.5,
(1c): Yield 1.97 g, 40%, a mixture of stereoisomers, (E/Z) = 65:35,
130.0, 128.9, 127.9, 124.0, 123.3, 52.4, 52.4 ppm. IR (KBr): ν =
˜
pale yellow solid, m.p. 58–60 °C. 1H NMR (CDCl3, 400 MHz): δ 2951, 1716, 1613, 1435, 1309, 1284, 1242, 1213, 1151, 1063, 752
= 7.76–7.66 (m, 1 H, Ar), 7.59–7.53 (m, 1 H, Ar), 7.38–7.33 (m, cm–1. HRMS (ESI): calcd. for C14H14O4Na [M + Na]+ 269.0784;
0.62 H, Ar), 7.31–7.27 (m, 1.38 H, Ar), 7.15–7.09 (m, 1 H, found 269.0788.
Eur. J. Org. Chem. 2010, 1358–1363
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1361

B. Hu, L. Jiang, J. Ren, Z. Wang
FULL PAPER
(Z)-Dimethyl 2-[3-(4-Bromophenyl)allylidene]malonate (2b): Yield
1220, 1102, 1057 cm–1. HRMS (ESI): calcd. for C15H16O4Na [M +
1
44 mg, 44%, colorless oil. H NMR (CDCl3, 400 MHz): δ = 7.72 Na]+ 283.0941; found 283.0947.
(d, J = 12.0 Hz, 1 H, PhCH=CHCH), 7.53 (d, J = 8.4 Hz, 2 H,
Diethyl 2-(3-Phenylallylidene)malonate (2i, 2iЈ): Yield 40 mg, 29%,
Ar), 7.18 (d, J = 8.4 Hz, 2 H, Ar), 6.93 (d, J = 11.2 Hz, 1 H,
PhCH=CH), 6.66 (t, J = 11.6 Hz, 1 H, PhCH=CHCH), 3.88 (s, 3
H, OCH3), 3.79 (s, 3 H, OCH3) ppm. 13C NMR (CDCl3,
100 MHz): δ = 165.6, 164.9, 140.3, 140.1, 134.5, 131.9, 131.0, 127.1,
slightly yellow liquid, a mixture of isomers [(Z/E) = 87:13]; data
1
for the major isomer: H NMR (CDCl3, 400 MHz): δ = 7.81 (d, J
= 12.4 Hz, 1 H, PhCH=CHCH), 7.44–7.30 (m, 5 H, Ar), 7.00 (d,
J = 11.2 Hz, 1 H, PhCH=CH), 6.65 (t, J = 11.6 Hz, 1 H,
PhCH=CHCH), 4.36 (q, J = 7.2 Hz, 2 H, OCH2CH3), 4.24 (q, J
= 7.2 Hz, 2 H, OCH2CH3), 1.36 (t, J = 7.2 Hz, 3 H, OCH2CH3),
1.28 (t, J = 7.2 Hz, 3 H, OCH2CH3) ppm. 13C NMR (CDCl3,
100 MHz): δ = 165.4, 164.6, 141.4, 139.9, 135.7, 129.6, 128.7, 128.6,
124.6, 123.1, 52.6, 52.5 ppm. IR (thin film): ν = 2953, 1731, 1619,
˜
1436, 1255, 1221, 1072, 1056 cm–1. HRMS (ESI): calcd. for
C14H13BrO4Na [M + Na]+ 346.9889; Found: 346.9896.
Dimethyl 2-[3-(2-Bromophenyl)allylidene]malonate (2c, 2cЈ): Yield
34 mg, 35%, yellow liquid, a mixture of isomers [(Z/E) = 77:23];
127.5, 124.0, 61.4, 61.3, 14.2, 14.1 ppm. IR (thin film): ν = 2982,
˜
1
1716, 1619, 1373, 1245, 1152, 1098, 1056, 1024 cm–1. HRMS (ESI):
calcd. for C16H18O4Na [M + Na]+ 297.1097; found 297.1103.
data for the major isomer: H NMR (CDCl3, 400 MHz): δ = 7.83
(dd, J = 12.0, 0.8 Hz, 1 H, PhCH=CHCH), 7.41–7.30 (m, 4 H,
Ar), 7.03 (d, J = 10.8 Hz, 1 H, PhCH=CH), 6.65 (t, J = 12.0 Hz,
1 H, PhCH=CHCH), 3.89 (s, 3 H, OCH3), 3.79 (s, 3 H, OCH3)
ppm. 13C NMR (CDCl3, 100 MHz): δ = 165.8, 165.0, 141.9, 140.8,
135.7, 129.6, 128.9, 128.8, 128.6, 127.9, 124.0, 52.5, 52.4 ppm. IR
Diisopropyl 2-(3-Phenylallylidene)malonate (2j, 2jЈ): Yield 109 mg,
60%, slightly yellow liquid, a mixture of isomers [(Z/E) = 88:12];
1
data for the major isomer: H NMR (CDCl3, 400 MHz): δ = 7.75
(thin film): ν = 2953, 1720, 1618, 1436, 1251, 1221, 1058 cm–1.
(d, J = 12.0 Hz, 1 H, PhCH=CHCH), 7.38–7.27 (m, 5 H, Ar),
6.95 (d, J = 11.6 Hz, 1 H, PhCH=CH), 6.61 (t, J = 11.6 Hz, 1 H,
PhCH=CHCH), 5.27–5.17 (m, 1 H, CH3CHCH3), 5.13–5.02 (m, 1
H, CH3CHCH3), 1.32 (d, J = 6.0 Hz, 6 H, CH3CHCH3), 1.24 (d,
J = 6.4 Hz, 6 H, CH3CHCH3) ppm. 13C NMR (CDCl3, 100 MHz):
δ = 164.0, 163.1, 139.9, 138.1, 134.7, 128.5, 127.6, 127.5, 122.9,
˜
HRMS (ESI): calcd. for C14H13BrO4Na [M + Na]+ 346.9889;
found 346.9886.
(Z)-Dimethyl 2-[3-(4-Chlorophenyl)allylidene]malonate (2d): Yield
1
49 mg, 58%, yellow liquid. H NMR (CDCl3, 400 MHz): δ = 7.73
(d, J = 12.0 Hz, 1 H, PhCH=CHCH), 7.37 (d, J = 8.4 Hz, 2 H,
Ar), 7.24 (d, J = 8.4 Hz, 2 H, Ar), 6.95 (d, J = 11.6 Hz, 1 H,
PhCH=CH), 6.65 (t, J = 11.6 Hz, 1 H, PhCH=CHCH), 3.88 (s, 3
H, OCH3), 3.79 (s, 3 H, OCH3) ppm. 13C NMR (CDCl3,
100 MHz): δ = 165.6, 164.9, 140.3, 140.1, 134.8, 134.1, 130.8, 128.9,
67.9, 67.8, 20.7 ppm. IR (thin film): ν = 2981, 1716, 1621, 1374,
˜
1258, 1218, 1182, 1145, 1108, 1045 cm–1. HRMS (ESI): calcd. for
C18H22O4Na [M + Na]+ 325.1415; found 325.1410.
(Z)-Dibenzyl 2-(3-Phenylallylidene)malonate (2k): Yield 91 mg,
1
127.1, 124.5, 52.5, 52.5 ppm. IR (thin film): ν = 2953, 1720, 1619,
˜
53%, yellow liquid, H NMR (CDCl3, 400 MHz): δ = 7.87 (d, J =
1437, 1254, 1220, 1091, 1055 cm–1. HRMS (ESI): calcd. for
C14H13ClO4Na [M + Na]+ 303.0395; found 303.0303.
12.0 Hz, 1 H, PhCH=CHCH), 7.40–7.23 (m, 15 H, Ar), 6.95 (d, J
= 11.6 Hz, 1 H, PhCH=CH), 6.65 (t, J = 11.6 Hz, 1 H,
PhCH=CHCH), 5.27 (s, 2 H, OCH2Ph), 5.17 (s, 2 H, OCH2Ph)
ppm. 13C NMR (CDCl3, 100 MHz): δ = 165.1, 164.4, 142.2, 141.6,
135.7, 135.5, 129.7, 128.9, 128.7, 128.6, 128.4, 128.2, 128.0, 126.5,
Dimethyl 2-[3-(3-Chlorophenyl)allylidene]malonate (2e, 2eЈ): Yield
37 mg, 44%, yellow liquid, a mixture of isomers [(Z/E) = 81:19];
1
data for the major isomer: H NMR (CDCl3, 400 MHz): δ = 7.73
124.0, 67.3, 67.0 ppm. IR (thin film): ν = 3064, 3033, 2957, 1716,
˜
(d, J = 12.4 Hz, 1 H, PhCH=CHCH), 7.35–7.28 (m, 3 H, Ar),
7.22–7.16 (m, 1 H, Ar), 6.94 (d, J = 11.2 Hz, 1 H, PhCH=CH),
6.68 (t, J = 11.6 Hz, 1 H, PhCH=CHCH), 3.89 (s, 3 H, OCH3),
3.80 (s, 3 H, OCH3) ppm. 13C NMR (CDCl3, 100 MHz): δ = 165.6,
164.8, 139.9, 139.8, 137.3, 134.6, 129.9, 129.3, 128.8, 127.6, 125.1,
1616, 1455, 1236, 1105, 1050, 747, 697 cm–1. HRMS (ESI): calcd.
for C26H22O4Na [M + Na]+ 421.1410; found 421.1408.
(E)-Methyl 2-Benzylidene-1-pentanoylcyclopropanecarboxylate (3a):
1
Yield 16 mg, 12%, colorless liquid. H NMR (CDCl3, 400 MHz):
52.6, 52.5 ppm. IR (thin film): ν = 2953, 1724, 1620, 1436, 1253,
˜
δ = 7.50 (d, J = 8.0 Hz, 2 H, Ar), 7.36 (t, J = 7.6 Hz, 2 H, Ar),
7.28 (d, J = 7.6 Hz, 1 H, Ar), 6.84 (s, 1 H, PhCH=C), 3.74 (s, 3 H,
OCH3), 2.86–2.74 (m, 1 H, COCH2CH2CH3), 2.70–2.58 (m, 1 H,
COCH2CH2CH3), 2.54 (d, J = 9.6 Hz, 1 H, CH2, cyclopropane),
2.45 (d, J = 9.6 Hz, 1 H, CH2, cyclopropane), 1.65–1.56 (m, 2 H,
COCH2CH2CH3), 1.38–1.28 (m, 2 H, COCH2CH2CH3), 0.91 (t, J
= 7.2 Hz, 3 H, COCH2CH2CH3) ppm. 13C NMR (CDCl3,
100 MHz): δ = 202.2, 169.5, 135.6, 128.7, 128.2, 127.4, 123.8, 119.3,
1221, 1057 cm–1. HRMS (ESI): calcd. for C14H13ClO4Na [M +
Na]+ 303.0395; found 303.0395.
(Z)-Dimethyl 2-[3-(4-Fluorophenyl)allylidene]malonate (2f): Yield
1
53 mg, 59%, yellow liquid. H NMR (CDCl3, 400 MHz): δ = 7.75
(d, J = 12.0 Hz, 1 H, PhCH=CHCH), 7.35–7.23 (m, 2 H, Ar), 7.08
(t, J = 8.4 Hz, 2 H, Ar), 6.96 (d, J = 11.2 Hz, 1 H, PhCH=CH),
6.63 (t, J = 11.6 Hz, 1 H, PhCH=CHCH), 3.88 (s, 3 H, OCH3),
3.78 (s, 3 H, OCH3) ppm. 13C NMR (CDCl3, 100 MHz): δ = 165.7,
164.9, 164.2, 161.7, 140.5, 140.3, 131.8, 131.8, 131.4, 131.3, 126.8,
52.6, 40.3, 37.4, 26.1, 22.2, 18.5, 13.9 ppm. IR (thin film): ν = 2957,
˜
2933, 2873, 1728, 1454, 1436, 1290, 1263, 1201, 1129, 1109, 753,
694 cm–1. HRMS (ESI): calcd. for C17H20O3Na [M + Na]+
295.1310; found 295.1304.
123.9, 115.9, 115.6, 52.5, 52.4 ppm. IR (thin film): ν = 2955, 1731,
˜
1619, 1594, 1508, 1437, 1251, 1158, 1106, 1058 cm–1. HRMS (ESI):
calcd. for C14H13FO4Na [M + Na]+ 287.0690; found 287.0698.
Ethyl 4-Benzyl-2-methylfuran-3-carboxylate (4): Yield 28 mg, 35%,
Dimethyl 2-(3-p-Tolylallylidene)malonate (2g, 2gЈ): Yield 60 mg, yellow liquid. 1H NMR (CDCl3, 400 MHz): δ = 7.31 (t, J = 7.2 Hz,
46%, slightly yellow liquid, a mixture of isomers [(Z/E) = 88:12];
data for the major isomer: H NMR (CDCl3, 400 MHz): δ = 7.84
(d, J = 12.0 Hz, 1 H, PhCH=CHCH), 7.26–7.16 (m, 4 H, Ar),
6.98 (d, J = 11.6 Hz, 1 H, PhCH=CH), 6.59 (t, J = 11.6 Hz, 1 H,
2 H, Ar), 7.23 (t, J = 7.2 Hz, 3 H, Ar), 6.24 (s, 1 H, CH-furan),
4.25 (q, J = 7.2 Hz, 2 H, OCH2CH3), 3.89 (s, 2 H, PhCH2C), 2.52
(s, 3 H, CCH3), 1.31 (t, J = 7.2 Hz, 3 H, OCH2CH3) ppm. 13C
NMR (CDCl3, 100 MHz): δ = 164.3, 158.3, 152.4, 137.5, 128.7,
1
PhCH=CHCH), 3.87 (s, 3 H, OCH3), 3.77 (s, 3 H, OCH3), 2.36 (s, 128.6, 126.7, 114.0, 107.0, 60.0, 34.2, 14.4, 13.8 ppm. IR (thin film):
3 H, PhCH3) ppm. 13C NMR (CDCl3, 100 MHz): δ = 165.8, 165.1, ν = 2980, 2959, 2929, 1716, 1583, 1286, 1217, 1081, 778, 700 cm–1.
˜
142.0, 141.2, 139.0, 132.9, 129.6, 129.4, 127.9, 126.1, 123.3, 52.4,
52.4, 21.3 ppm. IR (thin film): ν = 2953, 1720, 1617, 1436, 1251,
HRMS (ESI): calcd. for C15H16O3Na [M + Na]+ 267.0992; found
267.0996.
˜
1362
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 1358–1363

Ring-Opening Rearrangement of (Arylmethylene)cyclopropanes
Heiner, S. I. Kozhushkov, M. Noltemeyer, T. Haumann, R.
Boese, A. Meijere, Tetrahedron 1996, 52, 12185–12196; h) J.-W.
Huang, M. Shi, Org. Biomol. Chem. 2005, 3, 399–400.
Supporting Information (see also the footnote on the first page of
this article): Copies of 1H NMR and 13C NMR spectra of all com-
pounds and NOESY of 2a.
ˇ
ˇ
ˇ
ˇ
[5] D. Sepac, Z. Marinic´, T. Portada, M. Zinic´, V. Sunjic´, Tetrahe-
dron 2003, 59, 1159–1167.
[6] For reviews on the halogen-lithium exchange reaction, see: a)
N. Sotomayer, E. Lete, Curr. Org. Chem. 2003, 7, 275–300; b)
C. Nájera, J. M. Sansano, M. Yus, Tetrahedron 2003, 59, 9255–
9303; c) W. F. Bailey, J. I. Patricia, J. Organomet. Chem. 1988,
352, 1–46; d) W. E. Parham, C. K. Bradsher, Acc. Chem. Res.
1982, 15, 300–305.
Acknowledgments
We thank the National Natural Science Foundation of China
(20572045, 20972069) and the Ministry of Education of China
(RFDF20070055022) for financial support.
[7] a) J.-M. Lu, M. Shi, Org. Lett. 2008, 10, 1943–1946; b) J.-M.
Lu, M. Shi, Chem. Eur. J. 2009, 15, 6065–6073.
[1] A. Brandi, A. Goti, Chem. Rev. 1998, 98, 589–635.
[2] For selected reviews on reactions of MCPs, see: a) A. Goti,
F. M. Cordero, A. Brandi, Top. Curr. Chem. 1996, 178, 1–97;
b) A. Brandi, S. Cicchi, F. M. Cordero, A. Goti, Chem. Rev.
2003, 103, 1213–1269; c) I. Nakamura, Y. Yamamoto, Adv.
Synth. Catal. 2002, 344, 111–129; d) P. Binger, H. M. Buch,
Top. Curr. Chem. 1987, 135, 77–151; e) E. Nakamura, S. Yam-
ago, Acc. Chem. Res. 2002, 35, 867–877.
[8] a) J. C. Aponte, G. B. Hammond, B. Xu, J. Org. Chem. 2009,
74, 4623–4625; b) C. Fu, S. Ma, Org. Lett. 2005, 7, 1707–1712.
[9] a) We treated MCP 1,1-diester 1a with LDA or nBuLi in THF
at –90 °C, and the reaction was subsequently quenched with p-
anisaldehyde (or p-chlorobenzaldehyde). However, the result
was complex, and no desired products were detected; b) MCP
1a (0.10  solution in THF, 0.10 mmol) was added to LDA (in
4.0 mL of THF, 0.15 or 0.20 mmol) over 2–3 min at –90 °C,
and the reaction was immediately quenched with either DCl,
CF3CO2D or D2O. However, no deuterated product was de-
tected, and the recovered starting material 1a was not deuter-
ated either. Similar results were obtained when nBuLi was used.
[10] S. Ma, L. Lu, J. Zhang, J. Am. Chem. Soc. 2004, 126, 9645–
9660.
[3] a) B. Hu, J. Zhu, S. Xing, J. Fang, D. Du, Z. Wang, Chem. Eur.
J. 2009, 15, 324–327; b) B. Hu, S. Xing, Z. Wang, Org. Lett.
2008, 10, 5481–5484.
[4] a) E. W. Thomas, Tetrahedron Lett. 1983, 24, 1467–1470; b) E.
Sternberg, P. Binger, Tetrahedron Lett. 1985, 26, 301–304; c) A.
Meijere, S. I. Kozhushkov, Eur. J. Org. Chem. 2000, 3809–3822;
d) A. Meijere, S. I. Kozhushkov, T. Spath, M. Seebach, S. Lohr,
H. Nuske, T. Pohlmann, M. Es-Sayed, S. Brase, Pure Appl.
Chem. 2000, 72, 1745–1756; e) E. W. Thomas, J. R. Szmuszkov-
icz, J. Org. Chem. 1990, 55, 6054–6058; f) A. Meijere, S. I.
Kozhushkov, N. S. Zefirov, Synthesis 1993, 681–683; g) T.
[11] a) S. Ma, L. Lu, J. Org. Chem. 2005, 70, 7629–7633; b) L. Xu,
X. Huang, F. Zhong, Org. Lett. 2006, 8, 5061–5064.
[12] K. Mikami, H. Ohmura, Org. Lett. 2002, 4, 3355–3357.
Received: October 15, 2009
Published Online: January 12, 2010
Eur. J. Org. Chem. 2010, 1358–1363
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1363