Dihalogenation of gem-aryl-disubstituted methylenecyclopropanes by DEAD, DIAD/TiX4 or free halogen

Article abstract of DOI:10.1002/ejoc.200400388

The reaction of gem-aryl-disubstituted methylenecyclopropanes with TiX ₄/diethyl azodicarboxylate and TiX₄/diisopropyl azodicarboxylate in 1,2-dichloroethane gave the dihalogenated ring-opened product, 2,4-dihalobut-1-ene, in moderate-to-excellent yields under mild conditions. On the basis of the proposed Orton-type mechanism, we found that this reaction can also be carried out with free halogens such as bromine or iodine to give the same products in good yields. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200400388

FULL PAPER
Dihalogenation of gem-Aryl-Disubstituted Methylenecyclopropanes by DEAD,
DIAD/TiX4 or Free Halogen
Li-Xiong Shao,[a] Lin-Jing Zhao,[b] and Min Shi*[a,b]
Keywords: Dihalogenation / Ring-opening reactions / Lewis acids / Diisopropyl azodicarboxylate (DIAD) / Diethyl
azodicarboxylate (DEAD)
The reaction of gem-aryl-disubstituted methylenecyclo- this reaction can also be carried out with free halogens such
propanes with TiX4/diethyl azodicarboxylate and TiX4/diiso-
propyl azodicarboxylate in 1,2-dichloroethane gave the di-
halogenated ring-opened product, 2,4-dihalobut-1-ene, in
moderate-to-excellent yields under mild conditions. On the
basis of the proposed Orton-type mechanism, we found that
as bromine or iodine to give the same products in good
yields.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
In this paper we report a new transformation of MCPs
using TiX4/DEAD or TiX4/DIAD. In this system, the di-
halogenation/ring-opening reaction of MCPs 1 in the pres-
ence of metal halides (Lewis acids) and DEAD or DIAD
in 1,2-dichloroethane (DCE) occurred under mild con-
ditions to give 2,4-dihalobut-1-enes 3 (X ϭ Cl), 5 (X ϭ Br)
and 6 (X ϭ I) as products in moderate-to-excellent yields
(Scheme 1).[7] In addition, on the basis of the proposed
Orton-type mechanism, we further found that these ring-
opening reactions can also be carried out with free halogens
to give the same products under mild conditions
(Scheme 1).
Methylenecyclopropanes (MCPs) 1 are highly strained
but readily accessible molecules that have served as useful
building blocks in organic synthesis. MCPs 1 undergo a
variety of ring-opening reactions because the relief of ring
strain provides a potent thermodynamic driving force.[1]
Transition-metal-catalyzed (such as Pd, Rh, Ru, and Pt) re-
actions of MCPs 1 with various reactants have attracted
much attention.[2,3] In the Lewis acid catalyzed ring-open-
ing reactions of MCPs 1, we have found that the propane
ring of MCPs 1 can be opened with the use of alcohols and
other nucleophiles by a different, novel mechanism to give
the corresponding homoallylic derivatives in good yields
under mild conditions.[4,5] For example, the reaction of
MCPs 1 with titanium(iv) chloride (TiCl4) in dichlorometh-
ane (DCM) produced the corresponding homoallylic chlo-
rides in good yields at room temperature. This interesting
result encouraged us to investigate further the Lewis acid
catalyzed reactions of MCPs 1 with other reactants. Pre-
viously we reported the ring expansion of MCPs 1 in the
presence of Zr(OTf)4 (Lewis acid) and diethyl azodicarbox-
ylate (DEAD) or diisopropyl azodicarboxylate (DIAD) un-
der mild conditions.[6]
Scheme 1
[a]
State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences,
354 Fenglin Lu, Shanghai 200032, People’s Republic of China
[b]
Results and Discussion
School of Chemistry & Pharmaceutics,
East China University of Science and Technology, 130
Meilong Road,
Initially we carried out the reaction of (diphenylmethyl-
ene)cyclopropane (1a, 0.2 mmol) with various metal halides
(0.24 mmol) in the presence of DEAD (40% in toluene) (0.2
mmol) in 1,2-dichloroethane (DCE) at room temperature.
Shanghai, 200237, People’s Republic of China
Fax: (internat.) ϩ 86-21-64166128
E-mail: Mshi@pub.sioc.ac.cn
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
4894
© 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200400388
Eur. J. Org. Chem. 2004, 4894Ϫ4900

Dihalogenation of gem-Aryl-Disubstituted Methylenecyclopropanes
FULL PAPER
MCPs 1b and 1dϪg (both R1 and R2 are aromatic groups),
the reactions proceeded smoothly to give the dichlorinated
products 3b and 3dϪg in moderate-to-good yields (Table 2,
entries 1 and 3Ϫ6). With the unsymmetric MCPs 1b and 1e,
the corresponding dichlorinated products 3b and 3e were
obtained as mixtures of E and Z isomers (Table 2, entries 1
and 4). With MCP 1h (R1 is an aromatic group and R2 is
a hydrogen atom), this reaction also proceeded smoothly to
give the corresponding dichlorinated product 3h as the Z
isomer in 15% yield (Table 2, entry 7). The identity of the
Z isomer of 3h was determined by 1H NMR NOESY spec-
troscopic data (see the Supporting Information). With
MCP 1c (R1 is an aromatic group and R2 is a methyl
group), the desired product was not obtained (Table 2, en-
try 2).
Table 1. The effects of various metal chlorides (0.24 mmol) on the
dichlorination of MCP 1a (0.2 mmol) in the presence of DEAD
(0.2 mmol) in DCE
We found that different solvents and substituents on the
benzene ring of the MCP can significantly affect the nature
of the reaction products of this novel dihalogenation/ring-
opening reaction. The results are summarized in Table 3.
When the reaction was carried out in CH3CN, homoallylic
chloride 2 was obtained as the major product in many cases
along with dichlorinated product 3 or the ring-expansion
product 4[6] (Table 3, entries 1Ϫ3). With MCP 1a in
CH3CN, homoallylic chloride 2a was obtained in 89% yield
(Table 3, entry 1). With MCP 1d (electron-donating sub-
stituent on the benzene ring of the MCP) in CH3CN, the
homoallylic chloride 2d was obtained in 38% yield along
with the ring-expansion product 4d in 7% yield (Table 3,
entry 2). With MCP 1f (electron-withdrawing substituent
on the benzene ring of the MCP) in CH3CN, the dichlori-
nated product 3f was obtained in 12% yield along with
homoallylic chloride 2f in 32% yield (Table 3, entry 3).
When the reaction was carried out in Et2O, the dichlori-
nated product 3 was obtained in low yields for all of the
employed MCPs, 1a, 1d and 1f (Table 3, entries 4Ϫ6). With
substrate 1a and 1d (electron-donating substituents on the
benzene ring of the MCP), the ring-expansion product 4
was obtained along with the dichlorination product 3
(Table 3, entries 4 and 5). With substrate 1f (electron-with-
drawing substituent on the benzene ring of the MCP), the
[a]
[b]
1.2 equiv. of metal chloride (Lewis acid) was used.
Isolated
yields. [c] TiCl4 (1.0 mL) in CH2Cl2 (1 mol·LϪ1, 5.0 equiv.) was used
[d]
as the promoter and solvent.
TiCl4 (0.5 mL) in CH2Cl2 (1
mol·LϪ1, 2.5 equiv.) was used as the promoter and solvent (0.5 mL)
was added.
The results are summarized in Table 1. No major product
was obtained with DEAD in the presence of metal halides
such as ZnCl2, MgCl2, CuCl2, YbCl3, BiCl3, LaCl3 and
AlCl3 (Table 1, entries 2Ϫ8). The reaction only proceeded
smoothly to give the corresponding 1,1-diphenyl-2,4-di-
chlorobut-1-ene 3a in good yields in the presence of TiCl4.
Increasing the amount of TiCl4 did not significantly im-
prove the yields of 3a (Table 1, entries 9Ϫ11).
Next, we utilized TiCl4 as the Lewis acid reagent (0.24
mmol) to examine this dichlorination reaction with various
MCPs 1 (0.2 mmol) in the presence of DEAD (40% in tolu-
ene) (0.2 mmol). The results are shown in Table 2. With
Table 2. Dichlorination of MCPs 1 (0.2 mmol) in the presence of
TiCl4 (0.24 mmol) and DEAD (0.2 mmol) in DCE
Table 3. The effect of solvent on the dichlorination of MCPs 1 (0.2
mmol) in the presence of TiCl4 (0.24 mmol) and DEAD (0.2 mmol)
in DCE
[a]
[b]
[a]
Isolated yields. Mixtures of E and Z isomers were obtained.
Isolated yields.
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L.-X. Shao, L.-J. Zhao, M. Shi
FULL PAPER
dichlorinated product 3f was obtained as the sole product
in moderate yield (Table 3, entry 6). At this stage, we cannot
explain such solvent and substituents effects on this reac-
tion. However, by using Et2O or MeCN as the solvent, the
differences in the coordination of the solvent to the TiCl4
promoter may affect the activity of the latter in this reac-
tion.
Table 4. Dihalogenation of MCPs 1 (0.2 mmol) in the presence of
TiX4 (X ϭ Cl, Br, I) (0.24 mmol) and azo compound (0.2 mmol)
in DCE
In order to complete this set of dihalogenation/ring-
opening reactions with MCPs 1, we carried out the dibro-
mination/diiodination ring-opening reactions of MCPs 1
(0.2 mmol) in the presence of DEAD (40% in toluene) (0.2
mmol). The results are shown in Table 4. With MCPs 1a, 1d
and 1f (both R1 and R2 are aromatic groups), the reactions
proceeded smoothly to give the dibrominated and diiodin-
ated products 5a, 5d, 5f, 6a, 6d and 6f in high-to-excellent
yields (Table 4, entries 1Ϫ6). By using diisopropyl azodicar-
boxylate (DIAD) as the reagent under the same conditions,
similar results were obtained to those obtained with
DEAD. The results are also shown in Table 4. With MCPs
1a, 1d and 1f (0.2 mmol) in the presence of DIAD (0.2
mmol) and TiCl4 (0.24 mmol), the dichlorinated products
3a, 3d and 3f were obtained in 61, 75 and 87%, respectively
(Table 4, entries 7Ϫ9). The slight difference in yields may
[a]
Isolated yields.
In order to clarify the proposed mechanism, we at-
be due to the fact that the presence of toluene in the DEAD tempted the dibrominated and diiodinated ring-opening re-
[9]
solution affects this reaction to some extent.
actions of some MCPs 1 (0.2 mmol) with Br2 and I2 (0.2
A plausible mechanism for the dihalogenation/ring-open- mmol), respectively, under similar conditions. The results
ing reaction of MCPs 1 promoted by TiX4 and DEAD or are summarized in Table 5. We found that these reactions
DIAD, based on the Orton rearrangement mechanism, is proceeded smoothly to give the dibrominated or diiodinated
shown in Scheme 2.[8] The Lewis acid (TiX4) activates product 5 or 6 in good-to-high yields (Table 5, entries 1Ϫ8).
DEAD and an XϪ anion from the Lewis acid promoter With the symmetric MCPs 1a, 1d, 1f and 1i (both R1 and
(TiX4) attacks the NϭN double bond in a manner similar R2 are aromatic groups), these reactions proceeded very
to a Michael addition to give the intermediate A. Intramol- well to give the dibrominated or diiodinated product 5 or
ecular attack by XϪ gives X2 and intermediate B which is 6 in high yields (Table 5, entries 1Ϫ4, 6Ϫ8). The electron-
hydrolysed to give 1,2-bis(ethoxycarbonyl)hydrazine. The donating and electron-withdrawing substituents on the ben-
formation of 1,2-bis(ethoxycarbonyl)hydrazine was con- zene ring of MCPs 1 had a small effect on this reaction in
firmed by GLC and GC-MS (see Supporting Information). DCE. With the unsymmetric MCP 1c (R1 is an aromatic
The ring-opening of MCPs 1 by reaction with X2 furnishes group and R2 is an aliphatic group), the reaction also pro-
the dihalogenated products.
ceeded smoothly but gave the product in a somewhat lower
Scheme 2
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Eur. J. Org. Chem. 2004, 4894Ϫ4900

Dihalogenation of gem-Aryl-Disubstituted Methylenecyclopropanes
FULL PAPER
Finnigan MAϩ mass spectrometer. Satisfactory CHN microana-
lyses were obtained with a CarloϪErba 1106 analyzer. Melting
points are uncorrected. All reactions were monitored by TLC with
Huanghai GF254 silica-gel-coated plates. Flash column chromatog-
raphy was carried out using 300Ϫ400 mesh silica gel.
Table 5. Dihalogenation of MCPs 1 (0.2 mmol) by Br2 or I2 (0.2
mmol) in DCE
General Reaction Procedure for the Reaction of MCPs 1 in the Pres-
ence of TiX4 and DEAD: Under an argon atmosphere, MCPs 1
(0.20 mmol), DEAD (0.20 mmol), Lewis acid promoter (0.24
mmol) and 1,2-dichloroethane (1.0 mL) were added to a Schlenk
reaction tube. The mixture was stirred at room temperature for
about 8 h. The solvent was removed under reduced pressure and
the residue was purified by flash column chromatography (SiO2).
General Reaction Procedure for the Reaction of MCPs 1 with Bro-
mine: Under an ambient atmosphere, MCPs 1 (0.20 mmol), bro-
mine (0.20 mmol) and 1,2-dichloroethane (1.0 mL) were added to
a Schlenk reaction tube. The mixture was stirred at room tempera-
ture for about 8 h. The solvent was removed under reduced press-
ure and the residue was purified by flash column chromatography
(SiO2).
[a]
Isolated yields.
2,4-Dichloro-1,1-diphenylbut-1-ene (3a): A yellow solid; m.p. 64Ϫ67
°C. IR (CH2Cl2): ν˜ ϭ 3940, 3044, 2978, 2304, 1494, 1442, 1265,
1
yield (27%) as the E isomer, as determined by H NMR
739 cmϪ1 1H NMR (CDCl3, 300 MHz, TMS): δ ϭ 2.89 (t, J ϭ
.
NOESY spectroscopy (see Supporting Information)
(Table 5, entry 5). Therefore, it is clear that free halogens
6.6 Hz, 2 H), 3.77 (t, J ϭ 6.6 Hz, 2 H), 7.19Ϫ7.32 (m, 10 H, Ar)
ppm. 13C NMR (CDCl3, 75 MHz, TMS): δ ϭ 39.0, 41.9, 127.4,
can indeed react with MCPs 1 to give the dihalogenated 127.5, 128.0, 128.5, 128.9, 129.1, 129.2, 140.2, 140.7, 141.8 ppm.
MS (%): m/z ϭ 278 (100), 277 (26.35), 276 [Mϩ] (100), 227 (100),
191 (100). HRMS calcd. for C16H14Cl2: 276.0473; found: 276.0445.
ring-opened products. This result suggests that the halogen
generated in the reaction of TiX4 and DEAD or DIAD is
the real reagent for this type of dihalogenation transform-
ation.
In conclusion, we have disclosed a new transformation of
2,4-Dichloro-1-methoxyphenyl-1-phenylbut-1-ene (3b): A pale yel-
low solid, mixture of E and Z isomers (1:1); m.p. 73Ϫ75 °C. IR
(CH2Cl2): ν˜ ϭ 3956, 3059, 2970, 2311, 1605, 1416, 1265, 895, 742
cmϪ1. E or Z isomer: 1H NMR (CDCl3, 300 MHz, TMS): δ ϭ
2.87Ϫ2.94 (m, 2 H), 3.76Ϫ3.80 (m, 5 H, CH2 ϩ OCH3), 6.84Ϫ7.12
(m, 2 H, Ar), 7.19Ϫ7.34 (m, 7 H, Ar) ppm. Z or E isomer: 1H
NMR (CDCl3, 300 MHz, TMS): δ ϭ 2.87Ϫ2.94 (m, 2 H),
3.76Ϫ3.80 (m, 5 H, CH2 ϩ OCH3), 6.84Ϫ7.12 (m, 2 H, Ar),
7.19Ϫ7.34 (m, 7 H, Ar) ppm. E or Z isomer: 13C NMR (CDCl3,
75 MHz, TMS): δ ϭ 39.2, 42.0, 55.2, 113.8, 127.5, 128.2, 128.4,
129.2, 130.7, 133.0, 141.0, 141.4, 158.9 ppm. Z or E isomer: 13C
NMR (CDCl3, 75 MHz, TMS): δ ϭ 39.1, 42.0, 55.1, 113.3, 127.3,
128.0, 128.4, 129.1, 130.3, 132.5, 140.5, 141.3, 158.7 ppm. MS (%):
m/z ϭ 308 (54.71), 307 (22.56), 306 [Mϩ] (3.71), 257 (100), 222
(82.84). HRMS calcd. for C17H16Cl2O: 306.0573; found: 306.0565.
MCPs 1 in the presence of TiX4/DEAD or TiX4/DIAD to
give the corresponding dihalogenated products in moder-
ate-to-excellent yields. The ring-opening mode in this MCPs
system is due to the influence of aryl substituents on the
stability of the intermediate halogenaspiropentyl cation
shown in Scheme 2. The stabilized cation readily undergoes
nucleophilic attack by another halogen to give the dihal-
ogenation/ring-opened products 3, 5 and 6. It is interesting
that the dihalogenation of MCPs 1 is achieved in the pres-
ence of titanium(iv) halides and DEAD or DIAD under
mild conditions. On the basis of the proposed Orton-type
mechanism, we have also disclosed that free halogens, such
as bromine and iodine, are good reagents for the ring-open-
ing reaction of the MCPs reported in this paper and give
the dihalogenated ring-opened products in good yields un-
der mild conditions. Efforts are underway to elucidate the
mechanistic details of the reaction and to disclose its scope
and limitations. Work along this line is currently in pro-
gress.
2,4-Dichloro-1,1-bis(4-methylphenyl)but-1-ene (3d): A glutinous yel-
low liquid. IR (CH2Cl2): ν˜ ϭ 3941, 3054, 2978, 2304, 1422, 1265,
1
896, 746 cmϪ1. H NMR (CDCl3, 300 MHz, TMS): δ ϭ 2.33 (s, 6
H, 2CH3), 2.90 (t, J ϭ 7.2 Hz, 2 H), 3.77 (t, J ϭ 7.2 Hz, 2 H),
7.03Ϫ7.21 (m, 8 H, Ar) ppm. 13C NMR (CDCl3, 75 MHz, TMS):
δ ϭ 21.16, 21.23, 39.2, 42.0, 126.2, 128.1, 128.7, 128.9, 129.1, 129.3,
137.1, 137.2, 137.5, 138.0 ppm. MS (%): m/z ϭ 306 (52.43), 305
(19.25), 304 [Mϩ] (81.20), 255 (86.81), 219 (100), 205 (97.66).
HRMS calcd. for C18H18Cl2: 304.0780; found: 304.0773.
2,4-Dichloro-1-(2-chlorophenyl)-1-phenylbut-1-ene (3e):
A bright
yellow liquid, mixture of E and Z isomers (1:1). IR (CH2Cl2): ν˜ ϭ
3941, 3059, 2978, 2296, 1412, 1265, 891, 739 cmϪ1. E or Z isomer:
1H NMR (CDCl3, 300 MHz, TMS): δ ϭ 2.69Ϫ2.79 (m, 2 H),
3.65Ϫ3.87 (m, 2 H), 7.23Ϫ7.40 (m, 9 H, Ar) ppm. Z or E isomer:
1H NMR (CDCl3, 300 MHz, TMS): δ ϭ 2.69Ϫ2.79 (m, 2 H),
3.65Ϫ3.87 (m, 2 H), 7.23Ϫ7.40 (m, 9 H, Ar) ppm. E or Z isomer:
13C NMR (CDCl3, 75 MHz, TMS): δ ϭ 39.4, 41.7, 126.8, 127.4,
127.8, 128.1, 128.4, 128.9, 129.5, 129.7, 130.2, 130.0, 138.1, 138.3
Experimental Section
General Remarks: 1H NMR spectra were recorded on a Varian
Mercury 300 MHz spectrometer in CDCl3 using tetramethylsilane
as the internal standard. Infrared spectra were measured on a
Perkin-Elmer 983 spectrometer. Mass spectra were recorded on a
HP-5989 instrument and HRMS spectra were measured on a
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L.-X. Shao, L.-J. Zhao, M. Shi
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ppm. Z or E isomer: 13C NMR (CDCl3, 75 MHz, TMS): δ ϭ 38.2,
41.5, 126.8, 127.0, 127.6, 127.9, 128.2, 128.8, 129.2, 129.6, 129.93,
130.00, 131.2, 138.7 ppm. MS (%): m/z ϭ 312 (68.98), 311 (20.55),
310 [Mϩ] (70.73), 225 (100). HRMS calcd. for C16H13Cl3: 310.0077;
found: 310.0064.
m/z ϭ 310 [Mϩ], 275, 261, 226, 191, 163. HRMS (EI) calcd. for
C16H13Cl3: 310.0083; found: 310.0047.
2,2-Diphenylcyclobutanone (4a): A colorless liquid; this is a known
1
compound. H NMR (CDCl3, 300 MHz, TMS): δ ϭ 2.83 (t, J ϭ
8.1 Hz, 2 H, CH2), 3.15 (t, J ϭ 8.1 Hz, 2 H, CH2), 7.17Ϫ7.39 (m,
10 H, Ar) ppm [ref.[10] 1H NMR (CDCl3, 60 MHz, TMS): δ ϭ 2.76
(t, J ϭ 8.5 Hz, 2 H, CH2), 3.08 (t, J ϭ 8.5 Hz, 2 H, CH2), 7.0Ϫ7.8
(m, 10 H, Ar) ppm]. 13C NMR (CDCl3, 75 MHz, TMS): δ ϭ 25.5,
43.3, 76.1, 126.3, 126.9, 128.7, 142.0, 209.1 ppm. MS (%): m/z ϭ
222 [Mϩ] (1.68), 180 (100).
2,4-Dichloro-1,1-bis(4-chlorophenyl)but-1-ene (3f): A yellow liquid.
IR (CH2Cl2): ν˜ ϭ 3941, 3052, 2993, 2311, 1490, 1416, 1265, 896,
749 cmϪ1 1H NMR (CDCl3, 300 MHz, TMS): δ ϭ 2.91 (t, J ϭ
.
6.6 Hz, 2 H), 3.81 (t, J ϭ 6.6 Hz, 2 H), 7.15 (d, J ϭ 11.7 Hz, 2 H,
Ar), 7.27 (d, J ϭ 8.4 Hz, 2 H, Ar), 7.31 (d, J ϭ 6.0 Hz, 2 H, Ar),
7.33 (d, J ϭ 5.7 Hz, 2 H, Ar) ppm. 13C NMR (CDCl3, 75 MHz,
TMS): δ ϭ 38.9, 41.7, 128.4, 128.9, 130.1, 130.6, 130.7, 133.5,
133.9, 138.2, 138.6, 139.6 ppm. MS (%): m/z ϭ 346 (100), 344 [Mϩ]
(78.04), 295 (87.49). HRMS calcd. for C16H12Cl4 (M ϩ 2 H Ϫ 2
Cl): 276.0473; found (M ϩ 2 H Ϫ 2 Cl): 276.0445.
2,2-Bis(4-methylphenyl)cyclobutanone (4d): A colorless liquid. IR
(CH2Cl2): ν˜ ϭ 1781, 1510, 1266, 739 cmϪ1. 1H NMR (CDCl3, 300
MHz, TMS): δ ϭ 2.28 (s, 6 H, 2 CH3), 2.78 (t, J ϭ 8.7 Hz, 2 H),
3.13 (t, J ϭ 8.7 Hz, 2 H), 7.10 (d, J ϭ 8.7 Hz, Ar, 4 H), 7.24 (d,
J ϭ 8.7 Hz, 4 H, Ar) ppm. 13C NMR (CDCl3, 75 MHz, TMS):
δ ϭ 21.3, 25.9, 43.6, 75.9, 126.5, 129.6, 136.7, 139.6, 209.7 ppm. MS
(%): m/z ϭ 250 [Mϩ] (2.28), 208 (100). HRMS calcd. for C18H18O:
250.1358; found: 250.1330.
2,4-Dichloro-1,1-bis(4-fluorophenyl)but-1-ene (3g): A glutinous yel-
low liquid. IR (CH2Cl2): ν˜ ϭ 3956, 3054, 2993, 1601, 1422, 1265,
1
896, 742 cmϪ1. H NMR (CDCl3, 300 MHz, TMS): δ ϭ 2.89 (t,
J ϭ 6.3 Hz, 2 H), 3.79 (t, J ϭ 6.3 Hz, 2 H), 7.01Ϫ7.07 (m, 4 H,
Ar), 7.16Ϫ7.26 (m, 4 H, Ar) ppm. 13C NMR (CDCl3, 75 MHz,
TMS): δ ϭ 38.8, 41.8, 115.1 (d, JCϪF ϭ 21.45 Hz), 115.6 (d, JCϪF ϭ
2,4-Dibromo-1,1-diphenylbut-1-ene (5a): A white solid; m.p. 74Ϫ76
°C. IR (CH2Cl2): ν˜ ϭ 3933, 3054, 2985, 1486, 1443, 1265, 896, 746
cmϪ1 1H NMR (CDCl3, 300 MHz, TMS): δ ϭ 3.07 (t, J ϭ 6.9
.
21.45 Hz), 129.6, 130.9 (d, JCϪF ϭ 13.28 Hz), 131.0 (d, JCϪF
ϭ
Hz, 2 H), 3.62 (t, J ϭ 6.9 Hz, 2 H), 7.20Ϫ7.32 (m, 10 H, Ar) ppm.
13C NMR (CDCl3, 75 MHz, TMS): δ ϭ 31.0, 40.8, 123.2, 127.4,
127.6, 128.1, 128.5, 128.7, 128.8, 140.3, 142.7, 144.9 ppm. MS (%):
m/z ϭ 367 (16.93), 366 [Mϩ] (59.88), 192 (100). HRMS calcd. for
C16H14Br2: 363.9457; found: 363.9470.
13.35 Hz), 136.0 (d, JCϪF ϭ 3.45 Hz), 136.4 (d, JCϪF ϭ 3.30 Hz),
139.8, 161.9 (d, JCϪF ϭ 246.30 Hz), 162.1 (d, JCϪF ϭ 246.30 Hz)
ppm. MS (%): m/z ϭ 314 (37.62), 312 [Mϩ] (59.24), 263 (71.74), 227
(100). HRMS calcd. for C16H12Cl2F2: 312.0279; found: 312.0275.
1-(2,4-Dichlorobut-1-enyl)-4-methoxybenzene (3h):
A
colorless
2,4-Dibromo-1,1-bis(4-methylphenyl)but-1-ene (5d): A white solid;
m.p. 70Ϫ72 °C. IR (CH2Cl2): ν˜ ϭ 3941, 3054, 3000, 2296, 1422,
1265, 896, 739 cmϪ1. 1H NMR (CDCl3, 300 MHz, TMS): δ ϭ 2.33
(s, 6 H, 2 CH3), 3.08 (t, J ϭ 6.9 Hz, 2 H), 3.62 (t, J ϭ 6.9 Hz, 2
H), 7.06Ϫ7.17 (m, 8 H, Ar) ppm. 13C NMR (CDCl3, 75 MHz,
TMS): δ ϭ 21.2, 21.3, 31.2, 41.0, 122.4, 128.6, 128.7, 128.8, 129.2,
137.1, 137.3, 137.6, 134.0, 144.7 ppm. MS (%): m/z ϭ 295 (11.53),
294 [Mϩ] (54.85), 393 (7.46), 220 (100). HRMS calcd. for
C18H18Br2: 391.9770; found: 391.9778.
liquid. IR (CH2Cl2): ν˜ ϭ 3003, 2961, 2934, 1607, 1575, 1511, 1463,
1252, 897, 749 cmϪ1. 1H NMR (CDCl3, 300 MHz, TMS): δ ϭ 2.89
(t, J ϭ 6.9 Hz, 2 H), 3.78 (t, J ϭ 6.9 Hz, 2 H), 3.82 (s, 3 H, CH3O),
6.51 (s, 1 H), 6.89 (d, J ϭ 9.0 Hz, 2 H, Ar), 7.59 (d, J ϭ 9.0 Hz, 2
H, Ar) ppm. 13C NMR (CDCl3, 75 MHz, TMS): δ ϭ 41.8, 44.1,
55.2, 113.6, 126.9, 127.1, 127.6, 130.4, 159.1 ppm. MS (%): m/z ϭ
230 [Mϩ] (73.43), 181 (100). HRMS calcd. for C11H12Cl2O:
230.0265; found: 230.0293.
1-Chloro-4,4-diphenylbut-3-ene (2a): A colorless oil. IR (neat): ν˜ ϭ
2,4-Dibromo-1,1-bis(4-chlorophenyl)but-1-ene (5f): A white solid;
m.p. 78Ϫ80 °C. IR (CH2Cl2): ν˜ ϭ 3941, 3052, 2970, 2311, 1494,
3079, 3024, 2956, 1598, 1494, 1444, 1296, 1029 cmϪ1 1H NMR
.
1420, 1265, 896, 746 cmϪ1 1H NMR (CDCl3, 300 MHz, TMS):
.
(300 MHz, CDCl3): δ ϭ 2.56 (td, J ϭ 7.2, 7.2 Hz, 2 H), 3.55 (t,
J ϭ 7.2 Hz, 2 H), 6.12 (t, J ϭ 7.2 Hz, 1 H), 7.23Ϫ7.47 (m, 10 H,
Ar) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 33.0, 44.4, 124.8, 127.3,
127.3, 127.4, 128.2, 128.4, 129.8, 139.7, 142.2, 144.4 ppm. MS (EI):
m/z ϭ 242 [Mϩ], 193, 180, 165, 115, 104, 91. HRMS (EI) calcd.
for C16H15Cl: 242.0862; found: 242.0829.
δ ϭ 3.06 (t, J ϭ 6.9 Hz, 2 H), 3.63 (t, J ϭ 6.9 Hz, 2 H), 7.12Ϫ7.16
(m, 2 H, Ar), 7.19Ϫ7.21 (m, 2 H, Ar), 7.29Ϫ7.33 (m, 4 H, Ar)
ppm. 13C NMR (CDCl3, 75 MHz, TMS): δ ϭ 31.0, 40.5, 124.4,
128.4, 128.8, 130.2, 130.4, 133.6, 133.8, 138.3, 140.6, 142.6 ppm.
MS (%): m/z ϭ 436 (81.11), 435 (19.89), 434 [Mϩ] (91.07), 260
(100). HRMS calcd. for C16H12Br2Cl2: 431.8677; found: 431.8659.
1-Chloro-4,4-bis(4-methylphenyl)but-3-ene (2d): A colorless liquid.
IR (CH2Cl2): ν˜ ϭ 3022, 2955, 2921, 2862, 1904, 1747, 1609, 1567,
2,4-Diiodo-1,1-diphenylbut-1-ene (6a): A yellow solid; m.p. 68Ϫ70
1511, 1448, 1363, 1295, 1110, 1021 cmϪ1 1H NMR (CDCl3, 300
.
Ϫ1
˜
°C. IR (neat): ν ϭ 3045, 2877, 1954, 1597, 1490, 1245 cm
.
1H
MHz, TMS): δ ϭ 2.29 (s, 3 H, CH3), 2.32 (s, 3 H, CH3), 2.58 (q,
J ϭ 6.9 Hz, 2 H), 3.56 (t, J ϭ 6.9 Hz, 2 H), 6.03 (t, J ϭ 6.9 Hz, 1
H), 7.04Ϫ7.19 (m, 8 H, Ar) ppm. 13C NMR (CDCl3, 75 MHz,
TMS): δ ϭ 21.1, 21.2, 33.0, 44. 5, 123.7, 127.2, 127.6, 128.8, 129.0,
130.0, 136.8, 137.0, 139.5, 144.2 ppm. MS (%): m/z ϭ 270 [Mϩ]
(51.53), 221 (100). HRMS calcd. for C18H19Cl: 270.1175; found:
270.1194.
NMR (CDCl3, 300 MHz, TMS): δ ϭ 3.05 (t, J ϭ 6.9 Hz, 2 H),
3.36 (t, J ϭ 6.9 Hz, 2 H), 7.18Ϫ7.36 (m, 10 H, Ar) ppm. 13C NMR
(CDCl3, 75 MHz, TMS): δ ϭ 6.2, 44.3, 106.6, 127.51, 127.53,
128.48, 128.50, 128.52, 128.5, 139.9, 146.3, 150.6 ppm. MS (EI):
m/z ϭ 460 [Mϩ], 333, 254, 206, 178. HRMS (EI) calcd. for
C16H14I2: 459.9185; found: 459.9189.
1-(2,4-Diiodo-1-methylbut-1-enyl)-4-ethoxybenzene (6c): A pale red
liquid. IR (CH2Cl2): ν˜ ϭ 3046, 2980, 2918, 2868, 1606, 1570, 1506
1-Chloro-4,4-bis(4-chlorophenyl)but-3-ene (2f): A colorless oil. IR
(neat): ν˜ ϭ 3030, 2956, 2925, 1592, 1492, 1401, 1091 cmϪ1 1H cmϪ1 1H NMR (CDCl3, 300 MHz, TMS): δ ϭ 1.41 (t, J ϭ 6.9
. .
NMR (300 MHz, CDCl3): δ ϭ 2.57 (td, J ϭ 6.6, 6.6 Hz, 2 H), 3.58
Hz, 3 H), 2.21 (s, 3 H, CH3), 2.87 (t, J ϭ 7.5 Hz, 2 H), 3.22 (t, J ϭ
(t, J ϭ 6.6 Hz, 2 H), 6.11 (t, J ϭ 6.6 Hz, 1 H), 7.09Ϫ7.38 (m, 8 H, 7.5 Hz, 2 H), 4.02 (q, J ϭ 6.9 Hz, 2 H), 6.85 (d, J ϭ 6.6 Hz, 2 H,
Ar) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 33.0, 44.4, 126.2, 128.6,
128.8, 129.0, 131.3, 133.6, 133.7, 137.8, 140.4, 142.5 ppm. MS (EI):
Ar), 7.03 (d, J ϭ 6.6 Hz, 2 H, Ar) ppm. 13C NMR (CDCl3, 75
MHz, TMS): δ ϭ 5.4, 14.8, 32.3, 44.6, 63.3, 104.6, 114.3, 128.4,
4898
© 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 4894Ϫ4900

Dihalogenation of gem-Aryl-Disubstituted Methylenecyclopropanes
FULL PAPER
[2f]
132.7, 144.4, 158.0 ppm. MS (%): m/z ϭ 442 [Mϩ] (100), 188
(96.27). HRMS calcd. for C13H16I2O: 441.9291; found: 441.9292.
N. Tsukada, A. Shibuya, I. Nakamura, Y. Yamamoto, J.
[2g]
Am. Chem. Soc. 1997, 119, 8123Ϫ8124.
Y. Inoue, T. Hibi,
H. Sataka, H. Hashimoto, Chem. Commun. 1979, 982Ϫ982. [2h]
P. Binger, A. Germer, Chem. Ber. 1981, 114, 3325Ϫ3335.
Nakamura, B. H. Oh, S. Saito, Y. Yamamoto, Angew. Chem.
[2i]
I.
2,4-Diiodo-1,1-bis(4-methylphenyl)but-1-ene (6d): A yellow solid;
m.p. 104Ϫ106 °C. IR (CH2Cl2): ν˜ ϭ 3941, 3044, 2985, 1416, 1265,
[2j]
1
742, 705 cmϪ1. H NMR (CDCl3, 300 MHz, TMS): δ ϭ 2.32 (s, 3
Int. Ed. 2001, 40, 1298Ϫ1300.
B. H. Oh, I. Nakamura, S.
Saito, Y. Yamamoto, Tetrahedron Lett. 2001, 42, 6203Ϫ6205.
H, CH3), 2.33 (s, 3 H, CH3), 3.07 (t, J ϭ 6.9 Hz, 2 H), 3.36 (t, J ϭ
6.9 Hz, 2 H), 7.08 (t, J ϭ 8.1 Hz, 2 H, Ar), 7.13 (s, 6 H, Ar) ppm.
13C NMR (CDCl3, 75 MHz, TMS): δ ϭ 6.4, 21.2, 21.3, 44.4, 105.8,
128.39, 128.42, 128.8, 129.1, 137.15, 137.19, 143.6, 150.5 ppm. MS
(%): m/z ϭ 488 [Mϩ] (97.45), 219 (100). HRMS calcd. for C18H18I2:
487.9492; found: 487.9485.
[2k]
For the ring-opening of MCPs of type II or III, see:
A. G.
Bessmertnykh, K. A. Blinov, Y. K. Grishin, N. A. Donskaya,
E. V. Tveritinova, N. M. Yur’eva, I. P. Beletskaya, J. Org.
Chem. 1997, 62, 6069Ϫ6076. [2l] M. Lautens, C. Meyer, A. Lor-
[2m]
enz, J. Am. Chem. Soc. 1996, 118, 10676Ϫ10677.
T. Ishi-
[2n]
yama, S. Momota, N. Miyaura, Synlett 1999, 1790Ϫ1792.
M. Suginome, T. Matsuda, Y. Ito, J. Am. Chem. Soc. 2000,
[2o]
1,1-Bis(4-chlorophenyl)-2,4-diiodobut-1-ene (6f): A yellow solid;
m.p. 68Ϫ70 °C. IR (CH2Cl2): ν˜ ϭ 3948, 3696, 3054, 2993, 2304,
122, 11015Ϫ11016.
N. Chatani, H. Takaya, T. Hanafusa,
[2p]
Tetrahedron Lett. 1988, 29, 3979Ϫ3982.
The metal-cata-
lyzed co-cyclization reactions of MCPs with unsaturated car-
1727, 1501, 1422, 1265, 1095, 896, 746, 705 cmϪ1 1H NMR
.
bon bonds have been extensively studied, see: M. Lautens, W.
(CDCl3, 300 MHz, TMS): δ ϭ 3.03 (t, J ϭ 6.6 Hz, 2 H), 3.36 (t,
J ϭ 6.6 Hz, 2 H), 7.12 (d, J ϭ 8.4 Hz, 2 H, Ar), 7.17 (d, J ϭ 8.4
Hz, 2 H, Ar), 7.308 (d, J ϭ 8.4 Hz, 2 H, Ar), 7.314 (d, J ϭ 8.4
Hz, 2 H, Ar) ppm. 13C NMR (CDCl3, 75 MHz, TMS): δ ϭ 6.4,
43.9, 107.9, 128.6, 128.8, 130.0, 130.1, 133.7, 133.8, 137.9, 144.2,
148.3 ppm. MS (%): m/z ϭ 530 (38.25), 528 [Mϩ] (60.36), 239 (100).
HRMS calcd. for C16H12Cl2I2: 527.8400; found: 527.8418.
[2q]
Klute, W. Tam, Chem. Rev. 1996, 96, 49Ϫ92.
T. Ohta, H.
Takaya, in Comprehensive Organic Chemistry (Eds.: B. M.
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[3]
[3a]
For some more recent papers related to MCPs, see:
M. W.
2,4-Diiodo-1,1-bis(4-methoxyphenyl)but-1-ene (6i): A yellow solid;
m.p. 112Ϫ114 °C. IR (CH2Cl2): ν˜ ϭ 3046, 2954, 2833, 1605, 1508
Nötzel, K. Rauch, T. Labahn, A. de Meijere, Org. Lett. 2002,
[3b]
4, 839Ϫ841.
D. Takauchi, K. Dsakada, Chem. Commun.
cmϪ1 1H NMR (CDCl3, 300 MHz, TMS): δ ϭ 3.08 (t, J ϭ 7.2
.
[3c]
2002, 646Ϫ647.
A. de Meijere, A. Leonov, T. Heiner, M.
[3d]
Hz, 2 H), 3.37 (t, J ϭ 7.2 Hz, 2 H), 3.80 (s, 6 H, 2 CH3O), 6.85
(d, J ϭ 6.9 Hz, 2 H, Ar), 6.86 (d, J ϭ 6.9 Hz, 2 H, Ar), 7.07 (d,
J ϭ 6.9 Hz, 2 H, Ar), 7.16 (d, J ϭ 6.9 Hz, 2 H, Ar) ppm. 13C
NMR (CDCl3, 75 MHz, TMS): δ ϭ 6.6, 44.5, 55.1, 55.2, 105.5,
113.3, 113.8, 129.9, 130.1, 132.5, 139.0, 149.7, 158.7, 158.8 ppm.
MS (%): m/z ϭ 520 [Mϩ] (84.92), 266 (100). HRMS calcd. for
C18H18I2O2: 519.9396; found: 519.9406.
Noltemeyer, M. T. Bes, Eur. J. Org. Chem. 2003, 472Ϫ478.
V. N. Belov, A. I. Savchenko, V. V. Sokolov, A. Straub, A. de
[3e]
Meijere, Eur. J. Org. Chem. 2003, 551Ϫ561.
I. D. Kuchuk, V. V. Sokolov, T. Labahn, K. Rauch, M. Es-
A. de Meijere,
[3f]
Sayed, T. Krämer, Eur. J. Org. Chem. 2003, 985Ϫ997.
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I. Siriwardana, I. Nakamura, Y. Yamamoto, Tetrahedron Lett.
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[3h]
2003, 5, 579Ϫ582.
2003, 345, 963Ϫ966.
A. Goti, Chem. Rev. 2003, 103, 1213Ϫ1269.
L.-X. Shao, M. Shi, Adv. Synth. Catal.
A. Brandi, S. Cicchi, F. M. Cordero,
[3i]
Supporting Information Available: The spectroscopic data of the
compounds shown in Tables 1Ϫ5, the NOESY spectroscopy of 3h
and 6c, the GC and GC-MS spectroscopy for the formation of 1,2-
bis(diethoxycarbonyl)hydrazine. See also the footnote on the first
page of this article.
[4] [4a]
[4b]
M. Shi, B. Xu, Org. Lett. 2002, 4, 2145Ϫ2148.
M. Shi,
Y. Chen, B. Xu, J. Tang, Tetrahedron Lett. 2002, 43,
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[4d]
Tetrahedron Lett. 2000, 41, 1615Ϫ1618.
G. L. N. Peron, D.
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42, 347Ϫ349.
L. Patient, M. B. Berry, J. D. Kilburn, Tetra-
hedron Lett. 2003, 44, 1015Ϫ1017.
[5]
Acknowledgments
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[6b]
L.-X. Shao, M. Shi, Eur. J. Org. Chem. 2004, 426Ϫ430.
We thank the State Key Project of Basic Research (Project 973, No.
G2000048007), the Chinese Academy of Sciences (KGCX2-210-
01), Shanghai Municipal Committee of Science and Technology,
and the National Natural Science Foundation of China for finan-
cial support (203900502, 20025206, and 20272069).
A. T. Bottini, L. I. Cabral, Tetrahedron 1978, 34, 3187Ϫ3194.
Huang and co-workers recently reported that (Z)-2,4-dihalo-
butenes were obtained from the dihalogenation of MCPs
mediated by CuX2 (X ϭ Cl, Br, I) at 65 °C. H.-W. Zhou, X.
Huang, W.-L. Chen, Synlett 2003, 2080Ϫ2082.
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[1a]
Synthesis of MCPs:
98, 589Ϫ635.
A. Brandi, A. Goti, Chem. Rev. 1998,
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‘‘Carbocyclic Three-Membered Ring Com-
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For the ring opening of MCPs by type I, see:
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[8a]
For some reviews, see:
H. Shine, Aromatic Rearrangement,
American Elsevier Publishing Company, New York, 1967, pp.
[8b]
[2a]
221Ϫ230, 362Ϫ364.
A. Bieron, P. Dinan, in The Chemistry
D. H. Cama-
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Mechanism in Organic Chemistry, 1st ed., Cornell University
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C. K. Ingold, Structure and
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MCPs 1 with bromine at Ϫ5 °C in which 1,2-dibromo-1-meth-
ylenecyclopropanes were obtained.
[9a]
M. Hanack, T. Bassler,
Eur. J. Org. Chem. 2004, 4894Ϫ4900
www.eurjoc.org
© 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4899

L.-X. Shao, L.-J. Zhao, M. Shi
FULL PAPER
W. Eymann, W. E. Heyd, R. Kopp, J. Am. Chem. Soc. 1974,
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B. C. Anderson, J. Org.
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L. Volta, C. J. M. Stirling,
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[9g]
S. Kozhushkov, T. Spätch, T. Fiebig, B. Galland, M.-F.
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V. R. Kopp, M. Han-
R. Köster, S. Arora, P.
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Binger, Justus Liebigs Ann. Chem. 1973, 1619Ϫ1627 (the reac-
[10]
tion is described below).
Received June 2, 2004
4900
© 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 4894Ϫ4900