Synthesis and unusual [2+2]-cycloaddition reactions of ethyl 4-chloro-2-oxobut-3-ynoate with unactivated alkenes

Article abstract of DOI:10.1016/j.tet.2008.07.066

The highly activated acetylenes, ethyl 4-chloro-2-oxobut-3-ynoate and ethyl 4-bromo-2-oxobut-3-ynoate, were prepared from readily available bis(trimethylstannyl)acetylene in two steps with high overall yield. An unusual ability of the former to furnish [2

Full text of DOI:10.1016/j.tet.2008.07.066

Tetrahedron 64 (2008) 9555–9560
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Synthesis and unusual [2þ2]-cycloaddition reactions of ethyl 4-chloro-2-oxobut-
3-ynoate with unactivated alkenes
*
Andrey B. Koldobskii , Ekaterina V. Solodova, Ivan A. Godovikov, Valery N. Kalinin
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov Street 28, 119991 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
The highly activated acetylenes, ethyl 4-chloro-2-oxobut-3-ynoate and ethyl 4-bromo-2-oxobut-3-
ynoate, were prepared from readily available bis(trimethylstannyl)acetylene in two steps with high
overall yield. An unusual ability of the former to furnish [2þ2]-cycloadducts with 1,1-disubstituted al-
kenes in the absence of irradiation and catalysts was discovered. The cycloaddition of ethyl 4-chloro-2-
oxobut-3-ynoate to the 1,2-disubstituted alkenes was shown to be effectively catalyzed with stannic
chloride.
Received 17 April 2008
Received in revised form 10 July 2008
Accepted 17 July 2008
Available online 23 July 2008
Keywords:
Ó 2008 Elsevier Ltd. All rights reserved.
[2þ2]-Cycloaddition reaction
Electron-accepting acetylenes
1. Introduction
2. Results and discussion
Four-membered carbocycles are important building blocks in
the total synthesis of natural products, and are also very reactive
and useful tools in many transformations.1 Cycloaddition reactions
are among the most powerful and frequently used methods for the
construction of different rings,2 and the [2þ2]-cycloaddition of
alkenes and/or alkynes is a simple and versatile strategy in the
synthesis of cyclobutane and cyclobutene derivatives.3 This ther-
mally forbidden process by the Woodward–Hoffman rules,4 can be
achieved photochemically,5 by thermal radical reactions6 or by
using either Lewis acid catalysts7 or transition metal catalysts.8 In
the absence of irradiation and a catalyst, the cycloaddition is only
possible between unsaturated partners with strong donating and
strong accepting substituents, when stepwise mechanism is
realized.9
2.1. The synthesis of ethyl 4-halo-2-oxobut-3-ynoates
After numerous unsuccessful attempts using trimethylsilylace-
tylene and bis(trimethylsilyl)acetylene we discovered that readily
available11 bis(trimethylstannyl)acetylene 1 reacts with ethyl-
oxalylchloride at ambient temperature to form 2-oxo-4-trime-
thylstannyl-3-butynoate 2, which is stable under storage and
distillable in vacuum (Scheme 1).
O
O
O
C
O
Cl
OEt
20 °C, 1 week
Me3Sn-C
C
Me3Sn-C
C-SnMe3
C
+
Me3SnCl
OEt
2
1
2-Oxo-3-butynoic esters represent an important class of organic
compounds due to their unique structure with multiple functional
groups and strong activation of the triple bond. Although several
methods have been reported for their synthesis,10 the halogenated
acetylenes 3a, b were unknown until now. We expected these
compounds to be very reactive in the different cycloadditions and
the cycloadducts should be a versatile tool in heterocyclization
processes.
75 - 80%
Scheme 1.
Acetylene 2 can be easily halogenated to furnish the target
compounds 3a, b. The main challenge at this stage is to separate the
halogenated acetylenes from halotrimethylstannanes, simulta-
neously formed. The purification of compound 3a can be achieved
by washing the reaction mixture with cold water, whereas in the
case of 3b, fraction distillation is necessary, although it leads to
decreased yields (Scheme 2).
In this article, we describe the preparative synthesis and un-
usual [2þ2]-cycloaddition reactions of the halogenated acetylenes
3a, b with simple alkenes.
Acetylenes 3a, b appeared to be relatively stable compounds and
can be stored for a prolonged time and distilled in vacuum without
decomposition.
* Corresponding authors. Tel.: þ7 499 135 9251; fax: þ7 499 135 6549.
E-mail address: andikineos@rambler.ru (A.B. Koldobskii).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.07.066

9556
A.B. Koldobskii et al. / Tetrahedron 64 (2008) 9555–9560
O
O
O
C
O
C
O
O
Cl2 or Br2
CH2Cl2, -20 °C
or
Cl-C
3a
C
C
C
Br-C
3b
C
C
Me3Sn-C
C
C
OEt
OEt
OEt
2
94%
58%
Scheme 2.
2.2. Thermal [2D2]-cycloaddition reactions of ethyl 4-chloro-
2-oxobut-3-ynoate with 1,1-disubstituted alkenes
owing to the strong negative mesomeric effect of the ethoxyoxalyl
group. The resonance form describing such a redistribution of
electron density has ketenium structure, which enables the con-
certed [p2sþp2a]-cycloaddition (Scheme 4).
Investigating the reaction of acetylene 3a with 1,1-dis-
ubstitruted alkenes, we initially expected to receive the ene addi-
tion adducts under mild conditions due to the strong activation
effect of the ethoxyoxalyl function. It was found that this reaction
indeed takes place even at 60 ꢀC, but to our surprise [2þ2]-cyclo-
adducts 4 (head to head) were detected as the major products.
Cycloadducts (head to tail) 5 and ene adducts 6 were also formed in
small quantities. Fortunately, in some cases it was possible to
separate these isomeric substances by column chromatography
(Table 1, Scheme 3).
Thus, these cycloaddition reactions do not require either irra-
diation or catalysts. It was also found that the addition of radical
traps has no effect on the rate and direction of the reaction. Polar
solvents are known to accelerate considerably [2þ2]-dipolar cy-
cloadditions, however, addition of acetonitrile did not result in any
apparent acceleration of interactions. The formation of two
regioisomers 4 and 5 is also contradicting both the polar and the
radical mechanism. The above facts allowed us to suggest that
acetylene 3a undergoes addition to alkenes by a concerted mech-
anism although it is symmetry forbidden. To overcome this con-
tradiction, we supposed that the bond index of the terminal carbon
atom and halogen atom in the molecule 3a is sharply increased
It should be noted that according to the previously published
report, acetylenes such as acetylenedicarboxylic esters, hexa-
fluorobutyne-2, 1,1,1-trifluoropropine, and propiolic esters, mole-
cules, which do not contain a mesomeric electron donating
substituent at the C^C– bond, react with simple alkenes under
severe conditions to give only ene addition products.12
2.3. Catalytic [2D2]-cycloaddition reactions of ethyl 4-
chloro-2-oxobut-3-ynoate with 1,2-disubstituted or
monosubstituted alkenes
The further studies have shown that acetylene 3a possesses
insufficient electrophilicity for addition to the less reactive mono-
substituted and 1,2-disubstituted alkenes. The reaction did not take
place below 80–90 ꢀC, whereas the decomposition of the enophile
occurred under higher temperature. We discovered, however, that
SnCl4 exerts powerful catalytic effect and the cycloadditions were
complete within 1–2 h at 0 ꢀC. The process is stereospecific and the
resulted cyclobutenes conserve the configuration of the initial al-
kenes, but not regiospecific and hexene-1 forms two regioisomers
in the ratio 5:1 according to the 1H NMR spectroscopy data. A target
Table 1
The reactions of 2-oxo-4-chloro-3-ethylbutynoate 3a with 1,1-disubstituted alkenes
Entry
Alkene
Adduct 4 (head to head)
(isolated yield)
Adduct 5 (head to tail)
(isolated yield)
Ene adduct 6 (isolated yield)
Ratio 4/5/6 in reaction mixture
(according to 1H NMR spectroscopy)
CH3
Cl
H2C
H3C
Cl
CH3
COCOOEt
(50%)
Cl
H3C
COCOOEt
(0%)
H3C
CH3
H3C
a
15:3:5
20:7:3
(15%)
CH2
COCOOEt
CH2
COCOOEt
(52%)
Cl
COCOOEt
(0%)
Cl
Cl
b
c
(15%)
COCOOEt
COCOOEt
(37%)
COCOOEt
CH2
CH2
d
1:0:1
(37%)
Cl
Cl
COCOOEt
(53%)
Cl
(26%)
d
d
13:7: 0
COCOOEt
Cl
O
C
O
O
C
C
Cl
O
O
Cl
R
Cl
C
C
OEt
R
R
O
C
C
R
O
60 °C
24 h
OEt
OEt
C
+
Cl-C
+
H2C
C
+
OEt
R
R
R
6
3a
5
4
R
Scheme 3.

A.B. Koldobskii et al. / Tetrahedron 64 (2008) 9555–9560
9557
-
OH
O
O
H3C
+
CH
O
C
Cl
COOEt
CH3
3 -60 °C, SnCl4
CH2Cl2
O
Cl
C
C
C
Cl+
C
C
C
Cl
C
C
C
CH2
OEt
COOEt
COOEt
8
3a
CH2
Scheme 4.
Scheme 6.
ketones, which are very useful compounds for different hetero-
cyclization reactions.
Table 2
The catalytic reactions of ethyl 4-chloro-2-oxobut-3-ynoate 3a with 1,2-di-
substituted and monosubstituted alkenes
In order to distinguish the isolated isomers 4 and 5 we have
elaborated two simple methods. The first is a reaction with
pyridine. We supposed that isomers (head to head) would react
with pyridine match faster than the isomers (head to tail) owing
to the steric hindrances of the last. Indeed this was shown to be
the case: the isomers 4 form pyridinium salts almost quantita-
tively within 6 h at 20 ꢀC in ether whereas the isomers 5 give
only the traces of the products after a week. The second and
most convincing evidence is based on that the cycloadducts 4
are enolizable ketones whereas cycloadducts 5 are not. Due to
this structural feature isomers 4 undergo rapid H–D-exchange at
C-3 center in a solution of DCl/D2O in dioxane, and the progress
of the reaction can be easily monitored by 1H NMR spectroscopy.
Entry
Alkene
Adduct 7 (isolated yield, %)
Conditions (time)
1.5 h
Cl
a
85%
COCOOEt
Cl
b
c
1 h
88%
COCOOEt
Cl
H3C
H3C
H3C
H3C
H3C
68 %
40 min
COCOOEt
Cycloadducts
(Scheme 7).
5
remain unchangeable at these conditions
Cl
CH3
95 %
d
e
15 min
50 min
COCOOEt
H3C
H3C
Cl
3. Conclusion
H9C4
Cl
C4H9
CH2
+
The strongly activated acetylenes ethyl 4-chloro-2-oxobut-3-
ynoate and ethyl 4-bromo-2-oxobut-3-ynoate were obtained for
the first time in two simple steps. An unusual ability of 2-oxo-4-
chloro-3-ethylbutynoate to form [2þ2]-cycloadducts with 1,1-di-
substituted alkenes was discovered. It was also shown that the
addition of 3a to the less reactive 1,2-disubstituted alkenes is
effectively catalyzed with stannic chloride.
COCOOEt
unseparated
COCOOEt
H9C4
72%
R
Cl
R
O
C
O
0 °C, SnCl4
CH2Cl2
+
Cl
C
C
C
O
R
OEt
4. Experimental
4.1. General
C
O
C
R
OEt
Scheme 5.
Manipulations with trimethylstannylacetylenes were carried
out in an argon atmosphere, though the contact with air within the
several seconds is not critical. Ethyl oxalyl chloride was distilled
prior to use. Acetylene has been purified by passing through the
sulfuric acid and the cooling (dry ice) trap.
product 7e was isolated in a good yield, whereas we were unable to
separate the minor compound (head to tail) (Table 2, Scheme 5).
Inspired with these results, we tried to expand the catalytic
approach to the reaction of acetylene 3a with 1,1-disubstituted al-
kenes but unfortunately only a Prins reaction was found to take
place at low temperature to afford alcohol 8, whereas heating up to
0 ꢀC caused the polymerization of alkene (Scheme 6).
Currently, we do not have a reasonable explanation of such
a difference in the reaction ability between 1,2- and 1,1-di-
substituted alkenes, but we believe that the thermal and catalytic
methodologies complement each other. It should be also noted that
4.2. Bis(trimethylstannyl)acetylene (1)
This compound was obtained according to Ref. 12 with some
modifications, which allow to simplify the isolation and to increase
the yield.
To the vigorously stirred solution of BuLi (1.0 N) in hexane
(800 mL) at ꢁ35 ꢀC the strong stream of acetylene was introduced
until the absorption of the gas has stopped (gas counter at the exit
of the system). The reaction mixture was refluxed for 1 h, cooled to
all the cycloadducts have the structure of
b
-chloro–
a
,
b-unsaturated
O
C
O
O
O
R
R
O
C
C
O
R
D
R
C
C
C
OEt
DCl/D2O
dioxane
Py, Et2O
R
D
R
OEt
OEt
N+
25 °C, 6 h
Cl-
Cl
Cl
9
4
10
R, R = CH3 (9a), -(CH2)5- (9b)
R, R = CH3 (10a), -(CH2)5- (10b)
Scheme 7.

9558
A.B. Koldobskii et al. / Tetrahedron 64 (2008) 9555–9560
ꢁ35 ꢀC and the solution of trimethyltin chloride (160.00 g,
0.80 mol) in 200 mL of hexane was added in one portion to the
stirred suspension of lithium acetylenide. The mixture was refluxed
and stirred additionally for 1 h and then exposed in argon atmo-
sphere at ambient conditions overnight. The most part of the clear
solution was carefully decanted from lithium chloride, the pre-
cipitate was diluted with hexane and filtered off. The combined
hexane solution was concentrated and the residue was distilled in
vacuo with an air condenser in such a rate to prevent the crystal-
lization in the condenser. The distillate quickly solidified on
standing. The yield of 1 was 100.00–105.00 g (70.0–74.0%), bp
99–101 ꢀC (10 Torr), mp 58–60 ꢀC (lit.12 mp 58–60 ꢀC).
4.4.1. Ethyl (2-chloro-4,4-dimethylcyclobut-1-en-1-yl)(oxo)-
acetate (4a)
From 3a with isobutylene. Pale yellow oil; yield 0.34 g (50%);
[Found: C, 55.62; H, 6.22; Cl, 16.18. C10H13ClO3 requires: C, 55.44; H,
6.05; Cl,16.36%.] Rf¼0.3; IR (neat) 2965, 2874,1742, 1667, 1602 cmꢁ1
;
dH (400 MHz, CDCl3) 4.33 (2H, q, J 7.1 Hz, OCH2CH3), 2.59 (2H, s, –C–
CH2–C]), 1.36 (3H, t, J 7.1 Hz, OCH2CH3), 1.33 (6H, s, Me2C); dC
(100.6 MHz, CDCl3)178.6,162.7,143.7,143.1, 62.4, 50.9, 42.7, 24.2,13.9.
4.4.2. Ethyl (2-chloro-3,3-dimethylcyclobut-1-en-1-yl)(oxo)-
acetate (5a)
From 3a with isobutylene. Pale yellow oil; yield 0.10 g (15%);
[Found: C, 55.40; H, 6.18; Cl, 16.42. C10H13ClO3 requires: C, 55.44; H,
6.05; Cl, 16.36%.] Rf¼0.25; IR (neat) 2960, 2878, 1742, 1667,
4.3. Ethyl 2-oxo-4-(trimethylstannyl)but-3-ynoate (2)
1602 cmꢁ1
; dH (400 MHz, CDCl3) 4.35 (2H, q, J 7.1 Hz, OCH2CH3),
The suspension of acetylene 1 (50 g, 0.14 mol) in ethyl oxalyl
chloride (77.5 g, 0.570 mol) was magnetically stirred until the dis-
solution of the solid was complete, than the solution was stored for
1 week at 25 ꢀC. The excess of ethyl oxalyl chloride and trimethyltin
chloride were distilled off at 10 Torr with a short column until the
internal temperature reached 70 ꢀC (the distilled mixture can be
repeatedly fractionated at atmospheric pressure collecting the
major fraction in the temperature interval 128–134 ꢀC and using it
in the same synthesis), the dark residue was distilled in the deep
vacuum to furnish compound 2 (33.7 g, 82%) as a colorless liquid;
bp 95–97 ꢀC (0.6 Torr) (the less deep vacuum may caused the par-
tial decomposition); [Found: C, 37.02; H, 4.80; Sn, 40.80. C9H14O3Sn
requires: C, 37.42; H, 4.88; Sn, 41.08%.] IR (neat) 2987, 2190, 1748,
2.56 (2H, s, –C–CH2–C]), 1.38 (3H, t, J 7.1 Hz, OCH2CH3), 1.25 (6H, s,
Me2C); dC (100.6 MHz, CDCl3) 178.6, 162.4, 153.4, 132.1, 62.5, 48.0,
40.9, 22.8, 13.8.
4.4.3. Ethyl 1-chlorospiro[3.5]non-1-ene-2-carboxylate (4b)
From 3a with methylenecyclohexane. Pale yellow oil; yield
0.40 g (52%); [Found: C, 60.92; H, 6.69; Cl, 13.85. C13H17ClO3 re-
quires: C, 60.82; H, 6.67; Cl, 13.81%.] Rf¼0.3; IR (neat) 2929, 2854,
1744, 1666, 1600 cmꢁ1
; dH (400 MHz, CDCl3) 4.33 (2H, q, J 7.1 Hz,
OCH2CH3), 2.56 (2H, s, –C–CH2–C]), 1.91 (m), 1.65 (m), 1.50 (m),
1.23 (m) (totally 10H, –(CH2)5–), 1.35 (3H, t, J 7.1 Hz, OCH2CH3); dC
(100.6 MHz, CDCl3) 178.9, 162.9, 144.7, 144.1, 62.4, 48.4, 47.8, 33.2,
25.4, 25.0, 13.9.
1685 cmꢁ1
; dH (400 MHz, CDCl3) 4.32 (2H, q, J 7.1 Hz, OCH2CH3),
1.35 (3H, t, J 7.1 Hz, OCH2CH3), 0.4 (9H, s, Me3Sn); dC (100.6 MHz,
CDCl3) 168.6, 159.3, 110.6, 104.5, 63.0, 13.9, ꢁ7.7.
4.4.4. Ethyl 2-chlorospiro[3.5]non-1-ene-1-carboxylate (5b)
From 3a with methylenecyclohexane. Pale yellow oil; yield
0.12 g (15%); [Found: C, 60.90; H, 6.71; Cl, 13.88. C13H17ClO3 re-
quires: C, 60.82; H, 6.67; Cl, 13.81%.] Rf¼0.25; IR (neat) 2931, 2852,
4.3.1. Ethyl 4-chloro-2-oxobut-3-ynoate (3a)
To the stirred solution of compound 2 (20.70 g, 0.072 mol) in
CH2Cl2 (60 mL) at ꢁ30 ꢀC the solution of chlorine (5.90 g,
0.083 mol) in CCl4 (18 mL) was added dropwise. After the warming
to the ambient temperature the solvent was removed in vacuum
and the residue was diluted with hexane (150 mL). The resultant
solution was washed with cold water (3ꢂ100 mL), dried with
Na2SO4, concentrated, and the crude product was distilled to afford
acetylene 3a (9.0 g, 78%) as a colorless liquid; bp 53 ꢀC (1 Torr);
[Found: C, 44.59; H, 3.17; Cl, 22.18. C6H5ClO3 requires: C, 44.89; H,
1738, 1666, 1660 cmꢁ1
; dH (400 MHz, CDCl3) 4.42 (2H, q, J 7.1 Hz,
OCH2CH3), 2.53 (2H, s, –C–CH2–C]), 1.72 (m), 1.32 (m) (totally 10H,
–(CH2)5–), 1.40 (3H, t, J 7.1 Hz, OCH2CH3); dC (100.6 MHz, CDCl3)
178.5, 162.4, 153.4, 133.1, 62.4, 52.8, 38.8, 32.6, 23.2, 22.0, 14.0.
4.4.5. Ethyl 2-chlorospiro[3.4]oct-1-ene-1-carboxylate (4c)
From 3a with methylenecyclopentane. Pale yellow oil; yield
0.28 g (37%); [Found: C, 60.00; H, 6.22; Cl, 14.23. C12H15ClO3 re-
quires: C, 59.39; H, 6.23; Cl, 14.23%.] Rf¼0.3; IR (neat) 2954, 2867,
3.14; Cl, 22.08%.] IR (neat) 2988, 2195, 1742, 1691, 1141 cmꢁ1
;
dH
1740, 1667, 1602 cmꢁ1
; dH (400 MHz, CDCl3) 4.36 (2H, q, J 7.1 Hz,
(400 MHz, CDCl3) 4.36 (q, 2H, J 7.1 Hz, OCH2CH3),1.38 (3H, t, J 7.1 Hz,
OCH2CH3); dC (100.6 MHz, CDCl3) 168.1, 158.4, 79.8, 67.7, 63.6.
OCH2CH3), 2.68 (2H, s, –C–CH2–C]), 2.03 (m), 1.79 (m), 1.67 (m)
(totally 8H, –(CH2)4–),1.38 (3H, t, J 7.1 Hz, OCH2CH3); dC (100.6 MHz,
CDCl3) 178.6, 162.8, 143.2, 140.7, 62.3, 52.5, 52.1, 33.9, 24.4, 13.9.
4.3.2. Ethyl 4-bromo-2-oxobut-3-ynoate (3b)
To the stirred solution of compound 2 (20.70 g, 0.072 mol) in
CH2Cl2 (60 mL) at ꢁ30 ꢀC the solution of bromine (12.60 g,
0.078 mol) in CH2Cl2 (18 mL) was added dropwise. After warming
to the ambient temperature the solvent was removed in vacuum
and the residue was fractionated on effective column to afford
compound 3b (8.6 g, 58%) as a yellowish liquid; bp 76–77 ꢀC
(2 Torr); [Found: C, 34.89; H, 2.52; Br, 39.09. C6H5BrO3 requires: C,
4.4.6. Ethyl (3Z)-4-chloro-5-cyclopent-1-en-1-yl-2-oxopent-3-
enoate (6c)
From 3a with methylenecyclopentane. Pale yellow oil; yield
0.28 g (37%); [Found: C, 59.77; H, 6.22; Cl, 14.26. C12H15ClO3 re-
quires: C, 59.39; H, 6.23; Cl, 14.23%.] Rf¼0.1; IR (neat) 2950, 2862,
1738, 1667, 1580 cmꢁ1
; dH (400 MHz, CDCl3) 7.03 (1H, s, ]CH–
COCOOEt), 5.63 (1H, s, –CH2–CH]), 4.37 (2H, q, J 7.1 Hz, OCH2CH3),
3.35 (s, 2H, ]C–CH2–C]), 2.36 (m), 1.95 (m) (totally 6H, –(CH2)3–),
1.41 (3H, t, J 7.1 Hz, OCH2CH3); dC (100.6 MHz, CDCl3) 180.4, 161.9,
153.5, 137.6, 129.8, 119.4, 62.6, 43.8, 34.5, 32.6, 23.4, 13.9.
35.15; H, 2.46; Br, 38.98%.] IR (neat) 2993, 2199, 1745, 1690 cmꢁ1
; dH
(400 MHz, CDCl3) 4.38 (2H, q, J 7.1 Hz, OCH2CH3),1.39 (3H, t, J 7.1 Hz,
OCH2CH3); dC (100.6 MHz, CDCl3) 168.1, 158.3, 75.6, 64.5, 63.6.
4.4. General procedure for the thermal [2D2]-cycloaddition
reactions of ethyl 4-chloro-2-oxobut-3-ynoate 3a with 1,1-
disubstituted alkenes (Table 1)
4.4.7. Ethyl 2-chlorospiro[3.3]hept-1-ene-1-carboxylate (4d)
From 3a with methylenecyclobutane. Pale yellow oil; yield
0.36 g (53%); [Found: C, 57.52; H, 5.89; Cl, 15.82. C11H13ClO3 re-
quires: C, 57.78; H, 5.73; Cl, 15.50%.] Rf¼0.3; IR (neat) 2985, 2871,
Compound 3a (0.49 g, 0.0031 mol) and alkene (0.01 mol) were
heated in a sealed ampoule at 60 ꢀC for 24 h. The excess of alkene
was removed in vacuum and the residue was chromatographed on
a column (silica gel, hexane/AcOEt¼20:1).
1743, 1666, 1595 cmꢁ1
; dH (400 MHz, CDCl3) 4.42 (2H, q, J 7.1 Hz,
OCH2CH3), 2.93 (2H, s, –C–CH2–C]), 2.65 (m), 2.08 (m) (totally 6H,
–(CH2)3–), 1.43 (3H, t, J 7.1 Hz, OCH2CH3); dC (100.6 MHz, CDCl3)
178.7, 162.8, 143.8, 140.8, 62.4, 50.9, 47.6, 30.2, 16.0, 13.9.

A.B. Koldobskii et al. / Tetrahedron 64 (2008) 9555–9560
9559
4.4.8. Ethyl 1-chlorospiro[3.3]hept-1-ene-2-carboxylate (5d)
From 3a with methylenecyclobutane. Pale yellow oil; yield
0.18 g (26%); [Found: C, 57.62; H, 5.71; Cl, 15.18. C11H13ClO3 re-
quires: C, 57.78; H, 5.73; Cl, 15.50%.] Rf¼0.25; IR (neat) 2980, 2874,
4.5.5. Ethyl 4-butyl-2-chlorocyclobut-1-ene-1-carboxylate (7e)
From 3a and hexene-1, reaction time 50 min. Pale yellow oil;
yield 0.64 g (86%); [Found: C, 58.70; H, 6.87; Cl, 14.85. C12H17ClO3
requires: C, 58.90; H, 7.00; Cl, 14.49%.] Rf¼0.6; IR (neat) 2931, 2859,
1743, 1666, 1595 cmꢁ1
;
dH (400 MHz, CDCl3) 4.33 (2H, q, J 7.1 Hz,
1741, 1670, 1597, 1236 cmꢁ1
; dH (400 MHz, CDCl3) 4.31 (2H, q, J
OCH2CH3), 2.75 (2H, s, –C–CH2–C]), 2.35 (m), 2.17 (m), 1.94 (m)
(totally 6H, –(CH2)3–), 1.35 (3H, t, J 7.1 Hz, OCH2CH3); dC (100.6 MHz,
CDCl3) 178.2, 162.3, 149.5, 132.9, 62.4, 54.0, 40.3, 28.5, 16.0, 13.9.
7.1 Hz, OCH2CH3), 3.05 (1H, m, CH–Bu), 2.91 (dd, J 16.1, 4.6 Hz), 2.39
(dd, J 16.1, 1.0 Hz) (totally 2H, CH2), 1.86 (1H, m, C3H7CH), 1.85 (m),
1.24 (m) (totally 6H, –(CH2)3– from Bu), 1.33 (3H, t, J 7.1 Hz,
OCH2CH3), 0.84 (3H, t, Me); dC (100.6 MHz, CDCl3) 178.4, 162.5,
143.9, 140.6, 62.4, 41.9, 40.0, 31.8, 29.4, 22.6, 14.0, 13.9.
4.5. General procedure for stannic chloride catalyzed [2D2]-
cycloaddition reactions of 2-oxo-chloro-3-ethylbutynoate (3a)
with 1,2-disubstituted alkenes and with hexene-1 (Table 2)
4.6. Ethyl 2-(chloroethynyl)-2-hydroxy-4-methylpent-4-
enoate (8)
To the stirred solution of 3a (0.49 g, 0.0031 mol) and alkene
(0.0036 mol) in CH2Cl2 (25 mL) at 0 ꢀC the solution of SnCl4 (0.80 g,
0.0031 mol) in CH2Cl2 (5 mL) was added dropwise. The resultant
mixture was stirred at 0 ꢀC for the time specified for the each
compound below and than treated with the cold 10% HCl solution
(50 mL). The organic layer was separated, then the aqueous phase
was extracted with CH2Cl2 (20 mL), the combined organic solution
was washed with cold water (3ꢂ20 mL), dried with Na2SO4, con-
centrated in vacuum, and the crude material was purified by col-
umn chromatography (silica gel, hexane/AcOEt¼20:1).
This compound was obtained from isobutylene according to the
general procedure for 1,2-disubstituted alkenes with the exception
that the reactionwas carried out at ꢁ60 ꢀC for 1 h. Yellowish oil; yield
0.14 g (62%); [Found: C, 55.46; H, 5.98; Cl,16.37. C10H13ClO3 requires:
C, 55.44; H, 6.05; Cl,16.36%.] Rf¼0.2; IR (neat) 3489, 2983, 2226,1739,
1649, 1210 cmꢁ1
; dH (400 MHz, CDCl3) 4.88 (s), 4.78 (s) (totally 2H,
–C]CH2), 4.26(2H, q, J7.1 Hz,OCH2CH3), 3.58(OH), 2.64(2H, m, CH2),
1.77 (3H, s, ]C–Me), 1.31 (3H, t, J 7.1 Hz, OCH2CH3); dC (100.6 MHz,
CDCl3) 171.5, 139.8, 116.0, 71.2, 68.2, 64.1, 63.2, 47.5, 23.9, 14.0.
4.5.1. Ethyl 7-chlorobicyclo[3.2.0]hept-6-ene-6-carboxylate (7a)
From 3a and cyclopentene, reaction time 1.5 h. Pale yellow oil;
yield 0.60 g (85%); [Found: C, 56.92; H, 5.53; Cl, 15.04. C11H13ClO3
requires: C, 57.78; H, 5.73; Cl, 15.50%.] Rf¼0.5; IR (neat) 2960, 2862,
4.7. General procedure for preparation of the pyridinium
salts (9)
To the solution of pyridine (3.30 mmol) in Et2O (1.50 mL) com-
pound 4a or 4b (3.00 mmol) was added and the resultant solution
was stirred at 25 ꢀC for 6 h. The solid salt was filtered off, washed
with ether, and dried in vacuum.
1740, 1668, 1596, 734 cmꢁ1
; dH (400 MHz, CDCl3) 4.31 (2H, q, J
7.1 Hz, OCH2CH3), 3.40 (1H, dd, J 7.8, 3.4 Hz, CH), 3.29 (1H, dd, J 7.8,
3.4 Hz, CH), 1.73 (m), 1.48 (m) (totally 6H, –(CH2)3–), 1.29 (3H, t, J
7.1 Hz, OCH2CH3); dC (100.6 MHz, CDCl3) 178.0, 162.3, 145.6, 136.4,
62.4, 53.0, 49.7, 25.6, 24.3, 22.5, 13.9.
4.7.1. 1-{2-[Ethoxy(oxo)acetyl]-3,3-dimethylcyclobut-1-en-1-
yl}pyridinium chloride (9a)
4.5.2. Ethyl 8-chlorobicyclo[4.2.0]oct-7-ene-7-carboxylate (7b)
From 3a and cyclohexene, reaction time 1 h. Pale yellow oil;
yield 0.75 g (88%); [Found: C, 59.77; H, 6.20; Cl, 14.76. C12H15ClO3
requires: C, 59.39; H, 6.23; Cl, 14.61%.] Rf¼0.5; IR (neat) 2939, 2866,
White solid; mp 147–149 ꢀC; yield 0.83 g (94%); [Found: C,
61.07; H, 5.98; Cl, 11.67; N, 5.01. C15H18ClNO3 requires: C, 60.91; H,
6.13; Cl, 11.99; N, 4.74%.]; dH (400 MHz, CD3CN) 9.46 (2H, d, H-C2
arom.), 8.89 (1H, t, H-C4 arom.), 8.40 (2H, t, H-C3 arom.), 4.47 (2H, q,
J 7.1 Hz, OCH2CH3), 3.08 (2H, s, C–CH2–C]), 1.51 (3H, t, J 7.1 Hz,
OCH2CH3), 1.41 (6H, s, Me2C); dC (100.6 MHz, CD3CN) 182.4, 164.3,
156.2, 148.2, 146.4, 144.1, 134.7, 64.3, 56.7, 44.2, 17.0, 15.6.
1741, 1669, 1595 cmꢁ1
; dH (400 MHz, CDCl3) 4.31 (2H, q, J 7.1 Hz,
OCH2CH3), 3.40 (1H, dd, J 10.4, 5.0 Hz, CH), 3.08 (1H, dd, J 10.4,
5.0 Hz, CH), 1.78 (m), 1.48 (m) (totally 8H, –(CH2)4–), 1.35 (3H, t, J
7.1 Hz, OCH2CH3); dC (100.6 MHz, CDCl3) 178.2, 162.3, 147.9, 139.3,
62.3, 46.1, 38.0, 22.7, 21.9, 18.0, 17.9, 13.9.
4.7.2. 1-{1-[Ethoxy(oxo)acetyl]spiro[3.5]non-1-en-2-yl}pyridinium
chloride (9b)
4.5.3. Ethyl 2-chloro-3,4-(Z)-dimethylcyclobut-1-ene-1-
carboxylate (7c)
White solid; mp 154–155 ꢀC; yield 0.97 g (96%); [Found C, 64.45;
H, 6.93; Cl, 10.75; N, 4,46. C18H22ClNO3 requires: C, 64.38; H, 6.60;
Cl, 10.56; N, 4.17%.] dH (400 MHz, CD3CN) 9.49 (2H, d, H-C2 arom.),
8.90 (1H, t, H-C4 arom.), 8.44 (2H, t, H-C3 arom.), 4.46 (2H, q, J 7.1 Hz,
OCH2CH3), 3.11 (2H, s, C–CH2–C]), 1.99 (m), 1.70 (m), 1.24 (m)
From 3a and Z-butene-2, reaction time 40 min. Pale yellow oil;
yield 0.45 g (68%); [Found: C, 55.59; H, 6.07; Cl, 16.24. C10H13ClO3
requires: C, 55.44; H, 6.05; Cl, 16.36%.] Rf¼0.75; IR (neat) 2977, 1740,
1668, 1597 cmꢁ1
; dH (400 MHz, CDCl3) 4.27 (2H, q, J 7.1 Hz,
(totally 10H, –(CH2)5–); 1.50 (3H, t,
J 7.1 Hz, OCH2CH3); dC
OCH2CH3), 3.16 (1H, m, J 7.1, 4.75 Hz, CH–CH), 3.05 (1H, m, J 7.1,
4.75 Hz, CH–CH), 1.29 (3H, t, J 7.1 Hz, OCH2CH3), 1.08 (3H, d, J 7.1 Hz,
Me), 1.06 (3H, d, J 7.1 Hz, Me); dC (100.6 MHz, CDCl3) 178.6, 162.5,
148.5, 139.5, 62.4, 45.7, 37.7, 13.9, 12.6, 10.8.
(100.6 MHz, CD3CN) 181.9, 164.0, 158.5, 148.7, 145.4, 144.2, 134.2,
64.0, 56.2, 47.3, 35.9, 30.2, 27.4, 16.1.
4.8. General procedure for preparation of deuterium labeled
compounds (10)
4.5.4. Ethyl 2-chloro-3,4-(E)-dimethylcyclobut-1-ene-1-
carboxylate (7d)
From 3a and E-butene-2, reaction time 15 min. Pale yellow oil;
yield 0.63 g (95%); [Found: C, 55.07; H, 5.93; Cl, 16.75. C10H13ClO3
requires: C, 55.44; H, 6.05; Cl, 16.36%.] Rf¼0.6; IR (neat) 2983, 1741,
To the solution of D2O (2.00 g) and DCl (0.20 g) in dioxane
(6.00 mL) compound 4a or 4b (3.00 mmol) was added and the re-
sultant solution was exposed for 12 h at 25 ꢀC. The most part of D2O
and dioxane was removed in vacuum, the residue was diluted with
ether (10.00 mL), successively washed with the solution of NaOAc
(1 g) in D2O (5.00 mL) and D2O (5.00 mL), dried over Na2SO4, and
concentrated in vacuum. The resultant compounds 10a, b had
about 96–97%-deuterium purity at C-3 center.
1668, 1597 cmꢁ1
; dH (400 MHz, CDCl3) 4.28 (2H, q, J 7.1 Hz,
OCH2CH3), 2.62 (1H, dd, J 6.7, 1.3 Hz, CH–CH), 2.49 (1H, dd, J 6.7,
1.3 Hz, CH–CH), 1.32 (3H, t, J 7.1 Hz, OCH2CH3), 1.21 (3H, d, J 6.7 Hz,
Me), 1.17 (3H, d, J 6.7 Hz, Me); dC (100.6 MHz, CDCl3) 178.7, 162.4,
148.5, 138.3, 62.4, 50.8, 42.9, 16.4, 14.7, 13.9.

9560
A.B. Koldobskii et al. / Tetrahedron 64 (2008) 9555–9560
4.8.1. Ethyl (2-chloro-3,3-dideuterio-4,4-dimethylcyclobut-1-en-1-
yl)(oxo)acetate (10a)
References and notes
1. (a) Nemoto, H.; Fukumoto, K. Synlett 1997, 863–875; (b) Lee-Ruff, E.; Mlade-
nova, G. Chem. Rev. 2003, 103, 1449–1483.
2. Carruthers, W. Cycloaddition Reactions in Organic Synthesis; Pergamon: Oxford,
1990.
3. Trost, B. M.; Fleming, I.; Paquette, L. A. Comprehensive Organic Synthesis; Per-
gamon: Oxford, 1991; Vol. 5, Chapter 2.
4. Woodward, R. B.; Hoffman, R. The Conservation of Orbital Symmetry; Academic:
New York, NY, 1970.
Yellow oil; yield 0.58 g (88%); [Found: C, 55.62; H, D, 6.22; Cl,
16.18. C10H11D2ClO3 requires: C, 55.44; H, D, 6.05; Cl, 16.36%.] IR
(neat): 1742, 1671, 1605 cmꢁ1
; dH (400 MHz, CDCl3) 4.31 (2H, q, J
7.1 Hz, OCH2CH3), 1.36 (3H, t, J 7.1 Hz, OCH2CH3), 1.30 (6H, s,
(CH3)2C); dC (100.6 MHz, CDCl3) 178.6,162.6,143.3,142.9, 62.4, 50.8,
41.80 (quint, JCD 24.5 Hz, CD2–C), 24.0, 13.9.
5. Bach, T. Synthesis 1998, 683–708.
6. Roberts, J. D.; Kline, G. B.; Simmons, H. E. J. Am. Chem. Soc. 1953, 75, 4765–4768.
7. (a) Takasu, K.; Ueno, M.; Inanaga, K.; Ihara, M. J. Org. Chem. 2004, 69, 517–521;
(b) Boxer, M. B.; Yamamoto, H. Org. Lett. 2005, 7, 3127–3129 and references
therein.
8. (a) Villeneuve, K.; Jordan, R. W.; Tam, W. Synlett 2003, 2123–2126; (b) Shibata,
T.; Takami, K.; Kawachi, A. Org. Lett. 2006, 8, 1343–1345.
9. Miesch, M.; Wedling, F. Eur. J. Org. Chem. 2000, 3381–3392 and references
therein.
4.8.2. Ethyl 2-chloro-3,3-dideuterio-spiro[3.5]non-1-ene-1-
carboxylate (10b)
Yellow oil; yield 0.71 g (91%); [Found: C, 60.01; H, D 7.31; Cl,
13.57. C13H15D2ClO3 requires: C, 60.35; H, D 7.39; Cl, 13.70%.] IR
(neat): 1742, 1671, 1606 cmꢁ1
; dH (400 MHz, CDCl3) 4.33 (2H, q, J
7.1 Hz, OCH2CH3), 1.88 (m), 1.66 (m), 1.58 (m), 1.20 (m) (totally
10H, –(CH2)5–), 1.35 (3H, t, J 7.1 Hz, OCH2CH3); dC (100.6 MHz,
CDCl3) 179.3, 162.8, 144.3, 144.1, 62.5, 48.3, 47.1, 33.2, 25.4, 25.0,
13.9.
10. Guo, D. L.; Zhang, Z. J. Org. Chem. 2003, 68, 10172–10174 and references therein.
11. Organometallic Synthesis; Bruce King, R., Eisch, J. J., Eds.; Elsevier: Amsterdam,
1986; Vol. 3, pp 559–562.
12. Sauer, J. C.; Sausen, G. N. J. Org. Chem. 1962, 27, 2730–2732.