Synthesis of Highly Functionalized Cyclobutene Derivatives

Article abstract of DOI:10.1007/s00706-002-0609-1

Protonation of the reactive 1:1 intermediates produced in the reaction between triphenyl-phosphine and dialkyl acetylenedicarboxylates with CH-acids, such as ethyl 2,4-dioxo-hexanoate and ethyl 2,4-dioxo-5-methylhexanoate, lead to vinyltriphenylphosphonium salts, which undergo an intra-molecular Wittig reaction to produce cyclobutene derivatives in fairly high yields.

Full text of DOI:10.1007/s00706-002-0609-1

Monatshefte f€ur Chemie 134, 1221–1227 (2003)
DOI 10.1007/s00706-002-0609-1
Synthesis of Highly Functionalized
Cyclobutene Derivatives
ꢀ
Issa Yavari and Mohammad Bayat
Department of Chemistry, University of Tarbiat Modarres, P.O. Box 14115-175, Tehran, Iran
Received November 8, 2002; accepted November 29, 2002
Published online July 3, 2003 # Springer-Verlag 2003
Summary. Protonation of the reactive 1:1 intermediates produced in the reaction between triphenyl-
phosphine and dialkyl acetylenedicarboxylates with CH-acids, such as ethyl 2,4-dioxo-hexanoate and
ethyl 2,4-dioxo-5-methylhexanoate, lead to vinyltriphenylphosphonium salts, which undergo an intra-
molecular Wittig reaction to produce cyclobutene derivatives in fairly high yields.
Keywords. Cyclobutene derivatives; CH-acid; Intramolecular Wittig reaction; Acetylenic esters.
Introduction
Although several strategies for the synthesis of cyclobutenes have been developed
in the past [1–3], this class of cyclenes is generally not easily accessible. In recent
years, several routes to cyclobutenes via cycloaddition reactions have been
described [4–6]. However, the general applicability of these methods is limited.
We previously have described the synthesis of cyclobutene derivatives from the
stereoselective intramolecular Wittig reaction of a vinyltriphenylphosphonium salt
[7–9]. As part of our current studies on the development of new routes to hetero-
cyclic and carbocyclic systems, we now report a covenient and facile synthesis of
functionalized cyclobutene derivatives via intramolecular Wittig reaction.
Results and Discussion
The reactions of triphenylphosphine and dialkyl acetylenedicarboxylates 1 in the
presence of a strong CH-acid, such as ethyl 2,4-dioxopentanoate (2a), lead to
diastereomeric cyclobutene isomers 3 in high yields (Scheme 1).
We have not yet established a mechanism for the formation of 3 in an experi-
mental manner, but a possible explanation is proposed in Scheme 2. On the basis of
the well-established chemistry of trivalent phosphorus nucleophiles [10–14], it is
reasonable to assume that 3 results from initial addition of triphenylphosphine to
ꢀ
Corresponding author. E-mail: isayavar@yahoo.com

1222
I. Yavari and M. Bayat
Scheme 1
Scheme 2
the acetylenic ester and subsequent protonation of the 1:1 adduct by 2. Then, the
positively charged ion might be attacked by the conjugate base of the CH-acid to
form the phosphorane 4, which is converted to 3 under the reaction conditions
employed.
Compounds 3 possess two stereogenic centers, and two diastereoisomers are
expected. In fact, the NMR spectra of 3a–3i show the presence of both isomers.
The 3JHH values of the two adjacent methine groups have been employed to assign
the relative configuration.
The structures of 3a–3i were deduced from their elemental analyses and their
IR, 1H, and 13C NMR spectra. The 1H NMR spectra of the cyclobutene derivatives
display signals at about ꢀ ¼ 3.80–4.02 ppm for the two methine groups (doublets,
3JHH ¼ 3.0–6.0 Hz), in agreement with the cis geometry of these protons together

Synthesis of Cyclobutene Derivatives
1223
with signals at about ꢀ ¼ 3.55–4.12 ppm for the two methine groups (doublets,
3JHH ¼ 0.5–2.0 Hz) in agreement with a trans arrangement of these protons [15].
The 13C NMR spectra of cyclobutene derivatives 3a–3i exhibit two signals at
about ꢀ ¼ 44–46 and 44–52 ppm for the two CH groups of cis and trans isomers.
A partial assignment of 13C signals of 3a–3i is given in the Experimental. The
results show that bulky substituents prefere the trans geometry of 3. Diastereo-
1
meric ratios were determined by H NMR spectroscopy.
In conclusion, we have developed an efficient synthesis of highly function-
alized cyclobutene derivatives. The method carries the advantage of being per-
formed under neutral conditions and requires no activation or modification of
the educts. The procedure is simple, the reaction conditions are mild, and the yields
are fairly good.
Experimental
Elemental analyses were performed using a Heraeus CHN-O-Rapid analyzer. These results agreed
favorably with the calculated values. IR spectra were measured on a Shimadzu IR 460 spectrometer.
1H and 13C NMR spectra (CDCl3) were measured on a Bruker DRX-500 Avance spectrometer. The
mass spectra were recorded on a Shimadzu QP-1100-EX GC-Mass spectrometer operating at an
ionization potential of 70 eV. Dialkyl acetylenedicarboxylates 1 and triphenylphosphine were obtained
from Fluka (Buchs, Switzerland) and used without further purification.
Preparation of Ethyl 2,4-dioxoalkanoates 2 (See Ref. [16])
Compounds 2 were prepared from 10 mmol of diethyl oxalate and 10mmol of aliphatic ketones in the
presence of 10 mmol of sodium ethoxide using 30cm3 of ethanol as the solvent.
Ethyl 2,4-dioxopentanoate (2a, C7H10O4)
Colorless liquid, bp 130–135ꢁC=35 mm Hg (Ref. [17] 130ꢁC=37mm Hg), yield 1.26g (79%); IR
(KBr): ꢁꢀ¼ 1729 (C¼O), 1628 and 1592 (C¼C) cmꢂ 1
;
1H NMR (90 MHz, CDCl3): ꢀ ¼ 1.42
(t, J ¼ 7.0 Hz, CH3), 2.28 (s, CH3CO), 4.38 (q, J ¼ 7.0 Hz, OCH2), 6.40 (s, C¼C–H), 13.66 (br s,
OH) ppm; 13C NMR (22.5 MHz, CDCl3): ꢀ ¼ 13.31 (CH3), 26.79 (CH3CO), 61.81 (OCH2), 101.51
(¼C–H), 161.37 (C¼O ester), 166.46 (¼C–OH), 199.65 (C¼O) ppm.
Ethyl 2,4-dioxohexanoate (2b, C8H12O4)
Colorless liquid, bp 145–150ꢁC=35 mm Hg, yield 0.99g (57%); IR (KBr): ꢁꢀ¼ 1728 (C¼O), 1631 and
1591 (C¼C) cmꢂ 1
;
1H NMR (90 MHz, CDCl3): ꢀ ¼ 1.16 and 1.36 (2t, J ¼ 6.5Hz, 2CH3), 2.62
(q, J ¼ 6.5 Hz, CH2CO), 4.34 (q, J ¼ 6.5 Hz, OCH2), 6.42 (s, C¼C–H), 14.07 (br s, OH) ppm; 13C NMR
(22.4MHz, CDCl3): ꢀ ¼ 8.26 and 13.70 (2CH3), 33.84 (CH2CO), 62.18 (OCH2), 101.02 (C¼C–H),
161.90 (C¼O ester), 165.93 (C¼C–OH), 203.84 (C¼O) ppm.
Ethyl 5-methyl-2,4-dioxohexanoate (2c, C9H14O4)
Colorless liquid, bp 150–154ꢁC=30 mm Hg, yield 1.31g (70%); IR (KBr): ꢁꢀ¼ 1728 (C¼O), 1634 and
1592 (C¼C) cmꢂ 1; 1H NMR (90 MHz, CDCl3): ꢀ ¼ 1.22 (d, J ¼ 6.5 Hz, CHMe2), 1.42 (t, J ¼ 6.5 Hz,
CH3), 2.72 (sept, J ¼ 6.5 Hz, CHMe2), 4.42 (q, J ¼ 6.5 Hz, OCH2), 6.46 (s, C¼C–H), 14.01 (br s, OH)
ppm; 13C NMR (22.4MHz, CDCl3): ꢀ ¼ 13.56 (CH3), 18.12 (CHMe2), 38.56 (CHMe2), 61.97 (OCH2),
99.60 (C¼C–H), 161.70 (C¼O ester), 166.79 (C¼C–OH), 206.74 (C¼O) ppm.

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I. Yavari and M. Bayat
General Procedure for the Synthesis of 3 (Examplified by 3a)
To a magnetically stirred solution of 0.524 g of triphenylphosphine (1mmol) and 0.316g of ethyl 2,4-
dioxopentanoate 2a (1mmol) in 20cm3 of CH2Cl2 a mixture of 0.284g of dimethyl acetylenedicar-
boxylate (1mmol) in 2 cm3 of CH2Cl2 was added dropwise at ꢂ5ꢁC over 10min. The reaction mixture
was then allowed to warm to room temperature and stirred for 24h. The solvent was removed under
reduced pressure and the residue was purified by column chromatography (Merck silica gel 60, 70–230
mesh) using n-hexane:ethyl acetate ¼ 8:2 as eluent. The solvent was removed to afford 3a as a pale
1
yellow oil. The H NMR spectrum of the crude product was consistent with a mixture of cis:trans
isomers ¼ 9:1.
Dimethyl 4-acetyl-1-(ethoxycarbonyl)cyclobut-1-ene-2,3-dicarboxylate (3a, C13H16O7)
Pale yellow oil, yield 0.51g (90%); IR (KBr): ꢁꢀ¼ 1730 and 1696 (C¼O), 1635 (C¼C) cmꢂ 1; MS:
m=z (%) ¼ 285 (Mþ þ 1, 8), 254 (25), 211 (12), 181 (36), 122 (19), 59 (100).
1
Major isomer (cis-3a) (90%); H NMR (500 MHz, CDCl3): ꢀ ¼ 1.36 (t, J ¼ 7.0 Hz, CH3), 2.60
(s, CH3CO), 3.69 and 3.72 (2s, 2OCH3), 4.01 (d, J ¼ 5.5 Hz, CH), 4.03 (d, J ¼ 5.5 Hz, CH), 4.26–4.36
(m, OCH2) ppm; 13C NMR (125.7 MHz, CDCl3): ꢀ ¼ 14.03 (CH3), 29.39 (CH3CO), 44.65 and 44.66
(2CH), 52.47 and 52.49 (2OCH3), 61.69 (OCH2), 137.05 and 148.01 (C¼C), 159.93, 168.83, and
168.88 (3C¼O ester), 193.65 (C¼O) ppm.
1
Minor isomer (trans-3a) (10%); H NMR (500MHz, CDCl3): ꢀ ¼ 1.25 (t, J ¼ 7.0 Hz, CH3), 2.34
(s, CH3CO), 3.82 and 3.86 (2s, 2OCH3), 3.97 (d, J ¼ 1.6Hz, CH), 4.02 (d, J ¼ 1.6Hz, CH), 4.10–4.30
(m, OCH2) ppm; 13C NMR (125.7 MHz, CDCl3): ꢀ ¼ 14.02 (CH3), 29.45 (CH3CO), 45.14 and 52.33
(2CH), 52.41 and 52.81 (2OCH3), 61.56 (OCH2), 140.77 and 142.60 (C¼C), 159.86, 160.04, and
169.58 (3C¼O ester), 202.86 (C¼O) ppm.
Triethyl 4-acetylcyclobut-1-ene-1,2,3-tricarboxylate (3b, C15H20O7)
Pale green oil, yield 0.58 g (93%); IR (KBr): ꢁꢀ¼ 1725 and 1705 (C¼O), 1645 (C¼C) cmꢂ 1; MS: m=z
(%) ¼ 313 (Mþ þ 1, 10), 268 (60), 222 (35), 236 (78), 195 (100), 167 (68).
Major isomer (cis-3b) (60%); 1H NMR (500MHz, CDCl3): ꢀ ¼ 1.23–1.36 (3t, J ¼ 7.0 Hz, 3CH3),
2.60 (s, CH3CO), 3.99 (d, J ¼ 5.6 Hz, CH), 4.01 (d, J ¼ 5.6 Hz, CH), 4.10–4.34 (m, 3OCH2) ppm;
13C NMR (125.7MHz, CDCl3): ꢀ ¼ 14.04, 14.07, and 14.12 (3CH3), 29.32 (CH3CO), 44.77 and 45.00
(2CH), 61.40, 61.62, and 61.63 (3OCH2), 137.13 and 148.20 (C¼C), 160.05, 168.35, and 168.39
(3C¼O ester), 193.66 (C¼O) ppm.
Minor isomer (trans-3b) (40%); 1H NMR (500MHz, CDCl3): ꢀ ¼ 1.30–1.36 (3t, J ¼ 7.0 Hz,
3CH3), 2.34 (s, CH3CO), 3.82 (d, J ¼ 1.9Hz, CH), 3.98 (d, J ¼ 1.9 Hz, CH), 4.20–4.30 (m, 3OCH2)
ppm; 13C NMR (125.7MHz, CDCl3): ꢀ ¼ 14.10, 14.11, and 14.12 (3CH3), 29.32 (CH3CO), 44.77 and
53.09 (2CH), 61.40, 61.42, and 61.62 (3OCH2), 141.32 and 142.16 (C¼C), 159.69, 160.02, and 169.14
(3C¼O ester), 203.01 (C¼O) ppm.
Di-tert-butyl 4-acetyl-1-(ethoxycarbonyl)cyclobut-1-ene-2,3-dicarboxylate
(3c, C19H28O7)
Pale yellow oil, yield 0.68g (92%); IR (KBr): ꢁꢀ¼ 1722 and 1696 (C¼O), 1640 (C¼C) cmꢂ 1; MS:
m=z (%) ¼ 368 (Mþ , 4), 312 (42), 268 (100), 222 (57), 194 (60), 121 (29).
1
Major isomer (trans-3c) (80%); H NMR (500 MHz, CDCl3): ꢀ ¼ 1.34 (t, J ¼ 7.0 Hz, CH3), 1.47
and 1.51 (2s, 2OCMe3), 2.32 (s, CH3CO), 3.68 (d, J ¼ 1.5 Hz, CH), 3.89 (d, J ¼ 1.5Hz, CH), 4.27
(q, J ¼ 7.1 Hz, OCH2) ppm; 13C NMR (125.7MHz, CDCl3): ꢀ ¼ 14.14 (CH3), 27.95 and 27.80
(2OCMe3), 31.00 (CH3CO), 46.36 and 52.18 (2CH), 61.52 (OCH2), 82.32 and 82.71 (2OCMe3),
140.41 and 143.38 (C¼C), 158.94, 160.27, and 168.38 (3C¼O ester), 203.91 (C¼O) ppm.

Synthesis of Cyclobutene Derivatives
1225
1
Minor isomer (cis-3c) (20%); H NMR (500 MHz, CDCl3): ꢀ ¼ 1.10 (t, J ¼ 7.0 Hz, CH3), 1.43
and 1.44 (2s, 2OCMe3), 2.27 (s, CH3CO), 3.88 (d, J ¼ 5.5 Hz, CH), 4.00 (d, J ¼ 5.5Hz, CH), 4.21
(q, J ¼ 7.1 Hz, OCH2) ppm; 13C NMR (125.7MHz, CDCl3): ꢀ ¼ 13.95 (CH3), 27.72 and 27.98
(2OCMe3), 30.41 (CH3CO), 45.60 and 45.86 (2CH), 62.20 (OCH2), 81.90 and 82.70 (2OCMe3),
136.62 and 148.50 (C¼C), 159.06, 167.66, and 167.90 (3C¼O ester), 196.02 (C¼O) ppm.
Dimethyl 4-propionyl-1-(ethoxycarbonyl)cyclobut-1-ene-2,3-dicarboxylate (3d, C14H18O7)
Pale yellow oil, yield 0.58g (97%); IR (KBr): ꢁꢀ¼ 1730 and 1710 (C¼O), 1638 (C¼C) cmꢂ 1; MS:
m=z (%) ¼ 298 (Mþ , 15), 253 (100), 222 (23), 137 (54), 151 (37), 137 (60), 59 (78).
1
Major isomer (cis-3d) (90%); H NMR (500MHz, CDCl3): ꢀ ¼ 1.12 and 1.32 (2t, J ¼ 7.0 Hz,
2CH3), 2.97–3.04 (m, CH2CO), 3.72 and 3.76 (2s, 2OCH3), 4.01 (d, J ¼ 5.5 Hz, CH), 4.04
(d, J ¼ 5.5 Hz, CH), 4.26–4.30 (m, OCH2) ppm; 13C NMR (125.7MHz, CDCl3): ꢀ ¼ 7.20 and
13.90 (2CH3), 34.96 (CH2CO), 44.58 and 44.76 (2CH), 52.18 and 52.53 (2OCH3), 61.53 (OCH2),
136.30 and 148.17 (C¼C), 159.94, 168.84, and 168.91 (3C¼O ester), 196.83 (C¼O) ppm.
1
Minor isomer (trans-3d) (10%); H NMR (500MHz, CDCl3): ꢀ ¼ 1.09 and 1.43 (2t, J ¼ 7.1 Hz,
2CH3), 2.66–2.72 (m, CH2CO), 3.74 and 3.82 (2s, 2OCH3), 3.71 (d, J ¼ 1.02Hz, CH), 3.98
(d, J ¼ 1.02 Hz, CH), 4.70–4.80 (m, OCH2) ppm; 13C NMR (125.7 MHz, CDCl3): ꢀ ¼ 7.33 and
13.94 (2CH3), 35.04 (CH2CO), 44.60 and 51.14 (2CH), 52.34 and 52.49 (2OCH3), 61.54 (OCH2)
140.61 and 142.70 (C¼C), 159.71, 159.98, and 169.75 (3C¼O ester), 205.59 (C¼O) ppm.
Triethyl 4-propionylcyclobut-1-ene-1,2,3-tricarboxylate (3e, C16H22O7)
Pale yellow oil, yield 0.60g (92%); IR (KBr): ꢁꢀ ¼ 1728 and 1705 (C¼O), 1649 (C¼C) cmꢂ 1; MS:
m=z (%) ¼ 326 (Mþ , 6), 280 (100), 297 (58), 235 (35), 135 (56), 73 (70).
1
Major isomer (cis-3e) (60%); H NMR (500MHz, CDCl3): ꢀ ¼ 1.13 (t, J ¼ 7.2 Hz, CH3), 1.20–
1.41 (m, 3CH3), 2.99–3.06 (m, ABX3 system, CH2CO), 3.98 (d, J ¼ 5.5 Hz, CH), 4.02 (d, J ¼ 5.5 Hz,
CH), 4.12–4.31 (m, 3OCH2) ppm; 13C NMR (125.7 MHz, CDCl3): ꢀ ¼ 7.36, 14.05, 14.07, and 14.11
(4CH3), 35.17 (CH2CO), 44.82 and 45.04 (2CH), 61.42, 61.44, and 61.61 (3OCH2), 136.31 and 148.37
(C¼C), 160.13, 168.39, and 168.50 (3C¼O ester), 197.14 (C¼O) ppm.
Minor isomer (trans-3e) (40%); 1H NMR (500MHz, CDCl3): ꢀ ¼ 1.09 (t, J ¼ 7.2 Hz, CH3), 1.20–
1.41 (m, 3CH3), 2.59–2.74 (m, ABX3 system, CH2CO), 3.74 (d, J ¼ 1.6 Hz, CH), 3.97 (d, J ¼ 1.6 Hz,
CH), 4.12–4.31 (m, 3OCH2) ppm; 13C NMR (125.7 MHz, CDCl3): ꢀ ¼ 7.44, 14.07, 14.09, and 14.11
(4CH3), 35.79 (CH2CO), 45.15 and 52.08 (2CH), 61.43, 61.55, and 61.62 (3OCH2), 141.32 and 142.28
(C¼C), 159.69, 160.69, and 169.25 (3C¼O ester), 205.87 (C¼O) ppm.
Di-tert-butyl 4-propionyl-1-(ethoxycarbonyl)cyclobut-1-ene-2,3-dicarboxylate
(3f, C20H30O7)
Pale green oil, yield: 0.70 g (91%); IR (KBr): ꢁꢀ ¼ 1728 and 1696 (C¼O), 1542 (C¼C) cmꢂ 1; MS:
m=z (%) ¼ 382 (Mþ , 5), 337 (85), 282 (100), 208 (65), 135 (45), 106 (38).
1
Major isomer (trans-3f) (90%); H NMR (500MHz, CDCl3): ꢀ ¼ 1.06 and 1.30 (2t, J ¼ 7.0 Hz,
2CH3), 1.47 and 1.51 (2s, 2OCMe3), 2.59–2.74 (m, ABX3 system, CH2CO), 3.65 (s, CH), 3.89 (s, CH),
4.26 (q, J ¼ 7.1 Hz, OCH2) ppm; 13C NMR (125.7MHz, CDCl3): ꢀ ¼ 7.47 and 14.17 (2CH3), 27.95
and 27.98 (2CMe3), 35.59 (CH2CO), 46.49 and 51.79 (2CH), 61.37 (OCH2), 82.08 and 82.48
(2OCMe3), 140.57 and 143.29 (C¼C), 158.99, 160.24, and 168.39 (3C¼O ester), 206.38 (C¼O) ppm.
1
Minor isomer (cis-3f) (10%); H NMR (500MHz, CDCl3): ꢀ ¼ 1.12 and 1.33 (2t, J ¼ 7.0 Hz,
2CH3), 1.43 and 1.47 (2s, 2OCMe3), 2.94–3.07 (m, ABX3 system, CH2CO), 3.83 (d, J ¼ 5.3 Hz,
CH), 3.89 (d, J ¼ 5.3Hz, CH), 4.28 (q, J ¼ 7.2 Hz, OCH2) ppm; 13C NMR (125.7MHz, CDCl3):
ꢀ ¼ 7.30 and 14.17 (2CH3), 27.95 and 27.96 (2OCMe3), 35.10 (CH2CO), 46.64 and 45.87 (2CH),

1226
I. Yavari and M. Bayat
61.32 (OCH2), 81.94 and 82.01 (2OCMe3), 136.30 and 148.86 (C¼C), 160.32, 167.68, and 167.96
(3C¼O ester), 197.41 (C¼O) ppm.
Dimethyl 4-isobutyryl-1-(ethoxycarbonyl)cyclobut-1-ene-2,3-dicarboxylate (3g, C15H20O7)
Pale yellow oil, yield 0.60g (96%); IR (KBr): ꢁꢀ ¼ 1728 and 1700 (C¼O), 1670 (C¼C) cmꢂ 1; MS:
m=z (%) ¼ 313 (Mþ , 14), 226 (100), 208 (85), 166 (20), 139 (35), 80 (19).
1
Major isomer (cis-3g) (80%); H NMR (500MHz, CDCl3): ꢀ ¼ 1.15 and 1.16 (2d, J ¼ 7.0 Hz,
CHMe2), 1.32 (t, J ¼ 7.0 Hz, CH3), 3.60 (sept, J ¼ 7.0 Hz, CHMe2), 3.72 and 3.76 (2s, 2OCH3), 4.02
(d, J ¼ 5.5 Hz, CH), 4.07 (d, J ¼ 5.5 Hz, CH), 4.24–4.34 (m, OCH2) ppm; 13C NMR (125.7MHz,
CDCl3): ꢀ ¼ 14.04 (CH3), 17.34 and 18.57 (CHMe2), 38.80 (CHMe2), 44.74 and 45.03 (2CH), 52.42
and 52.60 (2OCH3), 61.57 (OCH2), 136.13 and 148.23 (C¼C), 159.74, 168.26, and 168.87 (3C¼O
ester), 199.72 (C¼O) ppm.
1
Minor isomer (trans-3g) (20%); H NMR (500MHz, CDCl3): ꢀ ¼ 1.12 and 1.22 (2d, J ¼ 7.0 Hz,
CHMe2), 1.32 (t, J ¼ 7.0 Hz, CH3), 2.86 (sept, J ¼ 7.0 Hz, CHMe2), 3.76 and 3.82 (2s, 2OCH3), 3.67
(d, J ¼ 1.5 Hz, CH), 4.12 (d, J ¼ 1.5 Hz, CH), 4.24–4.34 (m, OCH2) ppm; 13C NMR (125.7MHz,
CDCl3): ꢀ ¼ 14.01 (CH3), 17.67 and 17.68 (CHMe2), 40.89 (CHMe2), 44.42 and 50.30 (2CH), 52.27
and 52.65 (2OCH3), 61.71 (OCH2), 140.65 and 143.06 (C¼C), 159.78, 160.02, and 169.80 (3C¼O
ester), 209.13 (C¼O) ppm.
Triethyl 4-isobutyrylcyclobut-1-ene-1,2,3-tricarboxylate (3h, C17H24O7)
Pale yellow oil, yield 0.62g (91%); IR (KBr): ꢁꢀ ¼ 1728 and 1708 (C¼O), 1645 (C¼C) cmꢂ 1; MS:
m=z (%) ¼ 341 (Mþ þ 1, 6), 295 (23), 250 (38), 224 (75), 150 (44), 73 (100).
1
Major isomer (cis-3h) (60%); H NMR (500MHz, CDCl3): ꢀ ¼ 1.12 and 1.22 (2d, J ¼ 7:1 Hz,
CHMe2), 1.22–1.35 (3t, J ¼ 7.0 Hz, 3CH3), 2.86 (sept, J ¼ 7.1 Hz, CHMe2), 3.98 (d, J ¼ 5.5 Hz, CH),
4.04 (d, J ¼ 5.5 Hz, CH), 4.10–4.31 (m, 3OCH2) ppm; 13C NMR (125.7 MHz, CDCl3): ꢀ ¼ 14.04,
14.05, and 14.06 (3CH3), 17.23 and 18.71 (CHMe2), 38.83 (CHMe2), 44.87 and 45.11 (2CH), 61.38,
61.53, and 61.57 (3OCH2), 136.10 and 148.47 (C¼C), 159.62, 168.29, and 169.22 (3C¼O ester),
200.50 (C¼O) ppm.
1
Minor isomer (trans-3h) (40%); H NMR (500 MHz, CDCl3): ꢀ ¼ 1.16 and 1.17 (2d, J ¼ 7.1 Hz,
CHMe2), 1.22–1.35 (3t, J ¼ 7.0 Hz, 3CH3), 3.60 (sept, J ¼ 7.1 Hz, CHMe2), 3.74 (d, J ¼ 1.25 Hz, CH),
3.75 (d, J ¼ 1.25 Hz, CH), 4.10–4.31 (m, 3OCH2) ppm; 13C NMR (125.7MHz, CDCl3): ꢀ ¼ 14.10,
14.11, and 14.12 (3CH3), 17.66 and 17.84 (CHMe2), 40.91 (CHMe2), 45.64 and 50.14 (2CH), 61.35,
61.38, and 61.41 (3OCH2), 141.21 and 142.56 (C¼C), 159.90, 160.10, and 168.59 (3C¼O ester),
209.29 (C¼O) ppm.
Di-tert-butyl 4-isobutyryl-1-(ethoxycarbonyl)cyclobut-1-ene-2,3-dicarboxylate
(3i, C21H32O7)
Pale yellow oil, yield 0.75g (95%); IR (KBr): ꢁꢀ ¼ 1716 and 1704 (C¼O), 1645 (C¼C) cmꢂ 1; MS:
m=z (%) ¼ 397 (Mþ þ 1, 8), 352 (77), 251 (65), 195 (48), 163 (35), 71 (24), 57 (100).
1
Major isomer (trans-3i) (90%); H NMR (500 MHz, CDCl3): ꢀ ¼ 1.30 (t, J ¼ 7.1 Hz, CH3), 1.15
and 1.16 (2d, J ¼ 7.0 Hz, CHMe2), 1.48 and 1.52 (2s, 2OCMe3), 2.84 (sept, J ¼ 7.0 Hz, CHMe2), 3.55
(d, J ¼ 2.0 Hz, CH), 4.03 (d, J ¼ 2.0Hz, CH), 4.24 (q, J ¼ 7.1 Hz, OCH2) ppm; 13C NMR (125.7MHz,
CDCl3): ꢀ ¼ 14.11 (CH3), 17.68 and 17.83 (CHMe2), 27.89 and 27.99 (2OCMe3), 40.79 (CHMe2),
46.92 and 49.81 (2CH), 61.25 (OCH2), 82.00 and 82.36 (2OCMe3), 140.93 and 143.15 (C¼C), 158.87,
160.03, and 168.35 (3C¼O ester), 209.68 (C¼O) ppm.
Minor isomer (cis-3i) (10%); 1H NMR (500 MHz, CDCl3): ꢀ ¼ 1.33 (t, J ¼ 7.1 Hz, CH3), 1.11 and
1.21 (2d, J ¼ 7.1 Hz, CHMe2), 1.46 and 1.50 (2s, 2OCMe3), 3.60 (sept, J ¼ 7.0 Hz, CHMe2), 3.60
(d, J ¼ 5.5 Hz, CH), 3.90 (d, J ¼ 5.5Hz, CH), 4.31 (q, J ¼ 7.1 Hz, OCH2) ppm; 13C NMR (125.7MHz,

Synthesis of Cyclobutene Derivatives
1227
CDCl3): ꢀ ¼ 14.10 (CH3), 17.27 and 18.79 (CHMe2), 27.95 and 27.96 (2OCMe3), 38.62 (CHMe2),
45.67 and 45.83 (2CH), 61.12 (OCH2), 81.80 and 81.88 (2OCMe3), 136.54 and 148.48 (C¼C), 160.27,
167.59, and 167.90 (3C¼O ester), 200.26 (C¼O) ppm.
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