Stereoselective synthesis of trans-β-methoxycarbonyl-γ-aryl-γ-butyrolactones

Article abstract of DOI:10.1081/SCC-120004845

Stereoselective synthesis of trans-β-methoxycarbonyl-γ-aryl-γ-butyrolactones (5) by the reaction of methoxycarbonylmethyl triphenyl arsonium bromide (1) and 2,2-dimethyl-5-substituted-benzal-1,3-dioxa-4,6-dioxa-4,6-dione (2) is carried out in the presence

Full text of DOI:10.1081/SCC-120004845

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STEREOSELECTIVE SYNTHESIS OF TRANS-β-
METHOXYCARBONYL-γ-ARYL-γ-BUTYROLACTONES
Yali Chen a , Weiyu Ding a , Weiguo Cao a b & Cheng Lu a
a Department of Chemistry , Shanghai University , Shanghai, 200436, P.R. China
b Laboratory of Organometallic Chemistry , Academia Sinica , Shanghai, 200032, P.R. China
Published online: 16 Aug 2006.
To cite this article: Yali Chen , Weiyu Ding , Weiguo Cao & Cheng Lu (2002) STEREOSELECTIVE SYNTHESIS OF TRANS-β-
METHOXYCARBONYL-γ-ARYL-γ-BUTYROLACTONES, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 32:13, 1953-1960, DOI: 10.1081/SCC-120004845
To link to this article: http://dx.doi.org/10.1081/SCC-120004845
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SYNTHETIC COMMUNICATIONS, 32(13), 1953–1960 (2002)
STEREOSELECTIVE SYNTHESIS OF
TRANS-b-METHOXYCARBONYL-c-ARYL-
c-BUTYROLACTONES
Yali Chen,1, Weiyu Ding,1 Weiguo Cao,1,2
*
1
and ChengLu
1Department of Chemistry, Shanghai University,
Shanghai 200436, P.R. China
2Laboratory of Organometallic Chemistry of Academia
Sinica, Shanghai 200032, P.R. China
ABSTRACT
Stereoselective synthesis of trans-ꢀ-methoxycarbonyl-ꢁ-aryl-ꢁ-
butyrolactones (5) by the reaction of methoxycarbonylmethyl
triphenyl arsonium bromide (1) and 2,2-dimethyl-5-substi-
tuted-benzal-1,3-dioxa-4,6-dioxa-4,6-dione (2) is carried out
in the presence of potassium carbonate and trace water in
dimethoxyethane. 1,2-Cis-cyclopropane 3 is formed as an
intermediate. The stability of compound 3 in water is related
to the property of the aryl substituent. With strong electron-
donating groups [2a–c, Ar¼4-CH3O–C6H4; 3,4-OCH2O–C6H3
or 4-(CH3)2N–C6H4] at room temperature 3 is formed in situ
and transformed to ꢁ-butyrolactones 5a–c immediately,
whereas when the aryl substituent is H or a weak electron-
donating or electron-withdrawing group (2d–g, Ar¼4–CH3-
C6H4; C6H5; 4-Cl–C6H4 or 4-NO2–C6H4), 3 is stable to water
*Corresponding author.
1953
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

1954
CHEN ET AL.
at room temperature. On further heating in acetone, 3 is trans-
formed to ꢁ-butyrolactones 5d–g (stepwise synthesis). One-pot
synthesis of 5d–g from the reaction of 1 with 2d–g is also
studied.
Key Words: Arsenic ylide; Stepwise synthesis; One-pot
synthesis; ꢁ-Butyrolactone; Stereoselective synthesis
Compounds containing ꢁ-butyrolactone substructure show antiviral
and physiological activities.[1] Therefore, the synthesis of such compounds
is of current interest in synthetic organic chemistry. However, simple and
highly stereoselective synthetic methods to prepare such compounds are
rare. Recently, such a synthetic approach has been described by us.[2]
Further study on the stereoselective synthesis of trans-ꢀ-methoxycarbonyl-
ꢁ-aryl-ꢁ-butyrolactone (5) is reported here as well as a convenient one-pot
process.
RESULT AND DISCUSSION
In the stereoselective synthesis of trans-ꢀ-methoxycarbonyl-ꢁ-aryl-ꢁ-
butyrolactone (5), the reaction of methoxycarbonylmethyl triphenyl
arsonium bromide (1) and 2,2-dimethyl-5-substituted-benzal-1,3-dioxa-4,6-
dione (2) in the presence of potassium carbonate and trace water in
dimethoxyethane leads to form 1,2-cis-cyclopropane 3 first. The stability
of compound 3 to water is related to the property of the substituent on
aryl group. When the substituent on aryl is a strong electron-donating
group [2a–c, Ar¼4-CH3O–C6H4; 3,4-OCH2O–C6H3 or 4-(CH3)2N–C6H4],
3 is formed in situ and transformed to ꢁ-butyrolactone 5a–c immediately
(Scheme 1, Table 1). Whereas when the aryl substituent is H, weak electron-
donating or electron-withdrawing (2d–g, Ar¼4-CH3–C6H4; C6H5; 4-Cl–
C6H4 or 4-NO2–C6H4), 3d–g is stable to water at room temperature. The
ꢁ-butyrolactone 5d–g could be obtained from the isolated 3d–g by heating in
acetone–water (stepwise synthesis, Scheme 1). Moreover, the ꢁ-
butyrolactone 5d–g can also be obtained without the isolation of the reac-
tion product 3d–g by directly heating in DME–H2O (one-pot synthesis,
Scheme 2). Compared with stepwise synthesis, one-pot synthesis is simpler
and gives higher yield (Table 1).
The structures and configurations of compounds 3e–g, 5a, 5e,f have
been reported previously.[2,3] The structures of 3d, 5b–d, 5g were confirmed
by IR, 1H NMR, MS and elemental analyses (Table 2 and Table 3).

STEREOSELECTIVE SYNTHESIS OF c-BUTYROLACTONES
1955
Scheme 1.
Scheme 2.
Table 1. Preparation of Compounds 5a–g
Yield (%)
(One-Pot Synthesis)
Yield (%)a
(Stepwise Synthesis)
Product
Ar
5a
5b
5c
5d
5e
5f
4-CH3O–C6H4
3,4-OCH2O–C6H3
4-(CH3)2N–C6H4
4-CH3–C6H4
C6H5
64
74
67
55
43
56
48
/
/
/
44 ¼ 74% Â 60%
30 ¼ 53% Â 57%
46 ¼ 74% Â 62%
40 ¼ 83% Â 48%
4-Cl–C6H4
4-NO2–C6H4
5g
aYield (%) of 5d–g (stepwise synthesis) ¼ yield of 3d–g ꢀ yield of 5d–gb.
bThe compound 3d–g was heated in acetone–water to give ꢀ-butyrolactones 5d–g.
The trans-configuration of ꢀ-H and ꢁ-H of compound 5e was determined by
the 2D NOESY. The reaction mechanism shown in Scheme 3 would account
for the high stereoselectivity. The 1,2-cis-cyclopropane 3 is attacked by a
molecule of water at Ca from the less hindered side of the cyclopropane ring,
resulting in cleavage of the Ca–Cc bond of compound 3 to yield the inter-
mediate A. Intermediate A transforms into intermediate B after the rotation

1956
CHEN ET AL.

STEREOSELECTIVE SYNTHESIS OF c-BUTYROLACTONES
1957

1958
CHEN ET AL.
Table 3. 13C NMR Spectra Data of Product 5d
13C NMR (d-DMSO) d(ppm)
Compd.
5d
21.2(4-CH3–C6H4), 31.4(ꢀ-C), 46.7(ꢂ-C), 51.9(COOCH3), 81.2(ꢁ-C),
125.5(Ar), 129.2(Ar), 132.3(Ar), 138.8(Ar), 170.1(–CO–), 175.1(–CO–,
butyrolactone)
Scheme 3.
of Ca–Cc bond. The ꢀ,ꢁ-trans-ꢁ-butyrolactone 5 is formed through the
attacking of the hydroxy group to the ester group to break the Meldrum’s
acid ring with the elimination of a molecule of acetone and a molecule of
carbon dioxide.
This work indicates that the reaction of arsonium bromide 1 with
electron-deficient alkenes 2 is an efficient approach to synthesize trans-
ꢀ-methoxycarbonyl-ꢁ-aryl-ꢁ-butyrolactone (5) with high stereoselectivity
and the by-product triphenyl arsine can be reused. One-pot synthesis is
simpler with higher yield.
EXPERIMENTAL
Melting points were uncorrected and recorded on a WRS-1 melting
point apparatus. IR spectra were measured on a 7400 spectrometer
(Shanghai Analytical Instrument Factory, China) with KBr discs. NMR
spectra were determined with AC-100SC spectrometers, using solutions in
CDCl3 or d-DMSO with tetramethylsilane or d-DMSO as the internal stan-
dard for 1H and 13C nuclei respectively. Coupling constants were given in Hz.
Mass spectra were run on a HP 5989A spectrometer. Elemental data were
obtained from Foss Heraeus CHN-O-RAPID elemental analysis instrument.

STEREOSELECTIVE SYNTHESIS OF c-BUTYROLACTONES
1959
Synthesis of trans-b-Methoxycarbonyl-c-aryl-c-butyrolactone (5a–c)
and cis-methoxycarbonyl-2-aryl-6,6-dimethyl-5,7-dioxa-spiro
[2,5]-4,8-octadiones (3d–g)
General procedure—Methoxycarbonylmethyl triphenyl arsonium bro-
mide 1 (0.459 g, 1 mmol), 2,2-dimethyl-5-substituted-benzal-1,3,-dioxa-4,6-
dione 2a–g (1 mmol) and K2CO3 (0.15 g) were stirred in dimethoxyethane
(5 mL) in the presence of a drop of water at room temperature. At the end of
the reaction (monitored by TLC), the white solid was filtered off and the
solvent evaporated under reduced pressure. The residue was purified by
silica gel column chromatography (GF254, 200–300 mesh) with petroleum
ether–ethyl acetate mixture (v : v ¼ 7 : 3) as eluent. By-product triphenyl
arsine (reusable and the product 5a–c or 3d–g can be obtained easily. The
yields of the products 5a–c or 3d–g were illustrated in Table 1.
Synthesis of trans-b-Methoxycarbonyl-c-aryl-c-butyrolactones
(5d–g) (Stepwise Synthesis)
General procedure—Cis-1-methoxycarbonyl-2-aryl-6,6,-dimethyl-5,7-
dioxaspiro[2,5]-4,8-octadione 3d–g (1 mmol) was heated in 3 mL of
acetone–water (v : v ¼ 2 : 1) at 60ꢀC. At the end of the reaction (monitored
by TLC), the white solid was filtered off and the solvent evaporated under
reduced pressure. The residue was purified by silica gel column chromatog-
raphy (GF254, 200–300 mesh) with petroleum ether–ethyl acetate mixture
(v : v ¼ 7 : 3) as eluent. Then product 5d–g can be obtained. The yields of the
product 5d–g were illustrated in Table 1.
Synthesis of trans-b-Methoxycarbonyl-c-aryl-c-butyrolactone
(5d–g) (One-Pot Synthesis)
General procedure—Methoxylcarbonylmethyl triphenyl arsonium bro-
mide 1 (0.459 g, 1 mmol), 2,2-dimethyl-1,3-dioxane-4,6-dione 2d–g (1 mmol)
and K2CO3 (0.15 g) were stirred in dimethoxyethane (5 mL) in the presence
of a drop of water at room temperature. At the end of reaction (monitored
by TLC), the white solid was filtered off and 1 mL water was added into the
filtered solution. The mixture was heated to 60ꢀC. When the reaction was
completed (monitored by TLC), the solvent evaporated under reduced
pressure and the residue purified by silica gel column chromatography
(GF254, 200–300 mesh) with petroleum ether-ethyl acetate mixture
(v : v ¼ 7 : 3) as eluent. By-product triphenyl arsine (reusable) and the

1960
CHEN ET AL.
product 5d–g can be obtained. The yields of the products 5d–g were
illustrated in Table 1.
Analytical data were illustrated in this paper and previous paper.[2,3]
ACKNOWLEDGMENT
Thanks are due to the National Natural Science Foundation of China
and Laboratory of Organometallic Chemistry of Academia Sinica for
financial support.
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Stereoselective Synthesis of (Z)-ꢂ-(Alkoxycarbonyl) Methylene ꢀ-and
ꢁ-Lactones by Palladium-Catalysed Oxidative Carbonylation of
Alkynols. J. Chem. Soc. Perkin Trans 1 1997, 2, 147–154; Chem.
Abstr. 1997, 126, 238261f. (b) Uenishi, J.; Kobayashi, N.;
Yonemitsu, O.; Sasaki, T.; Yamada, Y. Synthesis and Cytotoxicity
of 5-Carbo Analogs of Acetomycin. Heterocycles 1997, 44, 277–287.
Chem Abstr. 1997, 126, 212340f.
2. Chem, Y.L.; Ding, W.Y. Chem. Simple Approach to Highly ꢀ, ꢁ-
Trans-ꢁ-butyrolactones. J. Chin. Univ. 1998, 19, 1614–1616. Chem.
Abstr. 1999, 130, 110119f.
3. Ding, W.Y.; Han, Z.H.; Chen, Y.L.; Zou, Y.J.; Liu, X. Stereoselective
Synthesis of Cis-1,2-cyclopropone Derivatives. Chem. Res. Chin. Univ.
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Received in the USA June 23, 2001