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Chinese Chemical Letters 21 (2010) 187–190

www.elsevier.com/locate/cclet

The stable planar conformation of the g-butyrolactone

ring in solution
Zhi Qiang Feng a,*, Cheng Lie Yin b
a
Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China
b
Department of Chemistry, Beijing Normal University, Beijing 100875, China
Received 8 July 2009

Abstract
The conformations of g-butyrolactone ring in solution were deduced on the basis of 1H NMR spectra of geminal protons of the
butyrolactone ring. A series of optically pure (Z)-()-4-(10 -alkoxyl-10 -carbalkoxy-methylene)-5(R)[(1R)-menthyloxy]-g-butyr-
olactones with a stable planar conformation of g-butyrolactone ring were found.
# 2009 Zhi Qiang Feng. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Keywords: b-Methylene-g-butyrolactone; Planar conformation; Envelope conformation

Because of the wide occurrence of g-butyrolactone moiety in natural and unnatural products displaying the wide
range of biological activity [1], their detailed stereochemistry is of great interest [2]. The preference for co-planarity of
the five atoms of the lactone group, C–C(O)–O–C, implies that the stable conformation of the g-butyrolactone ring is
restricted to an enantiomeric pair, in which the fifth ring atom is either above or below the lactone plane, oriented as
shown in conformation I and II (Fig. 1) [3]. This has been confirmed by X-ray structure analysis established [4]. In our
former study of the physical and spectral properties of a series of chiral trans-4,5-disubstituted-g-butyrolactones
(compounds II), we have observed that the optical rotation signs of the butyrolactones correlate strictly with the
relative order of the chemical shifts of the C3 methylene protons H3a and H3b [5]. In this paper, we will report our
further discovery of the stable planar conformation of g-butyrolactone ring.
Recently, in the study of an asymmetric synthesis of a natural product, we obtained a novel chiral compound with a
structure of b-methylene-g-butyrolactone, (Z)-()-4-(10 -ethoxyl-10 -carbethoxymethylene)-5(R)[(1R)- menthyloxy]-
g-butyrolactone (compounds III, m), and found that the 1H NMR spectra of the compound shows a signal as singlet for
the C3 methylene protons (Fig. 2, No. 3), which reveals that the chemical shifts of the C3 methylene protons H3a and
H3b are equal, or H3a and H3b are equivalent in chemical surroundings. But the conclusion appears in violation of a
definition by which the protons H3a and H3b are diastereotopic due to the presence of C5 chiral center and MenO–
group, and seems against the general rule by which the g-butyrolactone ring should assume the envelope conformation
[3]. In order to confirm further this singular case, we synthesized a series of (Z)-()-4-(10 -alkoxyl-10 -
carbalkoxymethylene)-5(R)[(1R)-menthyloxy]-g-butyrolactones (Fig. 1 compounds III), and found that the 1H

* Corresponding author.
E-mail address: fengzhq@imm.ac.cn (Z.Q. Feng).

1001-8417/$ – see front matter # 2009 Zhi Qiang Feng. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2009.10.023
188 Z.Q. Feng, C.L. Yin / Chinese Chemical Letters 21 (2010) 187–190

Fig. 1. The possible conformations of compounds II and III.

NMR spectra of all compounds III show a signal as singlet for the C3 methylene protons, which showed that the
equivalence of the C3 methylene protons H3a and H3b is not a mere coincidence.
This phenomenon appears impossible to the envelope conformation of the butyrolactone. In conformation IV, H3b
and H5 are quasi-axial protons, while H3a and bulky MenO– adopt the quasi-equatorial positions. On the contrary, in
conformation V, H3a and bulky MenO– assume the quasi-axial positions, while H3b and H5 are quasi-equatorial
protons. According to the proposed model of the anisotropic effect of the carbonyl group [6], the quasi-equatorial
protons of the C3 methylene in both conformation IV and V should resonate at higher magnetic fields than quasi-axial
protons, and the upfield shift of the allyl protons varies less from quasi-axial proton to quasi-equatorial proton, so in the
two assumed conformations IV and V, the chemical shifts of H3a and H3b should not be equal. Additionally, suppose
 Z.Q. Feng, C.L. Yin / Chinese Chemical Letters 21 (2010) 187–190 189

Fig. 2. 1H NMR spectra of nitronic ester (No. 1), a-keto ester (No. 2) and enol ether (No. 3).

the compounds III butyrolactone was a mixture of two rapidly interconverting conformations IV and V, the former
with the quasi-equatorial bulky MenO– group would predominate, thus the relative order of the chemical shifts of H3a
and H3b should be dH3a < dH3b. But this is not in accordance with the observed results (dH3a = dH3b). The
experiment showed that 1H NMR spectra of compounds III (R3 = R4 = Et) at 25 8C are almost identical with at 0 8C,
and the changes of R3 and R4 groups do not influence the equivalence of the C3 methylene protons H3a and H3b
(dH3a = dH3b) (Table 1). Therefore, it is untenable that the equivalence of H3a and H3b is explained by a fast
conformational interconversion between two conformations IV and V. The possibility of the compounds III assuming
conformation IV or V should be ruled out.
There seems to be only one interpretation for the equivalence of H3a and H3b in the chemical environment, which
is that the butyrolactone rings of compounds III adopt the planar conformation III. It has been reported [7] that the
preferred arrangement of the butyrolactone group five atoms (C–CO–O–C) is planar, and that additional strain is
needed to override this desire for planarity on the basis of X-ray and NMR studies. Additionally, the arrangement of six
atoms constituting C C double bond is undoubtedly planar. Therefore, in compounds III, a rigid polyatomic
coplanar structure consisting of nine atoms –C–O–CO–C–C C can be assembled, and that bisects the dihedral angle
formed by the protons H3a and H3b in the C3 methylene. In other words, H3a and H3b can be mirror-symmetrically
distributed on the two sides of the polyatomic coplanar structure, so H3a should be in the same co-deshielding region
of the adjacent C2 carbonyl group and vicinal C C double bond as H3b, which results in the equal chemical shift of
190 Z.Q. Feng, C.L. Yin / Chinese Chemical Letters 21 (2010) 187–190

Table 1
The partial structure data of compounds III.
Compounds III R4 R3 Configuration ( C C ) [a]25589 (acetone) 1
H NMR (CDCl3)a d H3

a CH3CH2 CH3 Z 25.90 (c = 2.57) 3.35 (s, 2H)

b CH3 CH3 Z 28.30 (c = 2.51) 3.35 (s, 2H)
c CH3CH2 CH3CH2CH2 Z 30.20 (c = 4.30) 3.34 (s, 2H)
d CH3 CH3(CH2)2CH2 Z 25.46 (c = 2.96) 3.32 (s, 2H)
e CH3CH2 CH3(CH2)3CH2 Z 24.77 (c = 2.16) 3.34 (s, 2H)
f CH3CH2 CH2 CHCH2 Z 27.10 (c = 1.09) 3.38 (s, 2H)
g CH3 CH2 CHCH2 Z 27.30 (c = 6.90) 3.38 (s, 2H)
h CH3 CH3(CH2)3CH2 Z 21.25 (c = 1.48) 3.34 (s, 2H)
i CH3CH2 PhCH2 Z 26.00 (c = 1.71) 3.40 (s, 2H)
j CH3 CH2COOEt Z 21.10 (c = 6.54) 3.43 (s, 2H)
k CH3CH2 CH2COOEt Z 30.75 (c = 3.61) 3.40 (s, 2H)
l CH3CH2 CH3(CH2)14CH2 Z 20.06 (c = 1.24) 3.33 (s, 2H)
m CH3CH2 CH3CH2 Z 26.16 (c = 1.15) 3.34 (s, 2H)
n CH3CH2 O2NC6H4CH2 Z 23.26 (c = 3.30) 3.44 (s, 2H)
a 1
H NMR spectra were recorded on a DMX instrument at 300 MHz using CDCl3 as the solvent and TMS as the internal standard.

H3a and H3b. Though the molecule is asymmetric to the plane of the butyrolactone ring of compounds III, resulting
from the existence of the C5 chiral center, that is, the protons H3a and H3b are diastereotopic, the effect of the C5
chiral center on the protons H3a and H3b is very small, due to the protons H3a and H3b locate at meta-position of the
C5 chiral center. The couplings between H5 and H3a or H3b were not observed (Fig. 2. a signal as singlet for the H5),
and the NOE between H3 and H5 was not observed by its NOESY1D spectrum. So the planar conformation of g-
butyrolactone ring should be a reasonable elucidation for the equivalence of the C3 methylene protons H3a and H3b,
which should be confirmed by the X-ray diffraction of single crystal, but they all are colorless liquids.
To our surprise, the bulky MenO– substituent in the compounds III does not obstruct the formation of the planar
conformation of the butyrolactone ring, but firm the planar conformation. In order to find the cause of forming the
planar conformation, we synthesized a compound free of MenO– group by acidic hydrolytic decomposition of
compounds III, the 1H NMR spectra (H3, a signal as 2d) of the compound shows that the g-butyrolactone ring adopts
the envelope conformation. Additionally, the strong NOE between H7 and H8 was observed from the NOESY1D
spectrum of compounds III, indicating that the polyatomic coplanar structure may relate to the crowding between
MenO– group and EtO– group. So the presence of the bulky MenO– substituent may be the main cause of leading to a
rigid polyatomic coplanar structure consisting of the planar C–O–CO–C and the planar C C groups.
In summary, the conformations of g-butyrolactone ring in solution were deduced on the basis of 1H NMR spectra of
geminal protons of the butyrolactone ring. A series of optically pure (Z)-()-4-(10 -alkoxyl-10 - carbalkoxymethylene)-
5(R)[(1R)-menthyloxy]–g-butyrolactones with a stable planar conformation of g-butyrolactone ring were found for
the first time.

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