Lactones. Part 16: Lactonization of γ,δ-epoxy esters with p-toluenesulfonic acid monohydrate

Article abstract of DOI:10.1016/S0040-4020(03)01052-4

The reaction of cyclic γ,δ-epoxy esters with p-toluenesulfonic acid monohydrate is described. The reaction carried out in benzene or methylene chloride gave tosyloxy lactones as product. The ethoxy or methoxy lactones were obtained when ethanol or methanol were used as solvent. A mechanism of this lactonization is proposed.

Full text of DOI:10.1016/S0040-4020(03)01052-4

Tetrahedron 59 (2003) 6595–6601
Lactones. Part 16: Lactonization of g,d-epoxy esters with
p-toluenesulfonic acid monohydrateq
a
Czesław Wawrzenczyk, Małgorzata Grabarczyk, Agata Białonska and Zbigniew Ciunik
a
b
b
,
*
´
´
aDepartment of Chemistry, Agricultural University, Norwida 25, 50-375 Wrocław, Poland
bFaculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland
Received 24 March 2003; revised 3 June 2003; accepted 26 June 2003
Abstract—The reaction of cyclic g,d-epoxy esters with p-toluenesulfonic acid monohydrate is described. The reaction carried out in benzene
or methylene chloride gave tosyloxy lactones as product. The ethoxy or methoxy lactones were obtained when ethanol or methanol were used
as solvent. A mechanism of this lactonization is proposed.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
The acid induced ring-closing procedure is well known as
an efficient method for the synthesis of lactones. Among the
acids, p-toluenesulfonic acid is very often used for the
synthesis of lactones from hydroxy esters,2–6 hydroxy
acids,7,8 hydroxy amides9 and epoxy esters.10,11
The substrates for lactonization, epoxy esters 2a–d,
were obtained by oxidation of corresponding, known
d,g-unsaturated esters 1a,12 1b13 and 1c14 with m-chloro-
perbenzoic acid (Scheme 1). Both, thin layer and gas
chromatography indicated that only one epoxy ester was
formed from 1a and 1b. In the case of epoxidation of ester
1c, the mixture of epoxy esters: cis (2c, 80%) and trans (2d,
20%) was obtained. The pure epoxy esters were separated
by column chromatography.
In the course of the lactonization of epoxy ester 2a with an
equimolar amount of p-toluenesulfonic acid monohydrate
in non-aqueous solvents, the formation of d-tosyloxy-g-
lactone and d-ethoxy-g-lactone was observed. Here, we
present the results of our studies on this reaction. We have
found it interesting for two reasons. The first reason is the
different course of this lactonization in comparison with
lactonization of epoxy esters carried out with this acid
earlier.10,11 The reaction of acyclic g,d-epoxy esters with
equimolar amounts of p-toluenesulfonic acid monohydrate
in benzene afforded d-hydroxy-g-lactones as the only
products.11 The lactonization of b,g-epoxy ester obtained
from methyl scalar-17(24)-en-25-oate with p-toluene-
sulfonic acid in chloroform afforded 16-unsaturated lactone
(scalar-16-en-25,24-olide) as the only product.10 The
second reason is a possibility of application of this reaction
to the synthesis of substituted derivatives of lactones via the
nucleophilic substitution of a tosyloxy group.
The small differences in chemical shifts of methyl groups at
C-5 (Dd¼0.04 for 2a and 0.02 for 2b) suggest that the
oxirane ring is relatively far away from trans pseudoaxial
methyl group at C-5. In the case of 2a, it is possibly in
twisted chair conformation of the cyclohexane ring with
C-1, C-2, C-3 and C-4 in one plane. The oxirane ring is cis
oriented in relation to the pseudoequatorial methyl-
carbethoxy group at C-1. For 2b, it is possible rather in
the boat conformation of this molecule with C-1 and C-4 as
stem and stern atoms then in the half or twisted chair
conformation. Coupling constants of H-1 with H-2 (3.8 Hz)
and H-3 with protons of CH2-4 (3.9 and 1.9 Hz) confirmed
this conformation. The oxirane ring is cis oriented to the
methylcarbethoxy group. In the case of epoxy ester 2c, the
half-chair conformation with C-1, C-2, C-3, C-4 and C-5 in
one plane is suggested. Such conformation and cis
orientation of epoxy ring toward the methylcarbethoxy
group in 2c could be proposed on the basis of the 1H NMR
spectral data. Lack of coupling constants of H-2 with H-1
and H-3 with one of H-4 in the multiplets of H-2 and H-3
indicates a conformation with dihedral angles between these
protons close to 908. Coupling constants of H-2 with H-1
(1.1 Hz) and H-3 with CH2-4 protons (2.1 and 1.8 Hz) found
in the spectrum of trans epoxy ester (2d) rather suggest a
q Part 15, see Ref. 1.
Keywords: lactones; acidic lactonization; epoxy esters; X-ray crystal
structures.
*
Corresponding author. Tel.: þ48-71-3205257; fax: þ48-71-3284124;
e-mail: c-waw@ozi.ar.wroc.pl
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)01052-4

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C. Wawrzenczyk et al. / Tetrahedron 59 (2003) 6595–6601
6596
Table 1. Compositions (according to GC) of the product mixtures of
lactonization of epoxy esters 2a–c
ethoxy lactones 4a–c were identified and isolated as the
other products of the reaction in this solvent. In the reactions
carried out in methyl or ethyl alcohol, the corresponding
d-methoxy- or d-ethoxy-g-lactones were formed as the main
products. They decidedly predominated (84–95%) over
d-tosyloxy-g-lactones (5–16%).
Substrate
Solvent
Benzene
3a,b,c
4a,b,c
5a,b,c
6a,b,c
2a
2b
2c
95 (67)
96 (63)
92 (71)
1
4
3
5
1
3
The ethoxy and methoxy lactones are not formed via the
substitution of tosyloxy group by ethanol or methanol but
directly from epoxides. We have verified this in a separate
experiment in which the tosyloxy lactone 3a was stirred in
ethanol with a catalytic amount of p-toluenesulfonic acid
at room temperature for 24 h. We did not observe any
exchange of tosyloxy group by ethoxy. The hydroxy lactones
6a–c identified intheproduct mixtureswerethe same(by GC)
as those obtained by lactonization of epoxy esters 2a–c with
perchloric or tartaric acid15,16 in aqueous solution.
2a
2b
2c
Methylene chloride 85 (67) 12 (8)
86 (70) 12 (8)
77 (75) 23 (20)
3
2
2a
2b
2c
Ethanol
16
8
6
84 (60)
92 (64)
94 (78)
2a
2b
2c
Methanol
7
16
5
1
1
92 (70)
83 (79)
95 (80)
Isolated yields are given in brackets.
The structures of compounds obtained were determined on
1
twisted chair conformation of cyclohexane ring with C-1,
C-2, C-3 and C-4 in one plane. The X-ray structures of
tosyloxy and hydroxy lactones formed from epoxy esters
2a–c fully confirmed the assignations presented above.
the basis of data from their H NMR and IR spectra and
X-ray analysis.
The X-ray structures of tosyloxy lactone (3a) and hydroxy
lactone (6a) (Fig. 1) showed that the cyclohexane ring in the
first molecule exists in a chair conformation, whereas in the
hydroxy lactone it exists in a twisted boat conformation. In
both molecules the lactone ring is trans orientated toward
the axial or pseudoaxial methyl group at C-4. The C–O
bonds of the tosyloxy or hydroxy group are trans with
respect to the C–O bond of the lactone ring. The X-ray
analysis of 6a indicates the presence of two symmetrically
independent molecules in the crystals.
Epoxy esters 2a–c were subjected to the reaction with
p-toluenesulfonic acid monohydrate at room temperature in
different solvents: benzene, methylene chloride, ethanol and
methanol (Scheme 1). The results of this reaction presented
in Table 1 indicate that the mixtures of compounds were
obtained.
The composition of the product mixture depends on the
solvent used in the reaction. The lactonization in benzene
gave the d-tosyloxy g-lactones 3a and 3b in almost
quantitative and 3c in 92% yield. trans Epoxy ester (2d)
in the same conditions afforded only a hydroxylactone
product with different retention time on GC compared to 6c.
Tosyloxy lactones were also main products (77–86%) when
the lactonization was carried out in methylene chloride. The
Such relative orientation of lactone ring and tosyloxy or
hydroxy group is also seen in the coupling constants values
between H-1 and H-2 and between them and neighbouring
protons. The values of coupling constant values of H-1 with
1
H-2 (5.7 Hz) and with H-6 (6.0 Hz) found in the H NMR
Scheme 1. (a) R¼CH3, R1¼H; (b) R, R1¼CH3; (c), (d) R, R1¼H.

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C. Wawrzenczyk et al. / Tetrahedron 59 (2003) 6595–6601
6597
Figure 1. Crystal structure of 3a and 6a.
spectrum of 6a are consist with torsion angles between C–H
bonds of these protons, 215 and 2228 respectively, from
X-ray structure. The coupling constants of this proton with
the H-2 (4.5 Hz) and H-6 (4.0 Hz) found in the spectrum of
3a indicate equatorial positions of H-1 and H-2.
analysis. Similar values of coupling constants JH-1,H-2¼6.5
1
(3b), 6.5 (4b), 6.4 (5b) and 7.7 Hz (6b) found in the H
NMR spectra of these compounds indicate that the
conformations of molecule and relative orientations of
substituents of cyclohexane ring are almost the same.
The trans diaxial orientation of C–O bonds and trans
equatorial positions of H-1 and H-2 can be ascribed also
in the ethoxy (4a) and methoxy lactones (5a). The values
X-Ray analysis of tosyloxy lactone (3c) (Fig. 3) obtained
from epoxy ester 2c showed that the cyclohexane ring exists
in a chair conformation and the lactone ring is cis located
towards the methyl group at C-4. The C–O bonds are
situated in trans axial positions.
of JH-1,H-2¼(4.8 Hz for 4a and 5.0 Hz for 5a) and JH-1,H-6
¼
(5.0 Hz for both compounds) indicate equatorial positions
of coupled protons.
The multiplet of H-1 in the 1H NMR spectrum of 3c, 4c, 5c
and 6c looks like a broad singlet. This shape indicates
equatorial orientations of H-2 and H-1.
The X-ray analysis of compounds obtained from epoxy ester
2b, the tosyloxy lactone (3b) and hydroxy lactone (6b),
indicated that the cyclohexane ring in all of them exists in a
slightly twisted chair conformation (Fig. 2). The additional
methyl group at C-6 forces the cis orientation of the lactone
ring to the axial methyl group at C-4. The C–O bonds of the
lactone moiety and tosyloxy or hydroxy group are in a trans
relation and occupy equatorial positions. The X-ray analysis
of 6b indicates the presence of two symmetrically
independent molecules in the crystals.
Results obtained from the experiments reported above are
not consistent with those presented earlier for lactonization
of acyclic d,g-epoxy esters.11 The lactonization of ethyl
3,7-dimethyl-3,4-epoxyoctanoate and its two 3- or 7-methyl
homologues with p-toluenesulfonic acid monohydrate
carried out in benzene afforded d-hydroxy-g-lactone as the
only product.
The coupling constants of H-1 and H-2 protons are
consistent with the torsion angles determined by X-ray
These two different results indicate that the mechanisms of
lactonization are probably different. This is perhaps due to
Figure 2. Crystal structures of 3b and 6b.

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C. Wawrzenczyk et al. / Tetrahedron 59 (2003) 6595–6601
6598
1. We did not identify the 2-hydroxy-3-tosyloxy or
2-hydroxy-3-alkoxy esters as intermediates in the course
of lactonization of 2a–c.
2. The stereospecificity of the lactonization process has
been observed. The tosyloxy or alkoxy group is always
situated in a trans position to the C–O bond of the
lactone ring.
4. Experimental
The purity of intermediates and isolated products was
checked by TLC: silica gel DC-Alufolien Kieselgel 60 F254
(Merck) with the application of hexane–acetone 9:1 (for
epoxy esters), hexane–acetone 3:1 (for hydroxy, tosyloxy
and alkoxy lactones) as the developing systems. The same
eluents were applied in the course of preparative column
chromatography (silica gel: Kieselgel 60, 230–400 mesh)
for the separation of product mixtures. GC analysis were
performed on Hewlett–Packard 5890 instrument using the
following capillary columns HP-1 (Crosslinked Methyl
Silicone Gum) 25 m£0.32 mm£0.52 mm and HP-5 (Cross-
linked Phenyl Methyl Silicone) 30 m£0.52 mm£0.88 mm.
1H NMR spectra were recorded for CDCl3 solutions with
TMS as internal standard on a Bruker Avance DRX 300
Spectrometer. IR spectra were determined with a Specord
M-80 and Mattson IR 300 infrared spectrophotometers.
Melting points (uncorrected) were determined on a Boetius
apparatus.
Figure 3. Crystal structure of 3c.
the difference in distance between the oxirane ring and
carboethoxy group in both types of epoxy esters.
Two possible mechanisms of the lactonization of 2a–c
could be taken into consideration. The relatively short
distance between the epoxy oxygen atom and carbon atom
˚
of carbonyl group (3.4 A for 2a, according to AM1 method,
HyperChem) in cyclic epoxy esters makes it possible that
this oxygen can easily attack (as a nucleophile) the carbonyl
carbon of the protonated carboethoxy group with synchro-
nous attack of nucleophiles present in the reaction medium
on C-3 (Scheme 2). The cis orientation of epoxy rings and
the methylcarboethoxy groups makes such mechanism of
lactonization possible.
All reagents were purchased from Fluka. The starting
materials: ethyl (5,5-dimethyl-2-cyclohexen-1-yl) acetate
(1a), ethyl (1,5,5-trimethyl-2-cyclohexen-1-yl) acetate (1b)
and ethyl 5-methyl-2-cyclohexen-1-yl)acetate (1c) were
obtained from dimedone12 isophorone16 and 5-methyl-1,3-
cyclohexanedione, respectively.
The second mechanism assumes opening of the oxirane ring
followed by lactonization of resulting 2-hydroxy-3-tosyloxy
or 2-hydroxy-3-alkoxy esters (Scheme 3).
3. Conclusions
4.1. X-Ray crystallographic data
Although, studies on the mechanism of this lactonization are
in progress, we incline towards mechanism 1 (Scheme 2).
This choice is suggested by the following observations.
All measurements of crystals were performed at 100 K
using an Oxford Cryosystem device on a Kuma KM4CCD
k-axis diffractometer with graphite-monochromated Mo Ka
Scheme 2. NuH¼TsOH, EtOH, MeOH or H2O.
Scheme 3. NuH¼TsOH, EtOH, MeOH or H2O.

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C. Wawrzenczyk et al. / Tetrahedron 59 (2003) 6595–6601
6599
˚
radiation (l¼0.71073 A). Crystals were positioned at
4.2.3. cis-Ethyl (5-methyl-2,3-epoxycyclohex-1-yl)acetate
(2c). 1.8 g, 60%. Colourless liquid; n2D0¼1.4540; [found: C,
66.7; H, 9.0. C11H18O3 requires C, 66.64; H, 9.15%]; nmax
(liquid film) 1748, 1192, 1040 cm21; dH (300 MHz, CDCl3)
4.13 (2H, q, J¼7.1 Hz, OCH2CH3), 3.16 (1H, dd, J¼5.1,
4.0 Hz, H-3), 3.10 (1H, d, J¼4.0 Hz, H-2), 2.49 (1H,
dd, J¼17.7, 9.7 Hz, CHaHb-7), 2.27–2.36 (2H, m, H-1,
CHaHb-7), 1.99 (1H, m, CHaHb-4), 1.25 (3H, t, J¼7.1 Hz,
OCH2CH3), 0.83 (3H, d, J¼6.2 Hz, CH3-5).
65 mm from the CCD camera. 612 frames were measured
at 0.758 intervals with a counting time of 10–20 s. Accurate
cell parameters were determined and refined by least-
squares fit of 1800–3100 the strongest reflections. The data
were corrected for Lorentz and polarization effects. No
absorption correction was applied. Data reduction and
analysis were carried out with the Oxford Diffraction
(Poland) Sp. z o.o. (formerly Kuma Diffraction Wrocław,
Poland) programs. Structures were solved by direct
methods (program SHELXS9717) and refined by the full-
matrix least-squares method on all F 2 data using the
SHELXL9718 programs. Non-hydrogen atoms were refined
with anisotropic displacement parameters; hydrogen atoms
were included from geometry of molecules and Dr maps.
They were refined with isotropic displacement parameters.
4.2.4. trans-Ethyl (5-methyl-2,3-epoxycyclohex-1-yl)ace-
tate (2d). 0.4 g, 15%. Colourless liquid; n2D0¼1.4573;
[found: C, 66.5; H, 9.2. C11H18O3 requires C, 66.64; H,
9.15%]; nmax (liquid film) 1744, 1244, 1168, 1040 cm21; dH
(300 MHz, CDCl3) 4.12 (2H, q, J¼7.1 Hz, OCH2CH3), 3.15
(1H, ddd, J¼3.8, 2.1, 1.8 Hz, H-3), 2.86 (1H, dd, J¼3.8,
1.1 Hz, H-2), 2.06–2.47 (7H, m, CH2-4, CH2-6, CH2-7,
H-1), 1.25 (3H, t, J¼7.1 Hz, OCH2CH3), 0.88 (3H, d,
J¼6.6 Hz, CH3-5).
Crystallographic data (excluding structure factors) for
crystals 3a,3b,3c, 6a and 6b in this paper, have been
deposited with the Cambridge Crystallographic Data Centre
as supplementary publication numbers CCDC 205102–
205106, respectively. Copies of the data can be obtained,
free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK (fax: þ44-1223-336033 or
e-mail: deposit@ccdc.cam.ac.uk).
4.3. Lactonization of epoxy esters 2a–c with perchloric
acid
Lactonization of epoxy esters 2a–c (4.5 mmol) with
perchloric acid in water–tetrahydrofurane solution
(40 mL, THF–H2O–HClO4, 10:5:0.1) was carried out as
described earlier.11,15 The yield, physical and spectral data
of hydroxy lactones 6a,6b,6c are given below.
4.2. Epoxidation of esters 1a–c
A solution of m-chloroperbenzoic acid (0.03 mol) in 60 cm3
of methylene chloride was added to a solution of ester
(0.015 mol) in methylene chloride (100 cm3). When the
reaction was completed (TLC, 24 h) the mixture was diluted
with ethyl ether and washed successively with aqueous
solutions of Na2CO3 and Na2SO3 and water. The crude
product was purified by column chromatography (silica gel,
hexane–acetone 9:1). The yields, physical and spectral data
of epoxy esters 2a, 2b and 2c are given below.
4.3.1. 2-Hydroxy-4,4-dimethyl-9-oxabicyclo[4.3.0]-
nonan-8-one (6a). 0.5 g, 63%. White crystals, mp 53–
548C; [found: C, 65.0; H, 8.8. C10H16O3 requires C, 65.19;
H, 8.75%]; nmax (KBr) 3464, 1784, 1183, 1028 cm21; dH
(300 MHz, CDCl3) 4.40 (1H, t, J¼5.9 Hz, H-1), 4.06 (1H,
dddd, J¼5.9, 5.5, 5.2, 4.2 Hz, H-2), 2.76 (1H, dd, J¼13.8,
8.3 Hz, CHaHb-7), 2.35 (1H, s, OH), 2.26 (1H, d, J¼
13.8 Hz, CHaHb-7), 1.59 (1H, dd, J¼14.0, 4.2 Hz,
CHaHb-3), 1.24–1.42 (3H, m, CH2-5, CHaHb-3), 1.04
(3H, s, C(CH3)2), 1.01 (3H, s, C(CH3)2).
4.2.1. Ethyl (5,5-dimethyl-2,3-epoxycyclohex-1-yl) acetate
(2a). 2.6 g, 81%. Colourless liquid; n2D0¼1.4535; [found: C,
67.6; H, 9.6. C12H20O3 requires C, 67.89; H, 9.50%]; nmax
(liquid film) 1748, 1188, 1152, 1032 cm21; dH (300 MHz,
CDCl3) 4.17 (2H, q, J¼7.0 Hz, OCH2CH3), 3.10–3.16 (2H,
m, H-2, H-3), 2.71 (1H, m, H-1), 2.56 (1H, dd, J¼14.9,
7.5 Hz, CHaHb-7), 2.29 (1H, dd, J¼14.9, 5.7 Hz, CHaHb-7),
1.60 (1H, ddd, J¼15.3, 5.0, 1.8 Hz, CHaHb-4), 1.54 (1H, d,
J¼15.3 Hz, CHaHb-4), 1.27 (3H, t, J¼7.0 Hz, OCH2CH3),
1.04 (1H, ddd, J¼3.0, 5.7, 1.9 Hz, CHaHb-6), 1.00 (1H, d,
J¼13.0 Hz, CHaHb-6), 0.90 (3H, s, C(CH3)2), 0.86 (3H, s,
C(CH3)2).
Crystal data for 6a. C10H16O3, Mw¼184.23, monoclinic,
˚
P21/c, a¼21.939(4), b¼13.311(3), c¼6.929(2) A, b¼
3
23
˚
94.97(2)8, V¼2015.7(8) A , Z¼8, Dc¼1.214 mg m
,
m¼0.088 mm21, F(000)¼800, crystal size 0.30£0.25£
0.20 mm3, 13713 collected refl., 4680 indep. refl.,
Rint¼0.0781, 363 parameters, S¼1.152, R1¼0.1120,
Rw(F 2)¼0.2606.
4.3.2. 2-Hydroxy-4,4,6-trimethyl-9-oxabicyclo[4.3.0]-
nonan-8-one (6b). 0.88 g, 99%. White crystals, mp 109–
1108C; [found: C, 66.3; H, 9.2. C11H18O3 requires C, 66.64;
H, 9.15%]; nmax (KBr) 3408, 1784, 1164, 1056 cm21; dH
(300 MHz, CDCl3) 3.90 (1H, d, J¼7.7 Hz, H-1), 3.86 (1H,
ddd, J¼7.7, 4.0, 2.1 Hz, H-2), 2.68 (1H, d, J¼17.5 Hz,
CHaHb-7), 2.15 (1H, d, J¼17.5 Hz, CHaHb-7), 2.12 (1H, s,
OH), 1.66 (1H, ddd, J¼13.7, 4.0, 2.1 Hz, CHaHb-3), 1.62
(1H, dd, J¼13.7, 2.1 Hz, CHaHb-3), 1.28–1.36 (2H, m,
CH2-5), 1.18 (3H, s, CH3-6), 1.06 (3H, s, C(CH3)2), 1.01
(3H, s, C(CH3)2).
4.2.2. Ethyl (1,5,5-trimethyl-2,3-epoxycyclohex-1-yl)ace-
tate (2b). 2.65 g, 78%. Colourless liquid; n2D0¼1.4600;
[found: C, 69.2; H, 9.4. C13H22O3 requires C, 68.88; H,
9.80%]; nmax (liquid film) 1748, 1372, 1364, 1240, 1156,
1036 cm21; dH (300 MHz, CDCl3) 4.12 (2H, q, J¼7.1 Hz,
OCH2CH3), 3.23 (1H, ddd, J¼3.9, 3.8, 1.9 Hz, H-3),
2.97 (1H, d, J¼3.8 Hz, H-2), 2.46 (1H, d, J¼14.2 Hz,
CHaHbCO2), 2.32 (1H, d, J¼14.2 Hz, CHaHbCO2), 1.61–
1.64 (2H, m, CH2-4), 1.23 (1H d, J¼14.1 Hz, CHaHb-6),
1.24 (3H, t, J¼7.1 Hz, OCH2CH3), 1.22 (3H, s, CH3-1),
1.10 (1H d, J¼14.1 Hz, CHaHb-6), 0.91 (3H, s, C(CH3)2),
0.89 (3H, s, C(CH3)2).
Crystal data for 6b. C22H36O6, Mw¼396.51, monoclinic,
˚
P21/c, a¼13.8460(15), b¼12.8157(11), c¼12.9695(13) A,
3
˚
b¼109.630(9)8,
V¼2167.6(4) A ,
Z¼4,
Dc¼

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C. Wawrzenczyk et al. / Tetrahedron 59 (2003) 6595–6601
6600
1.215 Mg m23, m¼0.087 mm21, F(000)¼864, crystal size
0.27£0.25£0.20 mm3, 14683 collected refl., 5009 indep.
refl., Rint¼0.0283, 397 parameters, S¼1.122, R1¼0.0428,
Rw(F 2)¼0.0944.
1.83 (1H, ddd, J¼14.0, 4.2, 1.0 Hz, He-3), 1.56 (1H, dd, J¼
14.0, 9.1 Hz, Ha-3), 1.50 (1H, d, J¼14.7 Hz, CHaHb-5), 1.25
(1H, d, J¼14.7 Hz, CHaHb-5), 1.23 (3H, s, CH3-6), 1.07
(3H, s, C(CH3)2), 1.03 (3H, s, C(CH3)2).
4.3.3. 2-Hydroxy-4-methyl-9-oxabicyclo[4.3.0]nonan-9-
one (6c). 0.75 g, 98%. Colourless liquid; n2D0¼1.4821;
[found: C, 64.0; H, 8.0. C9H14O3 requires C, 63.51; H,
8.29%]; nmax (liquid film) 3448, 2964, 1796, 1216, 1172,
1060 cm21; dH (300 MHz, CDCl3) 4.25–4.29 (2H, m, H-2,
H-1), 2.66 (1H, dd, J¼16.3, 6.7 Hz, CHaHb-7), 2.61 (1H, m,
H-6), 2.18 (1H, d, J¼16.3 Hz, CHaHb-7), 1.66–1.74 (4H, m,
CHaHb-3, CHaHb-5, H-4, OH), 1.34 (1-H, ddd, J¼14.5,
12.1, 2.6 Hz, CHaHb-3), 0.88 (3H, d, J¼6.6 Hz, CH3-4),
0.83 (1H, m, CHaHb-5).
Crystal data for 3b. C18H24O5S, Mw¼352.43, monoclinic,
˚
P21/c, a¼8.020(2), b¼19.520(4), c¼11.365(2) A, b¼
3
23
˚
101.45(3)8, V¼1743.8(6) A , Z¼4, Dc¼1.342 Mg m
,
m¼0.210 mm21, F(000)¼752, crystal size 0.30£0.25£
0.20 mm3, 11620 collected refl., 4034 indep. refl., Rint¼
0.0269, 313 parameters, S¼1.073, R1¼0.0392, Rw(F 2)¼
0.0885.
4.4.3. 2-Tosyloxy-4-methyl-9-oxabicyclo[4.3.0] nonan-8-
one (3c). 0.24 g, 75%. White crystals, mp 105–1068C;
[found: C, 59.3; H, 6.3; S, 9.8. C16H20O5S requires C, 59.23;
H, 6.21; S, 9.88%]; nmax (KBr) 2872, 1800, 1600, 1376,
1180, 840 cm21; dH (300 MHz, CDCl3) 7.30–7.73 (4H, m,
C6H4), 4.78 (1H, m, H-2), 4.23 (1H, m, H-1), 2.56 (1H, dd,
J¼16.0, 6.5 Hz, CHaHb-7), 2.54 (1H, m, H-6), 2.39 (3H, s,
C6H4–CH3), 2.13 (1H, d, J¼16.0 Hz, CHaHb-7), 0.83 (3H,
d, J¼6.5 Hz, CH3-4).
4.4. Lactonization epoxy esters with p-toluenesulfonic
acid monohydrate
Mixture of epoxy ester (1a–c) (1 mmol) and p-toluene-
sulfonic acid monohydrate (1.1 mmol) in corresponding
solvent (20 cm3) was stirred at room temperature for 24 h.
Then the reaction mixture in methylene chloride or benzene
was washed with saturated NaHCO3 aqueous solution, brine
and dried (MgSO4). In the case when the reaction was
carried and in methanol or ethanol the reaction mixture was
diluted with water and the product was extracted with
methylene chloride. The extracts were washed with
saturated NaHCO3 solution, brine and dried (MgSO4).
After solvent evaporation the product mixture was analysed
by GC and products were separated by column chroma-
tography (silica gel, hexane–acetone 3:1). The compo-
sitions of product mixtures and yields are presented in
Table 1. The physical and spectral data of compound
obtained are given below.
Crystal data for 3c. C16H20O5S, Mw¼324.38, monoclinic,
˚
P21/c, a¼19.798(2), b¼7.0236(8), c¼11.7633(16) A,
3
˚
b¼105.355(11)8,
V¼1577.3(3) A ,
Z¼4,
Dc¼
1.366 Mg m23, m¼0.226 mm21, F(000)¼688, crystal size
0.30£0.25£0.20 mm3, 10457 collected refl., 3701 indep.
refl., Rint¼0.0333, 279 parameters, S¼1.069, R1¼0.0466,
Rw(F 2)¼0.0866.
4.4.4. 2-Hydroxy-4-methyl-9-oxabicyclo[4.3.0]nonan-9-
one (6d). 0.16 g, 94%. Colourless liquid; n2D0¼1.4890;
[found: C, 63.8; H, 8.1. C9H14O3 requires C, 63.51; H,
8.29%]; nmax (liquid film) 3464, 1792, 1172, 1016 cm21; dH
(300 MHz, CDCl3) 4.25–4.29 (2H, m, H-1, H-2), 2.66
(1H, dd, J¼16.2, 6.7 Hz, CHaHb-7), 2.60 (1H, m, H-6),
2.18 (1H, d, J¼16.2 Hz, CHaHb-7), 1.67–1.84 (3H, m,
CHaHb-3, CHaHb-5, H-4), 1.33 (1H, dt, J¼13.5, 2.7 Hz,
CHaHb-3), 0.85 (3H, d, J¼6.2 Hz, CH3-4), 0.77 (1H, m,
CHaHb-5).
4.4.1. 2-Tosyloxy-4,4-dimethyl-9-oxabicyclo[4.3.0]nonan-
8-one (3a). 0.23 g, 67%. White crystals, mp 124–1258C;
[found: C, 60.2; H, 6.6; S, 9.3. C17H22O5S requires C, 60.33;
H, 6.55; S, 9.47%]; nmax (KBr) 3016, 1800, 1472, 1352,
1180, 836 cm21; dH (300 MHz, CDCl3) 7.36–7.80 (4H, m,
C6H4), 4.77 (1H, ddd, J¼4.6, 4.5, 4.0 Hz, H-2), 4.39 (1H,
dd, J¼4.5, 4.0 Hz, H-1), 2.26–2.73 (2H, m, CHaHb-7, H-6),
2.46 (3H, s, C6H4–CH3), 2.20 (1H, m, CHaHb-7), 1.56 (2H,
m, CH2-3), 1.26–1.43 (2H, m, CH2-5), 1.02 (3H, s,
C(CH3)2), 0.93 (3H, s, C(CH3)2).
4.4.5. 2-Ethoxy-4,4-dimethyl-9-oxabicyclo[4.3.0]nonan-
8-one (4a). 0.12 g, 60%. Colourless liquid; n2D0¼1.4665;
[found: C, 68.1; H, 9.1. C12H20O3 requires C, 67.89; H,
9.50%]; nmax (liquid film) 1792, 1180, 1128, 1012 cm21; dH
(300 MHz, CDCl3) 4.42 (1H, dd, J¼5.0, 4.8 Hz, H-1), 3.65
(1H, dt, J¼7.1, 4.8 Hz, H-2), 3.57 (2H, q, J¼6.9 Hz,
OCH2CH3), 2.72 (1H, dd, J¼15.9, 7.9 Hz, CHaHb-7), 2.66
(1H, m, H-6), 2.19 (1H, d, J¼15.9 Hz, CHaHb-7), 1.20–1.47
(4H, m, CH2-3, CH2-5), 1.19 (3H, t, J¼6.9 Hz, OCH2CH3),
1.02 (3H, s, C(CH3)2), 0.98 (3H, s, C(CH3)2).
Crystal data for 3a. C17H22O5S, Mw¼338.41, monoclinic,
˚
P21/c, a¼10.3028(9), b¼14.8023(13), c¼11.7590(14) A,
3
23
˚
b¼112.347(9)8, V¼1658.6(3) A , Z¼4, Dc¼1.355 Mg m
,
m¼0.218 mm21, F(000)¼720, crystal size 0.30£0.25£
0.20 mm3, 11260 collected refl., 3837 indep. refl., Rint¼
0.0302, 296 parameters, S¼1.102, R1¼0.0423, Rw(F 2)¼
0.0911.
4.4.6. 2-Ethoxy-4,4,6-trimethyl-9-oxabicyclo[4.3.0]no-
nan-8-one (4b). 0.14 g, 64%. Colourless liquid; n2D0¼
1.4638; [found: C, 70.0; H, 9.4. C13H22O3 requires C,
68.99; H, 9.80%]; nmax (liquid film) 1788, 1384, 1368, 1168,
1104, 1028 cm21; dH (300 MHz, CDCl3) 4.02 (1H, d, J¼
6.5 Hz, H-1), 3.58 (2H, q, J¼7.0 Hz, OCH2CH3), 3.51 (1H,
ddd, J¼10.0, 6.5, 4.1 Hz, H-2), 2.57 (1H, d, J¼17.3 Hz,
CHaHb-7), 2.18 (1H, d, J¼17.3 Hz, CHaHb-7), 1.60 (1H,
ddd, J¼13.7, 4.1, 1.0 Hz, He-3), 1.35 (1H, dd, J¼13.7,
10.0 Hz, Ha-3), 1.50 (1H, d, J¼14.7 Hz, CHaHb-5), 1.29
4.4.2. 2-Tosyloxy-4,4,6-trimethyl-9-oxabicyclo[4.3.0]-
nonan-8-one (3b). 0.25 g, 70%. White crystals, mp 113–
1148C; [found: C, 61.3; H, 6.8; S, 9.0. C18H24O5S requires
C, 61.34; H, 6.84; S, 9.10%]; nmax (KBr) 1796, 1472, 1372,
1180, 1036 cm21; dH (300 MHz, CDCl3) 7.36–7.80 (4H, m,
C6H4), 4.65 (1H, ddd, J¼9.1, 6.5, 4.2 Hz, H-2), 4.03 (1H, d,
J¼6.5 Hz, H-1), 2.52 (1H, d, J¼17.3 Hz, CHaHb-7), 2.46
(3H, s, C6H4–CH3), 2.18 (1H, d, J¼17.3 Hz, CHaHb-7),

´
C. Wawrzenczyk et al. / Tetrahedron 59 (2003) 6595–6601
6601
(1H, d, J¼14.7 Hz, CHaHb-5), 1.22 (3H, s, CH3-6), 1.18
Acknowledgements
(3H, t, J¼7.0 Hz, OCH2CH3), 1.03 (3H, s, C(CH3)2), 1.01
(3H, s, C(CH3)2).
This work was supported by the State Committee for
Scientific Research (KBN) Grant No. P 06B 031 20.
4.4.7. 2-Ethoxy-4-methyl-9-oxabicyclo[4.3.0]nonan-8-
one (4c). 0.15 g, 78%. Colourless liquid; n2D0¼1.4640;
[found: C, 66.7; H, 9.0. C11H18O3 requires C, 66.64; H,
9.15%]; nmax (liquid film) 1796, 1168, 1120, 1044 cm21; dH
(300 MHz, CDCl3), 4.30 (1H, m, H-1), 3.79 (1H, m, H-2),
3.52 (2H, m, OCH2CH3), 2.63 (1H, dd, J¼16.5, 6.6 Hz,
CHaHb-7), 2.54 (1H, m, H-6), 2.16 (1H, d, J¼16.5 Hz,
CHaHb-7), 1.51–1.76 (4H, m, CHaHb-3, CHaHb-5, H-4),
1.17 (3H, t, J¼7.0 Hz, OCH2CH3), 0.86 (3H, d, J¼6.4 Hz,
CH3-4), 0.75 (1H, m, CHaHb-5).
References
´
1. Lochynski, S.; Fra˛ckowiak, B.; Olejniczak, T.; Ciunik, Z.;
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(1H, m, H-2), 3.38 (3H, s, OCH3), 2.71 (1H, dd, J¼16.6,
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nonan-8-one (5b). 0.17 g, 79%. Colourless liquid; n2D0¼
1.4709; [found: C, 68.1; H, 9.1. C12H20O3 requires C, 67.89;
H, 9.50%]; nmax (liquid film) 1788, 1389, 1368, 1164,
1104 cm21; dH (300 MHz, CDCl3) 4.02 (1H, d, J¼6.4 Hz,
H-1), 3.45 (1H, m, H-2), 3.40 (3H, s, OCH3), 2.56 (1H, d,
J¼17.3 Hz, CHaHb-7), 2.19 (1H, d, J¼17.3 Hz, CHaHb-7),
1.61 (1H, dd, J¼13.7, 3.9 Hz, He-3), 1.32 (1H, dd, J¼13.7,
10.0 Hz, Ha-3), 1.49 (1H,d, J¼14.7 Hz, CHaHb-5), 1.30
(1H,d, J¼14.7 Hz, CHaHb-5), 1.22 (3H, s, CH3-6), 1.03 (3H,
s, C(CH3)2), 1.01 (3H, s, C(CH3)2).
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[found: C, 65.7; H, 8.3. C10H16O3 requires C, 65.19; H,
8.75%]; nmax (liquid film) 1800, 1216, 1168, 1088 cm21
;
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´ ´
16. Grabarczyk, M.; Gora, J.; Wawrzenczyk, C. Polish Patent
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CHaHb-7), 2.57 (1H, m, H-6), 2.17 (1H, d, J¼16.6 Hz,
CHaHb-7), 1.52–1.85 (3H, m, CHaHb-3, CHaHb-5, H-4),
1.15 (1H, m, CHaHb-3), 0.87 (3H, d, J¼6.4 Hz, CH3-4),
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Appl. P-342504, 2000.
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