Non-stabilized azomethine ylides in [3 + 2] cycloadditions. Pyrrolidinylfuranones from (5S)-5-menthyloxy-4-vinylfuran-2(5H)-one

Article abstract of DOI:10.1039/a803693d

Upon sonication with lithium fluoride in acetonitrile N-benzyl-N-methoxymethyl(trimethylsilylmethyl)amines 9a-c undergo chemoselective 1,3-dipolar cycloaddition with 4-vinylfuranones 2 and 6 to afford pyrrolidinylfuranones 10, 11a-c and 12a-c. The stereochemistry is assigned by X-ray analyses and proton NMR data comparison of related oxiranylfuranone 13.

Full text of DOI:10.1039/a803693d

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Non-stabilized azomethine ylides in [3 ؉ 2] cycloadditions.
Pyrrolidinylfuranones from (5S)-5-menthyloxy-4-vinylfuran-
2(5H)-one
Kai Gerlach,a H. M. R. Hoffmann*a and R. Wartchowb
a Department of Organic Chemistry, University of Hannover, Schneiderberg 1B,
30167 Hannover, Germany. E-mail: hoffmann@mbox.oci.uni-hannover.de;
Fax: ϩ49(511)7623011
b Department of Inorganic Chemistry, University of Hannover, Callinstr. 9, 30167 Hannover,
Germany
Received (in Cambridge) 18th May 1998, Accepted 1st September 1998
Upon sonication with lithium fluoride in acetonitrile N-benzyl-N-methoxymethyl(trimethylsilylmethyl)amines 9a–c
undergo chemoselective 1,3-dipolar cycloaddition with 4-vinylfuranones 2 and 6 to afford pyrrolidinylfuranones
10, 11a–c and 12a–c. The stereochemistry is assigned by X-ray analyses and proton NMR data comparison of
related oxiranylfuranone 13.
4-Vinylfuran-2(5H)-ones, which have received little attention
hitherto, are well suited for the construction of heteroprostan-
oids containing a pyrrolidine ring and also other heterocycles,
which are attached to an electron-deficient butenolide moiety.
We here describe the synthesis of (5S)-5-menthyloxy-4-
vinylfuran-2(5H)-one 6. Heterocycle 6 was obtained enantio-
merically pure and is useful for elucidating the stereochemistry
of simple [2 ϩ 3] and [2ϩ 1] cycloadditions to the vinyl group.
Carbon C-5 of the furan-2(5H)-one possesses an oxygenated
side-chain, as in simple derivatives and metabolites of
4-vinylfuran-2(5H)-one 2.
Results
The synthesis of (5S)-5-menthyloxy-4-vinylfuran-2(5H)-one 6
is described in Scheme 1. We had earlier reported the direct
Br
SnBu3, Pd(PPh3)2Cl2
Fig. 1 X-Ray structure of (5S)-4-bromo-5-menthyloxyfuran-2(5H)-
one 5.
O
O
THF/MeCN 10:1, 35 ºC,
2 d, 85 %
O
O
1
2
a severe drop in yield.3 We obtained the epimers of 5 in a
ratio of (5S)-5:(5R)-5 = 1.25:1. MM2 calculations suggest
that the major (5S)-4-bromo-5-menthyloxyfuran-2(5H)-one 5
is more stable (by ca. 2 kcal molϪ1) than its diastereomer.4 A
simple recrystallization from petroleum ether–diethyl ether
mixtures furnished enantiomerically pure (5S)-4-bromo-5-
menthyloxyfuran-2(5H)-one 5, the structure of which was
determined by X-ray crystal diffraction (Fig. 1).5 The diastereo-
mer of 5 (with respect to carbon C-5) was recycled to 4-bromo-
5-hydroxyfuran-2(5H)-one 4 by acidic hydrolysis.
Stille reaction with tributylvinylstannane gave cross-coupled
6 in good yield (82%). Similarly 4-vinylfuran-2(5H)-one 2 was
prepared readily from tetronic acid bromide 1 (yield 85%), no
doubt due to the activation of the carbon–bromine bond by the
vinylogous lactone carbonyl group.
i) (-)-Menthol,
DCM, Dean-
Stark separator,
reflux, 7 d, 80%
Br
Br
H2SO4 (30%)
O
O
ii) resolution
reflux, 1 h, 100 %
O
O
MeO
HO
3
4
SnBu3,
Br
Pd(PPh3)2Cl2
H
O
H
O
O
O
O
THF/MeCN
(10:1), 35 ºC,
2 d, 82%
O
6
5
Scheme 1 Synthesis of the dipolarophiles.
The synthesis of the azomethine ylide precursors 9a–c
required two steps. Benzylamines 7a–c were treated with tri-
methylsilylmethyl chloride using potassium carbonate in reflux-
ing acetonitrile to give the α-aminosilanes 8a–c in good yield
(Scheme 2). Subsequent reaction with methanolic 40% aqueous
formaldehyde afforded the tertiary amines 9a–c in satisfactory
yield and set the stage for the fluoride mediated 1,3-dipolar
cycloadditions.6,7
transacetalization of 4-bromo-5-methoxyfuran-2(5H)-one 3
with various alcohols in the melt.1 We now find that it is prefer-
able to carry out this conversion in two steps. Under forcing
conditions (30% H2SO4) methoxy acetal 3 was first of all con-
verted into hemiacetal 4 in quantitative yield.2 The subsequent
acetalization (4 → 5) proceeded in much milder conditions,
i.e. refluxing DCM with removal of the water liberated. In con-
trast, refluxing 4 in toluene under acid catalysis (PTSA) caused
Parent vinylfuranone 2 was converted into pyrrolidinyl-
J. Chem. Soc., Perkin Trans. 1, 1998, 3867–3872
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Table 1 Reaction of vinylfuranone 6 with amines 9a–c
Dipole precursor
Products
11/12
Yield
(%)
ratio
11:12
Entry
9
R
Conditions
1
2
3
4
5
6
b
c
a
b
b
c
(R)-Me
(S)-Me
H
(R)-Me
(R)-Me
(S)-Me
Ϫ40 ЊC, MeCN/THF
Ϫ40 ЊC, MeCN/THF
0 ЊC, sonication, 8 h
b
c
a
b
b
c
55
39
73
88
74
69
2:1
2.92:1
2.5:1
2:1
2.45:1
3.2:1
0 ЊC, sonication, 8 h
0 ЊC, sonication, cat. Eu(fod)3, 8 h
0 ЊC, sonication, 8 h
R
R
R
R
(i)
(ii)
NH2
N
SiMe3
N
SiMe3
OMe
N
SiMe3
OMe
H
7a–c
8a–c
9a–c
9 a-c
7
R
H
(R)-Me
(S)-Me
8
Yield (%)
9
Yield (%)
H
O
O
1
2
3
a
b
c
a
b
c
80
81
75
a
b
c
55
64
69
O
6
LiF, MeCN
cond. see Table 1
Scheme 2 Synthesis of azomethine ylide precursors. Reagents and
conditions: (i) Me3SiCH2Cl, K2CO3, MeCN, reflux, 4 d; (ii) CH2O(aq.)
K2CO3, MeOH, 0 ЊC, 2.5 h.
,
R
R
furanone 10 by cycloaddition of the azomethine ylide generated
in situ from 9a using lithium fluoride (Scheme 3). This test reac-
N
N
H
H
+
H
O
O
H
O
O
N
SiMe3
OMe
O
O
9 a
11 a-c
12 a-c
LiF, MeCN, 0 ºC,
sonication, 8 h, 67%
N
O
Scheme 4 Syntheses of pyrrolidinylfuranones.
O
2
The position and multiplicity of the new tertiary proton gave no
satisfactory stereochemical information.
O
10
O
However, epoxidation of (5S)-5-menthyloxy-4-vinylfuran-
2(5H)-one 6 with dimethyldioxirane in acetone furnished the
crystalline diastereomeric epoxides 13 and 14 under mild condi-
tions (69% yield, 71% diastereoselectivity, Scheme 5).12
Scheme 3
tion showed that it was possible to combine the electron-rich
amine with the oxacyclic Michael acceptor. We were pleased to
find that menthyloxy derivative 6 reacted similarly (Scheme 4).
Cycloaddition occurred exclusively at the more accessible ter-
minal olefinic bond. The more hindered C3–C4 double bond,
although potentially more electron-deficient, was not attacked.8
Because of the poor solubility of lithium fluoride in
acetonitrile, sonication at 0 ЊC (bp of acetonitrile 81 ЊC) was
helpful.9 This also applied to the reactions with enantiopure
vinylfuranone 6, which were carried out without sonication at
Ϫ40 ЊC in mixed solvent (acetonitrile–THF) and again with
sonication at 0 ЊC (Table 1). Lowering the temperature to
Ϫ40 ЊC had no noticeable effect on the diastereoselectivity of
the cycloaddition, while addition of the mild Lewis acid
Eu(fod)3 changed the diastereoselectivity slightly (from 2:1 to
2.45:1).10 Reaction of (1S)-N-phenylethyl-N-methoxymethyl-
(trimethylsilylmethyl)amine 9c with vinylfuranone 6 gave the
best diastereomeric ratio (Entry 6) possibly as a consequence of
double asymmetric induction.11
H
O
O
O
6
Me2CO, r.t.,
overnight, 69%
O
O
O
H
O
H
H
O
O
H
O
O
+
O
O
13
14
6 : 1
Scheme 5 Epoxidation of vinylfuranone 6.
The diasteromeric pyrrolidinylfuranones were separated by
medium pressure liquid chromatography.
Major oxiranylfuranone 13 was separated and purified twice
by recrystallization. X-Ray crystallography5 (Fig. 3) showed the
configuration of the new chiral centre to be S.
The stereochemistry of pyrrolidinylfuranones 11a–c and
12a–c could not easily be determined by common NMR spec-
troscopic methods. Investigation of the diastereomeric mixtures
by proton spectroscopy showed two sets of protons H-3 and
H-5, with characteristic chemical shift differences and charac-
teristic relative positions in each case (cf. Fig. 2, spectrum C).
The relative positions of the furanone 1H absorptions of
epoxides 13 and 14 were similar to those of the diastereomeric
pyrrolidinylfuranones 11c and 12c (cf. spectra A, B and C).
Thus it appears that the relative and also absolute configuration
of the title heterocycles 11a–c and 12a–c can be determined by
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Fig. 3 X-Ray structure of (5S)-5-menthyloxy-4-[(2S)-oxiran-2-yl]-
furan-2(5H)-one 13.
Experimental
General
Melting points were determined on a Büchi apparatus and are
uncorrected. Infrared spectra were recorded on a Perkin-Elmer
1
1710 infrared spectrometer. H NMR and 13C NMR spectra
were recorded on a Bruker WH 90, AM 200 and AM 400
spectrometer in deuterated chloroform unless otherwise stated,
with tetramethylsilane as internal standard. Coupling con-
stants, J, are given in Hz. Mass spectra were recorded on a
Finnigan MAT312 (70 eV) or a VG Autospec spectrometer.
Microanalyses were performed in the Department of Organic
Chemistry of the University of Hannover. Preparative column
chromatography was performed on J. T. Baker silica gel (par-
ticle size 30–60 mm). Analytical TLC was carried out on
aluminum-backed 0.2 mm silica gel 60 F254 plates (E. Merck).
Preparation of 4-bromofuran-2(5H)-one 1, 4-vinylfuran-
2(5H)-one 2 and 4-bromo-5-methoxyfuran-2(5H)-one 3 was
described previously.1
4-Bromo-5-hydroxyfuran-2(5H)-one 4 and (5S)-4-bromo-5-
menthyloxyfuran-2(5H)-one 5
4-Bromo-5-methoxyfuran-2(5H)-one 3 (1.93 g, 10 mmol) was
heated at reflux for 1 h in 30% aqueous sulfuric acid (60 cm3).
The mixture was poured onto ice and extracted with diethyl
ether (3×). The combined organic layers were freed from sol-
vent to give 4-bromo-5-hydroxyfuran-2(5H)-one 4 as a yellow
oil, which was transferred as a solution in DCM (30 cm3) into a
two-necked flask equipped with a Dean–Stark separator. (Ϫ)-
Menthol (2.5 g, 1.6 eq.) was added and the mixture was refluxed
for one week. Evaporation of the solvent and column chrom-
atography (silica gel, petroleum ether–diethyl ether 10:1)
afforded 4-bromo-5-menthyloxyfuran-2(5H)-one as a mixture
of epimers (white crystals, 2.54 g, 8 mmol, 80%, ratio (5S)-5/
(5R)-5 = 1.25:1). Recrystallization from petroleum ether (bp
40–60 ЊC)–diethyl ether furnished enantiopure (5S)-4-bromo-5-
menthyloxyfuran-2(5H)-one 5.
Fig. 2
simply comparing the proton NMR data with those of oxiran-
ylfuranones 13 and 14.
4-Bromo-5-hydroxyfuran-2(5H)-one 4
Crystallization of the crude viscous product from acetone gave
white crystals, mp 71 ЊC; νmax(KBr)/cmϪ1 3305, 3115, 1717,
1610, 1440, 1333, 1297, 1257, 1184, 1136, 1037, 956, 859, 843,
717; νmax(CHCl3)/cmϪ1 3584, 3120, 3040, 1796, 1768, 1612,
1420, 1320, 1248, 1120, 1032, 960, 892, 864, 840; δH(80 MHz;
CDCl3; Me4Si) 2.18 (s, Me2CO, solvated), 4.65 (1 H, br s, OH),
6.06 (1 H, s, H-5), 6.40 (1 H, d, J 0.5, H-3); δC(50 MHz; APT;
CDCl3; Me4Si) 31.00 (Ϫ, Me2CO, solvated), 99.66 (Ϫ, C-5),
Conclusion
We have prepared novel bicyclic conjugates by combining pro-
tected and electron-rich pyrrolidines with an oxacyclic Michael
acceptor by a σ-bond at carbon atoms C-3Ј and C-4, respect-
ively. These conjugates are potential heteroprostanoids and are
of interest as low molecular weight bioregulators.
J. Chem. Soc., Perkin Trans. 1, 1998, 3867–3872
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123.91 (Ϫ, C-3), 148.32 (ϩ, C-4), 169.62 (ϩ, C-2), 211.10 (ϩ,
Me2CO, solvated); m/z 181/179 (Mϩ ϩ 1, 1%/8%), 180/178 (Mϩ,
19/23), 163/161 (6/7), 152/150 (8/9), 135/133 (7/8), 134/132 (95/
100), 124/122 (3/3), 107/105 (13/14), 106/104 (25/26), 99 (29), 73
(8), 71 (6).
C-menthyloxy), 102.93 (Ϫ, C-5), 117.86 (Ϫ, C-3), 125.11 (ϩ,
C-2Ј), 126.94 (Ϫ, C-1Ј), 160.05 (ϩ, C-4), 170.52 (ϩ, C-2)
(Found: C, 68.6; H, 4.1. C16H24O3 requires C, 68.57; H, 4.03%);
IR, MS and HRMS data are consistent with those reported in
the literature.1
(5S)-4-Bromo-5-menthyloxyfuran-2(5H)-one 5
General procedure for the synthesis of N-(trimethylsilylmethyl)-
benzylamines 8a–c
Mp 132 ЊC; [α]D20 ϩ26.6 (c 1.02 in CHCl3); δH(200 MHz; CDCl3;
Me4Si) 0.75–1.75 (16 H, m, H-menthyl), 2.20–2.48 (2 H, m,
H-menthyl), 3.55 (1 H, dt, J 10/4, H-menthyloxy), 5.79 (1 H, d,
J 1, H-5), 6.38 (1 H, d, J 1, H-3); δC(50 MHz; APT; CDCl3;
Me4Si) 15.83 (Ϫ, C-menthyl), 20.88 (Ϫ, C-menthyl), 22.11 (Ϫ,
C-menthyl), 22.87 (ϩ, C-menthyl), 25.15 (Ϫ, C-menthyl), 31.44
(Ϫ, C-menthyl), 34.10 (ϩ, C-menthyl), 42.10 (ϩ, C-menthyl),
48.04 (Ϫ, C-menthyl), 84.02 (Ϫ, C-menthyl), 104.84 (Ϫ, C-5),
124.15 (Ϫ, C-3), 146.15 (ϩ, C-4), 168.00 (ϩ, C-2) (Found: C,
53.04; H, 6.7. C14H21BrO3 requires C, 53.15; H, 6.7%); IR, MS
and HRMS data are consistent with those reported in the
literature.1
Benzylamine (1.5 eq.) 7a–c was added to a suspension of
anhydrous potassium carbonate (2.1 g, 0.5 eq.) in acetonitrile
(60 cm3). After stirring for 15 min at r.t. trimethylsilylmethyl
chloride (4.2 cm3, 30 mmol) was added over a period of 20 min.
After being refluxed (4 d) the mixture was freed from solvent
and purified by column filtration (silica gel, petroleum ether–
diethyl ether 3:1) to give the monoalkylated products 8a–c.
N-(Benzyl)trimethylsilylmethylamine 8a
The synthesis was performed according to the general pro-
cedure for the synthesis of N-(trimethylsilylmethyl)benzyl-
amines to furnish a slightly yellow liquid (4.63 g, 24 mmol,
80%). The spectroscopic data are consistent with those reported
in the literature.6
X-Ray structure determination of compound 5
C14H21BrO3, M = 317.22, monoclinic, space group P21 (No. 4),
a = 8.292(1), b = 6.455(1), c = 14.465(2) Å, α = 90, β = 104.08(1),
γ = 90Њ, V = 751.0(2) Å3, Z = 2, Dc = 1.403 g cmϪ3, F(000) = 328,
crystal size 0.10 × 0.81 × 0.06 mm, T = 300 K, µ(Mo-Kα) =
27.4 cmϪ1. Data collection: diffractometer Stoe IPDS (Imaging
Plate), graphite-monochromated Mo-Kα radiation (fine-focus
sealed tube, λ = 0.71073 Å), 2θ range = 5.0–48.2Њ, data set h, k,
l Ϫ9: 9; Ϫ7: 7; Ϫ16: 16, total data 5435, unique data 2273,
observed data 1868 with I > 2σ(I), Rint = 0.032. Structure solu-
tion by SHELXS-8613 and refinement by SHELXL-93,14 hydro-
gen atoms in geometrically calculated positions, ∆ρmax = 0.24
e ÅϪ3, ∆ρmin = –0.25 e ÅϪ3, R (F1) = 0.025 based on 1868 reflec-
tions with Fo > 4σ(Fo), wR2 = 0.038, wR2 based on F2 of 2273
reflections, Flack × parameter Ϫ0.00(1).
(1R)-N-(1-Phenylethyl)trimethylsilylmethylamine 8b. The
synthesis was performed according to the general procedure for
the synthesis of N-(trimethylsilylmethyl)benzylamines to give a
colourless liquid (5.05 g, 24.4 mmol, 81%); δH(400 MHz;
CDCl3) 0.00 (9 H, m, SiMe3), 1.30 (3 H, d, J 6.62, Me), 1.84
(1 H, d, J 13.61, CH2SiMe3), 1.92 (1 H, d, J 13.42, CH2SiMe3),
3.63 (1 H, q, J 6.62, PhCHMe), 7.13–7.35 (5 H, m, Ph); δC(100
MHz; DEPT; CDCl3) Ϫ2.66 (CH3, SiMe3), 24.38 (CH3, Me),
37.90 (CH2, CH2SiMe3), 62.11 (CH, PhCHMe), 126.61 (CH,
Ph), 126.71 (CH, Ph), 128.25 (CH, Ph), 146.08 (C, Ph).
(1S)-N-(1-Phenylethyl)trimethylsilylmethylamine 8c
The synthesis was performed according to the general pro-
cedure for the synthesis of N-(trimethylsilylmethyl)benzyl-
amines to furnish a slightly yellow liquid (4.65 g, 22.4 mmol,
75%); δC(100 MHz; DEPT; CDCl3) Ϫ2.67 (CH3, SiMe3), 24.38
(CH3, Me), 37.89 (CH2, CH2SiMe3), 62.11 (CH, PhCHMe),
126.61 (CH, Ph), 126.70 (CH, Ph), 128.25 (CH, Ph), 146.06 (C,
Ph); the proton NMR data are consistent with those reported in
the literature.7
Minor diastereomer of 5
δH(200 MHz; CDCl3; Me4Si) 0.75–1.75 (16 H, m, H-menthyl),
2.06–2.26 (2 H, m, H-menthyl), 3.65 (1 H, dt, J 10/4,
H-menthyloxy), 5.88 (1 H, d, J 1, H-5), 6.37 (1 H, d, J 1, H-3);
δC(50 MHz; APT; CDCl3; Me4Si) 15.68 (Ϫ, C-menthyl), 20.83
(Ϫ, C-menthyl), 21.18 (Ϫ, C-menthyl), 23.03 (ϩ, C-menthyl),
25.15 (Ϫ, C-menthyl), 31.55 (Ϫ, C-menthyl), 34.03 (ϩ,
C-menthyl), 40.30 (ϩ, C-menthyl), 47.53 (Ϫ, C-menthyl), 80.50
(Ϫ, C-menthyl), 101.73 (Ϫ, C-5), 124.24 (Ϫ, C-3), 145.86 (ϩ,
C-4), 168.07 (ϩ, C-2); IR, MS, HRMS data are consistent with
those reported in the literature.1
N-Benzyl-N-methoxymethyl(trimethylsilylmethyl)amine 9a
The synthesis was performed according to the literature.6
Kugelrohr distillation (0.05 torr, bp 105 ЊC) gave a colourless
liquid, yield 55%. Identified by spectral comparison.
(5S)-5-Menthyloxy-4-vinylfuran-2(5H)-one 6
A solution of (5S)-4-bromo-5-menthyloxyfuran-2(5H)-one 5
(3.17 g, 10 mmol) in THF (4 cm3) was added dropwise to a
suspension of Pd(Ph3P)2Cl2 (350 mg, 5 mol%) in THF (6 cm3)
and acetonitrile (1 cm3) under argon atmosphere. After stirring
for 15 min at r.t. tributylvinylstannane (3.01 cm3, 1.05 eq.) was
added. The mixture was then stirred for two days at 35 ЊC.
Evaporation of the solvent and column chromatography (silica
gel, petroleum ether–diethyl ether 5:1) afforded (5S)-5-
menthyloxy-4-vinylfuran-2(5H)-one 6 as white crystals (2.16 g,
8.17 mmol, 82%), mp 89 ЊC; [α]D20 ϩ37.03 (c 1.045 in CHCl3);
δH(400 MHz; CDCl3; Me4Si) 0.75–1.17 (12 H, m, H-menthyl),
1.29–1.49 (2 H, m, H-menthyl), 1.63–1.72 (2 H, m, H-menthyl),
2.15–2.26 (1 H, m, H-menthyl), 2.30–2.38 (1 H, m, H-menthyl),
3.60 (1 H, dt, J 10.48/4.41, H-menthyloxy), 5.69 (1 H, d,
J 11.03, H-2Ј), 5.81 (1 H, d, J 17.83, H-2Ј), 6.02 (2 H, m, H-3
and H-5), 6.55 (1 H, dd, J 17.83/11.03, H-1Ј); δC(50 MHz; APT;
CDCl3; Me4Si) 15.61 (Ϫ, C-menthyl), 20.92 (Ϫ, C-menthyl),
22.03 (Ϫ, C-menthyl), 22.60 (ϩ, C-menthyl), 24.96 (Ϫ,
C-menthyl), 31.49 (Ϫ, C-menthyl), 33.88 (ϩ, C-menthyl),
42.29 (ϩ, C-menthyl), 48.00 (Ϫ, C-menthyl), 82.33 (Ϫ,
(1R)-N-1-Phenylethyl-N-methoxymethyl(trimethylsilylmethyl)-
amine 9b
The synthesis was performed according to the literature.7
Kugelrohr distillation (0.05 torr, bp 115 ЊC) gave a colourless
liquid, yield 64%; δC(100 MHz; DEPT; CDCl3) Ϫ1.43 (CH3,
SiMe3), 19.21 (CH3, Me), 39.84 (CH2, CH2SiMe3), 54.56 (CH3,
OMe), 61.77 (CH, PhCHMe), 85.82 (CH2, CH2OMe), 126.54
(CH, Ph), 127.45 (CH, Ph), 128.00 (CH, Ph), 145.23 (C, Ph);
identified by spectral comparison.
(1S)-N-1-Phenylethyl-N-methoxymethyl(trimethylsilylmethyl)-
amine 9c
The synthesis was performed according to the literature.7
Kugelrohr distillation (0.05 torr, bp 115 ЊC) gave a colourless
liquid, yield 69%. δC(100 MHz; DEPT; CDCl3) Ϫ1.44 (CH3,
SiMe3), 19.21 (CH3, Me), 39.82 (CH2, CH2SiMe3), 54.54 (CH3,
OMe), 61.77 (CH, PhCHMe), 85.80 (CH2, CH2OMe), 126.53
(CH, Ph), 127.43 (CH, Ph), 128.00 (CH, Ph), 145.22 (C, Ph);
identified by spectral comparison of (1R)-enantiomer 9b.
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General procedure for the 1,3-dipolar cycloaddition
2.42 (2ϩ1 H, m, H-menthyl and H-4Ј), 2.56–2.91 (4 H, m,
H-2Ј and H-5Ј), 3.02–3.21 (1 H, m, H-3Ј), 3.27–3.54 (1 H, m,
H-menthyloxy), 3.64 (2 H, m, PhCH2), 5.75 (1 H, m, H-5), 5.83
(1 H, t, J 1, H-3), 7.20–7.41 (5 H, m, Ph); δC(50 MHz; APT;
CDCl3; Me4Si) 15.71 (Ϫ, C-menthyl), 21.01 (Ϫ, C-menthyl),
22.13 (Ϫ, C-menthyl), 22.64 (ϩ, C-menthyl), 25.31 (Ϫ,
C-menthyl), 29.84 (ϩ, C-4Ј), 31.55 (Ϫ, C-menthyl), 34.02 (ϩ,
C-menthyl), 35.85 (Ϫ, C-3Ј), 48.13 (Ϫ, C-menthyl), 53.35 (ϩ,
C-5Ј), 57.91 (ϩ, C-2Ј), 59.96 (ϩ, PhCH2), 83.16 (Ϫ, C-menthyl),
104.48 (Ϫ, C-5), 116.29 (Ϫ, C-3), 127.08 (Ϫ, Ph), 128.29 (Ϫ,
Ph), 128.58 (Ϫ, Ph), 138.59 (ϩ, Ph), 170.44 (ϩ, C-4), 170.74 (ϩ,
C-2); MS and HRMS: see (3R)-isomer.
A flask containing 4-vinylfuranone 2 or 6 (1 mmol) and lithium
fluoride (60 mg, 2.3 eq.) was evacuated and flushed several
times with argon. A solution of N-benzyl-N-methoxymethyl-
(trimethylsilylmethyl)amine 9a–c (1.1 eq.) in acetonitrile (2.5
cm3) was added at 0 ЊC. Then the mixture was sonicated for 8 h
and stirred at Ϫ40 ЊC (addition of THF (1 cm3) was necessary
to maintain a liquid suspension) for several days. The reaction
mixture was poured into water and extracted with diethyl ether
(3 ×). The combined organic layers were dried over MgSO4
and concentrated on a rotary evaporator. The pyrrolidinyl-
furanones were obtained after column chromatography.
(5S)-4-{(3R and 3S)-N-[(1R)-1-Phenylethyl]pyrrolidin-3-yl}-
5-menthyloxyfuran-2(5H)-one 11b/12b. (5S)-5-Menthyloxy-4-
vinylfuran-2(5H)-one 6 (200 mg, 0.757 mmol) was treated with
(1R)-N-1-phenylethyl-N-methoxymethyl(trimethylsilylmethyl)-
amine 9b following the general procedure for the 1,3-dipolar
cycloaddition to furnish pyrrolidinylfuranones 11b and 12b
after chromatography (silica gel, diethyl ether–petroleum ether
1:2) as yellowish viscous oils (276 mg, 0.671 mmol, 88%, de
25%).
4-(N-Benzylpyrrolidin-3-yl)furan-2(5H)-one 10. 4-Vinyl-
furan-2(5H)-one 2 (110 mg, 1 mmol) was treated with N-benzyl-
N-methoxymethyl(trimethylsilylmethyl)amine 9a following the
general procedure for the 1,3-dipolar cycloaddition to furnish
pyrrolidinylfuranone 10 after chromatography (silica gel,
gradient diethyl ether → diethyl ether–MeOH 10:1) as a yel-
lowish viscous oil (163 mg, 0.670 mmol, 67%); νmax(CHCl3)/
cmϪ1 2960, 2928, 2800, 1784, 1748, 1636, 1452, 1348, 1144,
1032, 892, 856; δH(200 MHz; CDCl3; Me4Si) 1.65–1.84 (1 H, m,
H-4Ј), 2.10–2.32 (1 H, m, H-4Ј), 2.45–2.61 (2 H, m, H-5Ј), 2.63–
2.82 (2 H, m, H-2Ј), 3.10–3.27 (1 H, m, H-3Ј), 3.56 (1 H, d,
J 13, PhCH2), 3.66 (1 H, d, J 13, PhCH2), 4.75 (2 H, d, J 1.6,
H-5), 5.79 (1 H, dt, J 1.6/1, H-3), 7.21–7.37 (5 H, m, Ph);
δC(50 MHz; APT; CDCl3; Me4Si) 29.93 (ϩ, C-4Ј), 36.98 (Ϫ,
C-3Ј), 53.13 (ϩ, C-5Ј), 58.11 (ϩ, C-2Ј), 59.70 (ϩ, PhCH2), 71.91
(ϩ, C-5), 114.12 (Ϫ, C-3), 127.09 (Ϫ, Ph), 128.31 (Ϫ, Ph),
128.53 (Ϫ, Ph), 138.69 (ϩ, Ph), 173.50 (ϩ, C-4), 173.93
(ϩ, C-2); m/z 244 (Mϩ ϩ 1, 5%), 243 (Mϩ, 28), 166 (6), 152 (4),
149 (4), 134 (6), 133 (24), 132 (11), 93 (10), 92 (13), 91 (100), 77
(6), 65 (18); m/z (Mϩ) found 243.1258; C15H17NO2 requires
243.1259.
(5S)-{(3R)-N-[(1R)-1-Phenylethyl]pyrrolidin-3-yl}-5-
menthyloxyfuran-2(5H)-one 11b. [α]D20 ϩ25.27 (c 1.076 in
CHCl3); νmax(CHCl3)/cmϪ1 2960, 2920, 2872, 2796, 2360, 2340,
1760, 1648, 1452, 1376, 1328, 1228, 1128, 1096, 1048, 952;
δH(400 MHz; CDCl3; Me4Si) 0.64–1.68 (16 H, m, H-menthyl),
1.37 (3 H, d, J 6.62, PhCHMe), 1.81–1.93 (1 H, m, H-4Ј), 2.06–
2.10 (2 H, m, H-menthyl and H-4Ј), 2.04–2.31 (1 H, m,
H-menthyl), 2.34 (1 H, dd, J 9.19/6.25, H-5Ј), 2.46–2.54 (1 H,
m, H-5Ј), 2.69–2.77 (1 H, m, H-2Ј), 2.76–2.85 (1 H, m, H-2Ј),
3.02–3.12 (1 H, m, H-3Ј), 3.24 (1 H, q, J 6.62, PhCHMe), 3.41
(1 H, dt, J 10.66/4.23, H-menthyloxy), 5.65 (1 H, d, J 0.56,
H-5), 5.88 (1 H, dd, J 1.47/0.92, H-3), 7.19–7.38 (5 H, m, Ph);
δC(100 MHz; DEPT; CDCl3; Me4Si) 15.55 (CH3, C-menthyl),
21.00 (CH3, C-menthyl), 22.04 (CH3, C-menthyl), 22.64
(CH2, C-menthyl), 22.76 (CH3, PhCHMe), 25.21 (CH, C-
menthyl), 29.38 (CH2, C-4Ј), 31.56 (CH, C-menthyl), 33.98
(CH2, C-menthyl), 36.06 (CH, C-3Ј), 42.33 (CH2, C-menthyl),
48.12 (CH, C-menthyl), 51.68 (CH2, C-5Ј), 57.11 (CH2, C-2Ј),
65.21 (CH, C-menthyl), 83.18 (CH, PhCHMe), 104.75 (CH,
C-5), 116.95 (CH, C-3), 126.92 (CH, Ph), 127.07 (CH, Ph),
128.37 (CH, Ph), 144.85 (C, Ph), 170.56 (C, C-4), 170.84 (C,
C-2); m/z (140 ЊC) 412 (Mϩ ϩ 1, 1%), 411 (Mϩ, 4), 398 (4),
397 (27), 396 (Mϩ Ϫ Me, 92), 334 (8), 272 (21), 258 (14), 220 (3),
196 (4), 168 (9), 152 (8), 124 (6), 106 (11), 105 (100), 91 (6), 83
(12), 69 (9); m/z (Mϩ) found 411.2773; C26H37N1O3 requires
411.2777.
(5S)-4-(N-Benzylpyrrolidin-3-yl)-5-menthyloxyfuran-2(5H)-
one 11a/12a. (5S)-5-Menthyloxy-4-vinylfuran-2(5H)-one 6 (222
mg, 0.840 mmol) was treated with N-benzyl-N-methoxymethyl-
(trimethylsilylmethyl)amine 9a following the general procedure
for the 1,3-dipolar cycloaddition to furnish pyrrolidinyl-
furanones 11a and 12a after chromatography (silica gel, diethyl
ether–petroleum ether 1:1) as yellowish viscous oils (244 mg,
0.614 mmol, 73%, de 33%).
(5S)-4-[(3R)-N-Benzylpyrrolidin-3-yl]-5-menthyloxyfuran-
2(5H)-one 11a. νmax(CHCl3)/cmϪ1 2960, 2924, 2872, 2800,
1793, 1756, 1648, 1452, 1368, 1332, 1256, 1240, 1128, 952, 904;
δH(200 MHz; CDCl3; Me4Si) 0.63–1.50 (14 H, m, H-menthyl),
1.57–1.72 (2 H, m, H-menthyl), 1.82–2.02 (1 H, m, H-4Ј), 2.03–
2.42 (2 ϩ 1 H, m, H-menthyl and H-4Ј), 2.56–2.91 (4 H, H-2Ј
and H-5Ј), 3.02–3.21 (1 H, m, H-3Ј), 3.27–3.54 (1 H, m,
H-menthyloxy), 3.60 (1 H, d, J 13.4, PhCH2), 3.78 (1 H, d,
J 13.4, PhCH2), 5.68 (1 H, m, H-5), 5.90 (1 H, t, J 1, H-3),
7.20–7.41 (5 H, m, Ph); δC(100 MHz; DEPT; CDCl3; Me4Si)
15.57 (CH3, C-menthyl), 21.02 (CH3, C-menthyl), 22.10 (CH3,
C-menthyl), 22.67 (CH2, C-menthyl), 25.29 (CH, C-menthyl),
29.30 (CH2, C-4Ј), 31.63 (CH, C-menthyl), 34.01 (CH2,
C-menthyl), 36.27 (CH, C-3Ј), 42.39 (CH2, C-menthyl), 48.15
(CH, C-menthyl), 53.29 (CH2, C-5Ј), 58.25 (CH2, C-2Ј), 60.04
(CH2, PhCH2), 83.33 (CH, C-menthyl), 104.63 (CH, C-5),
116.91 (CH, C-3), 127.16 (CH, Ph), 128.36 (CH, Ph), 128.62
(CH, Ph), 138.58 (C, C-4), 170.29 (C, C-Ph), 170.87 (C, C-2);
m/z (110 ЊC) 397 (Mϩ, 2%), 396 (1), 313 (4), 269 (3), 259 (18),
258 (88), 242 (9), 241 (19), 213 (14), 168 (8), 150 (6), 133 (18),
105 (2), 91 (100), 83 (13), 69 (10); m/z (M Ϫ Hϩ) found
396.2539; C25H35NO3 Ϫ 1 requires 396.2545.
(5S)-{(3S)-N-[(1R)-1-Phenylethyl]pyrrolidin-3-yl}-5-
menthyloxyfuran-2(5H)-one 12b. δH(400 MHz; CDCl3; Me4Si)
0.68–1.45 (14 H, m, H-menthyl), 1.39 (3 H, d, J 6.63,
PhCHMe), 1.59–1.69 (2 H, m, H-menthyl), 2.08–2.23 (2 H, m,
H-4Ј), 2.25–2.34 (2 H, m, H-menthyl), 2.43–2.54 (2 H, m, H-5Ј),
2.75–2.86 (2 H, m, H-2Ј), 3.02–3.13 (1 H, m, H-3Ј), 3.26 (q,
J 6.63, PhCHMe), 3.50 (1 H, dt, J 10.66/4.23, H-menthyloxy),
5.74 (1 H, d, J 0.74, H-5), 5.87 (1 H, dd, J 1.47/0.92, H-3),
7.28–7.34 (5 H, m, Ph); δC(100 MHz; DEPT; CDCl3; Me4Si)
15.76 (CH3, C-menthyl), 21.07 (CH3, C-menthyl), 22.12 (CH3,
C-menthyl), 22.72 (CH2, C-menthyl), 23.02 (CH3, PhCHMe),
25.37 (CH, C-menthyl), 29.86 (CH2, C-4Ј), 31.67 (CH, C-
menthyl), 34.05 (CH2, C-menthyl), 35.88 (CH, C-3Ј), 42.42
(CH2, C-menthyl), 48.17 (CH, C-menthyl), 51.98 (CH2, C-5Ј),
56.96 (CH2, C-2Ј), 65.28 (CH, C-menthyl), 83.33 (CH,
PhCHMe), 104.62 (CH, C-5), 116.60 (CH, C-3), 127.02 (CH,
Ph), 127.12 (CH, Ph), 128.43 (CH, Ph), 144.98 (C, Ph), 170.47
(C, C-4), 170.95 (C, C-2); IR, MS and HRMS: see (3R)-isomer.
(5S)-4-[(3S)-N-Benzylpyrrolidin-3-yl]-5-menthyloxyfuran-
2(5H)-one 12a. νmax(CHCl3)/cmϪ1 2960, 2924, 2872, 2800,
1793, 1756, 1648, 1452, 1368, 1332, 1256, 1240, 1128, 952, 904;
δH(200 MHz; CDCl3; Me4Si) 0.63–1.50 (14 H, m, H-menthyl),
1.57–1.72 (2 H, m, H-menthyl), 1.72–1.98 (1 H, m, H-4Ј), 2.03–
(5S)-{(3R and 3S)-N-[(1S)-1-Phenylethyl]pyrrolidin-3-yl}-
5-menthyloxyfuran-2(5H)-one 11c/12c. (5S)-5-Menthyloxy-4-
vinylfuran-2(5H)-one 6 (172 mg, 0.651 mmol) was treated with
J. Chem. Soc., Perkin Trans. 1, 1998, 3867–3872
3871

View Article Online
(1S)-N-1-phenylethyl-N-methoxymethyl(trimethylsilylmethyl)-
amine 9c according to the general procedure for the 1,3-dipolar
cycloaddition to furnish pyrrolidinylfuranones 11c and 12c
after chromatography (silica gel, diethyl ether–petroleum ether
1:2) as yellowish viscous oils (185 mg, 0.450 mmol, 69%, de
41%).
(CH3, C-menthyl), 22.06 (CH3, C-menthyl), 22.78 (CH2,
C-menthyl), 25.29 (CH, C-menthyl), 31.65 (CH, C-menthyl),
33.97 (CH2, C-menthyl), 42.35 (CH2, C-menthyl), 46.65 (CH,
C-2Ј), 48.25 (CH, C-menthyl), 49.37 CH2, C-3Ј), 82.87 (CH,
C-menthyloxy), 102.75 (CH, C-5), 120.13 (CH, C-3), 163.11 (C,
C-4), 169.60 (C, C-2); m/z (60 ЊC) 280 (Mϩ, 0%), 249 (2), 195
(7), 155 (4), 138 (70), 125 (Mϩ Ϫ C10H19O, 62), 123 (18), 109
(10), 97 (22), 95 (59), 84 (34), 81 (100), 69 (66), 67 (20); m/z (Mϩ)
found 280.1675; C16H24O4 requires 280.1659 (Found: C, 62.85;
H, 3.7. C16H24O4 requires C, 62.83; H, 3.69%).
(5S)-{(3R)-N-[(1S)-1-Phenylethyl]pyrrolidin-3-yl}-
menthyloxyfuran-2(5H)-one 11c. [α]D20 Ϫ19.72 (c 1.014 in
CHCl3); νmax(CHCl3)/cmϪ1 2960, 2928, 2872, 2792, 1800, 1756,
1648, 1492, 1452, 1368, 1328, 1236, 1132, 952, 908; δH(400
MHz; CDCl3; Me4Si) 0.60–1.43 (14 H, m, H-menthyl), 1.38
(3 H, d, J 6.62, PhCHMe), 1.55–1.68 (2 H, m, H-menthyl),
1.84–1.94 (1 H, m, H-4Ј), 2.00–2.14 (1 H, m, H-4Ј), 2.04–2.33
(3 H, m, 2 H-menthyl and H-5Ј), 2.45 (1 H, dt, J 9.01/6.8, H-5Ј),
2.70–3.00 (2 H, m, H-2Ј), 3.02–3.13 (1 H, m, H-3Ј), 3.23 (1 H, q,
J 6.62, PhCHMe), 3.43 (1 H, dt, J 10.66/4.23, H-menthyloxy),
5.64 (1 H, m, H-5), 5.88 (1 H, dd, J 1.46/0.92, H-3), 7.20–7.37
(5 H, m, Ph); δC(100 MHz; DEPT; CDCl3; Me4Si) 15.45 (CH3,
C-menthyl), 20.96 (CH3, C-menthyl), 22.06 (CH3, C-menthyl),
22.64 (CH2, C-menthyl), 22.98 (CH3, PhCHMe), 25.25 (CH,
C-menthyl), 28.81 (CH2, C-4Ј), 31.59 (CH, C-menthyl), 33.99
(CH2, C-menthyl), 36.22 (CH, C-3Ј), 42.39 (CH2, C-menthyl),
48.13 (CH2, C-5Ј), 57.42 (CH2, C-2Ј), 65.33 (CH, C-menthyl),
83.26 (CH, PhCHMe), 104.75 (CH, C-5), 116.79 (CH, C-3),
126.92 (CH, Ph), 127.07 (CH, Ph), 128.41 (CH, Ph), 144.93 (C,
Ph), 170.02 (C, C-4), 170.82 (C, C-2); m/z (120 ЊC) 411 (Mϩ,
2%), 397 (15), 396 (53), 333 (4), 272 (12), 257 (8), 2190 (25), 167
(4), 151 (4), 115 (19), 105 (10), 104 (100); m/z (Mϩ) found
411.2773; C26H37N1O3 requires 411.2753.
X-Ray structure determination of compound 13
C16H24O4, M = 280.36, monoclinic, space group P21 (No.4),
a = 8.421(2), b = 6.173(1), c = 15.251(2) Å, α = 90, β = 94.28(2),
γ = 90Њ, V = 790.6(3) Å3, Z = 2, Dc 1.178 g cm3, F(000) = 304,
T = 300 K, µ(Mo-Kα) = 0.8 cmϪ1, crystal size 0.33 × 1.44 ×
0.22 mm. Data collection: diffractometer Stoe IPDS (Imaging
Plate), graphite-monochromated Mo-Kα radiation (fine-focus
sealed tube, λ = 0.71073 Å), 2θ range = 5.3–48.1Њ, scan type =
150 imaging plates, ∆φ = 1.5Њ, data set h, k, l Ϫ9: 9; Ϫ6: 6; Ϫ17:
17, total data 5638, unique data 2371, Rint = 0.025, observed
data 1817 with I > 2σ(I). Structure solution by SHELXS-86,
refinement by SHELXL-93, hydrogen atoms in geometrically
calculated positions, ∆ρmax = 0.07 e ÅϪ3, ∆ρmin = Ϫ0.06 e ÅϪ3, R
(F) = 0.0268 based on 1817 reflections with Fo > 4σ(Fo), wR2 =
0.0485, wR2 based on F2 of 2371 reflections.
Acknowledgements
(5S)-{(3S)-N-[(1S)-1-Phenylethyl]pyrrolidin-3-yl}-5-
We thank Janssen Research Foundation, Beerse, Belgium and
the Deutsche Forschungsgemeinsschaft for their support and
Ulrike Eggert for secretarial help.
menthyloxyfuran-2(5H)-one 12c. δH(400 MHz; CDCl3; Me4Si)
0.67–1.45 (17 H, m, H-menthyl), 1.59–1.69 (2 H, m, H-
menthyl), 2.07–2.34 (2 ϩ 2 H, m, H-4Ј ϩ H-menthyl), 2.42–
2.53 (2 H, m, H-5Ј), 2.68–2.90 (2 H, m, H-2Ј), 3.03–3.14 (1 H,
m, H-3Ј), 3.20–3.34 (1 H, m, PhCHMe), 3.39–3.54 (1 H, m,
H-menthyloxy), 5.76 (1 H, m, H-5), 5.81 (1 H, m, H-3), 7.18–
7.38 (5 H, m, Ph); δC(100 MHz; DEPT; CDCl3; Me4Si)
15.63 (CH3, C-menthyl), 20.93 (CH3, C-menthyl), 21.98 (CH3,
C-menthyl), 22.61 (CH2, C-menthyl), 22.82 (CH3, PhCHMe),
25.25 (CH, C-menthyl), 29.69 (CH2, C-4Ј), 31.53 (CH, C-
menthyl), 33.91 (CH2, C-menthyl), 35.58 (CH, C-3Ј), 42.28
(CH2, C-menthyl), 48.05 (CH, C-menthyl), 51.91 (CH2, C-5Ј),
56.70 (CH2, C-2Ј), 65.19 (CH, C-menthyl), 83.09 (CH, Ph-
CHMe), 104.30 (CH, C-5), 116.12 (CH, C-3), 126.80 (CH,
Ph), 127.07 (CH, Ph), 128.34 (CH, Ph), 144.67 (C, Ph), 170.53
(C, C-4), 170.77 (C, C-2); IR, MS and HRMS: see (3R)-isomer.
References
1 E. Lattmann and H. M. R. Hoffmann, Synthesis, 1996, 155.
2 F. Fariña, M. R. Martín and M. V. Martín, An. Quim., 1978, 74, 799.
3 Q. Chen, Z. Geng and B. Huang, Tetrahedron: Asymmetry, 1995, 6,
401.
4 MM2 Energy of (5S)-5: 37.058 kcal molϪ1, MM2 energy of its
enantiomer: 39.113 kcal molϪ1. Molecular mechanics calculations
were performed using the CS Chem3D Pro software for PC, ver. 3.2
from CambridgeSoft Corporation, Cambridge, MA. Minimum
RMS gradient 0.01.
5 Full crystallographic details, excluding structure factor tables, have
been deposited at the Cambridge Crystallographic Data Centre
(CCDC). For details of the deposition scheme, see ‘Instructions for
Authors’, J. Chem. Soc., Perkin Trans. 1, available via the RSC Web
page (http://www.rsc.org/authors). Any request to the CCDC for
this material should quote the full literature citation and the
reference number 101371.
6 I. F. Cottrell, D. Hands, D. J. Kennedy, K. J. Paul, S. H. B. Wright
and K. Hoogsteen, J. Chem. Soc., Perkin Trans. 1, 1991, 1091.
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9 M. T. Rispens, E. Keller, B. de Lange, R. W. J. Zijlstra and B. L.
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10 Z. Ma, S. Wang, C. S. Cooper, A. K. L. Fung, J. K. Lynch, F. Plagge
and D. T. W. Chu, Tetrahedron: Asymmetry, 1997, 8, 883.
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Angew. Chem., 1985, 97, 1.
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13 G. M. Sheldrick, SHELXS-86, Program for Crystal Structure
Determinations, University of Göttingen, Germany, 1986.
14 G. M. Sheldrick, SHELXL-93, Program for Crystal Structure
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(c) R. W. Murray, M. Singh, Org. Synth., 1997, 74, 91.
(5S)-5-Menthyloxy-4-[(2S)-oxiran-2-yl]furan-2(5H)-one 13
(5S)-5-Menthyloxy-4-vinylfuran-2(5H)-one
6 (1.06 g, 4
mmol) was dissolved in acetone (1 cm3). Epoxidation was
achieved by portionwise addition of a solution of dimethyl-
dioxirane15 in acetone (ca. 0.01 M, 1 eq./portion) until
complete reaction (TLC monitoring) at r.t. Then the mixture
was evaporated and purified by column chromatography on
silica gel (petroleum ether–diethyl ether 10:1) to give the
product as white-yellowish crystals (774 mg, 2.76 mmol, 69%,
de 71%). Recrystallization from diethyl ether–petroleum ether
afforded diastereomerically pure (5S)-5-menthyloxy-4-[(2S)-
oxiran-2-yl]furan-2(5H)-one 13 as white crystals, mp 105 ЊC;
[α]D20 ϩ81.81 (c 1.105 in CHCl3); νmax(KBr)/cmϪ1 2984, 2920,
2864, 1788, 1760, 1652, 1456, 1332, 1256, 1124, 988, 960, 924,
888, 856; δH(400 MHz; CDCl3; Me4Si) 0.78–1.13 (12 H, m,
H-menthyl), 1.23–1.50 (2 H, m, H-menthyl), 1.62–1.71 (2 H, m,
H-menthyl), 2.08–2.20 (1 H, m, H-menthyl), 2.21–2.29 (1 H, m,
H-menthyl), 3.02 (d, J 2.39) and 3.03 (d, J 2.58, 1 H, H-3Јα),
3.10 (d, J 4.41) and 3.11 (d, J 4.23, 1 H, H-3Јβ), 3.57 (1 H, dt,
J 10.66/4.41, H-menthyloxy), 3.71 (1 H, ddd, J 4.23/2.58/0.92,
H-2Ј), 5.87 (1 H, d, J 1.1, H-5), 6.13 (1 H, t, J 0.92, H-3); δC(100
MHz; DEPT; CDCl3; Me4Si) 15.72 (CH3, C-menthyl), 21.05
Paper 8/03693D
3872
J. Chem. Soc., Perkin Trans. 1, 1998, 3867–3872