Asymmetric [2+2+1] cyclopentannulation of olefins. Ring expansion of 2-N-methyl-N-tosyl-cyclobutanone

Article abstract of DOI:10.1016/S0040-4020(02)00694-4

α-N-Methyl-N-tosyl cyclobutanones 2 which had been previously prepared in good yields and high enantiomeric excesses from olefins and chiral keteniminium salts have been converted into the corresponding oxiranes 3 by reaction with dimethylsulfonium methylid. The stereochemistry of this reaction was found to be dependent on several factors which have been analyzed. Treatment of these oxiranes with a stoichiometric amount of lithium iodide in refluxing tetrahydrofuran gave excellent yields of monocyclic or fused cyclopentenones 4 resulting from a β-elimination of N-methyl-N-tosylamide from a primarily formed cyclopentanone. The ring-expansion was totally selective but for oxiranes attached to a bicyclo[4.2.0]octanone system. In all cases, the enantiomeric purities of the starting cyclobutanones were preserved throughout the sequence which thus represents a useful [2+2+1] strategy for the cyclopentannulation of olefins.

Full text of DOI:10.1016/S0040-4020(02)00694-4

Tetrahedron 58 (2002) 6991–7000
Asymmetric [21211] cyclopentannulation of olefins. Ring
expansion of 2-N-methyl-N-tosyl-cyclobutanone
a
Florence Mahuteau-Betzer and Leon Ghosez
a,b
,
*
´
aDepartment of Chemistry, University of Louvain, 1 Place Louis Pasteur, 1348 Louvain-la-Neuve, Belgium
bEuropean Institute of Chemistry and Biology, IECB-ENSCPB, 16 Avenue Pey-Berland, 33607 Pessac, France
Received 13 April 2002; accepted 15 May 2002
Abstract—a-N-Methyl-N-tosyl cyclobutanones 2 which had been previously prepared in good yields and high enantiomeric excesses from
olefins and chiral keteniminium salts have been converted into the corresponding oxiranes 3 by reaction with dimethylsulfonium methylid.
The stereochemistry of this reaction was found to be dependent on several factors which have been analyzed. Treatment of these oxiranes
with a stoichiometric amount of lithium iodide in refluxing tetrahydrofuran gave excellent yields of monocyclic or fused cyclopentenones 4
resulting from a b-elimination of N-methyl-N-tosylamide from a primarily formed cyclopentanone. The ring-expansion was totally selective
but for oxiranes attached to a bicyclo[4.2.0]octanone system. In all cases, the enantiomeric purities of the starting cyclobutanones were
preserved throughout the sequence which thus represents a useful [2þ2þ1] strategy for the cyclopentannulation of olefins. q 2002 Elsevier
Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
2.1. Preliminary results
Cyclobutanones and cyclobutenones are very useful inter-
mediates which have found applications in total syntheses of
complex molecular structures.1 As a consequence of their
high angle strain, the electrophilicity of the carbonyl group
is enhanced and carbon-carbon bonds are weakened offering
possibilities for mild and chemoselective cleavage of the
four-membered ring. The cheapest and most general method
to prepare these four-membered ring ketones involves a
[2þ2] cycloaddition of in situ generated ketenes or
keteniminium salts.2 The cycloaddition of ketenes with
olefins bearing a chiral substituent3 or the use of
keteniminium salts derived from amides bearing a chiral
auxiliary4 have opened a practical route towards enantio-
merically pure cyclobutanones and further extended their
utility in synthesis.
The ring enlargement of cyclobutanones with diazomethane
is well documented in spite of its limited preparative
value.1e The regioselectivity of the reaction is subtly
dependent on substitution at both a and b carbon atoms.7
From our previous results on Baeyer–Villiger oxidation of
2, we had anticipated that the reaction of 2b with
diazomethane would predominantly lead to regioisomer
6b. This was indeed the case (Scheme 2). However
bicyclo[4.2.0]octanone reacted sluggishly and yields were
Early studies of our laboratory have shown that the
asymmetric cycloadditions of keteniminium salt 1 to 1,2-
disubstituted olefins followed by a regioselective Baeyer–
Villiger oxidation of the resulting cyclobutanone was a
unique method for the enantioselective vicinal acylation of
an olefin (Scheme 1).5 More recently, we have examined the
transformation of these enantiomerically enriched cyclo-
butanones into cyclopentenones.6 We report herein the full
details of these studies.
Keywords: cyclopentannulation; rearrangement; cyclobutanone;
cyclopentenone.
*
Corresponding author. Tel.: þ32-10-47-27-41; fax: þ32-10-47-29-44;
e-mail: ghosez@chim.ucl.ac.be
Scheme 1.
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00694-4

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F. Mahuteau-Betzer, L. Ghosez / Tetrahedron 58 (2002) 6991–7000
low. We therefore decided to study a sequence whereby we
first generate an epoxide and then effect the rearrangement
of this oxaspiropentane following the procedure developed
by the groups of Leriverend and Trost.8
2.2. Synthesis of oxiranes
Scheme 2.
A preliminary study of the reaction of 2a with sulfonium
ylid reagents9 showed that the reaction was only successful
when the ylide was generated from trimethylsulfonium
tetrafluoroborate and n-BuLi (Scheme 3). Other sources of
dimethylsulfonium ylide or of the corresponding oxide gave
complex reaction mixtures.
Thus a series of racemic and enantiomerically enriched
a-N-methyl N-tosyl cyclobutanones 2a–j (Table 1) pre-
viously prepared from the corresponding olefins have been
converted into the corresponding oxiranes by treatment with
dimethyl sulfonium ylid generated from trimethylsulfonium
Scheme 3.
Table 1. Preparation of oxiranes 3
Entry
a
Cyclobutanone 2
Oxirane 3
endo:exo
Yield, % (ee%)
69 (89)
1:1
b
c
d
e
f
1.5:1
9:1
6:1
1:4
2.3:1
–
75 (92)
86
72 (86)
67 (92)
82
g
71 (98)

F. Mahuteau-Betzer, L. Ghosez / Tetrahedron 58 (2002) 6991–7000
6993
Table 1 (continued)
Entry
Cyclobutanone 2
Oxirane 3
endo:exo
Yield, % (ee%)
h
–
59 (92)
i
1:9
1:9
81
j
61
tetrafluoroborate and n-BuLi (Table 1). exo- and endo-
oxiranes could be easily separated by flash chromatography.
Stereochemical assignments by H NMR were not easy as
neighbouring proton geminal to the NTsMe group and was
in agreement with previous observations.12 This indicated
that the preferred conformations of the cyclobutanone ring
are those shown in Fig. 1.
1
the protons of the epoxide ring are too far away from the
other ring to generate a significant nOe effect. The structure
and stereochemistry of crystalline exo-3a, exo-3b and exo-
3e were established by X-ray diffraction analysis.10,11 In
these compounds, the hydrogen geminal to the NTsMe
group was deshielded with respect to that of the correspond-
ing endo-isomers. The stereochemistry of compounds exo-
and endo-3d was confirmed by hydrogenation to exo- and
endo-3b, respectively (Scheme 4). By analogy, we tenta-
tively assigned relative configurations for all oxiranes 3.
With cis-fused bicyclic ketones 2a,b,d,f (A, Fig. 1), little
selectivity was observed because both a and b faces are
hindered. When the large NTsMe group sits on the a face as
in 2c (B), selectivity increased in favour of the endo-adduct
endo-3c. The presence of a methyl group at the ring junction
2e (C) further hides the b face and, as a result, the exo-
adduct became the major isomer. With both the trans-fused
bicyclic ketones 2g–h (D) and the mono-substituted
cyclobutanones 2i–j (D), addition occurred preferentially
from the a face.
Table 1 shows that oxiranes 3a–j were formed in good to
excellent yields. The facial selectivity can be rationalized by
considering the approaches of the ylid reagent to the various
cyclobutanones in their preferred conformation. The 1H
NMR spectra of cyclobutanones 2 showed fairly strong
coupling between the proton at the ring junction and the
2.3. Rearrangement of oxiranes
A model study of the rearrangement of oxiranes 3 was
conducted on each of the two diastereomeric oxiranes exo-
3b and endo-3b which had previously been prepared from
the corresponding enantiomerically enriched bicyclo[4.2.0]-
octan-7-one 2b (ee 92%). The exo-isomer was selectively
Scheme 4.
Figure 1.
Scheme 5.

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F. Mahuteau-Betzer, L. Ghosez / Tetrahedron 58 (2002) 6991–7000
converted into (1S,6S ) bicyclo[4.3.0]non-8-en-7-one 4b (ee
92%) after 2 h in refluxing tetrahydrofuran containing a
catalytic amount (0.2 equiv.) of lithium iodide. The
formation of 4b was believed to result from a b-elimination
of N-methyl-N-tosyl amide from bicyclo[4.3.0]nonan-7-one
6b which was the expected ring-expanded product. This was
confirmed by the quantitative formation of 4b when
compound 6b (previously isolated from the diazomethane
ring expansion reaction, see Scheme 2) was refluxed in THF
containing lithium iodide.
The endo-isomer reacted more slowly: a stoichiometric
amount of lithium iodide was needed to bring the
rearrangement to completion after 2 hours in refluxing
Scheme 6.
Table 2. Rearrangement of diastereomeric mixture of 3 in refluxing THF containing a stoichiometric amount of lithium iodide
Entry
Diastereomeric mixture of 3
Enone 4
Yield (%)
ee (%)
Other products
a
95
89
b
c
81
90
92
rac
d
e
41
95
86
92
f
95
90
87
rac
98
92
g
h
i
j
94
96
rac
rac

F. Mahuteau-Betzer, L. Ghosez / Tetrahedron 58 (2002) 6991–7000
6995
THF. Also the ring expansion was less selective (3:1): the
major product was still 4b but there was a substantial
amount of bicyclo[4.3.0]octan-8-one 5b which is a
structural isomer of 6b (Scheme 5).13
fitted with Diacel Chiralpack-AD, -AS, -OB, -OD analytical
column. TLC were run on silica gel 60F254. Column
chromatographies were performed with gel 40 (230–
400 mm, Merck). All solvents were distilled before use.
All reagents were of reagent grade.
The exo- and endo isomers of the corresponding unsaturated
oxiranes exo- and endo-3d showed a similar behaviour
(4d:5d¼3:2) (Scheme 6). However all other exo- and endo-
oxiranes gave exclusively the cyclopentenone derivatives in
high yields when refluxed in THF containing a stoichio-
metric amount of lithium iodide. The results shown in
Table 2 are those obtained from the mixture of exo- and
endo-oxiranes obtained after flash chromatography of the
crude product of the ylid addition to 2. The rearrangement
occurred with retention of configuration at the ring junction
except when the five-membered ring was fused to a ring
larger than six. A small amount of trans-isomer was
observed when the cyclopentenone was fused to a seven-
membered ring 4f. Epimerization was completed with the
corresponding eight-membered ring derivative 4h.
4.1. General procedure for the preparation of epoxides
A solution of n-BuLi (2.5 M in hexanes, 1.2 equiv.) was
added to a 0.05 M solution of trimethylsulfonium tetra-
fluoroborate (1 equiv.) in THF at 2158C. After 15 min, the
mixture was cooled to 2788C and treated with a solution of
cyclobutanone (1 equiv.) in THF. After 15 h at room
temperature, the reaction mixture was diluted with ether
and washed twice with water. The organic layer was dried
over MgSO4, filtered and concentrated. The product was
purified by flash chromatography on silica gel (eluent
AcOEt/cyclohexane 2:8).
4.2. Preparation of epoxides exo- and endo-3a
Not surprisingly the enantiomeric purities of the original
cyclobutanones were retained throughout the sequence.
From 2a (250 mg, 0.85 mmol), trimethylsulfonium tetra-
fluoroborate (168 mg, 1.02 mmol), n-BuLi (2.0 M in
hexanes, 640 mL, 1.28 mmol). Yield: 85 mg (33%) of exo-
3a and 95 mg (36%) of endo-3a (89% ee).
3. Conclusions
4.2.1. (1R,5S,6R,7S )-7-(Methyltosylamino)spiro[bicy-
clo[3.2.0]heptane-6,20-oxirane] (exo-3a). Mp 888C;
[a ]2D0¼þ38.8 (c¼0.6, CHCl3); 1H NMR (300 MHz,
CDCl3) d 7.65 (d, J¼8.4 Hz, 2H), 7.29 (d, J¼8.4 Hz, 2H),
4.29 (dd, J¼4.2, 1.6 Hz, 1H), 3.06 (s, 3H), 2.87 (t,
J¼8.0 Hz, 1H), 2.71 (td, J¼8.0, 4.4 Hz, 1H), 2.53 (d,
J¼5.2 Hz, 1H), 2.42 (s, 3H), 2.30 (d, J¼5.2 Hz), 1.90–1.20
(m, 6H); 13C NMR (50 MHz, CDCl3) d 143.1, 136.4, 129.4,
127.1, 62.9, 62.4, 48.5, 45.1, 38.7, 31.5, 30.8, 29.4, 25.6,
21.5; IR (neat) n 2943, 2851, 1338, 1157; M (IE): 238
(100%), 155 (56%), 91 (72%); elemental analysis calcd (%)
for C16H21O3NS: C 62.52, H 6.88, N 4.56, S 10.43; found: C
62.19, H 6.83, N 4.48, S 10.13; HPLC (AD column; eluent
EtOH; flow: v¼0.35 mL/min; l¼254 nm): 15.4 min
(1S,5R,6R,7R) and 21.6 min (1R,5S,6S,7S ).
In conclusion, the combined results of this and the previous
publication6 provide a unified approach towards the
synthesis of enantiomerically pure four and five-membered
rings. The previous paper dealt with the enantioselective
synthesis of the four-membered ring. The present results
showed that these could be readily converted into various
types of enantiomerically enriched cyclopentenones. In this
[2þ2þ1] strategy for the cyclopentannulation of olefins, the
NTsMe group played a crucial role as a control element: as
we had anticipated, it acts as an electron-releasing group
controlling the regioselectivity of the ring expansion
reaction. However, this electronic effect can be counter-
balanced by what we believe to be conformational factors as
shown in the ring-expansion of cyclobutanones fused to a
six-membered ring. At this stage these factors are not well
understood. Also, the NTsMe group provides the right
oxidation state to allow the generation of the conjugate
double bond at the end of sequence, thus increasing the
synthetic utility of the products.
4.2.2. (1R,5S,6S,7S )-7-(Methyltosylamino)spiro[bicy-
clo[3.2.0]heptane-6,20-oxirane] (endo-3a). [a ]2D0¼þ29.2
1
(c¼1.1, CHCl3); H NMR (300 MHz, CDCl3) d 7.66 (d,
J¼8.4 Hz, 2H), 7.29 (d, J¼8.4 Hz, 2H), 4.31 (dd, J¼4.7,
1.6 Hz, 1H), 2.88 (s, 3H), 2.88–2.80 (m, 1H), 2.65–2.55
(m, 1H), 2.59 (d, J¼5.3 Hz, 1H), 2.43 (s, 3H), 2.29 (d,
J¼5.3 Hz, 1H), 1.90–1.20 (m, 6H); 13C NMR (50 MHz,
CDCl3) d 143.3, 136.9, 129.5, 127.2, 63.7, 61.0, 51.1, 41.6,
37.8, 31.9, 30.7, 26.6, 25.4, 21.5; IR (neat) n 2950, 1340,
1159; M (IE): 308 (24%), 238 (100%), 155 (36%); HRMS
calcd (%) for C16H21O3NS: 307.1242; found: 307.1249;
HPLC (AD column; eluent EtOH/hexane 10:90; flow:
v¼0.50 mL/min; l¼220 nm): 32.1 min (1S,5R,6S,7R ) and
36.9 min (1R,5S,6R,7S ).
4. Experimental
1H NMR spectra were recorded in CDCl3 on Varian
Gemini-200 or 300 spectrometers at 200 or 300 MHz at
room temperature. 13C NMR spectra were recorded in
CDCl3 at 50 or 75 MHz at room temperature. Chemical
1
shifts are given in ppm relative to (CH3)4Si (0 ppm, H) or
CDCl3 (77.0 ppm, 13C). Mass spectra were obtained on a
Finnigan MAT-TSQ 700 spectrometer. IR spectra were
recorded on a BIO-RAD TFS 135 FT-IR spectrometer. All
absorption values are expressed in wavenumbers (cm-1).
[a]D values were obtained on a Perkin–Elmer 241 MC
polarimeter. Melting points are uncorrected. Enantiomeric
excesses were measured on hplc with a Millipore Waters
600 Controller, UV Millipore Waters 486 as detector and
4.3. Preparation of epoxides exo- and endo-3b
From 2b (3.3 g, 10.8 mmol), trimethylsulfonium
tetrafluoroborate (2 g, 12.3 mmol), n-BuLi (6.5 mL,
16.2 mmol). Yield: 0.95 g (47%) of exo-3b and 0.58 g
(29%) of endo-3b (92% ee).

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F. Mahuteau-Betzer, L. Ghosez / Tetrahedron 58 (2002) 6991–7000
4.3.1. (1R,6S,7R,8S )-8-(Methyltosylamino)spiro[bicy-
clo[4.2.0]octane-7,20-oxirane] (exo-3b). [a ]2D0¼þ10.6
4.5. Preparation of epoxides exo- and endo-3d
1
(c¼0.85, CHCl3); H NMR (200 MHz, CDCl3) d 7.61 (d,
From 2d (3.1 g, 10.2 mmol), trimethylsulfonium
tetrafluoroborate (2 g, 12.3 mmol), n-BuLi (6.1 mL,
16.2 mmol). Yield: 338 mg (10%) of exo-3d and 2.02 g
(62%) of endo-3d (86% ee).
J¼8.3 Hz, 2H), 7.22 (d, J¼8.3 Hz, 2H), 4.61 (dd, J¼8.3,
1.4 Hz, 1H), 2.91 (s, 3H), 2.58–2.70 (m, 1H), 2.55 (d,
J¼4.6 Hz, 1H), 2.36 (d, J¼4.6 Hz, 1H), 2.42 (s, 3H), 2.25
(m, 1H), 1.70–0.70 (m, 8H); 13C NMR (50 MHz, CDCl3) d
143.2, 136.7, 129.5, 126.9, 66.5, 57.5, 46.8, 35.6, 33.4, 31.4,
24.9, 24.1, 22.3, 21.5, 21.4; IR (neat) n 2927, 2854, 1340,
1158; M (IE): 322 (2%), 238 (16%), 185 (24%), 155
(100%), 91 (72%); elemental analysis calcd (%) for
C17H23O3NS: C 63.52, H 7.21, N 4.35, S 9.97; found: C
63.43, H 7.34, N 4.13, S 10.04; HPLC (AD column; eluent
EtOH; flow: v¼0.35 mL/min; l¼254 nm): 14.1 min
(1S,6R,7S,8R) and 22.0 min (1R,6S,7R,8S )
4.5.1. (1R,6S,7R,8S )-8-(Methyltosylamino)spiro[bicy-
clo[4.2.0]oct-3-ene-7,20-oxirane] (exo-3d). [a ]2D0¼25.5
1
(c¼0.11, CH2Cl2); H NMR (300 MHz, CDCl3) d 7.64 (d,
J¼8.4 Hz, 2H), 7.28 (d, J¼8.4 Hz, 2H), 5.95–5.85 (m, 2H),
4.38 (dd, J¼6.1, 1.1 Hz, 1H), 3.06 (s, 3H), 2.90–2.65 (m,
2H), 2.53 (d, J¼4.8 Hz, 1H), 2.42 (s, 3H), 2.22 (d,
J¼4.8 Hz, 1H), 2.10–1.80 (m, 4H); 13C NMR (75 MHz,
CDCl3) d 143.2, 136.9, 129.5, 127.9, 127.6, 127.0, 64.3,
61.1, 48.2, 37.1, 32.9, 31.6, 25.0, 23.4, 21.5; IR (neat) n
3031, 2923, 2830, 1598, 1338, 1160; M (IE): 320 (1%), 212
(96%), 164 (28%), 91 (32%), 43 (100%); elemental analysis
calcd (%) for C17H21O3NS: C 63.93, H 6.63, N 4.39, S
10.04; found: C 63.80, H 6.58, N 4.38, S 10.24.
4.3.2. (1R,6S,7S,8S )-8-(Methyltosylamino)spiro[bicy-
clo[4.2.0]octane-7,20-oxirane] (endo-3b). Mp 1048C;
[a ]2D0¼20.95 (c¼0.85, CHCl3); 1H NMR (200 MHz,
CDCl3) d 7.70 (d, J¼8.2 Hz, 2H), 7.28 (d, J¼8.2 Hz, 2H),
4.83 (d, J¼9.1 Hz, 1H), 2.79 (s, 3H), 2.72 (d, J¼9.0 Hz,
1H), 2.49 (d, J¼9.0 Hz, 1H), 2.42 (s, 3H), 2.38–2.26 (m,
2H), 1.90–0.90 (m, 8H); 13C NMR (50 MHz, CDCl3) d
143.3, 136.4, 129.4, 127.2, 63.1, 57.9, 50.1, 32.9, 30.4, 29.6,
23.2, 22.4, 21.4, 21.3; IR (neat) n 2929, 2852, 1340, 1161;
M (IE): 321 (4%), 238 (72%), 166 (36%), 155 (32%), 91
(60%), 42 (100%); elemental analysis calcd (%) for
C17H23O3NS: C 63.52, H 7.21, N 4.35, S 9.97; found: C
63.46, H 7.25, N 4.29, S 10.35; HPLC (AD column;
eluent EtOH/hexane 10:90; flow: v¼1.00 mL/min;
l¼254 nm): 12.7 min (1R,6S,7R,8S ) and 14.4 min
(1S,6R,7S,8R).
4.5.2. (1R,6S,7S,8S )-8-(Methyltosylamino)spiro[bicy-
clo[4.2.0]oct-3-ene-7,20-oxirane] (endo-3d). Mp 1238C;
[a ]2D0¼þ18.1 (c¼0.70, CH2Cl2); 1H NMR (300 MHz,
CDCl3) d 7.66 (d, J¼8.2 Hz, 2H), 7.28 (d, J¼8.2 Hz, 2H),
6.00–5.90 (m, 1H), 5.88–5.80 (m, 1H), 4.60 (d, J¼6.5 Hz,
1H), 2.86 (s, 3H), 2.72–2.57 (m, 2H), 2.64 (d, J¼5.1 Hz,
1H), 2.42 (s, 3H), 2.32 (d, J¼5.1 Hz, 1H), 2.10–1.70 (m,
4H); 13C NMR (50 MHz, CDCl3) d 143.3, 136.3, 129.4,
127.7, 127.1, 125.5, 62.3, 61.7, 50.8, 32.5, 30.8, 29.8, 23.9,
21.4, 20.4; IR (neat) n 3030, 2963, 2836, 1598, 1339, 1159;
M (IE):319 (4%), 238 (36%), 164 (100%), 155 (52%), 91
(80%); HRMS calcd (%) for C17H21O3NS: 319.1242;
found: 319.1240.
4.4. Preparation of epoxides exo- and endo-3c
From 2c (500 mg, 1.6 mmol), trimethylsulfonium tetra-
fluoroborate (320 mg, 1.9 mmol), n-BuLi (975 mL,
2.4 mmol). Yield: 40 mg (8%) of exo-3c and 410 mg
(78%) of endo-3c.
4.6. Preparation of epoxides exo- and endo-3e
From 2e (250 mg, 0.85 mmol), trimethylsulfonium tetra-
fluoroborate (168 mg, 1.02 mmol), n-BuLi (610 mL,
1.5 mmol). Yield: 176 mg (54%) of exo-3e and 44 mg
(13%) of endo-3e (92% ee).
4.4.1. (1R p,6S p,7R p,8R p)-8-(Methyltosylamino)spiro[bi-
cyclo[4.2.0]octane-7,20-oxirane] (exo-3c). 1H NMR
(200 MHz, CDCl3) d 7.71 (d, J¼8.4 Hz, 2H), 7.28 (d,
J¼8.4 Hz, 2H), 4.83 (d, J¼8.5 Hz, 1H), 2.79 (s, 3H), 2.72
(d, J¼5.1 Hz, 1H), 2.50 (d, J¼5.1 Hz, 1H), 2.50–2.20 (m,
2H), 2.42 (s, 3H), 1.80–0.95 (m, 8H); 13C NMR (50 MHz,
CDCl3) d 143.3, 136.6, 129.5, 127.2, 63.2, 58.0, 50.1, 33.0,
30.4, 29.4, 23.2, 23.1, 22.4, 21.4, 21.3; IR (neat) n 2933,
2851, 1341, 1160; M (IE): 322 (2%), 238 (100%), 166
(54%), 155 (40%), 91 (46%), 42 (48%).
4.6.1. (1R,5S,6R,7S )-1-Methyl-7-(methyltosylamino)-
spiro[bicyclo[3.2.0]heptane-6,20-oxirane]
(exo-3e).
[a ]2D0¼þ37.9 (c¼0.9, CH2Cl2); 1H NMR (200 MHz,
CDCl3) d 7.63 (d, J¼7.8 Hz, 2H), 7.27 (d, J¼7.8 Hz, 2H),
4.31 (d, J¼1.5 Hz, 1H), 3.13 (s, 3H), 2.48 (d, J¼5.0 Hz,
1H), 2.50–2.40 (m, 1H), 2.42 (s, 3H), 2.14 (d, J¼5.0 Hz,
1H), 1.95–1.20 (m, 6H), 1.21 (s, 3H); 13C NMR (50 MHz,
CDCl3) d 143.1, 137.0, 129.4, 126.8, 64.6, 61.8, 51.8, 48.3,
48.1, 40.4, 34.4, 29.5, 26.2, 21.4, 20.8; IR (neat) n 2957,
2869, 1339, 1260, 1157; M (IE): 321 (4%), 239 (44%), 155
(28%), 91 (56%), 42 (100%); elemental analysis calcd (%)
for C17H23O3NS: C 63.52, H 7.21, N 4.36, S 9.97; found: C
63.38, H 6.99, N 4.07, S 9.97; HPLC (AD column; eluent
EtOH; flow: v¼0.35 mL/min; l¼254 nm): 13.2 min
(1S,5R,6R,7R ) and 15.8 min (1R,5S,6S,7S).
4.4.2. (1R p,6S p,7S p,8R p)-8-(Methyltosylamino)spiro[bi-
cyclo[4.2.0]octane-7,20-oxirane] (endo-3c). Mp 1488C; 1H
NMR (200 MHz, CDCl3) d 7.67 (d, J¼8.2 Hz, 2H), 7.31 (d,
J¼8.2 Hz, 2H), 4.25 (d, J¼9.1 Hz, 1H), 2.79 (s, 3H), 2.72–
2.50 (m, 2H), 2.44 (s, 3H), 2.42 (d, J¼9.1 Hz, 1H), 1.85–
0.95 (m, 4H); 13C NMR (50 MHz, CDCl3) d 143.3, 134.2,
129.5, 127.6, 68.5, 55.6, 44.5, 39.9, 33.3, 32.8, 23.8, 22.3,
22.1, 21.4, 19.3; IR (neat) n 2927, 2842, 1340, 1158; M (IE):
322 (2%), 238 (100%), 166 (46%), 155 (36%), 91 (50%), 42
(44%); elemental analysis calcd (%) for C17H23O3NS: C
63.52, H 7.21, N 4.35, S 9.97; found: C 63.49, H 7.37, N
4.23, S 10.26.
4.6.2. (1R,5S,6S,7S )-1-Methyl-7-(methyltosylamino)-
spiro[bicyclo[3.2.0]heptane-6,20-oxirane] (endo-3e). 1H
NMR (200 MHz, CDCl3) d 7.65 (d, J¼8.1 Hz, 2H), 7.29
(d, J¼8.1 Hz, 2H), 4.44 (d, J¼1.6 Hz, 1H), 2.93 (s, 3H),
2.66 (d, J¼5.1 Hz, 1H), 2.50–2.40 (m, 1H), 2.42 (s, 3H),

F. Mahuteau-Betzer, L. Ghosez / Tetrahedron 58 (2002) 6991–7000
6997
2.31 (d, J¼5.1 Hz, 1H), 2.00–1.10 (m, 6H), 1.18 (s, 3H);
13C NMR (50 MHz, CDCl3) d 143.2, 136.3, 129.5, 127.1,
66.0, 60.3, 52.1, 48.6, 48.0, 41.7, 33.6, 27.2, 26.4, 21.5,
20.4; IR (neat) n 2957, 2869, 1339, 1260, 1157; M (IE): 321
(12%), 185 (60%), 155 (40%), 91 (100%); HRMS calcd (%)
for C17H23O3NS: 321.1402; found: 321.1399.
2.30–2.15 (m, 1H), 1.90–1.65 (m, 4H), 1.60–1.45 (m, 1H),
1.40–1.10 (m, 7H); 13C NMR (75 MHz, CDCl3) d 143.1,
137.0, 129.5, 127.0, 66.6, 59.2, 46.1, 44.6, 40.9, 34.4, 31.7,
28.2, 27.4, 27.0, 26.8, 26.0, 21.4; IR (neat) n 2918, 2847,
1337, 1147; M (IE): 349 (12%), 306 (4%), 238 (100%), 194
(32%), 155 (24%), 91 (36%), 42 (72%); elemental analysis
calcd (%) for C19H27O3NS: C 65.30, H 7.74, N 4.01, S 9.17;
found: C 65.14, H 7.85, N 3.90, S 9.80.
4.7. Preparation of epoxides exo- and endo-3f
From 2f (400 mg, 1.2 mmol), trimethylsulfonium tetra-
fluoroborate (245 mg, 1.5 mmol), n-BuLi (2.3 M in
hexanes, 830 mL, 1.9 mmol). Yield: 84 mg (20%) of exo-
3f and 260 mg (62%) of endo-3f.
4.8. Preparation of epoxides exo- and endo-3i
From 2i (146 mg, 0.4 mmol), trimethylsulfonium tetra-
fluoroborate (73 mg, 0.4 mmol), n-BuLi (2.0 M in hexanes,
266 mL, 0.5 mmol). Yield: 111 mg (73%) of exo-3i and
12 mg (8%) of endo-3i.
4.7.1. (1R p,7S p,8R p,9S p)-9-(Methyltosylamino)spiro[bi-
cyclo[5.2.0]nonane-8,20-oxirane] (exo-3f). 1H NMR
(300 MHz, CDCl3) d 7.65 (d, J¼8.2 Hz, 2H), 7.28 (d,
J¼8.2 Hz, 2H), 4.45 (dd, J¼6.8, 1.2 Hz, 1H), 3.03 (s, 3H),
2.80–2.50 (m, 2H), 2.55 (d, J¼4.9 Hz, 1H), 2.42 (s, 3H),
2.29 (d, J¼4.9 Hz, 1H), 1.90–1.00 (m, 10H); 13C NMR
(50 MHz, CDCl3) d 143.2, 137.0, 129.5, 127.0, 63.6, 60.5,
47.8, 44.0, 39.8, 31.9, 31.5, 31.4, 29.1, 28.7, 28.3, 21.5; IR
(neat) n 2990, 2918, 2847, 1376, 1160; M (IE): 335 (4%),
238 (100%), 180 (40%), 155 (28%), 91 (32%), 42 (26%);
HRMS (CI) calcd (%) for C18H26O3NS: 336.1633; found:
336.1627.
4.8.1. (1R p,2S p,3R p)-2-(Methyltosylamino)-3-phenyl-
spiro[cyclobutane-1,20-oxirane] (exo-3i). 1H NMR
(200 MHz, CDCl3) d 7.40 (d, J¼8.1 Hz, 2H), 7.30–7.00
(m, 5H), 7.00 (d, J¼8.1 Hz, 2H), 4.96 (d, J¼9.5 Hz, 1H),
3.89 (q, J¼9.5 Hz, 1H), 3.10 (s, 3H), 2.70 (d, J¼4.3 Hz,
1H), 2.55 (d, J¼4.3 Hz, 1H), 2.48 (d, J¼9.5 Hz, 1H), 2.46
(d, J¼9.5 Hz, 1H), 2.35 (s, 3H); 13C NMR (50 MHz,
CDCl3) d 142.9, 141.3, 136.5, 129.4, 128.6, 126.9, 126.6,
126.5, 63.3, 62.2, 47.8, 41.5, 33.0, 31.6, 21.4; IR (neat) n
2923, 2855, 1340, 1166; M (IE): 343 (2%), 287 (76%), 239
(36%), 188 (80%), 155 (32%), 106 (98%), 91 (100%), 42
(34%); HRMS calcd (%) for C19H21O3NS: 343.1242;
found: 343.1254.
4.7.2. (1R p,7S p,8S p,9S p)-9-(Methyltosylamino)spiro[bi-
cyclo[5.2.0]nonane-8,20-oxirane] (endo-3f). 1H NMR
(300 MHz, CDCl3) d 7.67 (d, J¼8.2 Hz, 2H), 7.28 (d,
J¼8.2 Hz, 2H), 4.56 (d, J¼6.3 Hz, 1H), 2.83 (s, 3H), 2.60
(d, J¼5.0 Hz, 1H), 2.50–2.35 (m, 2H), 2.42 (s, 3H), 2.33 (d,
J¼5.0 Hz, 1H), 2.00–1.00 (m, 10H); 13C NMR (50 MHz,
CDCl3) d 143.2, 136.2, 129.4, 127.2, 63.5, 61.0, 50.0, 41.5,
36.9, 32.0, 30.7, 29.8, 28.1, 25.9, 21.4; IR (neat) n 2918,
2847, 1337, 1151; M (IE): 335 (4%), 238 (100%), 180
(26%), 155 (20%), 150 (8%), 91 (30%), 42 (54%).
4.8.2. (1S p,2S p,3R p)-2-(Methyltosylamino)-3-phenyl-
0
1
spiro[cyclobutane-1,2 -oxirane] (endo-3i). Mp 1348C; H
NMR (200 MHz, CDCl3) d 7.44 (d, J¼8.2 Hz, 2H), 7.30 (m,
5H), 7.05 (d, J¼8.2 Hz, 2H), 5.00 (d, J¼9.3 Hz, 1H), 3.40
(q, J¼9.3 Hz, 1H), 2.91 (s, 3H), 2.81 (d, J¼5.2 Hz, 1H),
2.60 (d, J¼5.2 Hz, 1H), 2.52–2.40 (m, 2H), 2.35 (s, 3H);
13C NMR (50 MHz, CDCl3) d 143.0, 141.0, 136.5, 129.3,
128.6, 127.0, 126.7, 126.7, 64.7, 59.5, 49.6, 36.3, 31.8, 30.9,
21.4; IR (neat) n 2926, 2855, 1339, 1166; M (IE): 343 (2%),
287 (92%), 239 (24%), 188 (96%), 155 (32%), 91 (100%),
42 (48%).
4.7.3. Preparation of epoxide (1R,7R,8R,9S )-9-(methyl-
tosylamino)spiro[bicyclo[5.2.0]nonane-8,20-oxirane]
(exo-3g). From 2g (348 mg, 1.1 mmol), trimethylsulfonium
tetrafluoroborate (213 mg, 1.3 mmol), n-BuLi (2.1 M in
hexanes, 785 mL, 1.6 mmol). Yield: 268 mg (74%); 1H
NMR (200 MHz, CDCl3) d 7.67 (d, J¼8.3 Hz, 2H), 7.29 (d,
J¼8.3 Hz, 2H), 4.34 (d, J¼9.4 Hz, 1H), 2.93 (s, 3H), 2.51
(s, 2H), 2.42 (s, 3H), 2.45–2.30 (m, 1H), 2.30–2.15
(m, 1H), 1.70–1.10 (m, 10H); 13C NMR (50 MHz,
CDCl3) d 143.1, 136.8, 129.5, 127.0, 66.9, 57.9, 45.9,
43.8, 40.6, 31.5, 31.3, 29.0, 28.0, 25.3, 23.5, 21.4; IR (neat)
n 2918, 2856, 1342, 1156; M (IE): 335 (4%), 238 (100%),
180 (26%), 155 (24%), 150 (10%), 91 (42%), 42 (52%);
HRMS calcd (%) for C18H25O3NS: 335.1555; found:
336.1555.
4.9. Preparation of epoxides exo- and endo-3j
From 2j (500 mg, 1.6 mmol), trimethylsulfonium tetrafluor-
oborate (300 mg, 1.9 mmol), n-BuLi (1.9 M in hexanes,
935 mL, 1.8 mmol). Yield: 320 mg (61%) of exo-3j and
25 mg (5%) of endo-3j.
4.9.1. (1R p,2S p,3R p)-3-Butyl-2-(methyltosylamino)-
spiro[cyclobutane-1,20-oxirane] (exo-3j). 1H NMR
(200 MHz, CDCl3) d 7.67 (d, J¼8.4 Hz, 2H), 7.29 (d,
J¼8.4 Hz, 2H), 4.40 (d, J¼8.0 Hz, 1H), 3.03 (s, 3H), 2.80–
2.40 (m, 1H), 2.54 (d, J¼4.6 Hz, 1H), 2.42 (s, 3H), 2.32 (d,
J¼4.6 Hz, 1H), 2.15 (ddd, J¼13.3, 9.8, 1.3 Hz, 1H), 1.92
(dd, J¼13.3, 9.8 Hz, 1H), 1.45–1.00 (m, 6H), 0.92 (t,
J¼6.6 Hz, 3H); 13C NMR (50 MHz, CDCl3) d 143.2, 137.2,
129.5, 127.0, 62.6, 60.8, 48.3, 36.8, 34.3, 31.7, 31.6, 29.3,
22.5, 21.4, 13.8; IR (neat) n 2959, 2930, 1348, 1251, 1157;
M (IE): 323 (6%), 267 (100%), 238 (42%), 168 (24%), 155
(48%), 91 (45%); elemental analysis calcd (%) for
C17H25O3NS: C 63.13, H 7.79, N 4.33, S 9.91; found: C
63.11, H 7.78, N 4.13, S 9.66.
4.7.4. Preparation of epoxide (1R,8R,9R,10S )-10-
(methyltosylamino)spiro[bicyclo[6.2.0]decane-9,20-oxi-
rane] (exo-3h). From 2h (431 mg, 1.3 mmol), trimethyl-
sulfonium tetrafluoroborate (253 mg, 1.5 mmol), n-BuLi
(2.0 M in hexanes, 965 mL, 1.9 mmol). Yield: 264 mg
(59%); mp 858C; [a ]D20¼230.7 (c¼0.8, CH2Cl2); 1H NMR
(300 MHz, CDCl3) d 7.67 (d, J¼8.2 Hz, 2H), 7.28 (d,
J¼8.2 Hz, 2H), 4.31 (d, J¼9.3 Hz, 1H), 2.96 (s, 3H), 2.45
(d, J¼4.5 Hz, 1H), 2.42 (s, 3H), 2.36 (d, J¼4.5 Hz, 1H),

6998
F. Mahuteau-Betzer, L. Ghosez / Tetrahedron 58 (2002) 6991–7000
4.9.2. (1S p,2S p,3R p)-3-Butyl-2-(methyltosylamino-
spiro[cyclobutane-1,20-oxirane] (endo-3j). 1H NMR
(200 MHz, CDCl3) d 7.69 (d, J¼8.1 Hz, 2H), 7.28 (d,
J¼8.1 Hz, 2H), 4.49 (d, J¼7.2 Hz, 1H), 2.81 (s, 3H), 2.65
(d, J¼4.9 Hz, 1H), 2.42 (s, 3H), 2.33 (d, J¼4.9 Hz, 1H),
2.25–2.10 (m, 2H), 1.90–1.70 (m, 1H), 1.50–1.30 (m, 4H),
1.40 (q, J¼6.7 Hz, 2H), 0.84 (t, J¼6.7 Hz, 3H),; 13C NMR
(50 MHz, CDCl3) d 143.2, 136.6, 129.4, 127.2, 63.2, 59.5,
49.8, 34.5, 32.1, 30.8, 30.4, 29.3, 22.5, 21.4, 13.8.
(90% ee). (1S,5S)-Bicyclo[3.3.0]oct-3-en-2-one (4a): RN
1388665-76-6; [a ]D20¼þ291.5 (c¼1.1, CH2Cl2); HPLC
(OB column; eluent iPrOH/hexane 2:98; flow:
v¼1.00 mL/min; l¼232 nm): 10.6 min (1R,5R ) and
12.2 min (1S,5S ).
4.13. Rearrangement of 2b
From exo-2b (200 mg, 0.62 mmol), lithium iodide (83 mg,
0.62 mmol). Yield: 80 mg (95%) of 4b (92% ee). From
endo-2b (200 mg, 0.62 mmol), lithium iodide (8 mg,
0.62 mmol). Yield: 60 mg (71%) of 4b and 48 mg (24%)
of 5b (92% ee).
4.10. Reaction of 2b with diazomethane
A 1 M solution of diazomethane in ether (10 mL) was added
to a solution of 2b (350 mg, 1.2 mmol) in a 1:1 mixture of
ether and ethyle actetate at 2108C. After one day, drops of
acetic acid were added and the mixture was concentrated in
vacuo and purified by flash chromatography on silica gel
(eluent AcOEt/cyclohexane 2:8). Yield 75 mg (19%) of 6
and 20 mg (5%) of 5 and 245 mg (70%) of starting material
2b.
(1S,6S)-Bicyclo[4.3.0]non-8-en-7-one (4b): RN 81255-91-
6; [a ]2D0¼þ35.3 (c¼0.1, CH2Cl2); HPLC (OB column;
eluent i PrOH/hexane 2:98; flow: v¼1.00 mL/min;
l¼232 nm): 8.0 min (1S,6S) and 17.0 min (1R,6R ).
4.13.1. (1S,6R,7S )-7-(Methyltosylamino)bicyclo[4.3.0]-
nonan-8-one (5b). [a ]2D0¼þ93.4 (c¼1.1, CHCl3); HPLC
(AD column; eluent EtOH; flow: v¼0.35 mL/min;
l¼254 nm): 17.9 min (1R,6S,7R ) and 30.9 min (1S,6R,7S ).
4.10.1. (1R p,6S p,9S p)-9-(Methyltosylamino)-bicyclo-
1
[4.3.0]nonan-7-one (6b). H NMR (400 MHz, CDCl3) d
7.67 (d, J¼7.9 Hz, 2H), 7.29 (d, J¼7.9 Hz, 2H), 4.59 (q,
J¼9.0 Hz, 1H), 2.71 (s, 3H), 2.41 (s, 3H), 2.32 (m, 1H), 2.22
(m, 1H), 2.14 (dd, J¼19.0, 8.0 Hz, 1H), 1.95 (ddd, J¼19.0,
9.0, 1.0 Hz, 1H), 1.68–1.58 (m, 3H), 1.50–1.37 (m, 3H),
1.33–1.15 (m, 2H); 13C NMR (100 MHz, CDCl3) d 215.3,
143.5, 136.1, 129.8, 127.0, 53.8, 47.8, 38.0, 37.4, 28.0, 23.8,
23.2, 22.9, 21.4, 20.7; IR (neat) n 2928, 2856, 1742, 1339,
1159; M (ICþ): 322 (2%), 186 (100%); HRMS calcd (%)
for C17H23O3NS: 321.1397; found: 321.1392.
4.14. Rearrangement of 3c
From exo-3c-rac (100 mg, 0.3 mmol), lithium iodide
(27 mg, 0.3 mmol) heated overnight. Yield: 36 mg (90%)
of 4a.
4.15. Rearrangement of 3d
From exo-3d (100 mg, 0.31 mmol), lithium iodide (42 mg,
0.31 mmol). Yield: 37 mg (88%) of 4d (86% ee). From
endo-3d (1 g, 3.13 mmol), lithium iodide (419 mg,
3.13 mmol). Yield: 205 mg (32%) of 4d and 320 mg
(49%) of 5d (86% ee).
4.10.2. (1S p,6R p,7S p)-7-(Methyltosylamino)bicyclo-
[4.3.0]nonan-8-one (5b). Mp 1048C; H NMR (400 MHz,
1
CDCl3) d 7.79 (d, J¼8.0 Hz, 2H), 7.31 (d, J¼8.0 Hz, 2H),
4.66 (d, J¼12.4 Hz, 1H), 2.59 (s, 3H), 2.43 (s, 3H), 2.29 (m,
1H), 2.25 (m, 2H), 2.02 (m, 1H), 1.92 (m, 1H), 1.76 (m, 1H),
1.72 (m, 1H), 1.59 (m, 2H), 1.57 (m, 1H), 1.28 (m, 1H), 1.14
(m, 1H); 13C NMR (100 MHz, CDCl3) d 213.5, 143.2,
136.8, 129.4, 127.6, 63.7, 43.9, 36.7, 31.4, 30.0, 29.2, 25.0,
21.4, 19.6; IR (neat) n 2927, 2854, 1749, 1338, 1156; M (IE):
321 (28%), 165 (100%), 136 (100%), 91 (56%); elemental
analysis calcd (%) for C17H23O3NS: C 63.52, H 7.21, N 4.36,
S 9.97; found: C 63.27, H 7.16, N 4.22, S 10.14.
4.15.1. (1S,6S)-Bicyclo[4.3.0]non-3,8-dien-7-one (4d).
RN 94344-47-5; [a]D20¼þ99.5 (c¼0.6, CH2Cl2); HPLC
(OB column; eluent i PrOH/hexane 2:98; flow:
v¼1.00 mL/min; l¼220 nm): 11.9 min (1S,6S) and
19.5 min (1R,6R).
4.15.2. (1S,6R,7S )-7-(Methyltosylamino)bicyclo[4.3.0]-
1
non-3-en-8-one (5d). H NMR (200 MHz, CDCl3) d 7.75
4.11. General procedure for the rearrangement of
epoxides
(d, J¼8.4 Hz, 2H), 7.30 (d, J¼8.4 Hz, 2H), 5.80–5.70 (m,
2H), 4.33 (d, J¼11.9 Hz, 1H), 2.65 (s, 3H), 2.43 (s, 3H),
2.50–2.15 (m, 6H), 1.80–1.55 (m, 2H); 13C NMR (50 MHz,
CDCl3) d 212.7, 143.0, 136.7, 129.2, 127.2, 124.3, 123.9,
65.6, 44.6, 35.0, 30.1, 27.2, 26.8, 23.4, 21.2; IR (neat) n
2922, 2840, 1749, 1338, 1153; M (IE): 319 (2%), 185
(28%), 155 (16%), 91 (26%), 43 (100%); HRMS calcd (%)
Lithium iodide (1 equiv.) was added to a 0.05 M solution of
epoxide (1 equiv.) in THF at room tempreature. The mixture
was heated for two hours at 658C. The mixture was cooled to
room tempretaure and concentrated in vacuo. The product
was purified by flash chromatography on silica gel (eluent
AcOEt/cyclohexane 2:8). When the separation of oxiranes
was not required, the crude reaction mixture was purified by
flash chromatography to afford a mixture of epoxides. The
rearrangement was done on these mixtures.
for
C17H21O3NS:
319.1242;
found:
319.1247;
[a ]2D0¼þ101.7 (c¼0.7, CH2Cl2); HPLC (AD column;
eluent EtOH; flow: v¼0.35 mL/min; l¼254 nm): 16.4 min
(1R,6S,7R) and 21.0 min (1S,6R,7S ).
4.16. Rearrangement of 3e
4.12. Rearrangement of 3a
From exo-3e and endo-3e (400 mg, 1.2 mmol), lithium
iodide (170 mg, 1.2 mmol). Yield: 160 mg (95%) of 4e
(92% ee).
From exo-3a and endo-3a (400 mg, 1.2 mmol), lithium
iodide (170 mg, 1.2 mmol). Yield: 130 mg (86%) of 4a

F. Mahuteau-Betzer, L. Ghosez / Tetrahedron 58 (2002) 6991–7000
6999
4.16.1. (1S,5S )-5-Methyl-bicyclo[3.3.0]oct-3-en-2-one
(4e). RN 39163-28-5; [a ]2D0¼þ14.8 (c¼0.5, CH2Cl2);
HPLC (AS column; eluent i PrOH/hexane 3:97; flow:
v¼0.35 mL/min; l¼220 nm): 15.9 min (1S,5S) and
19.7 min (1R,5R).
lithium iodide (60 mg, 0.44 mmol). Yield: 65 mg (94%) of
4i. 4-Phenylcyclopent-2-en-1-one (4i): RN 81255-96-1.
4.21. Rearrangement of 3j
From exo-3j-rac and endo-3j-rac (166 mg, 0.5 mmol),
lithium iodide (70 mg, 0.5 mmol). Yield: 68 mg (96%) of
4j. 4-Butylcyclopent-2-en-1-one (4j): RN 54814-22-1.
4.17. Rearrangement of 3f
From exo-3f-rac and endo-3f-rac (200 mg, 0.62 mmol),
lithium iodide (83 mg, 0.62 mmol). Yield: 80 mg (95%) of a
mixture of cis-4f and trans-4f in a ratio 85:15.
Acknowledgments
4.18. Rearrangement of exo-3g
`
This work was generously supported by the ‘Ministere de
l’Education et de la Recherche, Communaute franc¸aise de
´
From exo-3g (260 mg, 0.78 mmol), lithium iodide (104 mg,
0.78 mmol). Yield: 105 mg (90%) of a mixture of cis-4f and
trans-4f in a ratio 85:15 (92% ee). HPLC (AS column;
eluent i PrOH/hexane 3:97; flow: v¼1.00 mL/min;
l¼220 nm): 15.7 min (1R,7S ), 17.3 min (1R,7R ),
19.3 min (1S,7S) and 21.4 min (1S,7R).
´
Belgique’ (action concertee, conventions 96/01-197) and
the University of Louvain. We thank Professor E. de
Hoffmann for the mass spectra.
References
4.18.1. (1R,7S)-Bicyclo[6.3.0]dec-9-en-8-one (cis-4f). RN
81255-92-7; 1H NMR (400 MHz, CDCl3) d 7.55 (dd, J¼5.6,
2.0 Hz, 1H), 6.16 (dd, J¼5.6, 2.0 Hz, 1H), 3.13 (m, 1H),
2.50 (dt, J¼10.5, 6.5 Hz, 1H), 2.02 (m, 1H), 1.92 (m, 1H),
2.10–1.20 (m, 8H); 13C NMR (75 MHz, CDCl3) d 212.7,
168.7, 132.3, 50.4, 47.4, 31.0, 30.6, 28.1, 27.5; M (GC-IE):
150 (100%), 107 (60%), 95 (48%).
1. Selected reviews: (a) Trost, B. M. Top. Curr. Chem. 1986, 133,
3. (b) Wong, H. N. C.; Lau, K. L.; Tam, K. F. Top. Curr. Chem.
1986, 133, 83. (c) Krief, A. Top. Curr. Chem. 1987, 135, 1.
(d) Burger, P.; Buch, H. M. Top. Curr. Chem. 1987, 135, 77.
(e) Bellus, D.; Ernst, B. Ang. Chem. Int. Ed. Engl. 1988, 27,
797. (f) Lee-Ruff, E. Advances in Strain in Organic Chemistry;
Halton, B., Ed.; JAI: London, 1991; Vol. 1, pp 167–213.
2. (a) Review: Ghosez, L.; Chen, L. Y.; Gobeaux, B.; Houge, C.;
4.18.2. (1R,7R )-Bicyclo[6.3.0]dec-9-en-8-one (trans-4f).
1
RN 81255-93-8; H NMR (200 MHz, CDCl3) d 7.46 (d,
´
Marko, I. E.; Perry, M.; Saimoto, H. In Strain and its
J¼5.8 Hz, 1H), 6.28 (d, J¼5.8 Hz, 1H), 2.62 (d, J¼9.4 Hz,
1H), 2.15–1.85 (m, 2H), 1.80–1.20 (m, 11H); 13C NMR
(50 MHz, CDCl3) d 209.1 163.3, 134.8, 53.4, 47.4, 32.8,
31.1, 27.1, 27.0, 22.8; M (GC-IE): 150 (100%), 107 (60%),
95 (48%).
Implications in Organic Chemistry; de Meijere, A., Blechert,
S., Eds.; Kluwer: Dordrecht, 1989; pp 235–254. (b) Marchand-
Brynaert, J.; Ghosez, L. J. Am. Chem. Soc. 1972, 72,
2870–2872. (c) Falmagne, J. B.; Escudero, J. C.; Taleb-
Sahraoui, S.; Ghosez, L. Ang. Chem. Int. Ed. Engl. 1981, 20,
879–880.
4.19. Rearrangement of exo-3h
3. (a) Greene, A. E.; Charbonnier, F. Tetrahedron Lett. 1985, 26,
5525–5529. (b) Greene, A. E.; Charbonnier, F.; Luche, M. J.;
Moyano, A. J. Am. Chem. Soc. 1987, 109, 4752–4753.
(c) Redlich, H.; Lenfers, J. B.; Kopf, J. Ang. Chem. Int. Ed.
Engl. 1989, 28, 777–778. (d) Cagnon, J. R.; Le Bideau, F.;
Marchand-Brynaert, J.; Ghosez, L. Tetrahedron Lett. 1997, 38,
2291–2294.
From exo-3h (167 mg, 0.48 mmol), lithium iodide (64 mg,
0.48 mmol). Yield: 68 mg (87%) of a mixture of cis-4h and
trans-4h in a ratio 15:85 (98% ee). HPLC (AS column;
eluent i PrOH/hexane 3:97; flow: v¼1.00 mL/min;
l¼220 nm): 12.5 min (1R,8S ), 15.5 min (1R,8R ),
21.4 min (1S,8S), and 26.0 min (1S,8R).
4. (a) Houge, C.; Frisque-Hesbain, A. M.; Mockel, A.; Ghosez,
L. J. Am. Chem. Soc. 1982, 104, 2920–2921. (b) Saimoto, H.;
Houge, C.; Frisque, A. M.; Mockel, A.; Ghosez, L.
Tetrahedron Lett. 1983, 24, 2251–2254. (c) Chen, L. Y.;
Ghosez, L. Tetrahedron Lett. 1990, 31, 4467–4470. (d) Chen,
L. Y.; Ghosez, L. Tetrahedron Asym. 1991, 2, 1181–1184.
(e) Ghosez, L.; Genicot, C.; Gouverneur, V. Pure Appl. Chem.
1992, 64, 1849–1856. (f) Adam, J. M.; Ghosez, L.; Houk,
K. N. Ang. Chem. Int. Ed. 1999, 18, 2728–2730.
1
4.19.1. (1R,8S )-Bicyclo[6.3.0]dec-9-en-8-one (cis-4h). H
NMR (300 MHz, CDCl3) d 7.53 (dd, J¼5.6, 2.8 Hz, 1H),
6.11 (dd, J¼5.6, 2.3 Hz, 1H), 2.94 (m, 1H), 2.15 (m, 1H),
2.10–1.20 (m, 8H); M (GC-IE): 164 (100%), 135 (68%).
4.19.2. (1R,8R)-Bicyclo[6.3.0]dec-9-en-8-one (trans-4h).
1H NMR (300 MHz, CDCl3) d 7.44 (dd, J¼5.6, 2.2 Hz, 1H),
6.20 (ddd, J¼5.6, 2.2, 0.9 Hz, 1H), 2.72 (d, J¼12.5 Hz, 1H),
2.15–1.85 (m, 3H), 1.85–1.65 (m, 4H), 1.60–1.30 (m, 4H),
1.20–1.05 (m, 2H); 13C NMR (75 MHz, CDCl3) d
212.3167.9, 131.6, 129.2, 51.5, 47.4, 34.1, 29.6, 27.3,
26.8, 25.3, 25.1; M (GC-IE): 164 (100%), 135 (36%), 120
(44%), 107 (48%), 94 (36%).
5. (a) Genicot, C.; Gobeaux, B.; Ghosez, L. Tetrahedron Lett.
1991, 32, 3827–3830. (b) Genicot, C.; Ghosez, L.
Tetrahedron Lett. 1992, 33, 7357–7360. (c) Ghosez, L.;
Mahuteau-Betzer, F.; Genicot, C.; Vallribera, A.; Cordier, J. F.
Chem. Eur. J. 2002. in press.
6. Mahuteau-Betzer, F.; Ghosez, L. Tetrahedron Lett. 1999, 40,
5183–5186.
4.20. Rearrangement of 3i
`
´
7. See for instance: (a) Greene, A. E.; Depres, J. P.; Crabbe, P.
Tetrahedron Lett. 1977, 2365–2368. (b) Mock, W. L.;
Hartman, M. E. J. Org. Chem. 1977, 42, 466. (c) Greene,
From exo-3i-rac and endo-3i-rac (150 mg, 0.44 mmol),

7000
F. Mahuteau-Betzer, L. Ghosez / Tetrahedron 58 (2002) 6991–7000
`
A. E.; Luche, M. J.; Depres, J. P. J. Am. Chem. Soc. 1983, 105,
2435–2439. (d) Greene, A. E.; Luche, M. J.; Serra, A. A.
J. Org. Chem. 1985, 50, 3957–3962. (e) Reeder, L. M.;
Hegedus, L. S. J. Org. Chem. 1999, 64, 3306–3311.
Tetrahedron Lett. 1985, 26, 2713–2716. (j) Pirrung, M. C.;
Thomson, S. A. J. Org. Chem. 1988, 53, 227–230.
9. (a) Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1962, 84,
3782–3783. (b) Review:Trost, B. M.; Melvin, JrL. S. Sulfur
Ylides: Emerging Synthetic Intermediates; Academic: New
York, 1975; pp 145–151.
8. (a) Leriverend, M. L.; Leriverend, P. C. R. Acad. Sc., Ser. C
1975, 280, 791–792. (b) Leriverend, M. L.; Leriverend, P.
Chem. Ber. 1976, 109, 3492–3495. (c) Trost, B. M.; Latimer,
L. H. J. Org. Chem. 1978, 43, 1031–1040. (d) Morton, D. R.;
Brokaw, F. C. J. Org. Chem. 1979, 44, 2880–2887. (e) Krief,
A.; Halazy, S. J. Chem. Soc., Chem. Commun. 1982,
1200–1201. (f) Halazy, S.; Zutterman, F.; Krief, A.
Tetrahedron Lett. 1982, 23, 4385–4388. (g) Tobe, Y.;
Yamashita, S.; Yamashita, T.; Kakiuchi, K.; Odaira, Y.
J. Chem. Soc., Chem. Commun. 1984, 1259–1260. (h) Tobe,
Y.; Yamashita, T.; Kakiuchi, K.; Odaira, Y. J. Chem. Soc.,
Chem. Commun. 1985, 898–899. (i) Hart, T. W.; Comte, M. T.
10. Feneau-Dupont, J.; Declercq, J. P.; Vanwetswinckel, S.;
Genicot, C. Acta Crystallogr. 1993, 49, 561–565.
11. Tinant, B.; Mahuteau-Betzer, F.; Ghosez, L. Z. Kryst. 2002,
Two manuscripts submitted for publication.
12. Rey, M.; Roberts, S. M.; Dreiding, A. S.; Roussel, A.;
Vanlierde, H.; Toppet, S.; Ghosez, L. Helv. Chim. Acta 1982,
65, 703–720.
13. Compound 5b was assigned a wrong structure in our
preliminary account of this work.6