Synthesis of isopropenylcyclopropanes - Revision of the relative configuration of cyclopropyl ketones obtained by 1,3-elimination of γ-epoxy ketones

Article abstract of DOI:10.1002/1099-0690(200101)2001:2<339::AID-EJOC339>3.0.CO;2-J

Efficient stereoselective routes towards isopropenylcyclopropanes have been devised. Secondary cis-isopropenylcyclopropylcarbinols have been obtained either by regio- and stereoselective hydroxy-directed cyclopropanation of the corresponding dienols or from bicyclic cyclopropyl lactones derived from intramolecular cyclopropanation of allylic diazoacetates. Contrary to previous reports, base-induced 1,3-elimination of γ-epoxy ketones has been shown to afford trans-2-(hydroxymethyl)cyclopropyl ketones, and the reactivity of these compounds has been reinvestigated.

Full text of DOI:10.1002/1099-0690(200101)2001:2<339::AID-EJOC339>3.0.CO;2-J

FULL PAPER
Synthesis of Isopropenylcyclopropanes ؊ Revision of the Relative Configuration
of Cyclopropyl Ketones Obtained by 1,3-Elimination of γ-Epoxy Ketones
Janine Cossy,*[a] Nicolas Blanchard,[a] and Christophe Meyer*[a]
Keywords: Synthetic methods / Cyclopropanations / Alkenyl cyclopropanes / Diastereoselectivity / Configuration
determination
Efficient stereoselective routes towards isopropenylcyclopro- from intramolecular cyclopropanation of allylic diazoacet-
panes have been devised. Secondary cis-isopropenylcyclop- ates. Contrary to previous reports, base-induced 1,3-elimina-
ropylcarbinols have been obtained either by regio- and ster-
tion of γ-epoxy ketones has been shown to afford trans-2-
eoselective hydroxy-directed cyclopropanation of the corres- (hydroxymethyl)cyclopropyl ketones, and the reactivity of
ponding dienols or from bicyclic cyclopropyl lactones derived
these compounds has been reinvestigated.
Introduction
Thus, the readily available ( )-γ-iodoallylic alcohols
1a[5a] and 1b[5b] were converted into their zinc alkoxides by
treatment with -butylzinc bromide and then coupled with
isopropenylzinc bromide in the presence of a catalytic
amount of Pd(PPh3)4 [6] to afford the corresponding dienols
2a (66%) and 2b (97%). We next examined the cyclopropan-
ation of these compounds and the use of samarium car-
benoids as cyclopropanating reagents ensured complete re-
gioselectivity with exclusive reaction at the allylic alcohol
Cyclopropane-containing organic compounds can un-
dergo a wide variety of ring-opening reactions and are
therefore regarded as synthetically useful building blocks
for achieving cyclic and acyclic stereocontrol.[1] We have re-
cently reported that electrophilic additions to
-substi-
tuted isopropenylcyclopropanes proceed with high levels of
stereocontrol,[2,3] therefore providing a complementary
strategy to nucleophilic additions to cyclopropyl ketones for
the introduction of stereocenters adjacent to the cyclopro-
pane ring.[4] In order to broaden the scope of electrophilic
additions to -substituted isopropenylcyclopropanes, effi-
cient synthetic routes towards these compounds have had
to be devised, and we report herein our results concerning
the three different routes that have been investigated. With
regard to one route, several observations led us to rein-
vestigate the stereochemical outcome of the base-induced
1,3-elimination of γ-epoxy ketones.
moiety[7] to give the secondary
,
-isopropenylcyclopro-
pylcarbinols 3a (71%) and 3b (81%). As anticipated, these
hydroxy-directed cyclopropanations turned out to proceed
in a highly diastereoselective fashion (3a:
Ն 95:5; 3b:
Ն 98:2). The relative configuration of 3b was un-
ambiguously assigned by X-ray crystallographic analysis of
its crystalline 4-nitrobenzoate ester derivative 4, which
confirmed that the stereochemical outcome of the cyclo-
propanation was in agreement with literature results
(Scheme 2).[7b]
In order to have access to the epimeric cyclopropylcarbi-
nol, 3b was oxidized to the corresponding cyclopropyl ke-
tone 5 (82%) with PDC, and the latter was reduced with
Results and Discussion
sodium borohydride in methanol to furnish the
,
-iso-
According to a first retrosynthetic analysis, we anticip-
propenylcyclopropylcarbinol 3c (76%) in a highly diastereo-
selective fashion ( ϭ 97:3). The stereochemical outcome
of this reduction could be predicted on the basis of the
known sense of additions to cyclopropyl ketones, which in-
volve nucleophilic attack at the less crowded side of the car-
ated that
,
-isopropenylcyclopropylcarbinols could be
obtained by performing a regio- and stereoselective cyclo-
propanation of the corresponding dienyl alcohols, which, in
turn, should be accessible by standard cross-coupling reac-
tions of two alkenyl moieties (Scheme 1).
bonyl group in the bisected
-
conformation
(Scheme 3).[4]
Although this sequence allowed rapid access to the de-
sired - or -isopropenylcyclopropylcarbinols,
,
,
we have to point out that the overall chemical yield was
lower in the case of 3a due to the volatility of this com-
pound. Moreover, the crucial role played by the hydroxy
group during the cyclopropanation step precludes its pro-
tection in order to form less volatile derivatives. Therefore,
it became apparent that this procedure is not well suited for
the preparation of the -isopropenylcyclopropylmethanol
Scheme 1. Retrosynthetic analysis for
carbinols
-isopropenylcyclopropyl-
[a]
´
Laboratoire de Chimie Organique, associe au CNRS, ESPCI,
10 rue Vauquelin, 75231 Paris Cedex 05, France
Fax: (internat.) ϩ 33-1/40794660
E-mail: janine.cossy@espci.fr; christophe.meyer@espci.fr
2001, 339Ϫ348
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/0102Ϫ0339 $ 17.50ϩ.50/0
339

J. Cossy, N. Blanchard, C. Meyer
FULL PAPER
7,[9] respectively, and their transformation into the -iso-
propenylcyclopropane 11 was carried out according to two
different routes. In the first approach, 8 was treated with
two equivalents of methyllithium and then the primary li-
thioalkoxide was subjected to in situ silylation with
-
butylchlorodiphenylsilane to afford the tertiary alcohol 10
(90%). Upon treatment with excess methanesulfonyl chlor-
ide and triethylamine, 10 was cleanly dehydrated to give the
-isopropenylcyclopropane 11 (85%). In the second ap-
proach, 9 was reduced with lithium aluminum hydride to
give the corresponding diol 12 (100%; 1:1 mixture of dias-
tereomers). The primary hydroxy group was silylated with
-butylchlorodiphenylsilane and the resulting secondary
alcohol was oxidized with PCC to give the -cyclopropyl
ketone 13 (57%). The latter was subjected to a standard
Wittig methylenation to afford 11 (82%). Both routes
proved to be extremely convenient for the preparation of
-isopropenylcyclopropane 11 on a large scale. Further-
more, according to the first route, (ϩ)-11 ( Ն 95%) could
easily be obtained from (Ϫ)-8 by performing the intramole-
cular cyclopropanation of allyl diazoacetate 6 with Doyle’s
Rh2[(5 )-MEPY]4 catalyst (Scheme 5).[10,11]
Scheme 2. Synthesis of secondary
carbinols
,
-isopropenylcyclopropyl-
Scheme 3. Synthesis of
,
-isopropenylcyclopropylcarbinols
(R ϭ H) derivatives and hence a second strategy was de-
vised in order to achieve this goal.
The protected -isopropenylcyclopropylmethanol could
be obtained from either a secondary or a tertiary cyclopro-
pylcarbinol, which, in turn, could be obtained from bicyclic
Scheme 5. Preparation of protected -isopropenylcyclopropylme-
thanol
During the course of our investigations, a third route to-
wards -isopropenylcyclopropanes was also considered. It
has been reported that successive treatment of γ-ethylenic
ketones with -bromosuccinimide and potassium hydrox-
ide in DMSO affords 2-(hydroxymethyl)cyclopropyl ketones
lactones, thereby ensuring the
propane ring (Scheme 4).
configuration of the cyclo-
with unprecedentedly high
selectivities[12] as compared
to previously reported similar transformations.[13] More re-
cently, lithium hexamethyldisilazide (LiHMDS) in com-
bination with Sc(OTf)3 has been used to induce the same
1,3-elimination from γ-epoxy ketones (Scheme 6).[14]
For the synthesis of isopropenyl- or related alkenyl-sub-
Scheme 4. Retrosynthesis for
derivatives
-isopropenylcyclopropylmethanol
The bicyclic lactones 8 (74%) and 9 (58%; 1:1 mixture of
diastereomers) were obtained by copper-catalyzed intramo- stituted cyclopropanes, this route was considered as being
lecular cyclopropanation[8] of the allylic diazoacetates 6 and particularly attractive owing to its simplicity, since a simple
340
2001, 339Ϫ348

Synthesis of Isopropenylcyclopropanes
FULL PAPER
Scheme 6. Preparation of 2-(hydroxymethyl)cyclopropyl ketones
methylenation would, in principle, lead to the required
structures. However, we have been able to demonstrate that
the configuration of the cyclopropyl ketones generated by
this process was not correctly assigned. When carried out
with hex-5-en-2-one (14) and 1-phenylpent-4-en-1-one (15),
the sequence described above afforded the corresponding 2-
(hydroxymethyl)cyclopropyl ketones 16 (37%) and 17
(50%), respectively. Although these transformations were
effectively highly diastereoselective ( Ն 95:5), we and
others[14] were unable to reproduce the high yields claimed
by the authors for this transformation[12] due to difficulties
associated with the extraction of these polar compounds
from the reaction medium. Compounds 16 and 17 were
Scheme 7. Preparation of protected
-isopropenylmethanol and
related structures from 2-(hydroxymethyl)cyclopropyl ketones
Scheme 8. Correlation of configuration of compound 21
subsequently protected as
-butyldiphenylsilyl ethers to
the -cyclopropyl ketone 24 and its bicyclic hemiketal 25
(71%; 80:20 inseparable mixture, single diastereomers).[18a]
This mixture of 24 and 25 was found to be stable for a few
months when kept as a frozen benzene solution at Ϫ23 °C.
However, upon standing for several hours at room temper-
ature or in the presence of traces of acid (especially acidic
CDCl3), a new mixture was obtained containing variable
amounts of 24, 25, and the dimer 26 as a 1:1 mixture of
diastereomers, with the relative configuration of the ketal
give 18 (76%) and 19 (53%), respectively. The cyclopropyl
ketone 18 appeared to be different from -cyclopropyl ke-
tone 13, which was previously synthesized from the bicyclic
lactone 9 (Scheme 5). Furthermore, the spectral data of 17
and 18 are in agreement with those recently reported for
the
tone 18 was olefinated under standard Wittig conditions to
give the -isopropenylcyclopropane 20 (86%), which
diastereomers prepared by a different route.[15] Ke-
was clearly different from the -isopropenylcyclopropane
stereocenter
apparently
perfectly
controlled
11.[16] Therefore, cyclopropyl ketones 16 and 18 must have
(Scheme 9).[18,19]
a
relative configuration. Similarly, cyclopropyl ketone
19 was converted into the cyclopropylcarbinol 21 (72%) by
successive Wittig methylenation and desilylation with
-Bu4NF. The latter could also be obtained directly from
17 (43%) by performing the olefination with excess methyl-
enephosphorane, indicating that the Wittig reaction did not
alter the relative configuration of this compound when pro-
tection of the hydroxy group was omitted (Scheme 7; for the
sake of clarity, the revised configurations have been directly
indicated in this Scheme).
The
relative configuration of 21 was established by
reducing it with excess diimide to afford the cyclopropylcar-
binol 22 (94%; 1:1 mixture of diastereomers), which we have
previously synthesized by means of Sm-promoted cyclopro-
panation of the ( )-allylic alcohol 23 (Scheme 8).[17] These
Scheme 9. Preparation and behaviour of -2-(hydroxymethyl)cy-
clopropylethanone
results unambiguously confirmed the
relative config-
uration of the cyclopropyl ketones 17 and 19.
In order to confirm the structures of 25 and 26, the equi-
In order to further elucidate this discrepancy with the librium mixture of 24 and 25 was dissolved in CD3OD and
literature, we decided to prepare an authentic sample of a catalytic amount of pyridinium -toluenesulfonate was
-
1
2-(hydroxymethyl)cyclopropylmethyl ketone 24. Thus, when added. After several hours at room temperature, H and
13 was desilylated with -Bu4NF in THF, a clean reaction 13C NMR spectra indicated the complete formation of the
occurred, invariably leading to an equilibrium mixture of mixed ketal 27 with methanol (single diastereomer).[18a] Un-
2001, 339Ϫ348
341

J. Cossy, N. Blanchard, C. Meyer
FULL PAPER
der the same conditions, 26 was also quantitatively con-
verted into 27 (Scheme 10).
Scheme 11. Reactivity of - and
pylethanone
-2-(hydroxymethyl)cyclopro-
tablished them to be
, as a result of a thermodyn-
amically controlled process. Moreover, chemical trans-
formations which were thought to correspond to kinetically
and thermodynamically controlled isomerizations were ac-
tually simple esterification and saponification reactions,
which proceed without affecting the relative configurations
of the corresponding cyclopropyl ketones.
Scheme 10. Chemical behaviour of -2-(hydroxymethyl)cyclopro-
pylethanone
We have devised efficient routes towards -isopropenyl-
cyclopropanes and we are currently exploiting these com-
pounds as synthetically useful building blocks in natural
product synthesis.
Since other reactions and especially isomerizations invol-
ving 2-(hydroxymethyl)cyclopropyl ketones have also been
reported in the literature,[20] we wanted to reinvestigate
these results, having established the exact relative configura-
tion of these compounds. The
-cyclopropyl ketone 24
(mixture with 25) was quantitatively converted into the
-cyclopropyl ketone 16 upon treatment with sodium
methoxide in refluxing methanol for several hours.[21] Con-
trary to what was suggested previously,[20] this result indic-
Experimental Section
General Remarks: Unless otherwise specified, materials were pur-
chased from commercial suppliers and used without further puri-
fication. THF and diethyl ether were distilled from sodium/benzo-
phenone ketyl immediately prior to use. Dichloromethane, DMF,
toluene, and triethylamine were distilled from calcium hydride. Zinc
bromide was melted, cooled under argon, and handled as a 1 
solution in anhydrous THF. Ϫ Moisture-sensitive reactions were
carried out in oven-dried glassware under argon. Ϫ Analytical thin-
layer chromatography was performed on Merck precoated silica gel
(60 F254) plates. Ϫ Flash chromatography was performed on Merck
Kieselgel 60 (230Ϫ400 mesh). Ϫ Melting points were measured
with a Kofler apparatus. Ϫ IR: PerkinϪElmer 298. Ϫ Optical rota-
tions: PerkinϪElmer 241 MC polarimeter. Ϫ Elemental analyses:
ated that the
-2-(hydroxymethyl)cyclopropyl ketones
are the thermodynamically most stable isomers.[21,22] There-
fore, the high degree of stereoselectivity observed in the 1,3-
elimination of γ-epoxy ketones with either KOH in
[14]
DMSO[12] or LiHMDS/Sc(OTf)3
thermodynamic control.
is a consequence of
It has also been reported that treatment of the cyclopro-
pyl ketones derived from 1,3-elimination of γ-epoxy ketones
with trifluoroacetic acid (TFA) in chloroform induced their
so-called isomerization, whereas the reverse reaction was
observed under alkaline conditions.[20] When ketone 16 was
treated with excess TFA in CH2Cl2 at room temperature for
2Ϫ5 d, a very clean conversion into a less polar compound
was observed. However, the latter proved to be the trifluo-
roacetate 28 formed by esterification of the OH group of
16 with TFA. Its structure could have been confused with
´
´
Service Regional de Microanalyses de l’Universite P. et M. Curie.
Ϫ HRMS: Laboratoire de Spectrochimie de l’Ecole Normale
´
Superieure Ulm. Ϫ NMR: Bruker AC spectrometer (300 MHz and
75 MHz for 1H and 13C, respectively); chemical shifts (δ) are ex-
pressed in ppm relative to TMS (δ ϭ 0). Ϫ MS: Mass spectra were
obtained by GC/MS with a Hewlett Packard 5971 instrument oper-
ating in electron impact ionization mode at 70 eV.
1
that of an epimer of 16 by H NMR owing to their great
(Z)-6-Methylhepta-4,6-dien-3-ol (2a):[23] To a solution of -bu-
tylzinc bromide [prepared from -butyllithium (5.30 mL, 2.5  in
hexanes, 13.1 mmol, 1.1 equiv.) and zinc bromide (13.1 mL, 1  in
THF, 13.1 mmol, 1.1 equiv.) in THF (10 mL)], a solution of 1a[5a]
(2.50 g, 11.8 mmol) in THF (7 mL) was added dropwise at 0 °C.
After 20 min at this temperature, the reaction mixture was cannu-
lated into a solution of isopropenylzinc bromide [prepared from
isopropenylmagnesium bromide (36.0 mL, 0.5  in THF,
18.0 mmol, 1.5 equiv.) and zinc bromide (18 mL, 1  in THF,
18 mmol)]. Pd(PPh3)4 (0.420 g, 0.363 mmol, 0.03 equiv.) was added
in one portion (a slightly exothermic reaction started causing a
temperature increase to 28Ϫ30 °C) and, after refluxing for 1 h, the
reaction mixture was cooled to room temp., poured into saturated
aqueous NH4Cl solution, and extracted with diethyl ether. The
similarity and the absence of new signals, but the presence
of the trifluoroacetate group was unambiguously estab-
lished by IR, 13C NMR, and GC-MS analyses. Con-
sequently, treatment of the trifluoroacetate 28 with a base
such as sodium methoxide obviously resulted in reversion
to the initial compound 16, owing to the great sensitivity of
trifluoroacetic esters towards various bases (Scheme 11).
Conclusion
This study has enabled us to show that the relative con-
figurations of the 2-(hydroxymethyl)cyclopropyl ketones
generated by 1,3-elimination of γ-epoxy ketones were previ-
ously incorrectly assigned. We have now unambiguously es- combined extracts were successively washed with saturated aqueous
342 2001, 339Ϫ348

Synthesis of Isopropenylcyclopropanes
FULL PAPER
NaHCO3 solution, 20% aqueous Na2S2O3 solution, and brine,
dried with Na2CO3, filtered, and concentrated under reduced pres-
sure. The crude material was taken up in pentane (50 mL) and the
resulting mixture was refluxed, cooled to room temp., and filtered
through Celite in order to remove the catalyst. After evaporation
of the solvents, the crude material was purified by flash chromato-
graphy (pentane/diethyl ether, 90:10) to give 0.990 g (66%) of 2a as
a colorless oil. Ϫ IR (neat): ν˜ ϭ 3350, 3080, 1630, 1595, 1110,
H), 1.12 (m, 1 H), 0.96 (t, ϭ 7.3 Hz, 3 H), 0.81Ϫ0.71 (2 H). Ϫ
13C NMR (CDCl3): δ ϭ 142.5 (s), 110.6 (t), 72.2 (d), 30.6 (t), 24.6
(d), 24.2 (q), 22.9 (d), 9.9 (q), 7.0 (t). Ϫ MS (EI;
(%): 140 (2)
[Mϩ], 125 (32), 111 (44), 93 (67), 85 (39), 72 (66), 67 (81), 57 (100).
Ϫ C9H16O (140.22): calcd. C 77.09, H 11.50; found C 77.38,
H 11.61.
(S*)-[(1R*,2S*)-2-Isopropenylcyclopropyl]phenylmethanol (3b): To a
suspension of samarium powder (4.32 g, 28.7 mmol, 5.0 equiv.) in
THF (150 mL) were added dry HgCl2 (1.56 g, 5.75 mmol, 1.0
equiv.) and 2b (1.00 g, 5.75 mmol). To the vigorously stirred mix-
ture, ICH2Cl (2.10 mL, 28.7 mmol, 5.0 equiv.) was added dropwise
at Ϫ50 °C. The reaction mixture was gradually allowed to warm
to room temp. over a period of 2 h. It was then poured into cold
saturated aqueous K2CO3 solution (150 mL) overlaid with diethyl
ether (150 mL). After stirring for 20 min, the resulting mixture was
filtered through Celite and the removed solids were thoroughly
washed with diethyl ether. The aqueous layer was extracted with
diethyl ether and the combined extracts were washed with brine,
dried with Na2CO3, filtered, and concentrated under reduced pres-
sure. The crude material was purified by flash chromatography
(cyclohexane/AcOEt gradient, 90:10 to 80:20) to give 0.875 g (81%)
of 3b as a colorless oil. Ϫ IR (neat): ν˜ ϭ 3350, 3080, 3030, 1645,
1605, 1020 cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ 7.40Ϫ7.24 (5 H), 4.88
(quint., ϭ 1.5 Hz, 1 H), 4.71 (br. s, 1 H), 4.14 (m, 1 H), 1.98 (br.
s, 1 H, OH), 1.57 (s, 3 H), 1.54Ϫ1.47 (2 H), 0.98Ϫ0.89 (2 H). Ϫ
13C NMR (CDCl3): δ ϭ 144.2 (s), 142.7 (s), 128.3 (d), 127.6 (d),
126.4 (d), 110.5 (t), 73.7 (d), 25.8 (d), 24.6 (q), 23.1 (d), 7.9 (t). Ϫ
1
1050 cmϪ1. Ϫ H NMR (CDCl3): δ ϭ 5.94 (d, ϭ 11.8 Hz, 1 H),
5.39 (dd, ϭ 11.8, 9.2 Hz, 1 H), 4.98 (d, ϭ 1.5 Hz, 1 H), 4.89
(d, ϭ 1.5 Hz, 1 H), 4.55 (m, 1 H), 2.16 (br. s, 1 H, OH), 1.87 (s,
3 H), 1.67Ϫ1.43 (2 H), 0.93 (t, ϭ 7.45 Hz, 3 H). Ϫ 13C NMR
(CDCl3): δ ϭ 141.1 (s), 133.4 (d), 132.4 (d), 116.3 (t), 69.0 (d), 30.5
(t), 23.0 (q), 9.6 (q).
(Z)-4-Methyl-1-phenylpenta-2,4-dien-1-ol (2b): To a solution of
-
butylzinc bromide [prepared from -butyllithium (3.40 mL, 2.5 
in hexanes, 8.50 mmol, 1.1 equiv.) and zinc bromide (8.50 mL, 1 
in THF, 8.50 mmol, 1.1 equiv.) in THF (10 mL)], a solution of
1b[5b] (2.00 g, 7.69 mmol) in THF (7 mL) was added dropwise at
0 °C. After 20 min at this temperature, the reaction mixture was
cannulated into a solution of isopropenylzinc bromide [prepared
from isopropenylmagnesium bromide (30.8 mL, 0.5  in THF,
15.4 mmol, 2.0 equiv.) and zinc bromide (15.4 mL, 1  in THF,
15.4 mmol, 2.0 equiv.)]. Pd(PPh3)4 (0.500 g, 0.433 mmol, 0.056
equiv.) was added in one portion (a slightly exothermic reaction
started causing a temperature increase to 28Ϫ30 °C) and, after re-
fluxing for 1 h, the reaction mixture was cooled to room temp.,
poured into saturated aqueous NH4Cl solution, and extracted with
diethyl ether. The combined extracts were successively washed with
saturated aqueous NaHCO3 solution, 20% aqueous Na2S2O3 solu-
tion, and brine, dried with Na2CO3, filtered, and concentrated un-
der reduced pressure. The crude material was taken up in pentane
(50 mL) and the resulting mixture was refluxed, cooled to room
temp., and filtered through Celite in order to remove the catalyst.
After evaporation of the solvents, the crude material was purified
by flash chromatography (cyclohexane/AcOEt, 90:10 to 85:15) to
give 1.30 g (97%) of 2b as a colorless oil. Ϫ IR (neat): ν˜ ϭ 3350,
3080, 3060, 3020, 1640, 1600, 1010 cmϪ1. Ϫ 1H NMR (CDCl3):
δ ϭ 7.43Ϫ7.25 (5 H), 6.05 (d, ϭ 9.8 Hz, 1 H), 5.74Ϫ5.64 (2 H),
5.04 (s, 1 H), 4.93 (s, 1 H), 1.98 (br. s, 1 H, OH), 1.92 (s, 3 H). Ϫ
13C NMR (CDCl3): δ ϭ 143.4 (s), 140.8 (s), 132.8 (d), 132.1 (d),
128.6 (d), 127.6 (d), 126.2 (d), 116.6 (t), 70.0 (d), 23.1 (q). Ϫ MS
MS (EI);
(%): 188 (0.6) [Mϩ], 170 (9) [Mϩ Ϫ H2O], 120 (100),
105 (23), 91 (36), 79 (14), 77 (19). Ϫ C13H16O (188.27): calcd. C
82.94, H 8.57; found C 83.27, H 8.43.
(S*)-[(1R*,2S*)-2-Isopropenylcyclopropyl]phenylmethyl
4-Nitro-
benzoate (4): To a solution of 3b (0.112 g, 0.595 mmol) and 4-di-
methylaminopyridine (0.073 g, 0.597 mmol) in CH2Cl2 (10 mL) at
0 °C, was added 4-nitrobenzoyl chloride (0.111 g, 0.598 mmol).
After 1 h at room temp., the reaction mixture was quenched by the
addition of 1  aqueous hydrochloric acid solution and extracted
with AcOEt. The combined extracts were washed with saturated
aqueous NaHCO3 solution and brine, dried with MgSO4, filtered,
and concentrated under reduced pressure. The crude material was
purified by flash chromatography (cyclohexane/AcOEt, 95:5) to
give 0.167 g (83%) of 4 as pale-yellow crystals. Recrystallization
from diethyl ether/pentane yielded colorless crystals suitable for X-
ray crystallographic analysis; m.p. 97Ϫ99 °C. Ϫ IR (KBr): ν˜ ϭ
1718, 1605, 1523, 1272, 1103 cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ
8.28Ϫ8.21 (4 H), 7.47Ϫ7.26 (5 H), 5.65 (d, ϭ 10.0 Hz, 1 H), 4.98
(s, 1 H), 4.83 (s, 1 H), 1.79 (m, 1 H), 1.60 (m, 1 H), 1.58 (s, 3 H),
1.08 (m, 1 H), 0.97 (m, 1 H). Ϫ 13C NMR (CDCl3): δ ϭ 164.1 (s),
150.4 (s), 141.7 (s), 140.1 (s), 136.1 (s), 130.7 (d), 128.5 (d), 128.3
(d), 127.1 (d), 123.4 (d), 111.2 (t), 78.3 (d), 24.6 (q), 23.39 (d), 23.38
(d), 8.8 (t).
(EI);
(%): 174 (17) [Mϩ], 159 (13), 115 (10), 105 (100), 91 (11),
77 (33).
(1R*)-1-[(1R*,2S*)-2-Isopropenylcyclopropyl]propan-1-ol (3a): To a
suspension of samarium powder (5.90 g, 39.5 mmol, 5.0 equiv.) in
THF (150 mL) were added dry HgCl2 (1.72 g, 6.32 mmol, 0.8
equiv.) and 2a (1.00 g, 7.93 mmol). To the vigorously stirred mix-
ture, ICH2Cl (2.90 mL, 39.5 mmol, 5.0 equiv.) was added dropwise
at Ϫ50 °C. The reaction mixture was gradually allowed to warm
to room temp. over a period of 2 h. It was then poured into cold
saturated aqueous K2CO3 solution (100 mL) overlaid with diethyl
ether (100 mL). After stirring for 20 min, the resulting mixture was
filtered through Celite and the removed solids were thoroughly
washed with diethyl ether. The aqueous layer was extracted with
diethyl ether and the combined extracts were washed with brine,
dried with Na2CO3, filtered, and concentrated under reduced pres-
sure. The crude material was purified by flash chromatography
(pentane/diethyl ether, 80:20) to give 0.780 g (71%) of 3a as a color-
(1R*,2S*)-2-Isopropenylcyclopropyl Phenyl Ketone (5): To a vigor-
˚
ously stirred mixture of 3b (1.00 g, 5.31 mmol) and 4 A powdered
molecular sieves (4 g) in CH2Cl2 (40 mL) was added PDC (4.00 g,
10.6 mmol). After 3 h at room temp., the reaction mixture was fil-
tered through Florisil (CH2Cl2). After evaporation of the solvent,
the crude product was purified by flash chromatography (cyclohex-
ane/diethyl ether, 90:10) to give 0.816 g (82%) of 5 as a pale-yellow
oil. Ϫ IR (neat): ν˜ ϭ 3070, 3030, 1720, 1670, 1595, 1570, 1220,
1015 cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ 8.02 (m, 2 H), 7.56Ϫ7.42 (3
less oil. Ϫ IR (neat): ν˜ ϭ 3360, 3080, 1645, 1100, 1035 cmϪ1. Ϫ 1H H), 4.93 (s, 1 H), 4.85 (s, 1 H), 2.92 (ddd, ϭ 9.4, 7.5, 5.6 Hz, 1
NMR (CDCl3): δ ϭ 4.84 (s, 1 H), 4.65 (s, 1 H), 3.07 (ddd, ϭ 8.5,
7.3, 4.0 Hz, 1 H), 1.82 (s, 3 H), 1.72 (br. s, 1 H, OH), 1.65Ϫ1.46 (3
H), 2.19 (m, 1 H), 1.82 (ddd, ϭ 7.5, 5.6, 4.5 Hz, 1 H), 1.58 (s, 3
H), 1.20 (ddd, ϭ 8.1, 7.5, 4.5 Hz, 1 H). Ϫ 13C NMR (CDCl3):
2001, 339Ϫ348
343

J. Cossy, N. Blanchard, C. Meyer
δ ϭ 195.8 (s), 139.2 (s), 138.3 (s), 132.4 (d), 128.3 (d), 127.9 (d), 1 H), 3.69 (dd, ϭ 11.6, 9.8 Hz, 1 H), 3.19 (s, 1 H, OH), 1.47 (s,
FULL PAPER
113.8 (t), 31.7 (d), 25.4 (d), 23.3 (q), 11.4 (t).
3 H), 1.26 (s, 3 H), 1.24Ϫ1.06 (2 H), 1.06 (s, 9 H), 0.65 (m, 1 H),
0.39 (m, 1 H). Ϫ 13C NMR (CDCl3): δ ϭ 135.5 (d), 134.8 (d), 133.2
(s), 133.1 (s), 129.7 (d), 129.4 (d), 127.7 (d), 127.65 (d), 127.6 (d),
69.6 (s), 64.9 (t), 31.8 (q), 29.7 (q), 27.9 (d), 26.7 (q), 19.0 (s), 18.5
(R*)-[(1R*,2S*)-2-Isopropenylcyclopropyl]phenylmethanol (3c): To a
solution of 5 (0.430 g, 2.31 mmol) in MeOH (10 mL) at 0 °C was
added sodium borohydride (0.131 g, 3.46 mmol). After 1 h at room
temp., the reaction mixture was quenched with saturated aqueous
NH4Cl solution and extracted with diethyl ether. The combined
extracts were washed with brine, dried with Na2CO3, filtered, and
concentrated under reduced pressure. The crude material was puri-
fied by flash chromatography (cyclohexane/AcOEt, 90:10) to give
0.332 g (76%) of 3c as a waxy solid; m.p. 31 °C. Ϫ IR (neat): ν˜ ϭ
3350, 3060, 3020, 1640, 1595, 1035, 1010 cmϪ1. Ϫ 1H NMR
(CDCl3): δ ϭ 7.41Ϫ7.23 (5 H), 4.96 (s, 1 H), 4.73 (s, 1 H), 4.09 (d,
ϭ 9.7 Hz, 1 H), 2.00 (s, 3 H), 1.99 (br. s, 1 H, OH), 1.61 (m, 1
H), 1.41 (m, 1 H), 0.75 (m, 1 H), 0.62 (m, 1 H). Ϫ 13C NMR
(CDCl3): δ ϭ 144.5 (s), 142.8 (s), 128.3 (d), 127.3 (d), 126.0 (d),
110.8 (t), 73.7 (d), 26.2 (d), 24.3 (q), 23.6 (d), 7.6 (t). Ϫ MS (EI);
(%): 188 (0.2) [Mϩ], 170 (13) [Mϩ Ϫ H2O], 155 (10), 120 (100),
105 (16), 91 (44), 77 (18). Ϫ C13H16O (188.27): calcd. C 82.94, H
8.57; found C 83.22, H 8.46.
(d), 7.5 (t). Ϫ MS (EI);
Bu], 199 (100), 139 (26), 95 (21), 69 (76). Ϫ C23H32O2Si
(%): 353 (1) [Mϩ Ϫ CH3], 311 (5) [Mϩ
Ϫ
(368.59): calcd. C 74.95, H 8.75; found C 75.03, H 8.71.
(1R,2S)-1-{[(tert-Butyldiphenylsilyl)oxy]methyl}-2-isopropenyl-
cyclopropane [(؉)-11]: To a solution of (ϩ)-10 (2.5 g, 6.8 mmol), 4-
dimethylaminopyridine (0.99 g, 8.11 mmol, 1.2 equiv.) and triethyl-
amine (14.1 mL, 10.1 mmol, 15.0 equiv.) in CH2Cl2 (60 mL), meth-
anesulfonyl chloride (5.2 mL, 67.5 mmol, 10.0 equiv.) was added
dropwise at 0 °C. After 3 h at this temperature, the reaction mixture
was poured into saturated aqueous NH4Cl solution and extracted
with CH2Cl2. The combined extracts were washed with brine, dried
with MgSO4, filtered, and concentrated under reduced pressure.
The crude material was purified by flash chromatography (cyclo-
hexane/CH2Cl2 gradient, 100:0 to 90:10) to give 2.0 g (85%) of (ϩ)-
11 as a colorless oil. Ϫ [α]2D0 ϭ ϩ10.7 ( ϭ 1.025, CHCl3). Ϫ IR
(neat): ν˜ ϭ 3070, 1645, 1110, 1065 cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ
7.71Ϫ7.65 (4 H), 7.40Ϫ7.33 (6 H), 4.79 (s, 1 H), 4.51 (s, 1 H), 3.64
(dd, ϭ 10.9, 5.5 Hz, 1 H), 3.41 (dd, ϭ 10.9, 8.9 Hz, 1 H), 1.90
(s, 3 H), 1.48 (m, 1 H), 1.28 (m, 1 H), 1.05 (s, 9 H), 0.63 (m, 1 H),
0.36 (m, 1 H). Ϫ 13C NMR (CDCl3): δ ϭ 142.9 (s), 135.6 (d), 134.1
(s), 129.4 (d), 127.55 (d), 127.5 (d), 110.4 (t), 63.2 (t), 26.8 (q), 24.3
(1S*,5R*)-3-Oxabicyclo[3.1.0]hexan-2-one (8):[10] To a refluxing so-
lution of bis( -butylsalicylaldiminato)copper(II) (0.303 g,
0.730 mmol, 0.05 equiv.) in toluene (100 mL), a solution of 6 (1.84
g, 14.6 mmol) in toluene (50 mL) was added over a period of 3 h.
The resulting mixture was refluxed for a further 30 min and then
allowed to cool to room temp. It was diluted with methanol and
then concentrated under reduced pressure (bath temperature below
30 °C). When most of the solvent had evaporated, further methanol
was added and the process was repeated. The crude material was
purified by flash chromatography (pentane/diethyl ether, 30:70) to
give 1.10 g (74%) of 8 as a yellow liquid. Ϫ IR (neat): ν˜ ϭ 3080,
(q), 22.9 (d), 19.7 (d), 19.2 (s), 6.5 (t). Ϫ MS (EI);
(%): 350 (1)
[Mϩ], 293 (73) [Mϩ Ϫ Bu], 251 (60), 237 (45), 225 (50), 199 (100),
183 (44). Ϫ C23H30OSi (350.58): calcd. C 78.80, H 8.63; found C
78.82, H 8.65.
(1S*,4R*S*,5R*)-4-Methyl-3-oxabicyclo[3.1.0]hexan-2-one (9): To
a refluxing solution of bis( -butylsalicylaldiminato)copper(II)
(6.00 g, 14.4 mmol, 0.05 equiv.) in toluene (2.5 L), a solution of 7
(40.1 g, 286 mmol) in toluene (500 mL) was added over a period
of 4 h. The resulting mixture was refluxed for a further 30 min,
cooled to room temp., and concentrated under reduced pressure.
The crude material was purified by filtration through silica gel
(cyclohexane/diethyl ether gradient, 70:30 to 30:70) to give 18.6 g
(58%) of 9 as a yellow liquid (1:1 mixture of diastereomers). Ϫ IR
(neat): ν˜ ϭ 3080, 1760, 1290, 1050, 1020 cmϪ1. Ϫ 1H NMR
(CDCl3): δ ϭ 4.79 (qd, ϭ 6.1, 4.7 Hz, 1 H), 4.48 (q, ϭ 6.2 Hz,
1 H), 2.24 (m, 1 H), 2.11Ϫ2.04 (3 H), 1.42 (d, ϭ 6.1 Hz, 3 H),
1.36 (d, ϭ 6.2 Hz, 3 H), 1.26 (m, 1 H), 1.12 (m, 1 H), 0.92 (m, 1
H), 0.88 (m, 1 H). Ϫ 13C NMR (CDCl3): δ ϭ 176.1 (s), 175.7 (s),
77.3 (d), 75.5 (d), 23.5 (d), 21.8 (q), 22.0 (d), 18.5 (d), 17.5 (d), 17.5
1770, 1180, 1035 cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ 4.36 (dd,
ϭ
9.4, 4.8 Hz, 1 H), 4.23 (d, ϭ 9.4 Hz, 1 H), 2.25 (m, 1 H), 2.07
(m, 1 H), 1.28 (m, 1 H), 0.88 (m, 1 H). Ϫ 13C NMR (CDCl3): δ ϭ
176.4 (s), 69.4 (t), 17.5 (d), 17.3 (d), 12.2 (t). Ϫ MS (EI);
(%):
98 (100) [Mϩ], 70 (40), 68 (73), 55 (35), 53 (20).
(1S,5R)-3-Oxabicyclo[3.1.0]hexan-2-one [(؊)-8]:[10] To a refluxing
solution of Doyle’s catalyst Rh2[(5 )-MEPY]4 (0.050 g,
0.055 mmol, 0.001 equiv.) in freshly distilled CH2Cl2 (150 mL), a
solution of 6 (6.50 g, 51.5 mmol) in freshly distilled CH2Cl2 (350
mL) was added over a period of 30 h. The solvent was then distilled
off and the crude material was purified by flash chromatography
(pentane/diethyl ether gradient, 40:60 to 30:70) to give 4.55 g (90%)
of (Ϫ)-8 as a yellow oil. Ϫ [α]2D0 ϭ Ϫ65.0 ( ϭ 1.0, CHCl3) (
Ն 95%).[10,11]
(q), 12.3 (t), 8.5 (t). ؊ MS (EI);
(%): First diastereomer: 112
(18) [Mϩ], 97 (100) [Mϩ Ϫ CH3], 53 (15); second diastereomer: 112
(34) [Mϩ], 97 (100) [Mϩ Ϫ CH3], 68 (21), 55 (22), 53 (25).
2-[(1S,2R)-2-{[(tert-Butyldiphenylsilyl)oxy]methyl}cyclopropyl]-
propan-2-ol [(؉)-10]: To a solution of (Ϫ)-8 (1.00 g, 10.2 mmol) in
THF at Ϫ40 °C was added methyllithium (14.0 mL, 1.6  in diethyl
ether, 22.4 mmol, 2.2 equiv.). After 15 min at this temperature, a
1(R*S*)-[(1S*,2R*)-2-(Hydroxymethyl)cyclopropyl]ethanol (12): To
a stirred suspension of LiAlH4 (3.38 g, 89.2 mmol, 1.0 equiv.) in
solution of
-butylchlorodiphenylsilane (3.45 mL, 13.2 mmol, 1.3 dry THF (200 mL), 9 (10.0 g, 89.2 mmol) was added dropwise at
equiv.) and imidazole (1.80 g, 26.5 mmol, 2.6 equiv.) in DMF (5
mL) was added dropwise and the reaction mixture was allowed to
warm to room temp. After 1 h, it was quenched by the addition of
dilute aqueous NH4Cl solution and extracted with cyclohexane/
CH2Cl2 (9:1). The combined extracts were washed with brine, dried
with MgSO4, filtered, and concentrated under reduced pressure.
The crude material was purified by flash chromatography (cyclo-
hexane/CH2Cl2, 90:10) to give 3.4 g (90%) of (ϩ)-10 as a colorless
oil. Ϫ [α]2D0 ϭ ϩ15.2 ( ϭ 2.1, CHCl3). Ϫ IR (neat): ν˜ ϭ 3430,
0 °C. After 20 min at this temperature, the reaction mixture was
cautiously quenched by the dropwise addition of water (3.4 mL), a
15% aqueous solution of NaOH (3.4 mL), and further water (10.2
mL). After 1 h at room temp., the resulting mixture was filtered
through Celite. The removed solids were triturated three times with
boiling THF, the combined hot solutions were filtered through Cel-
ite, and the filtrate was concentrated under reduced pressure to give
10.4 g (100%) of 12 as a white solid (1:1 mixture of diastereomers).
An analytical sample of each diastereomer was obtained by flash
3060, 3040, 3020, 1110, 1065, 1045 cmϪ1. Ϫ 1H NMR (CDCl3): chromatography (cyclohexane/AcOEt gradient, 20:80 to 0:100). Ϫ
δ ϭ 7.74Ϫ7.68 (4 H), 7.42Ϫ7.34 (6 H), 4.12 (dd, ϭ 11.6, 6.0 Hz,
Less polar diastereomer: f ϭ 0.24 (cyclohexane/AcOEt, 10:90). Ϫ
2001, 339Ϫ348
344

Synthesis of Isopropenylcyclopropanes
FULL PAPER
1
IR (CHCl3): ν˜ ϭ 3320, 3060, 1190, 1170, 1115 cmϪ1. Ϫ H NMR (CDCl3): δ ϭ 208.4 (s), 64.1 (t), 30.0 (d), 29.4 (d), 26.7 (q), 14.9 (t).
(CDCl3): δ ϭ 3.75 (dd, ϭ 11.2, 7.1 Hz, 1 H), 3.64Ϫ3.55 (2 H),
[(1S*,2S*)-(2-Hydroxymethyl)cyclopropyl]phenylmethanone (17):[15]
To a solution of 1-phenylpent-4-en-1-one (15) (12.5 g, 78.1 mmol)
in DMSO (400 mL), containing water (4 mL), was added -bromo-
succinimide (15.3 g, 85.8 mmol, 1.1 equiv.) followed, after 15 min,
1.72 (br. m, 1 H, OH), 1.68 (br. s, 1 H, OH), 1.27 (m, 1 H), 1.08
(m, 1 H), 0.80 (m, 1 H), 0.33 (m, 1 H). Ϫ 13C NMR (CDCl3): δ ϭ
68.0 (d), 62.3 (t), 23.9 (d), 23.7 (q), 18.3 (d), 8.0 (t). Ϫ More polar
diastereomer:
ϭ 0.12 (cyclohexane/AcOEt, 10:90). Ϫ IR
f
by potassium hydroxide (21.9 g, 391 mmol, 5.0 equiv.). After 15 h
at room temp., the reaction mixture was diluted with water, neutral-
ized with AcOH, and extracted with AcOEt. The combined ex-
tracts were washed with brine, dried with MgSO4, filtered, and con-
centrated under reduced pressure. The crude material was purified
by flash chromatography (cyclohexane/AcOEt, 85:15) to give 6.98
g (50%) of 17 as an orange oil. Ϫ IR (neat): ν˜ ϭ 3480, 1710, 1680,
(CHCl3): ν˜ ϭ 3340, 3060, 1095, 1070, 1030, 1010 cmϪ1. Ϫ 1H
NMR (CDCl3): δ ϭ 4.53 (br. s, 2 H, OH), 4.10 (m, 1 H), 3.44 (m,
1 H), 3.23 (dd/pseudo t, ϭ 11.3 Hz, 1 H), 1.35 (d, ϭ 6.2 Hz, 3
H), 1.28 (m, 1 H), 1.05 (m, 1 H), 0.78 (m, 1 H), 0.17 (m, 1 H). Ϫ
13C NMR (CDCl3): δ ϭ 68.9 (d), 62.9 (t), 23.6 (d), 22.5 (q), 17.5
(d), 8.4 (t).
1
1-[(1S*,2R*)-2-{[(tert-Butyldiphenylsilyl)oxy]methyl}cyclopropyl]-
ethanone (13): To a solution of 12 (1:1 mixture of diastereomers)
(8.6 g, 74 mmol) and imidazole (11.1 g, 163 mmol, 2.2 equiv.) in
1595, 1580, 1220, 1025 cmϪ1. Ϫ H NMR (CDCl3): δ ϭ 7.97 (m,
2 H), 7.50 (m, 1 H), 7.39 (m, 2 H), 3.96 (br. s, 1 H, OH), 3.72 (dd,
ϭ 11.5, 5.5 Hz, 1 H), 3.49 (dd, ϭ 11.5, 6.8 Hz, 1 H), 2.65 (m,
1 H), 1.88 (m, 1 H), 1.41 (m, 1 H), 1.04 (ddd, ϭ 8.1, 6.2, 3.7 Hz,
1 H). Ϫ 13C NMR (CDCl3): δ ϭ 200.0 (s), 137.3 (s), 132.6 (d),
128.2 (d), 127.8 (d), 63.7 (t), 27.6 (d), 22.5 (d), 15.6 (t). Ϫ MS (EI);
(%): 176 (4) [Mϩ], 158 (32) [Mϩ Ϫ H2O], 157 (11), 145 (13),
DMF (20 mL), was added
-butylchlorodiphenylsilane (19.4 mL,
74.0 mmol, 1.0 equiv.). After 1 h at room temp., the reaction mix-
ture was quenched with saturated aqueous NH4Cl solution and
extracted with cyclohexane/CH2Cl2 (9:1). The combined extracts
were washed with brine, dried with MgSO4, filtered, and concen- 120 (27), 115 (10), 105 (100), 77 (57), 55 (15).
trated under reduced pressure. The crude material was dissolved in
1-[(1S*,2S*)-2-{[(tert-Butyldiphenylsilyl)oxy]methyl}cyclopropyl]-
˚
CH2Cl2 (400 mL), powdered 4 A molecular sieves (50 g) and PCC
ethanone (18):[15] To a solution of 16 (3.20 g, 28.1 mmol) and imida-
zole (4.20 g, 61.7 mmol, 2.2 equiv.) in DMF (30 mL), was added
-butylchlorodiphenylsilane (8.10 mL, 30.9 mmol, 1.1 equiv.).
After 2 h at room temp., the reaction mixture was quenched with
saturated aqueous NH4Cl solution and extracted with cyclohexane/
CH2Cl2 (9:1). The combined extracts were washed with brine, dried
with MgSO4, filtered, and concentrated under reduced pressure.
The crude material was purified by flash chromatography (cyclo-
hexane/diethyl ether, 90:10) to give 7.50 g (76%) of 18 as a colorless
(22.3 g, 103 mmol, 1.4 equiv.) were added, and after 90 min at room
temp. the reaction mixture was filtered through silica gel (CH2Cl2)
to give 14.9 g (57%) of 13 as white crystals; m.p. 58 °C. Ϫ IR
(CHCl3): ν˜ ϭ 3060, 3040, 1690, 1585, 1155, 1105, 1070 cmϪ1. Ϫ
1H NMR (CDCl3): δ ϭ 7.68Ϫ7.61 (4 H), 7.44Ϫ7.36 (6 H), 3.87
(dd, ϭ 11.1, 5.2 Hz, 1 H), 3.51 (dd, ϭ 11.1, 9.8 Hz, 1 H), 2.36
(s, 3 H), 2.16 (m, 1 H), 1.67 (m, 1 H), 1.14 (m, 1 H), 1.02 (s, 9 H),
0.87 (m, 1 H). Ϫ 13C NMR (CDCl3): δ ϭ 206.1 (s), 135.4 (d), 133.9
(s), 133.5 (s), 129.5 (d), 127.5 (d), 61.4 (t), 31.7 (q), 26.7 (q), 26.5
oil, slightly contaminated with
(neat): ν˜ ϭ 3060, 3040, 1685, 1110, 1080 cmϪ1. Ϫ 1H NMR
(CDCl3): δ ϭ 7.66Ϫ7.63 (4 H), 7.46Ϫ7.35 (6 H), 3.77 (dd,
-butyldiphenylsilanol. Ϫ IR
(d), 25.4 (d), 19.1 (s), 11.6 (t). Ϫ MS (EI);
Ϫ Bu], 239 (23), 225 (100), 199 (31), 191 (23), 183 (65), 165 (39).
(%): 295 (80) [Mϩ
ϭ
(1S*,2R*)-1-{[(tert-Butyldiphenylsilyl)oxy]methyl}-2-isopropenyl-
cyclopropane (11) from 15: To a solution of methyltriphenylphos-
phonium bromide (20.7 g, 58.0 mmol) in THF (200 mL), -butylli-
10.9, 4.7 Hz, 1 H), 3.51 (dd, ϭ 10.9, 6.1 Hz, 1 H), 2.18 (s, 3 H),
1.85 (m, 1 H), 1.67 (m, 1 H), 1.19 (m, 1 H), 1.06 (s, 9 H), 0.88 (m,
1 H). Ϫ 13C NMR (CDCl3): δ ϭ 208.0 (s), 135.5 (d), 133.5 (s),
thium (23.2 mL, 2.5  in hexanes, 58.0 mmol) was added dropwise 133.45 (s), 129.7 (d), 127.7 (d), 64.6 (t), 30.3 (q), 26.9 (d), 26.8 (q),
at 0 °C. After 15 min at this temperature, a solution of 13 (12.0 g, 26.3 (d), 19.2 (s), 14.6 (t). Ϫ MS (EI);
(%): 295 (100) [Mϩ
Ϫ
34.1 mmol) in THF (50 mL) was added dropwise. After 3 h at room
temp., the reaction mixture was poured into saturated aqueous
NH4Cl solution and extracted with diethyl ether. The combined
extracts were washed with brine, dried with MgSO4, filtered, and
concentrated under reduced pressure. The solid residue was taken
up in pentane and triturated several times. After filtration through
Celite and evaporation of the solvent under reduced pressure, the
crude material was purified by flash chromatography (cyclohexane/
diethyl ether, 95:5) to give 9.8 g (82%) of 11 as a colorless oil.
Bu], 265 (71), 251 (32), 225 (34), 217 (50), 199 (57), 197 (18), 187
(32), 183 (34), 181 (23), 139 (15).
(1S*,2S*)-1-{[(tert-Butyldiphenylsilyl)oxy]methyl}-2-isopropenyl-
cyclopropane (20): To a solution of methyltriphenylphosphonium
bromide (6.11 g, 17.1 mmol) in THF (80 mL), -butyllithium (6.80
mL, 2.5  in hexanes, 17.0 mmol) was added dropwise at 0 °C.
After 20 min at this temperature, a solution of 18 (5.00 g,
14.2 mmol) in THF (25 mL) was added dropwise. After a further
1 h at the same temperature, the reaction mixture was poured into
saturated aqueous NH4Cl solution and extracted with diethyl ether.
The combined extracts were washed with brine, dried with MgSO4,
filtered, and concentrated under reduced pressure. The solid residue
1-[(1S*,2S*)-2-(Hydroxymethyl)cyclopropyl]ethanone (16): To a so-
lution of hex-5-en-2-one 14 (5.0 mL, 43 mmol) in DMSO (150 mL)
containing water (1.5 mL), was added -bromosuccinimide (8.4 g,
47 mmol, 1.1 equiv.) followed, after 15 min, by potassium hydrox- was taken up in pentane and triturated several times. After filtra-
ide (12.1 g, 216 mmol, 5.0 equiv.). After 16 h at room temp., the
reaction mixture was diluted with water, neutralized with AcOH,
and extracted with AcOEt. The combined extracts were washed
with brine, dried with MgSO4, filtered, and concentrated under re-
duced pressure. The crude material was purified by flash chromato-
graphy (cyclohexane/AcOEt gradient, 40:60 to 30:70) to give 1.84
tion through Celite and evaporation of the solvent under reduced
pressure, the crude material was purified by flash chromatography
(cyclohexane/diethyl ether, 97:3) to give 4.30 g (86%) of 20 as a
colorless oil. Ϫ IR (neat): ν˜ ϭ 3070, 3050, 1650, 1640, 1590, 1430,
1110, 1070 cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ 7.69Ϫ7.66 (4 H),
7.42Ϫ7.34 (6 H), 4.65 (br. s, 2 H), 3.62 (dd, ϭ 10.7, 5.8 Hz, 1 H),
3.55 (dd, ϭ 10.7, 6.2 Hz, 1 H), 1.64 (s, 3 H), 1.25 (m, 1 H), 1.14
(m, 1 H), 1.05 (s, 9 H), 0.68 (m, 1 H), 0.51 (m, 1 H). Ϫ 13C NMR
g (37%) of 16 as a slightly yellow oil. Ϫ
ϭ 0.13 (cyclohexane/
f
AcOEt, 40:60). Ϫ IR (neat): ν˜ ϭ 3400, 1690, 1180, 1030 cmϪ1. Ϫ
1H NMR (CDCl3): δ ϭ 3.66 (dd, ϭ 11.5, 5.7 Hz, 1 H), 3.41 (dd, (CDCl3): δ ϭ 145.7 (s), 135.6 (d), 134.0 (s), 129.6 (d), 127.6 (d),
ϭ 11.5, 7.0 Hz, 1 H), 3.15 (br. s, 1 H, OH), 2.25 (s, 3 H), 1.94 108.1 (t), 66.8 (t), 26.9 (q), 23.1 (d), 21.5 (d), 20.8 (q), 19.2 (s), 9.8
(m, 1 H), 1.72 (m, 1 H), 1.24 (m, 1 H), 0.93 (m, 1 H). Ϫ 13C NMR (t). Ϫ MS (EI);
(%): 350 (0.4) [Mϩ], 293 (74) [M Ϫ Buϩ], 265
2001, 339Ϫ348
345

J. Cossy, N. Blanchard, C. Meyer
FULL PAPER
(22) 263 (20), 252 (24), 251 (100), 239 (20), 225 (25), 221 (21), 215
(s), 141.4 (s), 128.2 (d), 127.5 (d), 126.0 (d), 109.8 (t), 66.5 (t), 23.2
(24), 199 (81), 197 (24), 185 (30), 183 (35), 181 (26). Ϫ C23H30OSi (d), 21.5 (d), 11.4 (t). Ϫ MS (EI);
(%): 174 (21) [Mϩ], 143 (36),
(350.57): calcd. C 78.80, H 8.62; found C 78.81, H 8.65.
141 (34), 130 (61), 129 (100), 128 (76), 118 (24), 115 (62), 103 (20),
91 (27), 77 (21).
[(1S*,2S*)-2-{[(tert-Butyldiphenylsilyl)oxy]methyl}cyclopropyl]-
phenylmethanone (19): To a solution of 17 (0.300 g, 1.70 mmol) and
imidazole (0.255 g, 3.74 mmol, 2.2 equiv.) in DMF (5 mL), was
Correlation of Configuration for Compound 21
Reduction of 21
added
-butylchlorodiphenylsilane (0.49 mL, 1.87 mmol, 1.1
equiv.). After 1 h at room temp., the reaction mixture was quenched
by the addition of saturated aqueous NH4Cl solution and extracted
with cyclohexane/CH2Cl2 (9:1). The combined extracts were
washed with brine, dried with MgSO4, filtered, and concentrated
under reduced pressure. The crude material was purified by flash
chromatography (cyclohexane/AcOEt, 96:4) to give 0.373 g (53%)
of 19 as a colorless oil. Ϫ IR (neat): ν˜ ϭ 3070, 1670, 1220, 1110,
1075 cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ 8.00Ϫ7.97 (m, 2 H),
7.69Ϫ7.66 (4 H), 7.52Ϫ7.32 (9 H), 3.92 (dd, ϭ 10.9, 4.6 Hz, 1
H), 3.62 (dd, ϭ 10.9, 6.3 Hz, 1 H), 2.65 (m, 1 H), 1.86 (m, 1 H),
1.48 (m, 1 H), 1.07 (m, 1 H), 1.07 (s, 9 H). Ϫ 13C NMR (CDCl3):
δ ϭ 199.4 (s), 137.9 (s), 135.4 (d), 133.4 (s), 132.5 (d), 129.6 (d),
128.3 (d), 128.0 (d), 127.6 (d), 67.8 (t), 27.7 (d), 26.7 (q), 22.5 (d),
(1S*,2R*)-2-[(1R*S*)-1-Phenylethyl]cyclopropanemethanol (22): To
a suspension of 21 (0.080 g, 0.459 mmol) and potassium azodicar-
boxylate (1.36 g, 7.01 mmol, 15 equiv.) in absolute ethanol (5 mL),
a solution of acetic acid (0.47 mL, 8.30 mmol) in absolute ethanol
(5 mL) was added over a period of 1 h at 70 °C. The reaction
mixture was then cooled to room temp., concentrated under re-
duced pressure, and the residue was taken up in diethyl ether. The
precipitated salts were removed by filtration through a short plug
of silica gel (diethyl ether), and the filtrate was concentrated under
reduced pressure to give 76 mg (94%) of 22 as a colorless oil (1:1
inseparable mixture of diastereomers).
Cyclopropanation of 23
19.1 (s), 14.6 (t). Ϫ MS (EI);
(%): 357 (100) [Mϩ Ϫ Bu], 327
(1S*R*,2R*S*)-2-[(1R*)-1-Phenylethyl]cyclopropanemethanol (22):
To a suspension of samarium powder (0.930 g, 6.18 mmol, 5.0
equiv.) in THF (20 mL) was added dry HgCl2 (0.270 g, 0.994 mmol,
0.8 equiv.) and 23 (0.200 g, 1.23 mmol). To the vigorously stirred
mixture, ICH2Cl (0.450 mL, 6.18 mmol, 5.0 equiv.) was added
dropwise at Ϫ50 °C. The reaction mixture was then allowed to
warm to room temp. over a period of 1 h. After a further 1 h at
room temp., it was poured into cold saturated aqueous K2CO3 so-
lution (50 mL) overlaid with diethyl ether (50 mL). After stirring
for 10 min, the resulting mixture was filtered through Celite and
the removed solids were thoroughly washed with diethyl ether. The
aqueous layer was extracted with diethyl ether and the combined
extracts were washed with brine, dried with Na2SO4, and concen-
trated under reduced pressure. The residue was purified by flash
chromatography (cyclohexane/AcOEt, 85:15) to give 0.205 g (95%)
of 22 as a colorless oil (1:1 inseparable diastereomeric mixture).
Spectral data are given for each diastereomer of which authentic
samples have previously been prepared.[17]
(33), 249 (11), 227 (13), 225 (11), 223 (20), 199 (35), 183 (17), 117
(17), 105 (21), 77 (24).
[(1S*,2S*)-2-(1-Phenylethenyl)cyclopropyl]methanol (21) from 17:
To a solution of methyltriphenylphosphonium bromide (1.62 g,
4.25 mmol) in THF (15 mL), -butyllithium (1.80 mL, 2.5  in hex-
anes, 4.50 mmol) was added dropwise at 0 °C. After 10 min at this
temperature, a solution of 17 (0.320 g, 1.82 mmol) in THF (5 mL)
was added dropwise. After 30 min at room temp., the reaction mix-
ture was poured into saturated aqueous NH4Cl solution and ex-
tracted with diethyl ether. The combined extracts were washed with
brine, dried with MgSO4, filtered, and concentrated under reduced
pressure. The solid residue was taken up in pentane and triturated
several times. After filtration through Celite and evaporation of the
solvent under reduced pressure, the crude material was purified by
flash chromatography (CH2Cl2/AcOEt gradient, 90:10 to 80:20) to
give 0.136 g (43%) of 21 as a colorless oil.
[(1S*,2S*)-2-(1-Phenylethenyl)cyclopropyl]methanol (21) from 19:
To a solution of methyltriphenylphosphonium bromide (0.65 g,
1.82 mmol) in THF (10 mL), -butyllithium (0.73 mL, 2.5  in hex-
anes, 1.82 mmol) was added dropwise at 0 °C. After 10 min at this
temperature, a solution of 19 (0.300 g, 0.725 mmol) in THF (5 mL)
was added dropwise. After 30 min at the same temperature, the
reaction mixture was poured into saturated aqueous NH4Cl solu-
tion and extracted with diethyl ether. The combined extracts were
washed with brine, dried with MgSO4, filtered, and concentrated
under reduced pressure. The solid residue was taken up in pentane
and triturated several times. After filtration through Celite and
evaporation of the solvent under reduced pressure, the crude mat-
erial was dissolved in THF (2 mL) and -Bu4NF (1.4 mL, 1  in
THF, 1.4 mmol) was added. After 1 h at room temp., the reaction
mixture was quenched with saturated aqueous NH4Cl solution and
extracted with diethyl ether. The combined extracts were washed
with brine, dried with MgSO4, filtered, and concentrated under re-
duced pressure. The crude material was purified by flash chromato-
graphy (CH2Cl2/AcOEt, 90:10) to give 0.092 g (72%) of 21 as a
colorless oil. Ϫ IR (neat): ν˜ ϭ 3330, 3080, 3050, 1620, 1595, 1570,
1030 cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ 7.56 (m, 2 H), 7.36Ϫ7.24 (3
H), 5.28 (d, ϭ 1.0 Hz, 1 H), 4.95 (dd, ϭ 1.1, 1.0 Hz, 1 H), 3.64
(1S*,2R*)-2-[(1R*)-1-Phenylethyl]cyclopropanemethanol: IR (neat):
ν˜ ϭ 3340, 3050, 1600, 1490, 1050 cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ
7.22Ϫ7.05 (5 H), 3.20 (d, ϭ 7.0 Hz, 2 H), 2.00 (m, 1 H), 1.64 (s,
1 H, OH), 1.22 (d, ϭ 7.3 Hz, 3 H), 0.78 (m, 2 H), 0.43Ϫ0.34 (m,
2 H). Ϫ 13C NMR (CDCl3): δ ϭ 146.8 (s), 128.2 (d), 126.7 (d),
125.9 (d), 66.4 (t), 43.2 (d), 24.6 (d), 21.1 (q), 20.5 (d), 9.9 (t). Ϫ
MS (EI);
(%): 158 (17) [Mϩ Ϫ H2O], 143 (15), 118 (90), 117
(100), 115 (16), 106 (52), 105 (79), 91 (29). Ϫ C12H16O (176.26):
calcd. C 81.77, H 9.15; found C 81.72, H 9.18.
(1R*,2S*)-2-[(1R*)-1-Phenylethyl]cyclopropanemethanol: IR (neat):
ν˜ ϭ 3340, 3050, 3020, 1600, 1490, 1050 cmϪ1. Ϫ 1H NMR (CDCl3):
δ ϭ 7.26Ϫ7.10 (5 H), 3.42 (d, ϭ 7.0 Hz, 2 H), 2.05 (m, 1 H), 1.57
(s, 1 H, OH), 1.28 (d, ϭ 7.0 Hz, 3 H), 0.94 (m, 1 H), 0.80 (m, 1
H), 0.41Ϫ0.29 (m, 2 H). Ϫ 13C NMR (CDCl3): δ ϭ 146.6 (s), 128.3
(d), 126.9 (d), 125.9 (d), 66.9 (t), 43.3 (d), 24.6 (d), 21.5 (q), 21.3
(d), 9.7 (t). Ϫ MS (EI);
(%): 158 (5) [Mϩ Ϫ H2O], 143 (18),
132 (47), 118 (84), 117 (100), 115 (26), 106 (60), 105 (82), 104 (23),
103 (19), 91 (41), 78 (10), 77 (15). Ϫ C12H16O (176.26): calcd. C
81.77, H 9.15; found C 81.70, H 9.20.
1-[(1S*,2R*)-2-(Hydroxymethyl)cyclopropyl]ethanone (24) and
(dd, ϭ 13.5, 6.7 Hz, 1 H), 3.61 (dd, ϭ 13.5, 7.0 Hz, 1 H), 1.70 (1S*,2S*,5R*)-2-Methyl-3-oxabicyclo[3.1.0]hexan-2-ol (25): To a
(br. s, 1 H, OH), 1.59 (m, 1 H), 1.32 (m, 1 H), 0.88 (ddd, ϭ 8.4, solution of 13 (1.47 g, 4.17 mmol) in THF (2 mL) was added
-
5.5, 4.8 Hz, 1 H), 0.78 (m, 1 H). Ϫ 13C NMR (CDCl3): δ ϭ 148.1
Bu4NF (6.25 mL, 1  in THF, 6.25 mmol, 1.5 equiv.). After 1 h at
346
2001, 339Ϫ348

Synthesis of Isopropenylcyclopropanes
FULL PAPER
room temp., the reaction mixture was concentrated under reduced
pressure. The crude material was taken up in diethyl ether and the
precipitated salts were filtered off by passage through Celite and
thoroughly washed with further ether. The combined filtrate and
washings were concentrated under reduced pressure and the residue
was immediately purified by flash chromatography (cyclohexane/
AcOEt gradient, 30:70 to 10:90) to give 0.338 g (71%) of an insep-
arable equilibrium mixture of 24 and 25 (80:20 ratio). This product
could be stored for several months as a frozen benzene solution at
trifluoroacetic acid (0.840 mL, 10.9 mmol, 5.0 equiv.). After 4 d at
room temp., solid potassium carbonate was added to neutralize the
excess acid. The resulting mixture was filtered through a short plug
of Celite, the removed solids were rinsed with CH2Cl2, and the
combined filtrate and washings were concentrated under reduced
pressure. The crude material was immediately purified by rapid fil-
tration through silica gel (cyclohexane/AcOEt, 70:30) to give 0.392
g (85%) of 28 as a colorless liquid. Ϫ
ϭ 0.67 (cyclohexane/
f
AcOEt, 40:60). Ϫ IR (neat): ν˜ ϭ 3010, 1790, 1710, 1350, 1220,
1
Ϫ23 °C without a change in its composition. Ϫ
ϭ 0.20 (cyclo-
1160 cmϪ1. Ϫ H NMR (CDCl3): δ ϭ 4.35 (dd, ϭ 11.6, 6.5 Hz,
f
hexane/AcOEt, 40:60). Ϫ IR (neat): ν˜ ϭ 3400, 3010, 1690, 1170, 1 H), 4.14 (dd, ϭ 11.6, 7.9 Hz, 1 H), 2.26 (s, 3 H), 2.04 (m, 1 H),
1030 cmϪ1. ؊ 24: 1H NMR (CDCl3): δ ϭ 3.90 (dd, ϭ 11.8, 1.85 (m, 1 H), 1.34 (m, 1 H), 0.97 (m, 1 H). Ϫ 13C NMR (CDCl3):
4.4 Hz, 1 H), 3.64 (dd, ϭ 11.8, 8.4 Hz, 1 H), 2.35 (s, 3 H), 2.21 δ ϭ 206.1 (s), 157.4 (s, COCF3,
ϭ 45 Hz), 114.4 (s, CF3,
CϪF
(br. s, 1 H, OH), 2.13 (m, 1 H), 1.72 (m, 1 H), 1.26 (m, 1 H), 1.12
ϭ 286 Hz), 69.7 (t), 30.5 (q), 26.6 (d), 21.7 (d), 14.9 (t). Ϫ
CϪF
(m, 1 H). Ϫ 13C NMR (CDCl3): δ ϭ 208.1 (s), 58.8 (t), 31.5 (q), MS (EI);
(%): 210 (0.4) [Mϩ], 167 (30) [Mϩ Ϫ CH3CO], 103
1
26.5 (d), 25.2 (d), 12.5 (t). Ϫ 25: H NMR (CDCl3): δ ϭ 3.99 (dd,
ϭ 8.1, 2.6 Hz, 1 H), 3.79 (d, ϭ 8.1 Hz, 1 H), 2.21 (br. s, 1 H,
OH), 1.68Ϫ1.61 (2 H), 1.49 (s, 3 H), 0.61 (m, 1 H), 0.24 (m, 1 H).
(30), 97 (58), 96 (87) [Mϩ Ϫ CF3COOH], 95 (52), 83 (89), 81 (77),
69 (100), 55 (59), 54 (26), 53 (64).
Saponification of 28: To a solution of 28 (100 mg, 0.476 mmol) in
methanol (2 mL) was added sodium methoxide (51 mg,
0.95 mmol). After 5 min at room temp., TLC analysis indicated
complete reversion of 28 to 16.
؊
13C NMR (CDCl3): δ ϭ 103.9 (s), 67.4 (t), 25.2 (d), 23.1 (q),
15.7 (d), 7.2 (t).
1-[(1S*,2R*)-2-({[(1S*R*,2S*R*,5R*S*)-2-Methyl-3-oxabicyclo-
[3.1.0]hexan-2-yl]oxy}methyl)cyclopropyl]ethanone (26): Prolonged
storage of the above equilibrium mixture of 24 and 25 at room
temperature or exposure to traces of acid led to the formation of
variable amounts of 26 (1:1 mixture of diastereomers), which could
be isolated by flash chromatography (cyclohexane/AcOEt, 80:20).
X-ray Crystallographic Study of Compound 4: Crystal data: molecu-
lar formula: C20H19O4N, molecular mass: 337.4, temperature:
295 K; crystal system: monoclinic; space group: 21/ ; unit cell di-
˚
˚
˚
mensions: ϭ 7.155(4) A, ϭ 13.394(4) A, ϭ 18.649(5) A, β ϭ
3
˚
100.21(3)°, volume: 1759(1) A ;
ϭ 4; density (calculated): 1.27
Ϫ
ϭ 0.53 (cyclohexane/AcOEt, 40:60). Ϫ IR (neat): ν˜ ϭ 3450,
f
g·cmϪ3
;
absorption coefficient: 0.8 cmϪ1
.
Diffractometer:
1695, 1170, 1160, 1130, 1040 cmϪ1. ؊ 1H NMR (CDCl3): δ ϭ 3.89
(d, ϭ 8.1 Hz, 1 H), 3.81 (dd, ϭ 7.7, 5.1 Hz, 1 H), 3.80Ϫ3.67 (4
˚
EnrafϪNonius CAD4; radiation: Mo- α; wavelength: 0.71069 A;
θ range for data collection 1Ϫ25°; no. of reflections collected: 3521;
no. of independent reflections: 3091 [ (int) ϭ 0.04]; final indices:
H), 3.36 (dd/pseudo t, ϭ 9.9 Hz, 1 H), 3.19 (dd/pseudo t,
ϭ
9.9 Hz, 1 H), 2.32 (s, 2 ϫ 3 H), 2.19Ϫ2.11 (2 H), 1.74Ϫ1.51 (6 H),
1.37 (s, 3 H), 1.29 (s, 3 H), 1.26Ϫ1.16 (2 H), 1.05Ϫ0.87 (2 H),
0.58Ϫ0.51 (2 H), 0.23Ϫ0.16 (2 H). ؊ 13C NMR (CDCl3): δ ϭ 206.1
(s), 206.0 (s), 107.2 (s), 107.1 (s), 69.0 (t), 68.5 (t), 58.6 (t), 58.55
(t), 31.7 (q, 2C), 26.0 (d), 25.8 (d), 25.5 (d), 25.3 (d), 24.0 (d), 23.9
(d), 19.8 (q), 19.0 (q), 16.3 (d), 16.1 (d), 12.0 (t), 11.7 (t), 7.3 (t),
7.1 (t).
ϭ 0.0490,
ϭ 0.0617; ∆ρmin ϭ Ϫ 0.16 eAϪ3, ∆ρmax ϭ 0.16
˚
eAϪ3. Crystallographic data have been deposited at the Cambridge
Crystallographic Data Centre under the depository no. CCDC-
142407. Copies of the data can be obtained free of charge
on application to the CCDC, 12 Union Road, Cambridge
˚
CB2 1EZ, U.K. [Fax: (internat.)
deposit@ccdc.cam.ac.uk].
ϩ 44-1223/336-033; E-mail:
(1S*,2S*,5R*)-2-([2H3]Methoxy)-2-methyl-3-oxabicyclo[3.1.0]-
hexan-2-ol (27)
Acknowledgments
Preparation from 24 and 25: To a solution of 24 and 25 (4:1 mix-
ture) (42 mg, 0.37 mmol) in CD3OD (0.8 mL) was added pyridin-
ium -toluenesulfonate (ca. 2 mg, 8 µmol). After 36 h, NMR ana-
lysis of the reaction mixture indicated complete conversion to 27.
`
We thank the Ministere de l’Education Nationale de la Recherche
et de la Technologie (MRET) for a grant (N. B).
[1] [1a]
(Ed.: Z. Rappo-
Preparation from 26: To a solution of 26 (62 mg, 0.27 mmol) in
CD3OD (0.8 mL) was added pyridinium -toluenesulfonate (ca. 2
mg, 8 µmol). After 36 h, NMR analysis of the reaction mixture
port), John Wiley & Sons, Chichester, 1987, parts 1 and 2. Ϫ
[1b]
D. B. Collum, F. Mohamadi, J. S. Hallock,
[1c]
1983,
, 6882Ϫ6889. Ϫ
D. B. Collum, W. C. Still, F.
[1d]
Mohamadi,
1986,
, 2094Ϫ2096. Ϫ
1
indicated complete conversion to 27. Ϫ H NMR (CD3OD): δ ϭ
H. N. C. Wong, M.-Y. Hon, C.-W. Tse, Y.-C. Yips, J. Tanko,
[1e]
4.89 (s, HOD), 3.87 (dd, ϭ 8.1, 2.6 Hz, 1 H), 3.75 (d, ϭ 8.1 Hz,
1 H), 1.74Ϫ1.65 (2 H), 1.36 (s, 3 H), 0.64 (m, 1 H), 0.22 (m, 1 H).
T. Hudlicky,
1989, , 165Ϫ198. Ϫ
P. Mohr,
[1f]
1995, , 7221Ϫ7224. Ϫ
Y. Landais, L.
1996, , 1209Ϫ1212. Ϫ
1997,
[1g]
13C NMR (CD3OD): δ ϭ 109.1 (s), 70.0 (t), 49.1 (s) (overlapped
Parra-Rapado,
؊
A. G. M. Barrett, W. Tam,
,
1997,
1998,
1998,
with solvent signal), 27.1 (d), 19.3 (q), 17.3 (d), 8.1 (t).
4653Ϫ4664.[1h] A. G. M. Barrett, W. Tam,
, 7673Ϫ7678. Ϫ [1i] M. Lautens, J. Blackwell,
537Ϫ546. Ϫ [1j] A. B. Charette, J. Naud,
, 7259Ϫ7262.
Base-Induced Isomerization of 24 to 16: To a solution of 24 and 25
(4:1 mixture) (0.100 g, 0.877 mmol) in dry methanol (5 mL) was
added sodium methoxide (0.332 g, 6.11 mmol, 7.0 equiv.). After
refluxing for 12 h, the reaction mixture was concentrated under
reduced pressure. The crude material was taken up in diethyl ether
and filtered through silica gel (diethyl ether) to give 88 mg (88%)
[2] [2a]
J. Cossy, N. Blanchard, C. Hamel, C. Meyer,
[2b]
1999, , 2608Ϫ2609. Ϫ
J. Cossy, N. Blanchard, C. Meyer,
1999, 1063Ϫ1075.
[3]
J. Cossy, N. Blanchard, C. Meyer,
1999,
1973,
,
,
8361Ϫ8364.
[4] [4a]
of 16 as a colorless liquid (
/
Ն 95:5).
G. Descotes, A. Menet, F. Collonges,
[4b]
2931Ϫ2935. Ϫ
Fallis,
A. I. Meyers, J. L. Romine, S. A. Fleming,
1988,
[4c]
[(1S*,2S*)-2-Acetylcyclopropyl]methyl Trifluoroacetate (28): To a
solution of 16 (0.250 g, 2.19 mmol) in CH2Cl2 (5 mL) was added
, 7245Ϫ7247. Ϫ
B. Lei, A. G.
1990,
, 4609Ϫ4610. Ϫ [4d] M. Lau-
2001, 339Ϫ348
347

J. Cossy, N. Blanchard, C. Meyer
FULL PAPER
tens, P. H. M. Delanghe,
1995, , 2474Ϫ2487.
1996,
Miyaoka, T. Shigemoto, Y. Yamada,
, 7407Ϫ7408.
1996,
Ϫ
[4e] S. Ono, S. Shuto, A. Matsuda,
,
221Ϫ224. Ϫ [4f] E. A. Mash, T. M. Gregg, M. A. Kaczynski,
1996, , 2743Ϫ2752. Ϫ [4g] C. Barloy-Da Silva, A.
Benhouider, P. Pale, 2000, , 3077Ϫ3081.
[14]
[15]
[16]
P. Crotti, V. Di Bussolo, L. Favero, F. Macchia, M. Pineschi,
E. Napolitano,
1999, , 5853Ϫ5866.
A. Nelson, S. Warren,
3425Ϫ3433.
1999,
[5] [5a]
I. Marek, C. Meyer, J.-F. Normant,
1997,
,
[5b]
For a synthesis of
-1,2-disubstituted isopropenylcyclopro-
194Ϫ204. Ϫ
Platzer,
D. Beruben, I. Marek, J.-F. Normant, N.
panes involving homoallylic participation, see: T. Nagasawa, Y.
1995, , 2488Ϫ2501.
Handa, Y. Onoguchi, K. Suzuki,
, 31Ϫ39.
1996,
[6]
E.-I. Negishi, M. Ay, Y. V. Gulevich, Y. Noda,
1993, , 1437Ϫ1440.
[17]
J. Cossy, N. Blanchard, C. Meyer,
5728Ϫ5729.
1998,
,
[7] [7a]
G. A. Molander, J. B. Etter,
1987,
1984,
,
,
[7b]
3942Ϫ3944. Ϫ
G. A. Molander, L. S. Harring,
[18] [18a] The relative configuration of the ketal stereocenter was not
determined, but was anticipated to be that represented in the
1989, , 3525Ϫ3532.
[8]
E. J. Corey, A. G. Myers,
3559Ϫ3562.
schemes on the basis of the stereoelectronic effects of the cyclo-
[18b]
propane ring. Ϫ
Compound 26 could easily be separated
[9]
from 24 and 25 by flash chromatography and then character-
ized, but its stability appeared to be limited as in time it re-
verted back to a mixture containing 24 and 25, probably due
to the presence of unavoidable traces of moisture.
For the preparation of allylic diazoacetates, see: M. P. Doyle,
W. R. Winchester, M. N. Protopopova, A. P. Kazala, L. J. Wes-
trum,
1996, , 13Ϫ24.
[10]
M. P. Doyle, R. E. Austin, S. Bailey, M. P. Dwyer, A. B. Dyat-
kin, A.V. Kalinin, M. M. Y. Kwan, S. Liras, C. J. Oalmann, R.
J. Pieters, M. N. Protopopova, C. E. Raab, G. H. P. Roos, Q.-L.
[19]
Related epoxy compounds have recently been described: P.
Pale, J. Chuche,
2000, 1019Ϫ1025.
[20] [20a]
L. Dechoux, E. Doris,
1994,
,
Zhou, S. F. Martin,
1995,
, 5763Ϫ5775.
[20b]
2017Ϫ2020. Ϫ
bach,
L. Dechoux, E. Doris, L. Jung, J. F. Stam-
[11] [11a] The enantiomeric purity was checked by treating (Ϯ)-8 and
(Ϫ)-8 with ( )-(Ϫ)-phenylethylamine ( Ն 99%) in the pres-
ence of 2-hydroxypyridine[11b] and then quantifying the re-
sulting diastereomers by 1H NMR. An enantiomeric purity
1994, , 5633Ϫ5636.
[21] [21a]
B. J. Fitzsimmons, B. Fraser-Reid,
1984,
,
1279Ϫ1287. Ϫ [21b] D. Grandjean, P. Pale, J. Chuche,
1991, , 1215Ϫ1230.
corresponding to
Ն 95% could be evaluated, in agreement
[22] [22a]
Y. Ohfune, K. Shimamoto, M. Ishida, H. Shinozaki,
with literature results.[10]
enicke,
Ϫ
T. Schotten, W. Boland, L. Ja-
1986, , 2349Ϫ2352.
[11b]
[22b]
1993, , 15Ϫ18. Ϫ
1993, 919Ϫ920. Ϫ
K. Shimamoto,
[22c]
Y. Ohfune,
oto, H. Takahashi, S. Kobayashi,
7045Ϫ7048.
N. Imai, K. Sakam-
[12]
L. Dechoux, M. Ebel, L. Jung, J. F. Stambach,
1994,
,
1993, , 7405Ϫ7408.
[13] [13a] Y. Gaoni,
A. J. Tortorello,
Gaoni,
1971, , 63Ϫ69. Ϫ [13b] J. H. Babler,
P. Miginiac, G. Zamlouty,
1740Ϫ1744.
1975,
[23]
[13c]
1976, , 885Ϫ887. Ϫ
Y.
[13d]
1982, , 2564Ϫ2570. Ϫ
M. Majew-
Received May 22, 2000
[O00263]
ski, V. Snieckus,
1984, , 2682Ϫ2687. Ϫ [13e] H.
348
2001, 339Ϫ348