Preparation of oxocanes by electrophilic cyclizations of unsaturated alcohols in the presence of bis(collidine)halonium(I) hexafluorophosphates

Article abstract of DOI:10.1002/ejoc.200390080

7-Octen-1-ols substituted in the sp³-sp³ carbon chain with carbocyclic (phenyl and cyclopropane) and heterocyclic (epoxide and dioxolane) moieties were prepared and their cyclizations in the presence of bis(collidine)iodonium(I) and-bromonium(I) hexafluorophosphates as electrophiles were studied. Oxocanes were obtained in modest to good yields when a rigid cyclic moiety (cyclopropane or phenyl) was present in the chain, while yields of cyclizations were lower if the cyclic component had a certain flexibility (dioxolane). Low yields were obtained with substrates bearing an epoxide substituent, probably because of stability problems due to the presence of collidine. With the vinylcyclopropane alcohol 12 we observed mainly the opening of the cyclopropane ring and the cyclization produced a tetrahydropyran derivative. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200390080

FULL PAPER
Preparation of Oxocanes by Electrophilic Cyclizations of Unsaturated Alcohols
in the Presence of Bis(collidine)halonium( ) Hexafluorophosphates
I
[a]
[a]
[a]
[a]
`
Christelle Mendes, Sylvie Renard, Mazin Rofoo, Marie-Claude Roux, and
[a]
´
Gerard Rousseau*
Keywords: Alcohols / Cyclic ethers / Cyclizations / Entropy / Medium-sized rings / Synthetic methods
7-Octen-1-ols substituted in the sp3−sp3 carbon chain with
carbocyclic (phenyl and cyclopropane) and heterocyclic (ep-
oxide and dioxolane) moieties were prepared and their cyc-
the cyclic component had a certain flexibility (dioxolane).
Low yields were obtained with substrates bearing an epoxide
substituent, probably because of stability problems due to
the presence of collidine. With the vinylcyclopropane alcohol
12 we observed mainly the opening of the cyclopropane ring
and the cyclization produced a tetrahydropyran derivative.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
lizations in the presence of bis(collidine)iodonium(
I) and
-bromonium( ) hexafluorophosphates as electrophiles were
I
studied. Oxocanes were obtained in modest to good yields
when a rigid cyclic moiety (cyclopropane or phenyl) was pre-
sent in the chain, while yields of cyclizations were lower if
Introduction
sequently, we reported the preparation of medium-sized
lactones with this reagent. However, the introduction of
conformational constraint in the chain to be cyclized, which
decreases the activation entropy of the reaction, is necessary
to obtain satisfactory yields. We now wish to report our
results concerning the formation of oxocanes by such an ap-
proach.
The formation of oxocanes has been the subject of many
studies during the last decade. The simplest method to ob-
tain these compounds consists of the cyclization of linear
substrates. The difficulty in this approach arises from the
high activation enthalpy associated with the high activation
entropy necessary for the formation of medium-sized ring
compounds.[1] Many reactions have been examined, with
greater or lesser degrees of success. Among the most prom-
ising we can cite the rhodium carbenoid cyclization of α-
diazocarbonyl compounds[2] (reported yields were in the
40Ϫ73% range), the nucleophilic cyclization of iodides,[3]
epoxides,[4] and esters[5] (60Ϫ87%), the cyclization of hexa-
carbonyldicobalt complexes[6] (43Ϫ84%), the cyclization of
allylsilanes with methoxymethyl ethers[7] (53%), the cycliza-
tion of allyltin compounds with acetals[8] and of allylbor-
anes with aldehydes[9] (30Ϫ35%), the cyclization of olefins
with acetals[10] or thioacetals[11] induced by titanium salts
or other Lewis acids (50Ϫ70%), radical cyclization with ter-
minal double bonds[12] (40Ϫ50%), the reaction of alcohols
with thioacetals[13] (55%), the palladium-induced cycliza-
tion of allyl carbonates[14] (74%), and the metathesis of di-
enes in the presence of ruthenium[15] and molybdenum[16]
complexes (26Ϫ95%). We recently reported an efficient
method for the preparation of oxepanes by electrophilic
cyclization of 6-hepten-1-ols[17] in the presence of bis(collid-
ine)iodonium() hexafluorophosphate as electrophile. Sub-
Results
We decided to study the influence of the introduction of
a rigid (phenyl, epoxide, or cyclopropane) or a conforma-
[a]
´
Laboratoire des Carbocycles (Associe au CNRS), Institut de
´
´
ˆ
Chimie Moleculaire et des Materiaux d’Orsay, Bat. 420,
´
Universite de Paris-Sud,
91405 Orsay, France
E-mail: grousseau@icmo.u-psud.fr
Scheme 1
Eur. J. Org. Chem. 2003, 463Ϫ471  2003 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/03/0203Ϫ0463 $ 20.00ϩ.50/0
463

´
C. Mendes, S. Renard, M. Rofoo, M.-C. Roux, G. Rousseau
FULL PAPER
Scheme 2. a: MeOH/Hϩ (75%); b: LiAlH4, THF (1: 93%; 17: 80%; 2: 98%; 23: 80%; 7: 96%; 8: 83%); c: [Ph3PϩCH3]BrϪ, nBuLi, THF
(16: 40%; 34: 53%: 37: 93%; 43: 81%; 47: 87%); d: (COCl)2, DMSO, NEt3, CH2Cl2 (18: 90%; 33: 70%; 36: 83%; 42: 73%; 46: 87%); e:
[Ph3PϩCH2OMe]ClϪ, nBuLi, THF (46%); f: HClO4, THF (80%). g: 1-bromo-4-pentene, NH3, LiNH2 (97%); h: H2 (1 atm), Lindlar
catalyst (22 in acetone: 90%; 30 in hexane: 95%); i: VO(acac)2, tBuOOH, benzene (3: 72%; 4: 75%); j: vinyl acetate, tBuOMe, PS lipase
(95%); k: BF3·Et2O, acetone (95%); l: K2CO3, MeOH (5, 6: 95%; 9: 70%; 35: 95%; 41: 99%); m: N2CHCO2Et, Rh2(OAc)4, benzene (60%);
n: ethylene oxide, nBuLi, THF (82%); o: Ac2O, DMAP, THF (77%); p: Et2Zn, CH2ICl, (CH2Cl)2 (31: 90%; 40: 93%); q. nBu4NϩFϪ,
THF (32: 100%; 10: 82%); r: MeOH, cat. ClSiMe3 (11: 86%; 12: 93%); s: imidazole, THF, ClSiMe2tBu (94%); t: Et2Zn, CH2I2, toluene,
Ϫ40 °C (92%)
tionally more flexible (dioxolane) cyclic system into the car- the carbonϪcarbon double bond was introduced in a ter-
bon chains of 7-octenol-1-ols. The structures of the exam- minal position to avoid the competitive formation of nine-
ined alcohols 1Ϫ12 are reported in Scheme 1. In all cases membered cyclic ethers by endo-mode cyclizations.[18,19]
464
Eur. J. Org. Chem. 2003, 463Ϫ471

Preparation of Oxocanes by Electrophilic Cyclizations of Unsaturated Alcohols
FULL PAPER
tained in a satisfactory overall yield. All compounds 1Ϫ47
were fully characterized by analysis of their NMR and IR
spectra.
Preparation of Alcohols 1؊12
The benzyl alcohol 1 was obtained in two steps from the
benzoic acid 13[19] by esterification (cat. SOCl2 in MeOH)
followed by lithium aluminum hydride reduction of the es-
ter 14. (Scheme 2). The styryl alcohol 2 was prepared in
four steps, starting from the ester 15.[20] Methylenation of
the aldehyde function, followed by reduction of the ester
function, gave the alcohol 17, which was oxidized to the
aldehyde 18. This was homologated to the aldehyde 20 in
two steps, and reduction of the aldehyde function furnished
the desired alcohol 2 (Scheme 2). The cis-epoxide 3 was eas-
ily obtained in three steps from butynol. Coupling with 1-
bromo-3-butene gave the required enyne 21,[21] which was
selectively reduced with hydrogen in the presence of Lindlar
catalyst to give the dienol 22. The double bond β to the
alcohol function was then selectively oxidized in the pres-
ence of vanadyl acetylacetonate and tert-butyl hydroperox-
ide[22] to afford the cis-epoxide 3. Lithium aluminum hy-
dride reduction of the enyne 21 gave the (2E)-dienol 23,
which was transformed into the trans-epoxide 4 as reported
for the preparation of compound 3 (Scheme 2). The acetate
24 was easily obtained by acetylation of alcohol 3 in the
presence of Pseudomonas cepacia lipase (LP) in the presence
of vinyl acetate (95%). The same acetate 24 was obtained
in poorer yields (20%) by treatment of alcohol 3 with acetic
anhydride and pyridine. In the presence of boron
trifluorideϪdiethyl ether in acetone, this acetate was trans-
formed into a cis/trans mixture (1:2) of dioxolanes 25. After
cleavage of the acetate function, the mixture of alcohols 5/
6 was separated by flash chromatography. A cis/trans mix-
ture of unsaturated esters 26 (40:60) was obtained by treat-
ment of 1,6-heptadiene with ethyl diazoacetate.[23] After
separation, the two esters were reduced with lithium alumi-
num hydride to give the alcohols cis-7 and trans-8. Protec-
tion of 5-hexyn-1-ol as the tert-butyldimethylsilyl ether 27,
followed by treatment of the corresponding lithium
acetylide with ethylene oxide, afforded the alcohol 28, which
was acetylated to give the compound 29; cis hydrogenation
of the carbonϪcarbon triple bond (Lindlar catalyst) pro-
vided compound 30, which was treated with chloroiodome-
thane in the presence of diethylzinc to give the cyclopro-
pane derivative 31 (Scheme 2). Selective cleavage of the silyl
ether afforded the alcohol 32, which was oxidized under
Swern conditions to give the aldehyde 33. Methylenation
by a Wittig reaction at the aldehyde function, followed by
cleavage of the acetate, gave the desired unsaturated alcohol
9. Selective cleavage of the acetate function of the com-
pound 31, followed by the same reaction sequence as used
for the preparation of the alcohol 9, afforded the alcohol
11. The trans diastereomer 10 was obtained from the bi-
functional compound 38[24] by treatment with chloroiodo-
methane in the presence of diethylzinc, followed by the se-
quence of reactions used for the preparation of the alcohol
9 (Scheme 2). The (2Z)-allylic alcohol 44[25] was trans-
formed into the cyclopropyl alcohol 45 in high yield. After
Preparation of Oxocanes
We then studied the haloetherification of alcohols 1Ϫ12
with bis(collidine)iodonium() and -bromonium() hexa-
fluorophosphates[26] as electrophiles. The cyclizations were
carried out in dichloromethane at room temperature. After
completion of the reaction, the products were isolated by
flash chromatography on silica gel and characterized by
their NMR and IR spectra. Our results are reported in
Table 1. Alcohol 1 reacted with bis(collidine)iodonium()
hexafluorophosphate to produce the oxocane 48 in almost
quantitative yield. (Table 1, Entry a). Use of the bromo re-
agent under the same reaction conditions gave the oxocane
49 in moderate yield (45%) in a mixture with the aldehyde
50 (10%) (Entry b). This aldehyde was formed by oxidation
of the benzyl alcohol, followed by attack of the PF6Ϫ anion
on the intermediate bromonium species. The oxidative na-
ture of bis(collidine)bromonium() hexafluorophosphate
had been reported previously.[27] With the styryl alcohols 2
(Entries c, d) the cyclizations appeared less efficient, al-
though the iodooxocane 51 was obtained in a satisfactory
yield. With the epoxides 3 and 4 (Entries eϪg) the cycliza-
tions were much less favorable. No product was isolated
from the trans diastereomer 4, while the oxocanes 53 and
54 were obtained only in low yields from the cis diastere-
omer 3. These poor yields seem to be due to the low
stability of the epoxides in the presence of collidine. No
stability problems were observed with dioxolanes 5 and 6.
Surprisingly, both cis and trans diastereomers gave compar-
able results with the iodo reagent (Entries h and j), while
with the bromo reagent only the cis diastereomer gave a
satisfactory result (Entry j). Unlike the dioxolanes 5 and 6,
the trans-cyclopropyl alcohols 8 and 10 (Entries m and o)
did not produce the desired oxocanes. As expected, ox-
ocanes were obtained with satisfactory yields when starting
from the cis compounds 7, 9, and 11 (Entries l, n, p, q).
However, an exception was noted in the case of the alcohol
12 (Entry r), in which we observed mainly the ring-opening
of the cyclopropane ring and the tetrahydropyran derivative
64 as the major product. Its formation can be explained by
delocalization of the positive charge over carbon atoms 5,
7, and 8 of the intermediate iodonium species (Scheme 3).
No oxocane was detected in the reaction mixture when the
alcohol 12 was treated with the bromo reagent. Comparison
of Entries a and c or l and nϪp shows that the shorter the
chain bearing the alcohol function, the higher is the yield
in oxocane. When the cyclic system is conformationally ri-
gid, the two chains to be cyclized must have a cis stereo-
chemistry; however, if the cycle allows a certain mobility it
makes no difference whether the two chains have cis or trans
stereochemistry. In general, a 50:50 mixture of diastereo-
mers was obtained during these cyclizations. This absence
of diastereoselectivity is due to the long distance between
oxidation of the alcohol function, Wittig reaction, and the carbonϪcarbon double bond and the cycle. However,
cleavage of the silyl ether, the resulting alcohol 12 was ob- in two cases (Entries n and r), only one diastereomer was
Eur. J. Org. Chem. 2003, 463Ϫ471
465

´
C. Mendes, S. Renard, M. Rofoo, M.-C. Roux, G. Rousseau
FULL PAPER
isolated. While this result for the alcohol 12 is probably due
to the presence of the cyclopropane ring α to the
carbonϪcarbon double bond, the result obtained with alco-
hol 8 is much more surprising, and we do not for the mo-
ment have any explanation for it.
Table 1. Haloetherification of alcohols 1Ϫ12
Scheme 3
In conclusion, we show in this publication that formation
of oxocanes in satisfactory yields by electrophilic cyclization
of unsaturated alcohols is possible if a cyclic substituent is
introduced into the carbonϪcarbon chain of the alcohol to
be cyclized. The results obtained with dioxolanes also show
access to functionalized oxocanes. Applications of these re-
sults to the preparation of natural products is to be exam-
ined.
Experimental Section
General Remarks: All NMR spectra were measured in CDCl3, and
chemical shifts are expressed in ppm in relation to internal CHCl3.
All solvents were purified by known standard procedures; in par-
ticular, dichloromethane was distilled from CaH2.
[2-(Pent-4-enyl)phenyl]methanol (1): This alcohol was obtained in
two steps from 2-(pent-4-enyl)benzoic acid (13).[19] Thionyl chlor-
ide (1.0 mL) was added dropwise at 0 °C to 2-(pent-4-enyl)benzoic
acid (2.500 g, 0.0131 mol) in solution in methanol (50 mL). After
12 h at room temp., the solvent was removed under vacuum. The
residue was purified by chromatography on silica gel (diethyl ether/
pentane, 30:70) to give 2.000 g (75%) of methyl 2-(pent-4-enyl)ben-
1
zoate (14). H NMR (250 MHz): δ ϭ 7.90 (dd, J ϭ 11 and 1 Hz,
11 H), 7.40 (m, 1 H), 7.22 (m, 2 H), 5.85 (m, 1 H), 5.00 (m, 2 H),
3.90 (s, 3 H), 2.96 (dd, J ϭ 10 and 0.5 Hz), 2.15 (m, 2 H), 1.73 (m,
2 H) ppm. A solution of ester 14 (2.000 g, 9.8 mmol) in diethyl
ether (5 mL) was added under argon at 0 °C and over 30 min to a
suspension of lithium aluminum hydride (0.266 g, 7 mmol) in di-
ethyl ether (50 mL). The mixture was stirred at reflux for 3 h. After
conventional workup, the residue was purified by liquid chromato-
graphy on silica gel (diethyl ether/pentane, 50:50) to give 1.600 g
(93%) of [2-(pent-4-enyl)phenyl]methanol (1). 1H NMR
(250 MHz): δ ϭ 7.42Ϫ7.18 (m, 4 H), 5.89 (m, 1 H), 5.05 (m, 2 H),
4.73 (br. s, 2 H), 2.71 (dd, J ϭ 10 and 0.5 Hz, 2 H), 2.15 (m, 2 H),
1.73 (m, 2 H) ppm. C12H16O (176.3): calcd. C 81.77, H 9.15; found
C 81.82, H 9.17.
Methyl 3-(2-Vinylphenyl)propanoate (16): nBuLi (1.6  solution in
hexane, 87.50 mL) was added at Ϫ20 °C under argon to a suspen-
sion of methyltriphenylphosphonium bromide (50.300 g, 0.14 mol)
in THF (150 mL). After the mixture had been kept at this temper-
ature for 30 min, methyl 3-(2-formylphenyl)propanoate[20] (15,
21.100 g, 0.11 mol) was added over 15 min. The mixture was al-
lowed to warm to room temp., and after one night the solvents were
removed. The residue was purified by chromatography on silica gel
[a]
[b]
50:50 mixture of diastereomers.
Only one diastereomer was
isolated.
466
Eur. J. Org. Chem. 2003, 463Ϫ471

Preparation of Oxocanes by Electrophilic Cyclizations of Unsaturated Alcohols
FULL PAPER
(diethyl ether/pentane, 30:70) to give unsaturated ester 16 (8.400 g,
40%). 1H NMR (250 MHz): δ ϭ 7.50 (m, 1 H), 7.30Ϫ7.25 (m, 3
H), 7.00 (dd, J ϭ 10.6, 15.9 Hz, 1 H), 5.65 (d, J ϭ 10.0 Hz, 1 H),
1H NMR (250 MHz): δ ϭ 7.50 (m, 1 H), 7.10 (m, 3 H), 7.00 (dd,
J ϭ 16 and 10 Hz, 1 H), 5.65 (dd, J ϭ 16 and 0.5 Hz, 1 H), 5.30
(dd, J ϭ 10 and 0.5 Hz, 1 H), 3.65 (m, 2 H), 2.70 (m, 2 H), 1.51
5.30 (d, J ϭ 10.0 Hz, 1 H), 3.67 (s, 3 H), 3.02 (t, J ϭ 8 Hz, 2 H), (m, 5 H) ppm. 13C NMR: δ ϭ 139.5, 136.2, 134.4, 129.3, 128.2,
2.55 (m, 2 H) ppm.
126.0, 125.5, 115.1, 62.3, 32.8, 32.3, 27.0 ppm. C12H16O (176.3):
calcd. C 81.77, H 9.15; found C 81.88, H 9.25.
3-(2-Vinylphenyl)propan-1-ol (17): This alcohol was prepared by
treatment of the ester 16 with lithium aluminum hydride in THF
by the procedure described for the preparation of the alcohol 1
(2Z)-Octa-2,7-dien-1-ol (22): Coupling[21] of propargylic alcohol
with 1-bromo-4-pentene in ammonia at Ϫ40 °C gave oct-7-en-2-
yn-1-ol (21, 97%). Subsequent reduction with hydrogen (1 atm) in
the presence of Lindlar catalyst in acetone gave the alcohol 22[28]
(90%).
1
(97%). H NMR (250 MHz): δ ϭ 7.52 (m, 1 H), 7.40Ϫ7.10 (m, 3
H), 7.02 (dd, J ϭ 16 and 10 Hz, 1 H), 5.68 (dd, J ϭ 0.5 and 16 Hz,
1 H), 5.32 (dd, J ϭ 7 and 10 Hz, 1 H), 3.15 (t, J ϭ 9 Hz, 2 H),
2.80 (m, 2 H), 1.88 (m, 3 H) ppm. 13C NMR: δ ϭ 139.1, 136.3,
134.4, 129.4, 127.6, 126.2, 125.6, 115.3, 61.9, 33.6, 29.3 ppm.
(2E)-Octa-2,7-dien-1-ol (23): Lithium aluminum hydride reduction
of the acetylenic alcohol 21 in THF gave the alcohol 23[28] (80%).
3-(2-Vinylphenyl)propionaldehyde (18): 3-(2-Vinylphenyl)propan-1-
ol (17, 4.900 g, 0.03 mol) was added at Ϫ78 °C to a solution of
oxalyl chloride (3.50 mL) in dichloromethane (20 mL). After the
mixture had been kept at this temperature for 15 min, triethylamine
(25.30 mL) was added. After the mixture had then been allowed to
warm to room temp., water (30 mL) was added and the aqueous
phase was extracted with diethyl ether (3 ϫ 30 mL). The organic
phase was dried (MgSO4) and concentrated under vacuum to give
the aldehyde 18 (4.750 g, 99%). The aldehyde was used without
(2S*,3S*)-2,3-Epoxy-7-octen-1-ol (3): Vanadyl acetylacetonate
(0.013 g, 0.05 mmol) and tert-butyl hydroperoxide (0.320 g,
3.6 mmol) were added to a benzene solution (5 mL) of (2Z)-octa-
2,7-dien-1-ol (22, 0.300 g, 2.4 mmol). After the mixture had been
kept at room temp. for 6 h, the solvent was removed and the crude
mixture was purified by chromatography on silica gel (diethyl ether/
pentane, 50:50) to give (2S*,3S*)-epoxy-7-octen-1-ol (3) (0.243 g,
72%). The compound has been described previously.[21]
1
purification for the next step. H NMR (250 MHz): δ ϭ 9.80 (s, 1
(2S*,3R*)-2,3-Epoxy-7-octen-1-ol (4): This compound[29] was pre-
pared from (2E)-octa-2,7-dien-1-ol (23) by the procedure described
for the preparation of compound 3 (75%).
H), 7.50 (m, 1 H), 7.30 (m, 3 H), 6.95 (dd, J ϭ 17 and 10 Hz, 1
H), 5.65 (d, J ϭ 17 Hz, 1 H), 5.30 (d, J ϭ 10 Hz, 1 H), 3.00 (t, J ϭ
7 Hz, 2 H), 2.70 (t, J ϭ 7 Hz, 2 H) ppm. 13C NMR: δ ϭ 201.2,
137.4, 136.3, 133.9, 129.1, 127.8, 126.6, 125.9, 116.0, 44.5, 25.3
ppm.
[(2S*,3S*)-3-(Pent-4-enyl)-2-oxiranyl]methyl Acetate (24): Vinyl
acetate (9 mL) and Pseudomonas cepacia lipase (0.350 g) were ad-
ded to a solution of epoxide 3 (4.600 g, 0.0324 mol) in tert-butyl
methyl ether (10 mL). After one night at room temp., the suspen-
sion was filtered and the filtrate was concentrated under vacuum.
The acetate 24[29] (5.700 g, 96%) was pure enough to be used with-
out purification.
1-[(3Z)- and (3E)-4-Methoxybut-3-enyl]-2-vinylbenzene (19): tert-
Butyllithium (1.7  solution in pentane (44 mL, 0.0747 mol) was
added under argon at Ϫ78 °C to a suspension of (methoxymethyl)-
triphenylphosphonium chloride (25.600 g, 0.0747 mol) in THF
(175 mL). After 30 min, the aldehyde 18 (4.750 g, 0.0297 mol) was
added. After the mixture had warmed to room temp., the solvents
were removed under vacuum, and the residue was purified by chro-
matography on silica gel (pentane/diethyl ether, 92:8) to give an
(E)/(Z) mixture (50:50) of the enol ethers 19 (2.500 g, 46%). 1H
NMR (250 MHz): δ ϭ 7.55Ϫ6.92 (m, 5 H), 6.35 [d, J ϭ 16 Hz,
1 H (first isomer)], 6.30 [d, J ϭ 21 Hz, 1 H (second isomer)], 5.65
(d, J ϭ 18 Hz, 1 H), 5.30 (d, J ϭ 16 Hz, 1 H), 4.80 (m, 1 H), 3.50
[s, 3 H (first isomer)], 3.48 [s, 3 H (second isomer)], 2.95Ϫ2.60 (m,
4 H), 2.30Ϫ2.10 (m, 4 H) ppm.
cis- and trans-[2,2-Dimethyl-5-(pent-4-enyl)-1,3-dioxolan-4-yl]methyl
Acetates (cis- and trans-25): Boron trifluorideϪdiethyl ether
(0.2 mL) was added at 0 °C to [3-(pent-4-enyl)oxiranyl]methyl acet-
ate (24, 2.380 g, 0.0129 mol) in acetone (40 mL). After the mixture
had been kept at room temp. for 20 h, the solvent was removed
under vacuum. The crude mixture (2.810 g, 90%) was used without
purification for the next step. Its NMR spectra show the presence
of two diastereomers. (2S*,3S*) diastereomer (60%): 1H NMR
(250 MHz): δ ϭ 5.91Ϫ5.72 (m, 1 H), 5.08Ϫ4.95 (m, 2 H), 4.30 (dd,
J ϭ 2.6, 12.9 Hz, 1 H), 4.05 (dd, J ϭ 6 and 8 Hz, 1 H), 3.80 (m, 2
H), 2.10 (s, 3 H), 1.70Ϫ1.20 (m and 2 s, 12 H) ppm. (2S*,3R*)
diastereomer (40%): 1H NMR (250 MHz): δ ϭ 5.91Ϫ5.72 (m, 1
H), 5.08Ϫ4.95 (m, 2 H), 4.15 (q, J ϭ 5.1 Hz, 1 H), 3.95 (m, 1 H),
3.80 (m, 2 H), 2.10 (s, 3 H), 1.70Ϫ1.00 (m and 2 s, 12 H) ppm.
4-(2-Vinylphenyl)butyraldehyde (20): Perchloric acid (70%, 20 mL)
was added at 0 °C to a THF solution (40 mL) of enol ether 19
(2.300 g, 12.2 mmol). After the mixture had been kept at room
temp. for 1 h, a 10% aqueous solution of sodium bicarbonate was
added slowly until pH ϭ 7 was reached. The aqueous phase was
extracted with dichloromethane (3 ϫ 50 mL), and the organic
phase was dried (MgSO4) and concentrated under vacuum. The
residue was purified by chromatography on silica gel (diethyl ether/
pentane, 20:80) to give the aldehyde 20 (1.700 g, 80%). 1H NMR
(250 MHz): δ ϭ 9.75 (br. s, 1 H), 7.52 (dd, J ϭ 5 and 7 Hz, 1 H),
7.10 (m, 3 H), 7.04 (dd, J ϭ 14 and 10 Hz, 1 H), 5.70 (dd, J ϭ 20
and 0.5 Hz, 1 H), 5.35 (dd, J ϭ 14 and 0.5 Hz, 1 H), 2.75 (t, J ϭ
10 Hz, 2 H), 2.50 (t, J ϭ 10 Hz, 2 H), 2.00 (m, 2 H) ppm. 13C
NMR: δ ϭ 202.0, 138.5, 136.3, 134.2, 129.4, 128.4, 127.7, 125.7,
115.5, 43.0, 32.2, 23.1 ppm.
[2,2-Dimethyl-(5-pent-4-enyl)-1,3-dioxolan-4-yl]methanols (5 and 6):
K2CO3 (0.50 g) was added to the mixture of acetates 25 (2.500 g,
0.0103 mol) in methanol (50 mL) and the suspension was stirred
for 1 h at room temp. After filtration, the filtrate was concentrated
under vacuum and the residue was purified by chromatography (di-
ethyl ether/pentane, 50:50). Elution gave 1.240 g (54%) of the (2S*,
3S*) isomer and 0.820 g (36%) of the (2S*,3R*) isomer. (2S*,3S*)
diastereomer 5: 1H NMR (250 MHz): δ ϭ 5.91Ϫ5.72 (m, 1 H),
5.08Ϫ4.95 (m, 2 H), 4.07Ϫ3.93 (m, 2 H), 3.81Ϫ3.70 (m, 1 H),
3.57Ϫ3.43 (m, 1 H), 2.21Ϫ2.02 (m, 3 H), 1.78Ϫ1.22 (m and 2 s, 10
H) ppm. 13C NMR: δ ϭ 138.4, 114.7, 109.3, 79.1, 72.1, 66.1, 33.5,
33.0, 26.6, 25.3, 24.7 ppm. (2S*,3R*) diastereomer 6: 1H NMR
(250 MHz): δ ϭ 5.91Ϫ5.72 (m, 1 H), 5.08Ϫ4.95 (m, 2 H),
4-(2-Vinylphenyl)butan-1-ol (2): This alcohol was prepared by re-
duction of aldehyde 20 with lithium aluminum hydride in THF by
the procedure described for the preparation of the alcohol 1 (98%).
Eur. J. Org. Chem. 2003, 463Ϫ471
467

´
C. Mendes, S. Renard, M. Rofoo, M.-C. Roux, G. Rousseau
FULL PAPER
4.07Ϫ3.93 (m, 2 H), 3.80Ϫ3.69 (m, 1 H), 3.62Ϫ3.52 (m, 1 H),
2.21Ϫ2.02 (m, 3 H), 1.78Ϫ1.22 (m and 2s, 10 H) ppm.
(3Z)-7-[(tert-Butyldimethylsilyl)oxy]hept-3-en-1-yl Acetate (30):
Lindlar catalyst (48 mg) was added to a solution of acetate 29
(1.890 g, 6.65 mmol) in hexane (20 mL), and the mixture was
stirred under 1 atm of hydrogen. After absorption of 1 equiv. of
hydrogen (24 h), the solution was filtered and the filtrate was con-
centrated under vacuum (1.810 g, 95%). The olefin 30 was pure
enough to be used without further purification. 1H NMR
(250 MHz): δ ϭ 5.50 (m, 1 H), 5.38 (m, 1 H), 4.05 (t, J ϭ 6 Hz, 2
H), 3.60 (t, J ϭ 6 Hz, 2 H), 2.38 (q, J ϭ 7 Hz, 2 H), 2.10 (q, J ϭ
7 Hz, 2 H), 2.05 (s, 3 H), 1.57 (q, J ϭ 6 Hz, 2 H), 0.9 (s, 9 H), 0.05
(s, 6 H) ppm. 13C NMR: δ ϭ 171.0, 132.2, 124.8, 63.9, 62.7, 62.4,
32.6, 25.9, 23.5, 20.9, 18.3, Ϫ5.3 ppm. IR (film): ν˜max ϭ 3013, 2955,
2930, 2858, 1742, 1656, 1472, 1385, 1362, 1239, 1101, 837, 776
Ethyl 2-(Pent-4-enyl)cyclopropane-1-carboxylate (26): This com-
pound was prepared as already reported.[23] The cis/trans mixture
of esters was separated by chromatography on silica gel (diethyl
ether/pentane, 2:98) (60%). trans isomer: 1H NMR (250 MHz): δ ϭ
5.82 (m, 1 H), 4.95 (m, 2 H), 4.12 (q, J ϭ 7 Hz, 2 H), 2.00 (m, 2
H), 1.50Ϫ0.98 (m, 10 H), 0.60 (m, 1 H) ppm. 13C NMR: δ ϭ 174.2,
138.3, 114.4, 60.0, 33.1, 32.2, 28.1, 22.4, 20.0, 15.2, 14.1 ppm. IR
(film): ν˜max ϭ 3078, 2926, 1727, 1641, 1446, 1403, 1381, 1176, 910
cmϪ1. cis isomer: 1H NMR (250 MHz): δ ϭ 5.80 (m, 1 H), 5.05
(m, 2 H), 4.15 (q, J ϭ 7 Hz, 2 H), 2.06 (m, 2 H), 1.75Ϫ1.10 (m, 9
H), 1.10Ϫ0.80 (m, 2 H) ppm. 13C NMR: δ ϭ 172.8, 138.6, 114.2,
cmϪ1
.
60.0, 33.3, 28.8, 26.3, 21.5, 18.0, 14.2, 13.1 ppm. IR (film): ν˜max
ϭ
3078, 2980, 2928, 1726, 1641, 1447, 1409, 1176, 911 cmϪ1
.
2-(cis-2-{3-[(tert-Butyldimethylsilyl)oxy]propyl}cyclopropyl)ethyl
Acetate (31): Diethylzinc (1  solution in hexane, 5.73 mL,
5.73 mmol) was added under argon at 0 °C to a solution of acetate
30 (0.820 g, 2.86 mmol) in 1,2-dichloroethane (10 mL). After
15 min, chloroiodomethane (2.020 g, 11.4 mmol) was added drop-
wise. After warming to room temp., the mixture was stirred for 1 h.
The reaction mixture was then quenched by addition of aqueous
NH4Cl (10%, 50 mL). The aqueous phase was extracted with di-
ethyl ether (3 ϫ 20 mL). The organic phases were dried and con-
centrated under vacuum, and the residue was purified by chromato-
graphy on silica gel (diethyl ether/pentane, 85:15) to give the cyclo-
propyl compound 31 (0.790 g, 90%). 1H NMR (250 MHz): δ ϭ
4.11 (m, 2 H), 3.65 (m, 2 H), 2.05 (s, 3 H), 1.85Ϫ1.10 (m, 7 H),
0.85 (s, 9 H), 0.85Ϫ0.55 (m, 3 H), 0.03 (s, 6 H), Ϫ0.2 (m, 1 H)
ppm. 13C NMR: δ ϭ 171.2, 64.9, 62.9, 33.2, 27.7, 25.9, 24.9, 21.0,
18.3, 15.1, 12.2, 10.6, Ϫ5.3 ppm. IR (film): ν˜max ϭ 3062, 2930,
[cis-2-(Pent-4-enyl)cyclopropyl]methanol (7): This alcohol was pre-
pared by LiAlH4 reduction of the cis ester 26 in THF by the pro-
cedure described for the preparation of alcohol 1 (96%). H NMR
1
(250 MHz): δ ϭ 5.82 (m, 1 H), 5.00 (m, 2 H), 3.60 (m, 3 H), 2.10
(m, 2 H), 1.65Ϫ0.65 (m, 7 H), 0.00 (q, J ϭ 5 Hz, 1 H) ppm. 13C
NMR: δ ϭ 138.7, 114.2, 62.8, 33.4, 29.5, 27.8, 17.8, 15.8, 9.3 ppm.
IR (film): ν˜max ϭ 3341, 3065, 2926, 1640, 1457, 1032, 909 cmϪ1
.
C9H16O (140.2): calcd. C 77.09, H 11.50; found C 77.35, H 11.66.
[trans-2-(Pent-4-enyl)cyclopropyl]methanol (8): This alcohol was
prepared by the procedure used for the preparation of alcohol 7
(83%). 1H NMR (250 MHz): δ ϭ 5.80 (m, 1 H), 5.00 (m, 2 H),
3.42 (dd, J ϭ 2 and 7 Hz, 2 H), 2.05 (m, 2 H), 1.60Ϫ0.50 (m, 7 H),
0.45Ϫ0.25 (m, 2 H) ppm. 13C NMR 138.8, 114.2, 66.9, 33.4, 32.9,
28.7, 21.0, 16.8, 9.8 ppm. IR (film): ν˜max ϭ 3339, 3065, 2925, 1641,
1441, 1032, 909 cmϪ1. C9H16O (140.2): calcd. C 77.09, H 11.50;
found C 77.71, H 11.81.
2858, 1744, 1472, 1387, 1363, 1247, 1101, 837, 776 cmϪ1
.
2-[cis-2-(3-Hydroxypropyl)cyclopropyl]ethyl Acetate (32): Tetrabu-
tylammonium fluoride (1  solution in THF, 4 mL, 4 mmol) was
added to a THF solution (4 mL) of silyl ether 31 (0.600 g,
1.99 mmol). After the mixture had been kept at room temp. for
12 h, the solvent was removed under vacuum and the residue was
purified by chromatography on silica gel (pentane/diethyl ether,
60:40) to give the alcohol 32 (0.372 g, 100%). 1H NMR (250 MHz):
δ ϭ 4.08 (t, J ϭ 7 Hz, 2 H), 3.65 (t, J ϭ 7 Hz, 2 H), 3.45 (m, 1 H),
2.03 (s, 3 H), 1.68 (m, 2 H), 1.48 (m, 2 H), 1.20 (m, 2 H), 0.90Ϫ0.55
(m, 3 H), Ϫ0.22 (1 H) ppm. 13C NMR: δ ϭ 171.2, 64.9, 62.6, 33.0,
27.7, 24.9, 20.9, 15.1, 12.2, 10.5 ppm. IR (film): ν˜max ϭ 3348, 3061,
7-[(tert-Butyldimethylsilyl)oxy]hept-3-yn-1-ol (28): nBuLi (1.0  so-
lution in hexane, 26.30 mL, 0.042 mol) was added under argon at
Ϫ78 °C to a THF solution (200 mL) of 5-[(tert-butyldimethylsilyl)-
oxy]pent-1-yne (27,[30] 6.400 g, 0.0323 mol). After the mixture had
been kept at Ϫ78 °C for 1.5 h, ethylene oxide (16.20 mL, 0.0323
mol) and boron trifluorideϪdiethyl ether (5 mL, 0.0452 mol) were
added. After 3 h at Ϫ78 °C, the solution was allowed to warm to
room temp. and aqueous ammonium chloride (10%, 150 mL) was
added. The aqueous phase was extracted with ethyl acetate (3 ϫ
100 mL). The organic phases were washed with brine, dried, and
concentrated under vacuum. The residue was purified by chromato-
graphy on silica gel (pentane/ethyl acetate, 7:3) to give the alcohol
2930, 2858, 1472, 1386, 1255, 1101, 1037, 836, 775 cmϪ1
.
1
28 (6.360 g, 82%). H NMR (250 MHz): δ ϭ 3.55 (m, 4 H), 2.40
2-[cis-2-(3-Oxopropyl)cyclopropyl]ethyl Acetate (33): This aldehyde
was prepared by oxidation of the alcohol 32 by the procedure de-
scribed for the preparation of the aldehyde 18 (70%). 1H NMR
(250 MHz): δ ϭ 9.85 (br. s, 1 H), 4.13 (t, J ϭ 7 Hz, 2 H), 2.55 (t,
J ϭ 7 Hz, 2 H), 2.05 (s, 3 H), 1.90Ϫ1.60 (m, 2 H), 1.60Ϫ1.40 (m,
2 H), 0.95Ϫ0.55 (m, 3 H), Ϫ0.22 (m, 1 H) ppm. 13C NMR: δ ϭ
202.4, 172.7, 64.7, 44.2, 27.7, 21.4, 21.0, 14.8, 12.6, 10.6 ppm. IR
(m, 1 H), 2.23 (m, 2 H), 1.66 (m, 2 H), 1.28 (m, 2 H), 0.88 (s, 9
H), 0.02 (s, 6 H) ppm. 13C NMR: δ ϭ 81.9, 76.5, 61.6, 61.2, 31.8,
25.8, 23.0, 18.2, 15.0, Ϫ3.7 ppm. IR (film): ν˜max ϭ 3315, 2954,
2930, 2858, 1742, 1472, 1256, 1106, 836, 777 cmϪ1
.
7-[(tert-Butyldimethylsilyl)oxy]hept-3-yn-1-yl Acetate (29): Acetic
anhydride (4.5 mL) and DMAP (0.300 g, 2.7 mmol) were added to
a solution of alcohol 28 (6.000 g, 0.0248 mol) in diethyl ether
(80 mL). After 16 h at room temp., the mixture was filtered and
the filtrate was concentrated under vacuum. The residue was puri-
(film): ν˜max ϭ 3064, 2955, 1737, 1387, 1364, 1245, 1037 cmϪ1
.
2-[cis-2-(But-3-enyl)cyclopropyl]ethyl Acetate (34): The Wittig reac-
fied by chromatography on silica gel to give the acetate 29 (5.390 g, tion was conducted on aldehyde 33 as reported for the preparation
1
1
77%). H NMR (250 MHz): δ ϭ 4.12 (t, J ϭ 6 Hz, 2 H), 3.65 (t, of the olefin 16 (53%). H NMR (250 MHz): δ ϭ 5.85 (m, 1 H),
J ϭ 6 Hz, 2 H), 2.45 (m, 2 H), 2.22 (m, 2 H), 2.07 (s, 3 H), 1.65 5.00 (m, 2 H), 4.10 (dt, J ϭ 7 and 2 Hz, 2 H), 2.13 (q, J ϭ 8 Hz,
(q, J ϭ 6 Hz, 2 H), 0.85 (s, 9 H), 0.03 (s, 6 H) ppm. 13C NMR:
2 H), 2.03 (s, 3 H), 1.85Ϫ1.20 (m, 4 H), 0.85Ϫ0.60 (m, 3 H), Ϫ0.20
δ ϭ 170.8, 81.5, 75.6, 62.8, 61.5, 31.8, 25.9, 20.8, 19.2, 18.2, 15.0, (m, 1 H) ppm. 13C NMR: δ ϭ 172.5, 138.7, 114.2, 64.8, 34.1, 28.1,
Ϫ5.4 ppm. IR (film): ν˜max ϭ 2955, 2930, 2857, 1746, 1472, 1239,
27.8, 20.9, 14.9, 12.2, 10.5 ppm. IR (film): ν˜max ϭ 3063, 2926, 2856,
1742, 1640, 1435, 1364, 1247, 1038, 911, 744, 697 cmϪ1
1105, 1044, 837, 777 cmϪ1
.
.
468
Eur. J. Org. Chem. 2003, 463Ϫ471

Preparation of Oxocanes by Electrophilic Cyclizations of Unsaturated Alcohols
FULL PAPER
2-[cis-2-(But-3-enyl)cyclopropyl]ethanol (9): This alcohol was pre-
pared by cleavage of the acetate 34 by the procedure described for
the preparation of compounds 5, 6 (70%). 1H NMR (250 MHz):
δ ϭ 5.80 (m, 1 H), 5.00 (m, 2 H), 3.70 (t, J ϭ 7 Hz, 2 H), 2.10 (m,
2 H), 1.90Ϫ1.10 (m, 5 H), 1.00Ϫ0.50 (m, 3 H), 0.20 (m, 1 H) ppm.
13C NMR: δ ϭ 138.8, 114.2, 63.2, 34.1, 31.6, 28.3, 14.7, 12.1,
10.5 ppm. IR (film): ν˜max ϭ 3337, 3062, 2992, 2926, 2860, 1640,
1455, 1436, 1055, 910. C9H16O (140.2): calcd. C 77.09, H 11.50;
(s, 6 H) ppm. 13C NMR: δ ϭ 171.2, 130.9, 127.6, 63.2, 63.9, 36.2,
28.9, 28.2, 25.9, 21.0, 18.3, Ϫ5.3 ppm.
3-(trans-2-{2-[(tert-Butyldimethylsilyl)oxy]ethyl}cyclopropyl)propyl
Acetate (40): The cyclopropanation was conducted on the unsatur-
ated compound 39 as reported for the preparation of the com-
pound 31 (93%). 1H NMR (250 MHz): δ ϭ 4.08 (t, J ϭ 7 Hz, 2
H), 3.65 (t, J ϭ 7 Hz, 2 H), 2.06 (s, 3 H), 1.90Ϫ1.10 (m, 6 H), 0.88
(s, 9 H), 0.90Ϫ0.00 (m, 4 H), 0.06 (s, 6 H) ppm. 13C NMR: δ ϭ
171.1, 64.3, 63.1, 37.4, 30.4, 28.5, 25.9, 20.9, 18.3, 17.8, 15.4, 11.4,
Ϫ5.3 ppm. IR (film): ν˜max ϭ 3062, 2929, 1743, 1472, 1364, 1254,
found C 77.62, H 11.32 cmϪ1
.
2-(cis-2-{3-[(tert-Butyldimethylsilyl)oxy]propyl}cyclopropyl)ethanol
(35): This alcohol was prepared by cleavage of the acetate 31 by
the procedure used for the preparation of the alcohols 5, 6 (95%).
1H NMR (250 MHz): δ ϭ 3.75 (q, J ϭ 7 Hz, 2 H), 3.65 (t, J ϭ
7 Hz, 2 H), 3.50 (d, J ϭ 7 Hz, 1H (OH)], 1.70Ϫ1.20 (m, 7 H), 0.90
(s, 9 H), 0.80Ϫ0.60 (m, 2 H), 0.04 (s, 6 H), Ϫ0.20 (m, 1 H) ppm.
13C NMR: δ ϭ 63.5, 63.0, 33.2, 31.6, 25.9, 25.0, 18.3, 14.8, 12.2,
10.5, Ϫ5.3 ppm. IR (film): ν˜max ϭ 3350, 3061, 2930, 2858, 1472,
1100, 836, 776 cmϪ1
.
3-(trans-2-{2-[(tert-Butyldimethylsilyl)oxy]ethyl}cyclopropyl)propan-
1-ol (41): The cleavage of the acetate function of the compound 40
was conducted as reported for the preparation of compounds 5, 6
(99%). 1H NMR (250 MHz): δ ϭ 3.61 (t, J ϭ 7 Hz, 4 H),
1.90Ϫ1.10 (m, 6 H), 0.88 (s, 9 H), 0.55Ϫ0.10 (m, 4 H), 0.05 (s, 6
H) ppm. 13C NMR: δ ϭ 63.2, 62.7, 37.5, 32.6, 30.3, 25.9, 18;3,
18.1, 15.4, 11.4, Ϫ5.3 ppm. IR (film): ν˜max ϭ 3349, 3060, 2929,
1255, 1101, 836, 776 cmϪ1
.
2857, 1670, 1472, 1255, 1101, 836, 775 cmϪ1
.
2-(cis-2-{3-[(tert-Butyldimethylsilyl)oxy]propyl}cyclopropyl)-
acetaldehyde (36): This aldehyde was prepared by oxidation of the
alcohol 35 by the procedure described for the preparation of the
3-(trans-2-{2-[(tert-Butyldimethylsilyl)oxy]ethyl}cyclopropyl)pro-
pionaldehyde (42): This aldehyde was prepared by oxidation of the
alcohol 41 according to the procedure used for the preparation of
the aldehyde 18 (73%). 1H NMR (250 MHz): δ ϭ 9.80 (t, J ϭ
0.5 Hz, 1 H), 3.65 (t, J ϭ 7 Hz, 2 H), 2.52 (dt, J ϭ 7 and 0.5 Hz,
2 H), 1.55 (q, J ϭ 7 Hz, 2 H), 1.40 (q, J ϭ 7 Hz, 2 H), 0.90 (s, 9
H), 0.50 (m, 2 H), 0.25 (m, 2 H), 0.05 (s, 6 H) ppm. 13C NMR:
δ ϭ 156.1, 68.2, 56.2, 52.0, 45.4, 44.9, 44.6, 39.7, 38.4, 35.9,
25.2 ppm. IR (film): ν˜max ϭ 3063, 2929, 2857, 1728, 1255, 1101,
1
compound 18 (83%). H NMR (250 MHz): δ ϭ 9.83 (t, J ϭ 1 Hz,
1 H), 3.61 (t, J ϭ 7 Hz, 2 H), 2.40 (dq, J ϭ 14 and 6 Hz, 2 H),
1.62 (m, 2 H), 1.50Ϫ1.00 (m, 2 H), 0.88 (s, 9 H), 1.00Ϫ0.70 (m, 3
H), 0.05 (s, 6 H), 0.10 (m, 1 H) ppm. 13C NMR: δ ϭ 202.7, 62.7,
43.1, 32.9, 25.9, 25.2, 18.3, 14.7, 10.7, 9.00, Ϫ5.3 ppm. IR (film):
ν˜max ϭ 3062, 2929, 2712, 1729, 1689, 1472, 1387, 1255, 1100, 836,
775 cmϪ1
.
836, 776 cmϪ1
.
{3-[cis-2-(Prop-2-enyl)cyclopropyl]propoxy}(tert-butyl)dimethyl-
silane (37): The Wittig reaction was conducted on the aldehyde 36
as reported for the preparation of the olefin 16 (93%). 1H NMR
(250 MHz): δ ϭ 5.95 (m, 1 H), 5.00 (m, 2 H), 3.62 (t, J ϭ 6 Hz, 2
H), 2.20Ϫ1.90 (m, 2 H), 1.75Ϫ1.15 (m, 4 H), 0.90 (s, 9 H),
1.00Ϫ0.60 (m, 3 H), 0.05 (s, 6 H), 0.21 (s, 1 H) ppm. 13C NMR:
δ ϭ 138.8, 114.0, 63.1, 33.3, 32.7, 25.9, 24.9, 18.3, 15.5, 14.8, 10.6,
Ϫ5.2 ppm. IR (film): ν˜max ϭ 3063, 2930, 2858, 1641, 1472, 1255,
{2-[trans-2-(But-3-enyl)cyclopropyl]ethoxy}(tert-butyl)dimethylsilane
(43): The Wittig reaction was conducted on the aldehyde 42 as
reported for the preparation of the olefin 16. 1H NMR (250 MHz):
δ ϭ 5.85 (m, 1 H), 5.00 (m, 2 H), 3.65 (t, J ϭ 7 Hz, 2 H), 2.12 (m,
2 H), 1.60Ϫ1.15 (m, 4 H), 0.88 (s, 9 H), 0.60Ϫ0.10 (m, 4 H), 0.04
(s, 6 H) ppm. 13C NMR: δ ϭ 138.9, 114.2, 63.2, 37.6, 33.9, 33.7,
29.7, 25.9, 18.1, 15.4, 11.5, Ϫ5.3 ppm. IR (film): ν˜max ϭ 3063, 2928,
1102, 836, 775 cmϪ1
.
2857, 1641, 1472, 1255, 1102, 910, 836, 775 cmϪ1
.
3-[cis-2-(Prop-2-enyl)cyclopropyl]propan-1-ol (11): ClSiMe3 (three
drops) was added at room temp. to silyl ether 37 (0.350 g,
13.7 mmol) in methanol (20 mL). After 2 h, the solvent was re-
moved under vacuum and the residue was purified by chromato-
graphy on silica gel to give the alcohol 11 (0.164 g, 86%). 1H NMR
(250 MHz): δ ϭ 5.90 (m, 1 H), 5.00 (m, 2 H), 3.65 (t, J ϭ 7 Hz, 2
H), 2.05 (m, 2 H), 1.70Ϫ1.15 (m, 5 H), 0.95Ϫ0.60 (m, 3 H), 0.21
(m, 1 H) ppm. 13C NMR: δ ϭ 138.6, 114.0, 62.6, 33.0, 32.6, 24.8,
15.4, 14.7, 10.6 ppm. IR (film): ν˜max ϭ 3324, 3062, 2993, 2932,
2861, 1640, 1455, 1059, 910 cmϪ1. C9H16O (140.2): calcd. C 77.09,
H 11.50; found C 77.01, H 11.87.
2-[trans-2-(But-3-enyl)cyclopropyl]ethanol (10): This compound was
obtained by cleavage of the silyl ether 43 according to the procedure
described for the preparation of the alcohol 32 (82%). 1H NMR
(250 MHz): δ ϭ 5.82 (m, 1 H), 5.05 (m, 2 H), 3.65 (t, J ϭ 7 Hz, 2
H), 2.12 (m, 2 H), 1.55Ϫ1.10 (m, 5 H), 0.95Ϫ0.20 (m, 4 H) ppm.
13C NMR: δ ϭ 138.8, 114.2, 62.9, 37.1, 33.8, 33.5, 17.9, 15.2,
11.3 ppm. IR (film): ν˜max ϭ 3324, 3063, 2928, 2857, 1641, 1470,
1254, 1051, 910, 836, 780 cmϪ1. C9H16O (140.2): calcd. C 77.09, H
11.50; found C 77.21, H 11.55.
(cis-2-{4-[(tert-Butyldimethylsilyl)oxy]butyl}cyclopropyl)methanol
(45): Diiodomethane (3.01 mL, 0.0372 mol) and diethylzinc (1 
solution in hexane, 18.60 mL, 0.0186 mol) were added under argon
at Ϫ40 °C to (2Z)-7-[(tert-butyldimethylsilyl)oxy]hept-2-en-1-ol[25]
(44, 2.270 g, 0.0093 mol) in toluene (45 mL). After 30 min at this
(4E)-7-[(tert-Butyldimethylsilyl)oxy]hept-4-enyl Acetate (39): Imida-
zole (2.250 g, 0.0331 mol) and (tert-butyl)(chloro)dimethylsilane
(5.000 g, 0.034 mol) were added at room temp. to (4E)-7-hy-
droxyhept-4-enyl acetate (38, 4.75 g, 0.0276 mol) in DMF temperature, the mixture was allowed to warm to room temp. and
(250 mL). The mixture was stirred for 16 h at room temp., and
water (350 mL) was added. The mixture was extracted with diethyl
ether (3 ϫ 150 mL). The organic phase was dried (MgSO4) and
concentrated under vacuum. The residue was purified by chromato-
quenched by addition of a 10% aqueous solution of NH4Cl
(150 mL). The aqueous phase was extracted with diethyl ether (3 ϫ
50 mL). The organic phases were dried (MgSO4) and concentrated
under vacuum. The residue was purified by chromatography on
silica gel (diethyl ether/pentane, 1:9) to give the alcohol 45 (2.250 g,
graphy on silica gel (pentane/diethyl ether, 80:20) to give the silyl
1
ether 39 (7.400 g, 94%). H NMR (250 MHz): δ ϭ 5.20 (m, 2 H), 92%). 1H NMR (250 MHz): δ ϭ 3.65 (m, 4 H), 1.65Ϫ1.00 (m, 7
4.06 (t J ϭ 7 Hz, 2 H), 3.60 (t, J ϭ 7 Hz, 2 H), 2.40Ϫ1.95 (m, 4 H), 1.00Ϫ0.80 (m, 2 H), 0.90 (s, 9 H), 0.75 (m, 1 H), 0.05 (s, 6 H),
H), 2.04 (s, 3 H), 1.67 (quint, J ϭ 8 Hz, 2 H), 0.88 (s, 9 H), 0.05
Eur. J. Org. Chem. 2003, 463Ϫ471
Ϫ0.02 (q, J ϭ 5 Hz, 1 H) ppm. 13C NMR: δ ϭ 63.1 (2C), 32.6,
469

´
C. Mendes, S. Renard, M. Rofoo, M.-C. Roux, G. Rousseau
FULL PAPER
28.2, 26.3, 25.9, 18.3, 18.1, 9.4, 5.3 ppm. IR (film): ν˜max ϭ 3347,
1 H), 1.60Ϫ1.40 (m, 3 H) ppm. 13C NMR: δ ϭ 139.7 (2C), 131.6,
128.1, 127.0, 126.0, 82.4, 70.9, 32.7, 27.7, 25.9, 12.0 ppm. C12H15IO
(302.2): calcd. C 47.70, H 5.00; found C 48.15, H 5.33.
2931, 2858, 1472, 1255, 1100, 836, 775 cmϪ1
.
cis-2-{4-[(tert-Butyldimethylsilyl)oxy]butyl}cyclopropane-1-carb-
aldehyde (46): The oxidation of alcohol 44 was carried out as re-
ported for the preparation of aldehyde 18 (87%). 1H NMR
(250 MHz): δ ϭ 9.35 (d, J ϭ 6 Hz, 1 H), 3.65 (t, J ϭ 7 Hz, 2 H),
2.00Ϫ1.10 (m, 10 H), 0.90 (s, 9 H), 0.05 (s, 6 H) ppm. 13C NMR:
δ ϭ 201.8, 63.0, 32.3, 27.9, 27.7, 26.2, 25.9, 24.7, 18.3, 14.7,
Ϫ5.3 ppm. IR (film): ν˜max ϭ 2931, 2858, 2713, 1728, 1472, 1388,
1-(Bromomethyl)-3,4,5,6-tetrahydro-1H-benzo[c]oxocine (52): Oil.
1H NMR (250 MHz): δ ϭ 7.30Ϫ7.15 (m, 2 H), 7.15Ϫ7.00 (m, 2
H), 4.80 (dd, J ϭ 5 and 8 Hz, 1 H), 4.00 (q, J ϭ 8 Hz, 1 H),
3.80Ϫ3.50 (m, 4 H), 2.65 (m, 1 H), 1.94 (m, 1 H), 1.70Ϫ1.45 (m,
3 H) ppm. 13C NMR: δ ϭ 140.2, 138.7, 131.6, 128.3, 127.1, 126.0,
82.4, 70.8, 37.6, 32.7, 27.8, 26.1 ppm. C12H15BrO (255.2): calcd. C
56.49, H 5.93; found C 56.65, H 6.11.
1255, 1098, 836, 776 cmϪ1
.
(tert-Butyl)dimethyl[4-(cis-2-vinylcyclopropyl)butoxy]silane (47): A
Wittig reaction was conducted on the aldehyde 46 as reported for
the preparation of compound 16 (87%). 1H NMR (250 MHz): δ ϭ
5.55 (m, 1 H), 5.05 (m, 2 H), 3.60 (t, J ϭ 7 Hz, 2 H), 1.65Ϫ1.25
(m, 7 H), 1.05Ϫ0.80 (m, 2 H), 0.88 (s, 9 H), 0.25 (m, 1 H), 0.04 (s,
6 H) ppm. 13C NMR: δ ϭ 138.5, 113.7, 63.2, 32.7, 28.9, 26.0, 25.9,
19.7, 18.7, 18.3, 12.7, Ϫ5.2 ppm. IR (film): ν˜max ϭ 3078, 2930,
4-(Iodomethyl)-3,9-dioxabicyclo[6.1.0]nonane (53): Oil (50:50 mix-
ture of diastereomers). 1H NMR (250 MHz): δ ϭ 4.80 [dd, J ϭ 14
and 3 Hz, 1 H, (first diastereomer)], 4.05 [dq, J ϭ 13 and 3 Hz, 2 H,
(second diastereomer)], 3.07Ϫ3.30 [m, 2 H, (two diastereomers)],
3.30Ϫ2.90 [m, 2 H, (two diastereomers)], 2.05Ϫ1.40 [m, 6 H, (two
diastereomers)] ppm. C8H13IO2 (268.1): calcd. C 35.84, H 4.89;
found C 36.14, H 5.20.
2857, 1641, 1472, 1255, 1103, 910, 836, 775 cmϪ1
.
4-(Bromomethyl)-3,9-dioxabicyclo[6.1.0]nonane (54): Oil (50:50 mix-
ture of diastereomers). 1H NMR (250 MHz): δ ϭ 4.80 [dd, J ϭ 14
and 3 Hz, 1 H, (first diastereomer)], 4.05 [dq, J ϭ 13 and 3 Hz, 2 H,
(second diastereomer)], 3.60Ϫ3.20 [m, 4 H, (two diastereomers)],
3.15Ϫ2.95 [m, 2 H, (two diastereomers)], 2.00Ϫ1.40 [m, 6 H, (two
diastereomers)] ppm. 13C NMR (first diastereomer): δ ϭ 80.3, 67.1,
54.6, 53.2, 36.7, 31.9, 23.9, 22.6 ppm; (second diastereomer): δ ϭ
80.1, 66.4, 55.9, 54.8, 33.3, 29.6, 27.4, 20.6 ppm. C8H13BrO2
(221.1): calcd. C 43.46, H 5.93; found C 43.81, H 5.97.
4-(cis-2-Vinylcyclopropyl)butan-1-ol (12): This compound was ob-
tained by cleavage of the silyl ether 47 by the procedure reported
for the preparation of the alcohol 11 (93%). H NMR (250 MHz):
δ ϭ 5.55 (m, 1 H), 5.00 (m, 2 H), 3.65 (t, J ϭ 7 Hz, 2 H), 1.70Ϫ1.25
(m, 7 H), 1.05Ϫ0.65 (m, 3 H), 0.25 (m, 1 H) ppm. 13C NMR: δ ϭ
138.4, 113.8, 62.9, 32.5, 28.8, 25.8, 19.7, 18.6, 12.6 ppm. IR (film):
ν˜max ϭ 3334, 3067, 2997, 2933, 2859, 1634, 1458, 1053, 988, 894
cmϪ1. C9H16O (140.2): calcd. C 77.09, H 11.50; found C 77.38,
H 11.41.
1
(10S*,11S*)-6-(Iodomethyl)-2,2-dimethylhexahydro-4H-[1,3]-
dioxolo[4,5-c]oxocine (55): Oil (50:50 mixture of diastereomers). 1H
NMR (250 MHz) (mixture): δ ϭ 4.20Ϫ3.71 (m, 3 H), 3.56Ϫ3.10
(m, 4 H), 2.00Ϫ1.15 (m, 6 H), 1.45 (s, 3 H), 1.39 (s, 3 H) ppm.
C11H19IO3 (326.2): calcd. C 40.51, H 5.87; found C 40.80, H 5.89.
General Procedure for the Haloetherification: A solution of unsatur-
ated alcohol (1 mmol) in dichloromethane (5 mL) was added over
4 h at room temp. to a solution of bis(collidine)halonium() hexa-
fluorophosphate (1.22 mmol) in dichloromethane (15 mL). The re-
sulting solution was stirred for an additional 1 h, and silica gel
(2 g) was added. The solvent was removed under vacuum and the
resulting solid was introduced onto the top of a silica gel column.
Elution with a pentane/diethyl ether mixture gave products 48Ϫ64.
(10S*,11S*)-6-(Bromomethyl)-2,2-dimethylhexahydro-4H-[1,3]-
dioxolo[4,5-c]oxocine (56): Oil (50:50 mixture of diastereomers). 1H
NMR (250 MHz) (mixture): δ ϭ 4.23Ϫ4.04 (m, 1 H), 4.04Ϫ3.96
(m, 1 H), 3.75Ϫ3.67 (m, 1 H), 3.67Ϫ3.38 (m, 3 H), 3.38Ϫ3.30 (m,
1 H), 2.02Ϫ1.13 (m, 6 H), 1.45 (s, 3 H), 1.37 (s, 3 H) ppm. 13C
NMR (first isomer): δ ϭ 109.4, 78.2, 77.7, 71.9, 65.4, 35.6, 29.5,
26.5, 26.2, 26.0, 25.5 ppm; (second diastereomer): δ ϭ 109.5, 77.3,
76.8, 71.5, 65.6, 53.4, 32.7, 26.5, 26.1, 25.4, 17.8 ppm. C11H19BrO3
(279.2): calcd. C 47.33, H 6.86; found C 47.64, H 6.96.
3-(Iodomethyl)-3,4,5,6-tetrahydro-1H-benzo[c]oxocine (48): Oil. 1H
NMR (250 MHz): δ ϭ 7.33Ϫ7.12 (m, 4 H), 5.02Ϫ4.69 (2 d, AB
system, J ϭ 12 Hz, 2 H), 3.58Ϫ3.47 (m, 1 H), 3.31Ϫ3.13 (m, 2
H), 3.13Ϫ3.03 (m, 1 H), 2.93Ϫ2.79 (m, 1 H), 2.06Ϫ1.92 (m, 1 H),
1.86Ϫ1.48 (m, 3 H) ppm. C12H15IO (302.2): calcd. C 47.70, H 5.00;
found C 47.76, H 5.08.
3-(Bromomethyl)-3,4,5,6-tetrahydro-1H-benzo[c]oxocine (49): Oil.
Rf ϭ 0.66 (diethyl ether/pentane, 50:50). 1H NMR (250 MHz): δ ϭ
7.25Ϫ7.02 (m, 4 H), 5.02Ϫ4.69 (2 d, AB system, J ϭ 15 Hz, 2
H), 3.71Ϫ3.57 (m, 1 H), 3.48Ϫ3.28 (m, 2 H), 3.18Ϫ3.00 (m, 1 H),
2.92Ϫ2.77 (m, 1 H), 2.10Ϫ1.46 (m, 4 H) ppm. 13C NMR: δ ϭ
141.2, 136.4, 130.4, 128.9, 128.3, 126.4, 77.1, 70.6, 37.0, 32.1, 31.3,
28.0 ppm. C12H15BrO (255.2): calcd. C 56.49, H 5.93; found C
56.65, H 6.02.
(10S*,11R*)-6-(Iodomethyl)-2,2-dimethylhexahydro-4H-[1,3]-
dioxolo[4,5-c]oxocine (57): Oil (50:50 mixture of diastereomers). 1H
NMR (250 MHz) (mixture): δ ϭ 4.20Ϫ4.05 (m, 1 H), 4.05Ϫ3.90
(m, 1 H), 3.90Ϫ3.75 (m, 1 H), 3.70Ϫ3.12 (m, 4 H), 2.00Ϫ1.13 (m,
6 H), 1.45 (br. s, 3 H), 1.48 (2s, 3 H) ppm. 13C NMR (mixture):
δ ϭ 109.5 (A), 109.4 (B), 78.0 (A), 77.7 (B), 77.0 (A), 76.8 (B), 72.4
(A), 71.0 (B), 66.7 (A), 65.7 (B), 31.0 (A), 27.4 (B), 26.5 (A), 26.3
(A), 26.0 (A), 25.6 (B), 25.4 (B), 22.8 (A), 17.8 (B), 9.8 (A), 7.0 (B)
ppm. C11H19IO3 (326.2): calcd. C 40.51, H 5.87; found C 40.90,
H 5.73.
2-(5-Bromo-4-fluoropentyl)benzaldehyde (50): Oil. Rf ϭ 0.54 (di-
1
ethyl ether/pentane, 50:50). H NMR (250 MHz): δ ϭ 10.28 (s, 1
H), 7.72 (dd, J ϭ 7 and 1 Hz, 1 H), 7.52Ϫ7.11 (m, 3 H), 3.78Ϫ3.52
(m, 2 H), 3.45Ϫ2.95 (m, 3 H), 2.39Ϫ1.60 (m, 4 H) ppm.
C12H14BrFO (273.1): calcd. C 52.77, H 5.17; found C 52.91, H
5.50.
(10S*,11R*)-6-(Bromomethyl)-2,2-dimethylhexahydro-4H-[1,3]-
dioxolo[4,5-c]oxocine (58): Oil (50:50 mixture of diastereomers). 1H
NMR (250 MHz) (mixture): δ ϭ 4.25Ϫ3.95 (m, 3 H), 3.85Ϫ3.40
(m, 4 H), 1.90Ϫ1.15 (m, 6 H), 1.45 (s, 3 H), 1.36 (s, 3 H) ppm. 13C
NMR (mixture): δ ϭ 109.6, 109.4, 78.3, 77.8, 77.2, 76.8, 72.0, 71.6,
1-(Iodomethyl)-3,4,5,6-tetrahydro-1H-benzo[c]oxocine (51): Oil. 1H
NMR (250 MHz): δ ϭ 7.30Ϫ7.15 (m, 4 H), 7.15Ϫ7.00 (m, 2 H), 65.8, 65.7, 35.6, 32.7, 29.6, 26.5, 26.3, 26.1, 26.0, 25.5, 25.4, 22.6,
4.65 (dd, J ϭ 5 and 8 Hz, 1 H), 4.00 (q, J ϭ 8 Hz, 1 H), 3.80Ϫ3.55 17.9, 15.2 ppm. C11H19BrO3 (279.2): calcd. C 47.33, H 6.86; found
(m, 2 H), 3.50Ϫ3.30 (m, 2 H), 2.70Ϫ2.55 (m, 1 H), 2.05Ϫ1.85 (m, C 47.66, H 6.67.
470
Eur. J. Org. Chem. 2003, 463Ϫ471

Preparation of Oxocanes by Electrophilic Cyclizations of Unsaturated Alcohols
FULL PAPER
(1S*,8S*)-4-(Iodomethyl)-4-oxabicyclo[6.1.0]nonane (59): Oil (50:50
mixture of diastereomers). 1H NMR (250 MHz) (mixture): δ ϭ
[1]
G. Illuminati, L. Mandolini, Acc. Chem. Res. 1981, 14,
95Ϫ102.
4.40 [dd, J ϭ 13 and 4 Hz, 1 H (first diastereomer)], 4.17 [dd, J ϭ
11 and 2 Hz, (second diastereomer)], 3.95 [m, 1 H (second diastere-
omer)], 3.35Ϫ3.10 (m, 3 H), 3.00 [dd, J ϭ 13 and 11 Hz, 1 H (first
diastereomer)], 2.25Ϫ0.60 (m, 9 H), Ϫ0.15 (m, 1 H) ppm. 13C
NMR (first diastereomer): δ ϭ 80.1, 71.1, 34.4, 26.1, 24.1, 16.1,
13.9, 13.6, 7.6 ppm; (second diastereomer): δ ϭ 75.1, 65.2, 34.5,
29.0, 27.6, 15.8, 14.3, 13.4, 7.5 ppm. IR (film): ν˜max ϭ 3063, 2951,
1468, 1095, 1077 cmϪ1. MS (EI): m/z (%) ϭ 266 (0.2) [Mϩ], 255
(5), 139 (4), 97 (10), 95 (6), 93 (9), 81 (10), 79 (13), 71 (100), 69
(10), 67 (39), 55 (30), 53 (16), 43 (32), 41 (89), 39 (62). C9H15IO
(266.1): calcd. C 40.62, H 5.68; found C 40.86, H 5.81.
[2]
[3]
[2a] H. Meir, E. Stravridov, S. Roth, W. Mayer, Chem. Ber. 1990,
[2b]
123, 1411Ϫ1414.
J. S. Clark, S. A. Krowiak, L. J. Street,
Tetrahedron Lett. 1993, 34, 4385Ϫ4388.
[3a] M. T. Mujica, M. M. Afonso, A. Galindo, J. A. Palenzuela,
[3b]
Tetrahedron Lett. 1994, 35, 3401Ϫ3404.
E. Alvarez, M.
`
´
Delgado, M. T. Dıaz, L. Hanxing, R. Perez, J. D. Martin, Tet-
rahedron Lett. 1996, 37, 2865Ϫ2868.
[4]
[5]
M. Martin, M. M. Afonso, A. Galindo, J. A. Palenzuela, Syn-
lett 2001, 117Ϫ119.
E. L. Grimm, S. Levac, L. A. Trimble, Tetrahedron Lett. 1994,
35, 6847Ϫ6850.
[6] [6a]
[7]
`
J. M. Palazon, V. S. Martin, Tetrahedron Lett. 1995, 36,
(1S*,8S*)-5-(Iodomethyl)-4-oxabicyclo[6.1.0]nonane (60): Oil. 1H
NMR (250 MHz): δ ϭ 4.08 (dt, J ϭ 13 and 2 Hz, 1 H), 3.85 (m,
1 H), 3.55 (t, J ϭ 13 Hz, 1 H), 3.20 (m, 2 H), 2.15Ϫ0.50 (m, 9 H),
Ϫ0.10 (m, 1 H) ppm. 13C NMR: δ ϭ 80.5, 73.4, 34.4, 32.8, 29.7,
23.9, 14.3, 12.2, 10.7 ppm. IR (film): ν˜max ϭ 3060, 2933, 2854,
1455, 1263, 1115, 1031, 613 cmϪ1. MS (EI): m/z (%) ϭ 266 (5)
[Mϩ], 141 (3), 139 (5), 127 (6), 97 (6), 95 (11), 93 (11), 85 (17), 83
(27), 81 (18), 79 (25), 69 (11), 67 (72), 55 (100), 41 (86), 39 (70).
C9H15IO (266.1): calcd. C 40.62, H 5.68; found C 40.95, H 5.77.
[6b]
3549Ϫ3552.
T.-S. Liu, M. Isobe, Synlett 2000, 266Ϫ268.
R. Chakraborty, N. S. Simpkins, Tetrahedron 1991, 47,
7689Ϫ7698.
[8]
[9]
J.-i. Yamada, T. Asano, I. Kadota, Y. Yamamoto, J. Org. Chem.
1990, 55, 6066Ϫ6068.
J. Krüger, R. W. Hoffmann, J. Am. Chem. Soc. 1997, 119,
7499Ϫ7504.
[10] [10a] M. Mortimore, G. S. Cockerill, P. Kocienski, R. Treadgold,
[10b]
Tetrahedron Lett. 1987, 28, 3747Ϫ3750.
M. Bratz, W. H.
Bullock, L. E. Overman, T. Takemoto, J. Am. Chem. Soc. 1995,
117, 5958Ϫ5966.
(1S*,8S*)-3-(Iodomethyl)-4-oxabicyclo[6.1.0]nonane (61): Oil (50:50
mixture of diastereomers). 1H NMR (250 MHz) (mixture): δ ϭ
4.10 (m, 1 H), 3.70 (m, 1 H), 3.55Ϫ3.05 (m, 3 H), 2.30Ϫ0.60 (m,
9 H), Ϫ0.20 (m, 1 H) ppm. 13C NMR (first diastereomer): δ ϭ
82.2, 70.6, 36.6, 29.5, 23.7, 14.0, 13.7, 11.1, 10.0 ppm; (second dia-
stereomer): δ ϭ 78.8, 69.7, 30.8, 30.0, 28.7, 15.5, 9.7, 8.5, 8.3 ppm.
IR (film) (mixture): ν˜max ϭ 3059, 2990, 2919, 2865, 1468, 1454,
1180, 1121, 1093, 1028 cmϪ1. C9H15IO (266.1): calcd. C 40.62, H
5.68; found C 41.21, H 5.50.
[11]
T. Fujiwara, Y. Kato, T. Taketa, Tetrahedron 2000, 56,
4859Ϫ4869.
[12] [12a]
J. H. Udding, J. P. M. Giesselink, H. Hiemstra, W. N.
[12b]
Skeckamp, J. Org. Chem. 2001, 66, 6671Ϫ6682.
S.-K.
Kang, B.-S. Ko, Y.-H. Ha, J. Org. Chem. 2001, 66, 3630Ϫ3633.
K. C. Nicolaou, C. V. C. Prasad, C.-K. Hwang, M. E. Duggan,
C. A. Veale, J. Am. Chem. Soc. 1989, 111, 5321Ϫ5330.
Y.-G. Suh, B. A. Koo, E.-N. Kim, N.-S. Choi, Tetrahedron Lett.
1995, 36, 2089Ϫ2092.
[13]
[14]
[15] [15a]
R. J. Linderman, J. Siedlecki, S. A. O’Neill, H. Sun, J.
[15b]
(1S*,8S*)-3-(Bromomethyl)-4-oxabicyclo[6.1.0]nonane (62): Oil
Am. Chem. Soc. 1997, 119, 6919Ϫ6920.
M. Delgado, J. D.
Martin, J. Org. Chem. 1999, 64, 4798Ϫ4816. [15c] S. D. Edwards,
1
(50:50 mixture of diastereomers). H NMR (250 MHz) (mixture):
T. Lewis, R. J. K. Taylor, Tetrahedron Lett. 1999, 40,
δ ϭ 4.15 (m, 1 H), 3.85Ϫ3.65 (m, 1 H), 3.65Ϫ3.47 (m, 1 H),
3.47Ϫ3.10 (m, 2 H), 2.30Ϫ0.55 (m, 9 H) ppm. 13C NMR (mixture):
δ ϭ 82.0, 78.3, 70.8, 69.9, 36.7, 35.4, 34.3, 30.0 (2 diastereomers),
29.4, 28.9, 23.7, 15.5, 14.0, 13.7, 10.0, 9.8, 8.7 ppm. IR (film):
ν˜max ϭ 3061, 2991, 2923, 2868, 1468, 1455, 1227, 1093, 1031, 670
cmϪ1. C9H15BrO (219.1): calcd. C 49.33, H 6.90; found C 49.61,
H 7.23.
[15d]
4267Ϫ4270.
M. T. Crimmins, E. A. Tabet, J. Am. Chem.
Soc. 2000, 122, 5473Ϫ5476. [15e] J. S. Clark, O. Hamelin, Angew.
Chem. Int. Ed. 2000, 39, 372Ϫ374. [15f] T. Oishi, H. Uehara, Y.
Nagumo, M. Shoji, J.-Y. Le Brazidec, M. Kosaka, M. Hirama,
Chem. Commun. 2001, 381Ϫ382.
[16]
[17]
[18]
[19]
J. S. Clark, J. G. Kentle, Tetrahedron 1999, 55, 8231Ϫ8248.
Y. Brunel, G. Rousseau, J. Org. Chem. 1996, 61, 5793Ϫ5800.
F. Homsi, G. Rousseau, Chem. Soc. Rev. 1997, 453Ϫ461.
M.-C. Roux, R. Paugam, G. Rousseau, J. Org. Chem. 2001,
66, 4304Ϫ4310.
W. F. K. Schnatter, O. Almarsson, T. C. Bruice, Tetrahedron
1991, 47, 8687Ϫ8700.
P. C. B. Page, C. M. Rayner, I. O. Sutherland, J. Chem. Soc.,
Perkin Trans. 1 1990, 1375Ϫ1382.
K. B. Sharpless, R. C. Michaelson, J. Am. Chem. Soc. 1973,
95, 6136Ϫ6137.
C. Descoins, M. Julia, Bull. Soc. Chim. Fr. 1970, 1816Ϫ1822.
B. B. Snider, G. B. Phillips, J. Org. Chem. 1983, 48, 464Ϫ469.
K. C. Nicolaou, C. V. C. Prasad, P. K. Somers, C.-K. Hwang,
J. Am. Chem. Soc. 1989, 111, 5335Ϫ5340.
F. Homsi, S. Robin, G. Rousseau, Org. Synth. 2000, 77,
206Ϫ211.
G. Rousseau, S. Robin, Tetrahedron Lett. 2000, 41, 8881Ϫ8885.
R. G. Salomon, D. J. Coughlin, S. Ghosh, M. G. Zagorski, J.
Am. Chem. Soc. 1982, 104, 998Ϫ1007.
A. Rodriguez, M. Nomen, B. W. Spur, J.-J. Godfroid, T. H.
Lee, Eur. J. Org. Chem. 2000, 2991Ϫ3000.
C. H. Lin, J. Org. Chem. 1976, 41, 4045Ϫ4047.
Received March 15, 2002
(1S*,8S*)-2-(Iodomethyl)-3-oxabicyclo[6.1.0]nonane (63): Oil. 1H
NMR (250 MHz): δ ϭ 4.07 (dd, J ϭ 13 and 7 Hz, 1 H), 3.60 (dd,
J ϭ 13 and 7 Hz, 1 H), 3.50Ϫ3.25 (m, 2 H), 2.95 (m, 1 H),
2.25Ϫ0.60 (m, 9 H), Ϫ0.09 (m, 1 H) ppm. 13C NMR: δ ϭ 77.5,
[20]
[21]
[22]
69.0, 29.1, 27.1, 26.9, 19.6, 14.4, 12.0, 8.3 ppm. IR (film): ν˜max
ϭ
3062, 2990, 2924, 2854, 1462, 1196, 1102, 1017 cmϪ1. MS (EI):
m/z (%) ϭ 266 (0.6) [Mϩ], 139 (0.4) [Mϩ Ϫ I], 127 (3), 95 (4), 85
(100), 79 (12), 67 (23), 57 (15), 55 (27), 41 (45). MS (CI; NH3):
m/z (%) ϭ 284 (42) [Mϩ ϩ NH4ϩ], 267 (100) [Mϩ ϩ Hϩ], 139 (12).
C9H15IO (266.1): calcd. C 40.62, H 5.68; found C 41.53, H 5.74.
[23]
[24]
[25]
2-(4-Iodobut-2-enyl)tetrahydropyran (64): Oil. 1H NMR (250 MHz):
δ ϭ 5.90Ϫ5.50 (m, 2 H), 4.10Ϫ3.80 (m, 3 H), 3.50Ϫ3.20 (m, 2 H),
2.25Ϫ2.05 (m, 2 H), 1.90Ϫ1.15 (m, 6 H) ppm. 13C NMR: δ ϭ
131.0, 129.7, 76.9, 68.5, 39.1, 31.4, 25.9, 23.3, 6.5 ppm. IR (film):
[26]
[27]
[28]
ν˜max ϭ 3027, 2933, 2847, 1655, 1438, 1150, 1087, 1046, 964 cmϪ1
.
MS (EI): m/z (%) ϭ 266 (0.1) [Mϩ], 139 (10) [Mϩ Ϫ I], 127 (5), 85
[29]
[30]
(100), 67 (19), 55 (24), 54 (13), 53 (8), 43 (17), 41 (40), 39 (22). MS
(CI; NH3): m/z (%) ϭ 284 (42) [Mϩ ϩ NH4ϩ], 267 (100) [Mϩ
ϩ
Hϩ], 139 (7). C9H15IO (266.1): calcd. C 40.62, H 5.68; found C
40.31, H 5.81.
[O02142]
Eur. J. Org. Chem. 2003, 463Ϫ471
471