Different pathways in the base-promoted isomerization of benzyl oxiranyl ethers

Article abstract of DOI:10.1021/jo960226d

The base-promoted isomerization of benzyl oxiranyl ethers was investigated. In particular it was shown that the reaction may proceed toward two main regioisomeric products: a benzyl vinyl ether or a 2-aryl-3-(hydroxyalkyl)oxetane, depending on subtle variations in the substitution on the phenyl ring. Disubstituted oxetanes were obtained in a stereoselective manner, thus providing a good entry to this class of synthetically useful compounds.

Full text of DOI:10.1021/jo960226d

4374
J . Org. Chem. 1996, 61, 4374-4378
Differ en t P a th w a ys in th e Ba se-P r om oted Isom er iza tion of Ben zyl
Oxir a n yl Eth er s
Alessandro Mordini,* Simona Bindi, Sabina Pecchi, Alessandro Degl’Innocenti,
Gianna Reginato, and Alessandro Serci
Centro CNR Composti Eterociclici, c/ o Dipartimento di Chimica Organica “U. Schiff”, via G. Capponi 9,
50121 Firenze, Italy
Received February 2, 1996X
The base-promoted isomerization of benzyl oxiranyl ethers was investigated. In particular it was
shown that the reaction may proceed toward two main regioisomeric products: a benzyl vinyl ether
or a 2-aryl-3-(hydroxyalkyl)oxetane, depending on subtle variations in the substitution on the phenyl
ring. Disubstituted oxetanes were obtained in a stereoselective manner, thus providing a good
entry to this class of synthetically useful compounds.
We have recently reported1,2 that oxiranyl ethers 1 can
be isomerized to hydroxy enethers 2 with good regio- and
stereocontrol, the latter being mainly due to steric
interactions in the transition state for a syn-periplanar
â-elimination3 pathway (Scheme 1).
Sch em e 2
Sch em e 1
Treatment of 5 with 1 equiv of base gave 6 as well.
We can assume that 6 is formed by initial deprotonation
of the benzylic position of 5 followed by a 1,2-Wittig
rearrangement6 with migration of the vinylic moiety.7
This unexpected pathway induced us to submit other
benzyloxy oxiranes to treatment with mixed metal bases.
The unsubstituted 1-(benzyloxy)-2,3-epoxyoctane (7), af-
ter reaction with both 1 and 2 equiv of lithium diisopro-
pylamide/potassium tert-butoxide, gave 2-phenyl-3-(1-
hydroxyhexyl)oxetane (8) as the only product (Scheme
3).
Due to the possibility of preparing 1 following the
Sharpless epoxidation protocol,4 enethers 2 may be
considered masked enantiopure 3-hydroxy aldehydes 3
if the carbon-oxygen bond of the methoxymethyl group
could be easily cleaved to afford the free carbonyl group.
2
Some problems related to the latter process (formation
of variable amounts of R,â-unsaturated aldehydes)
prompted us to extend our base-promoted methodology
to differently protected oxiranyl alcohols in order to avoid
acidic cleavage conditions. At first we chose 1-[(4-
methoxybenzyl)oxy]-2,3-epoxyoctane (4), easily prepared
from 1-hydroxy-2,3-epoxyoctane with sodium hydride and
4-methoxybenzyl bromide. When 4 was treated with 1
equiv of the equimolar mixture lithium diisopropylamide
and potassium tert-butoxide (LIDAKOR)5 in tetrahydro-
furan, the expected enether 5 was obtained as a Z:E
mixture in a 40:60 ratio (Scheme 2). The use of two equiv
of base led to a mixture of 5 and the unsaturated diol 6,
the former in a 23:77 Z:E isomeric composition and the
latter, which was then purified by chromatography and
fully characterized, as pure Z isomer.
Sch em e 3
Oxetane 8 is certainly formed by attack of the initially
formed benzylic carbanion 9 on the oxirane ring via a
4-exo ring closure.8
The reaction is stereospecific, only one diasteroisomer
being formed in the ring closure. This is probably due
X Abstract published in Advance ACS Abstracts, J une 1, 1996.
(1) Degl'Innocenti, A.; Mordini, A.; Pecchi, S.; Pinzani, D.; Reginato,
G.; Ricci, A. Synlett 1992, 803.
(2) Mordini, A.; Pecchi, S.; Capozzi, G.; Capperucci, A.; Degl'Innocenti,
A.; Reginato, G.; Ricci, A. J . Org. Chem. 1994, 59, 4784.
(3) Gschwend, H. W.; Rodriguez, H. R. Org. React. 1979, 26, 1.
(4) Finn, M. G.; Sharpless, K. B. In Asymmetric Synthesis; Morrison,
J . D., Ed.; Academic Press: London, 1985; Vol. 5, p 247.
(5) Margot, C.; Schlosser, M. Tetrahedron Lett. 1985, 26, 1035.
Mordini, A.; Ben Rayana, E.; Margot, C.; Schlosser, M. Tetrahedron
1990, 46, 2401.
(6) Wittig, G. Angew. Chem. 1970, 82, 795. Scho¨llkopf, U. Angew.
Chem. 1970, 82, 795; Angew. Chem., Int. Ed. Engl. 1970, 9, 763.
(7) Rautenstrauch, V.; Bu¨chi, G.; Wu¨est, H. J . Am. Chem. Soc. 1974,
96, 2576. Eichinger, P. C. H.; Bowie, J . H. J . Chem. Soc., Perkin Trans.
2 1990, 1763.
(8) Still, W. C. Tetrahedron Lett. 1976, 25, 2115.
S0022-3263(96)00226-5 CCC: $12.00 © 1996 American Chemical Society

Isomerization of Benzyl Oxiranyl Ethers
J . Org. Chem., Vol. 61, No. 13, 1996 4375
to steric interactions between the phenyl ring and the
alkyl chain in the transition state for a syn-selective
closure which is completely absent in the transition state
for the anti one (Scheme 4).
and the hydroxy enether 16a , in a 56:44 ratio, when the
superbasic mixture was used in pentane (Scheme 6). In
addition, 52% of the starting material was recovered. The
recovery of epoxy alcohol may be due to deprotonation of
the benzylic methyl group followed by carbon-oxygen
bond cleavage. For this reason we then turned our
attention to the 1-[(4-tert-butylbenzyl)oxy]-2,3-epoxyoc-
tane (14b) which, upon treatment with the LIDAKOR
base in THF at -50 °C, gave then a mixture of oxetane
15b and hydroxy enether 16b in a 37:63 ratio, the latter
as a 48:52 Z:E mixture (66% overall yield). When the
reaction was performed at -100 °C, a similar isomeric
ratio (15b:16b ) 25:75) was found, with a very low
overall yield (27%).
Sch em e 4
Sch em e 6
The anti relationship in compound 8 has been verified
by NOE experiments. Irradiation of the hydrogen atom
at carbon 2 of the ring caused a nuclear Overhauser effect
on the methine bonded to the hydroxyl group while
irradiation on hydrogen at carbon 3 caused an effect on
the phenyl hydrogen atoms in the ortho position.
At a first sight one might then argue that electron-
donating groups favor deprotonation of the methylene
group adjacent to the oxiranyl ring, while electron-
withdrawing substituents should enhance the acidity of
the benzylic position, thus increasing the chances for a
nucleophilic attack on the oxiranyl ring. On this basis,
we repeated the base-induced rearrangement on 1-[(4-
fluorobenzyl)oxy]-2,3-epoxyoctane (10), expecting results
similar to those obtained with the benzyl oxiranyl ether
7. Inversely, a 44:56 mixture of products 11 and 12 was
found, the former as a pure anti-stereoisomer and the
latter as a 30:70 Z:E mixture (Scheme 5).
In an attempt to rationalize the above results we have
created Scheme 7. We presume that the first deproto-
nation occurs on the benzylic position to form the ben-
zylmetallic intermediate 17 which is in equilibrium with
the transmetalated species 18, unstable and hence ir-
reversibly transformed into alcoholate 19. The benzyl-
metallic species may lead to the oxetane 20 via intramo-
lecular nucleophilic attack on the oxirane ring. The 19:
20 ratio is related to the equilibrium between the species
17 and 18. When an electron-donating group is present
on the aromatic ring (Y ) OCH3), the equilibrium is
shifted toward 18 and hence 19 is formed as exclusive
product. If Y is hydrogen or fluorine, 17 is predominant
and undergoes nucleophilic attack on the oxirane ring
in the former case, while it looks not reactive enough
toward the epoxide ring and then is slowly transformed
into the alcoholate 19, in the latter.
Sch em e 5
Sch em e 7
Furthermore we have studied 1-[(4-nitrobenzyl)oxy]-
and 1-[(4-methylbenzyl)oxy]-2,3-epoxyoctane (13 and 14a).
The former remained unchanged after treatment with
bases regardless of the reaction conditions used, and the
latter underwent decomposition to the original epoxy
alcohol. The p-nitro-substituted compound is actually
deprotonated on the benzylic position, and the benzyl-
metallic intermediate does not react intramolecularly
with the oxirane ring as shown by the formation of the
deuterated derivatives upon addition of deuterium oxide.
The p-methyl substituted ether 14a could be partially
isomerized in a 38% overall yield to both the oxetane 15a
Oxetane 8 was prepared in an optically pure form as
well. Treatment of 1-hydroxy-2-octene with tert-butyl

4376 J . Org. Chem., Vol. 61, No. 13, 1996
Mordini et al.
at 25 °C and then cooled to 0 °C. The precipitated m-
chlorobenzoic acid was rapidly filtered off and washed with
cold CH2Cl2 (2 × 3 mL). The organic solution was then washed
with saturated aqueous NaHCO3 (2 × 10 mL), saturated
aqueous Na2S2O3 (2 × 10 mL), and brine (10 mL) and dried.
After evaporation of the solvent the residue was purified by
column chromatography (petroleum ether/ether 1:2), affording
5.8 g (81%) of (E)-2,3-epoxyoctan-1-ol, which directly crystal-
lized as a white solid:14 mp 33-34 °C; 1H-NMR (CDCl3)δ 3.90
(1H, dd, J ) 12.6, 4.4), 3.60 (1H, dd, J ) 12.6, 4.4), 2.92 (2H,
m), 2.68 (1H, bs), 1.54 (2H, m), 1.3 (6H, m), 0.88 (3H, t, J )
6.6); 13C-NMR (CDCl3)δ 61.6, 58.6, 56.0, 31.5, 31.5, 25.6, 22.5,
14.0; MS m/ z 101 (M+ - C3H7, 4), 83 (95), 71 (10), 69 (12), 61
(11), 57 (67), 56 (44), 55 (100).
hydroperoxide, titanium isopropoxide, and L-(+)-diethyl
tartrate9 led to (2S,3S)-1-hydroxy-2,3-epoxyoctane in a
68% chemical yield and 96% enantiomeric excess which
was then benzylated with benzyl bromide and sodium
hydride to (S,S)-7. The latter was submitted to treat-
ment with LIDAKOR to afford (2S,3R,1′S)-2-phenyl-3-
(1′-hydroxyhexyl)oxetane (8) in a 70% yield and 96%
diastereomeric excess.
The results illustrated above show that a subtle change
in the stereoelectronic structure of benzyl oxiranyl ethers
may lead to different rearranged products. In particular,
the stereospecific formation of a disubstituted oxetane10
deserves attention, and a careful study on a wide range
of oxiranyl ethers will be undertaken.
(E)-(2S,3S)-2,3-E p oxyoct a n -1-ol. After a suspension of
powdered 4 Å molecular sieves (3.0 g) and CH2Cl2 was cooled
to -20 °C, L-(+)-diethyl tartrate (DET, 1.24 g, 6.0 mmol) and
titanium isopropoxide (1.42 g, 5.0 mmol) were consecutively
added. tert-Butyl hydroperoxide (67.0 mL of a 3 M solution
in isooctane, 200 mmol; dried by treatment with 4 Å molecular
sieves immediately before the use) was then added and the
mixture kept under stirring at -20 °C for 30 min. (E)-2-
Octenol (12.8 g, 100 mmol) was then slowly (20 min) added,
and the suspension was stirred for 4 h at -20 °C. After that
time it was poured into a solution of iron(II) sulfate heptahy-
drate (33.0 g, 120 mmol) and citric acid monohydrate (11.0 g,
60.0 mmol) at 0 °C. The phases were separated, and the
aqueous layer was extracted with ether (2 × 30 mL). The
organic phase was then stirred for 1 h at 0 °C with a 30%
solution of NaOH in brine and extracted again with ether (2
× 50 mL) after diluting with water (50 mL). The residue (12.8
g) after evaporation of the solvent was purified by recrystal-
lization from petroleum ether, giving 10.1 g (70%) of (E)-
(2S,3S)-2,3-epoxyoctan-1-ol: mp 37-38 °C (lit.9b mp, 38-39.5
Exp er im en ta l Section
Gen er a l. Air and moisture sensitive compounds were
stored in Schlenk tubes or in Schlenk burettes. They were
protected by and handled under an atmosphere of 99.99% pure
nitrogen. Ethereal extracts were dried with sodium sulfate.
The temperature of dry ice-ethanol baths is consistently
indicated as -78 °C, that of ice bath as 0 °C, and “room
temperature” as 25 °C. If no reduced pressure is specified,
boiling ranges were determined under ordinary atmospheric
conditions (720 ( 35 mmHg). Purifications by flash column
chromatography11 were performed using glass columns (10-
50 mm wide), silica gel 230-400 mesh was chosen as station-
ary phase (15 cm high), with an elution rate of 5 cm/min.
Nuclear magnetic resonance spectra of hydrogen and carbon-
13 nuclei were recorded at 200 or 300 MHz and at 50.3 or 75.5
MHz, respectively. Chemical shifts were determined relative
to the residual solvent peak (CHCl3:7.26 and 77.0 ppm,
respectively). Mass spectra were obtained at a 70 eV ioniza-
tion potential.
Ma ter ia ls. Starting materials are commercially available
unless otherwise stated. All commercial reagents were used
without further purification except diisopropylamine which
was distilled over calcium hydride. Tetrahydrofuran was
obtained anhydrous by distillation over sodium wire after the
characteristic blue color of in situ generated sodium diphen-
ylketyl12 was found to persist. Dimethylformamide was
distilled over calcium hydride and then stored over 4 Å
molecular sieves. Methylene chloride was purified by the
standard procedure, dried over calcium chloride, and stored
over 4 Å molecular sieves. Petroleum ether, unless specified,
is the 40-70 °C boiling fraction.
P r ep a r a tion of th e Ben zyloxy Oxir a n yl Eth er s. (E)-
2-Octen -1-ol. A suspension of LiAlH4 (96 mg, 25.3 mmol) in
ether (70 mL) was added, during a period of 40 min, to a stirred
solution of (E)-2-octenal (12.6 g, 100.0 mmol) in ether (30 mL),
cooled to -10 °C. The reaction mixture was stirred for 1 h at
25 °C and then treated with H2O (50 mL) and 10% H2SO4 (50
mL). The two phases were separated, the aqueous phase was
extracted with ether (2 × 50 mL), and the organic exctracts
were collected and dried. After solvent removal, 12.0 g of crude
(E)-2-octen-1-ol13 were obtained and not submitted to further
purification: 1H-NMR (CDCl3)δ 5.70 (1H, dt, J ) 15.3, 4.8),
5.60 (1H, dt, J ) 15.3, 5.3), 4.05 (2H, d, J ) 4.8), 2.04 (2H, dt,
J ) 7.8, 5.3), 1.3 (7H, m), 0.89 (3H, t, J ) 6.3).
°C); [R]20 -40.5 (c 4.04, CHCl3).
D
P r ep a r a tion of th e Ben zyl Eth er s. Gen er a l P r oce-
d u r e: Meth od A. NaH (0.24 g, 10.0 mmol) suspended in THF
(10 mL) was added to a precooled (-5 °C) solution of (E)-2,3-
epoxyoctan-1-ol (1.4 g, 10.0 mmol) in THF (10 mL). After 1 h
at -5 °C the benzyl halide (12.0 mmol) in THF (10 mL) was
added and the mixture stirred for 14 h at 25 °C before it was
treated with water-ice (25 mL) and extracted with ether (3
× 15 mL). The organic phase was washed with brine (30 mL)
and dried.
Meth od B. NaH (0.22 g, 9.0 mmol) in DMF (8 mL) was
added to a precooled (-5 °C) solution of (E)-2,3-epoxyoctan-
1-ol (0.9 g, 7.0 mmol) in DMF (8 mL). After 30 min at -5 °C
the benzyl halide (8.5 mmol) in DMF (8 mL) was added and
the mixture warmed up to 25 °C. After 4 h water-ice (5 mL)
was added, the mixture was extracted with ether (3 × 10 mL),
and the organic phase was washed with water (4 × 10 mL)
and brine (2 × 20 mL) and dried.
(E)-1-[(4-Meth oxyben zyl)oxy]-2,3-ep oxyocta n e (4). (E)-
1-[(4-Methoxybenzyl)oxy]-2,3-epoxyoctane was prepared ac-
cording to procedure A, giving 6.14 g of crude which was then
purified by column chromatography (petroleum ether/ether,
3:1), affording 3.12 g (59%) of 4: 1H-NMR (CDCl3)δ 7.3-7.2
(2H, m), 6.9-6.8 (2H, m), 4.50 (2H, AB system), 3.80 (3H, s),
3.68 (1H, dd, J ) 11.4, 3.4), 3.43 (1H, dd, J ) 11.4, 5.6), 2.93
(1H, dd, J ) 5.6, 3.4, 2.2), 2.81 (1H, app td, J ) 5.4, 2.2), 1.6-
1.2 (8H, m), 0.89 (3H, t, J ) 6.6); 13C-NMR (CDCl3)δ 159.21,
130.01, 129.35, 113.74, 72.87, 70.16, 57.00, 56.16, 55.24, 31.62,
31.54, 25.59, 22.54, 13.96; MS m/ z 138 (10), 137 (100), 136
(27), 135 (25), 121 (83), 109 (12), 78 (14), 77 (17), 55 (10).
(E)-1-(Ben zyloxy)-2,3-epoxyoctan e (7). (E)-1-(Benzyloxy)-
2,3-epoxyoctane was prepared according to procedure A, giving
4.42 g of crude product which was then purified by column
chromatography (petroleum ether/ethyl acetate, 10:1), afford-
ing 2.81 g (60%) of 7: 1H-NMR (CDCl3)δ 7.4-7.2 (5H, m), 4.58
(2H, AB system), 3.72 (1H, dd, J ) 11.4, 3.4), 3.47 (1H, dd, J
) 11.4, 5.8), 2.95 (1H, ddd, J ) 5.8, 3.4, 2.6), 2.82 (1H, app td,
J ) 5.6, 2.6), 1.6-1.2 (8H, m), 0.89 (3H, t, J ) 6.6); 13C-NMR
(CDCl3)δ 137.96, 128.39, 127.70, 73.21, 70.47, 56.98, 56.15,
(E)-2,3-Ep oxyocta n -1-ol. m-CPBA (1.72 g, 10.0 mmol) in
CH2Cl2 (15 mL) was added, during a period of 20 min, to a
solution of (E)-2-octen-1-ol (6.4 g, 5.0 mmol) in CH2Cl2 (8 mL)
under N2 at 0 °C. The reaction mixture was stirred for 15 h
(9) (a) Rossiter, B. E. in Asymmetric Synthesis; Morrison, J . D., Ed.;
Academic Press: London, 1985; Vol. 5, p 194. (b) Gao, Y.; Hanson, R.
M.; Klunder, J . M.; Ko, S. Y.; Masamune, H.; Sharpless, K. B. J . Am.
Chem. Soc. 1987, 109, 5765.
(10) Searles, S. In Comprehensive Heterocyclic Chemistry; Lwowsky,
W., Ed.; Pergamon Press: Oxford, 1984; Vol. 7, p 363.
(11) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.
(12) Schlenk, W.; Bergmann, E. Liebigs Ann. Chem. 1928, 464, 22.
(13) Hochstein, F. A.; Brown, W. G. J . Am. Chem. Soc. 1948, 70,
3484.
(14) Yadav, J . S.; Deshpande, P. K.; Sharma, G. V. M. Tetrahedron
1992, 48, 4465.

Isomerization of Benzyl Oxiranyl Ethers
J . Org. Chem., Vol. 61, No. 13, 1996 4377
31.63, 31.54, 25.61, 22.55, 13.98; MS m/ z 233 (2), 108 (17),
107 (100), 105 (20), 104 (21), 92 (26), 91 (95), 89 (12), 86 (16),
84 (26), 79 (39), 77 (22), 71 (14), 65 (38), 57 (41), 56 (12), 55
(43), 51 (17), 47 (10), 44 (11), 43 (48), 42 (20), 41 (78).
(a ) (E)-1-[(4-Meth ylben zyl)oxy]-2-octen e. Method B was
used leading to 2.36 g (70%) (E)-1-[(4-Methylbenzyl)oxy]-2-
octene which was used without further purification in the next
step: 1H-NMR (CDCl3)δ 7.3-7.0 (4H, m), 5.8-5.5 (2H, m), 4.46
(2H, s), 3.95 (2H, d, J ) 6.0), 2.34 (3H, s), 2.1-2.0 (2H, m),
1.5-1.2 (6H, m), 0.89 (3H, t, J ) 6.6).
(E)-1-[(4-F lu or oben zyl)oxy]-2,3-ep oxyocta n e (10).
A
modified procedure was used in this case. The allylic alcohol
was first benzylated and then submitted to the epoxidation
reaction.
(a ) (E)-1-[(4-F lu or oben zyl)oxy]-2-octen e. Method B was
used, affording 2.36 g (70%) of (E)-1-[(4-fluorobenzyl)oxy]-2-
octene which was used without further purification in the next
step: 1H-NMR (CDCl3)δ 7.4-7.2 (2H, m), 7.1-7.0 (2H, m), 5.65
(2H, m), 4.46 (2H, s), 3.96 (2H, d, J ) 5.8), 2.05 (2H, app q, J
) 6.7), 1.5-1.2 (6H, m), 0.89 (3H, t, J ) 6.3).
(b) (E)-1-[(4-F lu or oben zyl)oxy]-2,3-ep oxyocta n e (10).
m-CPBA (3.59 g, 21 mmol) in CH2Cl2 (30 mL) was added to
(E)-1-[(4-fluorobenzyl)oxy]-2-octene (2.36 g, 10 mmol) in CH2Cl2
(15 mL) at 0 °C during 20 min. The mixture was then warmed
up to 25 °C and stirred for 15 h. After cooling to 0 °C the
mixture was filtered to remove m-chlorobenzoic acid. The
residue was washed with CH2Cl2 (2 × 3 mL), and the organic
solution thus obtained was washed with saturated NaHCO3
(2 × 25 mL), saturated Na2S2O3 (2 × 25 mL), and saturated
NaCl (25 mL) and dried. After the solvent was removed under
reduced pressure, 2.02 g of crude product was obtained and
purified by column chromatography (petroleum ether/ethyl
acetate, 10:1), affording 1.55 g (60%) of 10: 1H-NMR (CDCl3)δ
7.4-7.2 (2H, m), 7.1-7.0 (2H, m), 4.59 (2H, AB system), 3.72
(1H, dd, J ) 11.4, 3.4), 3.44 (1H, dd, J ) 11.4, 5.4), 2.94 (1H,
ddd, J ) 5.4, 3.4, 2.6), 2.81 (1H, app td, J ) 5.4, 2.6), 1.6-1.2
(8H, m), 0.89 (3H, t, J ) 6.6); 13C-NMR (CDCl3)δ 162.34 (d, J
) 244.0), 133.71 (d, J ) 2.9), 129.45 (d, J ) 8.1), 115.24 (d, J
) 20.9), 72.49, 70.49, 56.95, 56.07, 31.60, 31.54, 25.59, 22.54,
13.97; MS m/ z 125 (94), 110 (11), 109 (100), 83 (13), 57 (15),
55 (10). Anal. Calcd for C15H21O2F: C, 71.40; H, 8.39.
Found: C, 71.74; H, 8.29.
(E)-1-[(4-Nitr oben zyl)oxy]-2,3-epoxyoctan e (13). A modi-
fied procedure was used in this case. The allylic alcohol was
first benzylated and then submitted to the epoxidation reac-
tion.
(a ) (E)-1-[(4-Nitr oben zyl)oxy]-2-octen e. Ag2O (4.63 g,
20 mmol) was added to p-nitrobenzyl bromide (6.48 g, 30 mmol)
in CH2Cl2 (30 mL). (E)-2-Octenol (2.56 g, 20 mmol) in CH2Cl2
(20 mL) was added at -5 °C, refluxed during 60 h and then
filtered through a short plug of silica gel to remove Ag2O. After
evaporation of the solvent 7.31 g of crude material were
obtained and purified by column chromatography (eluent
petroleum ether/ether 4:1) affording 1.72 g (33%) of (E)-1-[(4-
nitrobenzyl)oxy]-2-octene.
(b) (E)-1-[(4-Nitr oben zyl)oxy]-2,3-ep oxyocta n e (13). m-
CPBA (1.28 g, 7.4 mmol) in CH2Cl2 (11 mL) was added to (E)-
1-[(4-nitrobenzyl)oxy]-2-octene (0.99 g, 3.7 mmol) in CH2Cl2
(4 mL) at 0 °C during 20 min. The mixture was then warmed
up to 25 °C and stirred for 15 h. After cooling to 0 °C the
mixture was filtered to remove m-chlorobenzoic acid. The
residue was washed with CH2Cl2 (2 × 3 mL), and the organic
solution thus obtained was washed with saturated NaHCO3
(2 × 10 mL), saturated Na2S2O3 (2 × 10 mL), saturated NaCl
(10 mL) and dried. After the solvent was removed under
reduced pressure, 0.90 g of crude was obtained and purified
by column chromatography (petroleum ether/ethyl acetate, 15:
1), affording 0.52 g (50%) of 13: 1H-NMR (CDCl3)δ 8.21 (2H,
app d, J ) 8.8), 7.51 (2H, app d, J ) 8.8), 4.68 (2H, AB system),
3.84 (1H, dd, J ) 11.4, 3.0), 3.47 (1H, dd, J ) 11.4, 6.0), 2.98
(1H, m), 2.84 (1H, app td, J ) 5.4, 2.2), 1.7-1.2 (8H, m), 0.89
(3H, t, J ) 6.6); 13C-NMR (CDCl3)δ 147.34, 145.67, 127.61,
123.54, 71.81, 71.14, 56.80, 55.84, 31.53, 31.49, 25.54, 22.49,
13.90; MS m/ z 152 (21), 149 (10), 137 (15), 136 (100), 107 (10),
106 (41), 95 (10), 90 (20), 89 (24), 82 (13), 81 (17), 78 (29), 71
(14), 68 (16), 67 (11), 57 (41), 55 (33), 43 (25), 41 (28). Anal.
Calcd for C15H21NO4: C, 64.50; H, 7.58; N, 5.01. Found: C,
64.32; H, 7.62; N, 5.40.
(b) (E)-1-[(4-Meth ylben zyl)oxy]-2,3-ep oxyocta n e (14a ).
m-CPBA (2.76 g, 16 mmol) in CH2Cl2 (30 mL) was added to
(E)-1-[(4-methylbenzyl)oxy]-2-octene (1.86 g, 8 mmol) in CH2Cl2
(11 mL) at 0 °C during 20 min. The mixture was then warmed
up to 25 °C and stirred for 15 h. After cooling to 0 °C the
mixture was filtered to remove m-chlorobenzoic acid. The
residue was washed with CH2Cl2 (2 × 3 mL), and the organic
solution thus obtained was then washed with saturated
NaHCO3 (2 × 25 mL), saturated Na2S2O3 (2 × 25 mL), and
saturated NaCl (25 mL) and dried. After the solvent was
removed under reduced pressure, 1.89 g of crude was obtained
and purified by column chromatography (eluent petroleum
ether/ether, 6:1), affording 1.12 g (56%) of 14a : 1H-NMR
(CDCl3)δ 7.3-7.0 (4H, m), 4.53 (2H, AB system), 3.68 (1H, dd,
J ) 11.4, 3.2), 3.45 (1H, dd, J ) 11.4, 5.4), 2.93 (1H, ddd, J )
5.4, 3.2, 2.2), 2.81 (1H, app td, J ) 5.6, 2.2), 2.34 (3H, s), 1.6-
1.2 (8H, m), 0.89 (3H, t, J ) 6.6); 13C-NMR (CDCl3)δ 137.40,
134.88, 129.04, 127.82, 73.09, 70.27, 56.98, 56.18, 31.62, 31.54,
25.59, 22.54, 21.15, 13.96; MS m/ z 248 (2, M+), 233 (9), 122
(22), 121 (100), 119 (28), 106 (13), 105 (96), 103 (11), 93 (34),
91 (14), 79 (15), 77 (19), 57 (15), 55 (17), 43 (14), 41 (20). Anal.
Calcd for C16H24O2: C, 77.38; H, 9.74. Found: C, 77.26; H,
9.72.
(E)-1-[(4-ter t-Bu tylben zyl)oxy]-2,3-ep oxyocta n e (14b).
(E)-1-[(4-tert-Butylbenzyl)oxy]-2,3-epoxyoctane was prepared
according to procedure A, giving 3.32 g of crude which was
then purified by column chromatography (petroleum ether/
ethyl acetate, 10:1), affording 1.88 g (65%) of 14b: 1H-NMR
(CDCl3)δ 7.4-7.2 (4H, m), 4.54 (2H, AB system), 3.70 (1H, dd,
J ) 11.4, 3.2), 3.47 (1H, dd, J ) 11.4, 5.4), 2.94 (1H, m), 2.82
(1H, app td, J ) 5.4, 2.2), 1.6-1.2 (8H, m), 1.31 (9H, s), 0.89
(3H, t, J ) 6.6); 13C-NMR (CDCl3)δ 150.70, 134.92, 127.62,
125.33, 73.07, 70.43, 57.02, 56.22, 31.63, 31.56, 31.32, 25.61,
22.55, 13.98; MS m/ z 289 (1.3, M+), 164 (13), 163 (100), 147
(61), 132 (18), 131 (14), 119 (19), 117 (29), 91 (21), 57 (35), 55
(19), 43 (12), 41 (20). Anal. Calcd for C19H30O2: C, 78.56; H,
10.42. Found: C, 78.48; H, 10.82.
Isom er ization of th e Ben zyloxy Oxir an yl Eth er s. Gen -
er a l P r oced u r e. The solvent was partially evaporated under
reduced pressure from a solution of butyllithium in hexane
(0.55 mmol) and the residue dissolved at -78 °C in precooled
THF (1 mL). Then diisopropylamine (0.56 g, 0.55 mmol) and
potassium tert-butoxide (0.62 g, 0.55 mmol) were added, and
the mixture was stirred for 15 min. After the addition of the
substrate (0.55 mmol), the reaction mixture was kept 15 h at
-50 °C before it was treated with ether (3 mL) and H2O (2
mL) and allowed to reach 25 °C. The aqueous phase was then
extracted with ether (2 × 3 mL) and the organic solution dried.
After evaporation of the solvent the residue was purified.
Isom er iza tion of (E)-1-[(4-Meth oxyben zyl)oxy]-2,3-ep -
oxyocta n e (4). The general procedure was used obtaining
110 mg (84%) of a 40:60 mixture of (Z)- and (E)-1-[(4-
methoxybenzyl)oxy]-1-octen-3-ol (5).
(E)-1-[(4-Meth oxyben zyl)oxy]-1-octen -3-ol [(E)-5): 1H-
NMR (CDCl3)δ 7.4-7.2 (2H, m), 7.0-6.8 (2H, m), 6.56 (1H, d,
J ) 12.8), 4.93 (1H, dd, J ) 12.8, 8.6), 4.68 (2H, s), 4.1-4.0
(1H, m), 3.82 (3H, s), 1.6-1.2 (9H, m), 0.89 (3H, t, J ) 6.0);
13C-NMR (CDCl3)δ 159.47, 148.46, 129.33, 113.92, 107.92,
70.96, 70.81, 55.27, 55.27, 37.93, 31.69, 25.34, 22.61, 14.04;
MS m/ z 264 (M+), 121 (100), 91 (14), 78 (26), 77 (34), 55 (11).
(Z)-1-[(4-Meth oxyben zyl)oxy]-1-octen -3-ol [(Z)-5] (di-
agnostic signals): 1H-NMR (CDCl3)δ 6.09 (1H, d, J ) 5.8), 4.6-
4.4 (2H, m).
Rea ction w ith 2 equ iv of LIDAKOR. The general
procedure was followed with BuLi (1.1 mmol), diisopropyl-
amine (11 mg, 1.1 mmol), and KOtBu (123 mg, 1.1 mmol),
obtaining 148 mg of crude material which was then purified
by column chromatography (petroleum ether/ether, 1:2) to
afford 58 mg of a 23:77 mixture of (Z)- and [(E)-1-[(4-
(E)-1-[(4-Meth ylben zyl)oxy]-2,3-ep oxyocta n e (14a ). A
modified procedure was used in this case. The allylic alcohol
was first benzylated and then submitted to the epoxidation
reaction.

4378 J . Org. Chem., Vol. 61, No. 13, 1996
Mordini et al.
methoxybenzyl)oxy]-1-octen-3-ol (5) and 22 mg of (Z)-1-(4-
methoxyphenyl)-2-nonene-1,4-diol (6).
(52%), 1-[(4-methylbenzyl)oxy]-1-octen-3-ol (16a ) (21%, Z/E 84:
16), and 2-(4-methylphenyl)-3-(1-hydroxyhexyl)oxetane (15a )
(27%) was obtained, which after purification by column chro-
matography (petroleum ether/ethyl acetate, 3:1) gave 9 mg of
15a and 7 mg of 16a .
2-(4-Meth ylp h en yl)-3-(1-h yd r oxyh exyl)oxeta n e (15a ):
1H-NMR (CDCl3)δ 7.2-7.1 (4H, m), 5.48 (1H, d, J ) 6.2), 4.71
(2H, d, J ) 7.4), 4.0-3.8 (1H, m), 2.91 (1H, m), 2.36 (3H, s),
1.59 (1H, bs), 1.6-1.0 (8H, m), 0.88 (3H, t, J ) 4.4); 13C-NMR
(CDCl3)δ 139.49, 137.83, 129.23, 125.64, 84.80, 72.35, 70.02,
49.74, 34.96, 31.69, 25.00, 22.54, 21.19, 13.97; MS m/ z 167
(9), 149 (100), 121 (36), 119 (14), 105 (12), 97 (15), 94 (11), 93
(13), 91 (13), 85 (22), 84 (24), 83 (19), 71 (27), 70 (13), 69 (28),
57 (49), 55 (39). Anal. Calcd for C16H24O2: C, 77.38; H, 9.14.
Found: C, 77.10; H, 10.00.
(Z)-1-(4-Meth oxyp h en yl)-2-n on en e-1,4-d iol (6): 1H-NMR
(CDCl3)δ 7.4-7.2 (2H, m), 7.0-6.8 (2H, m), 5.76 (1H, ddd, J
) 7.2, 5.6, 0.8), 5.56 (1H, ddd, J ) 7.2, 5.6, 0.8), 5.52 (1H, d,
J ) 5.6), 4.6-4.5 (1H, m), 3.80 (3H, s), 2.8-2.2 (2H, m), 1.4-
1.2 (6H, m), 0.86 (3H, t, J ) 4.6); 13C-NMR (CDCl3)δ 159.14,
135.30, 134.30, 133.94, 127.39, 114.04, 69.59, 67.76, 55.29,
31.19, 31.67, 25.01, 22.56, 13.98; MS m/ z 264 (0.05, M+), 247
(6), 246 (28), 189 (100), 175 (48), 163 (18), 150 (34), 147 (35),
137 (16), 135 (76), 121 (34), 115 (21), 109 (21), 107 (15), 103
(15), 94 (25), 91 (35), 84 (18), 81 (38), 78 (17), 77 (61), 55 (24),
43 (37).
Isom er iza t ion of (E)-1-(Ben zyloxy)-2,3-ep oxyoct a n e
(7). The general procedure was used, obtaining 81 mg (70%)
of a crude product which was then purified by column
chromatography (petroleum ether/ether, 1:2), giving 38 mg
(33%) 2-phenyl-3-(1-hydroxyhexyl)oxetane (8): 1H-NMR (CD-
Cl3)δ 7.5-7.2 (5H, m), 5.52 (1H, d, J ) 6.6), 4.72 (2H, d, J )
7.6), 4.0-3.9 (1H, m), 2.91 (1H, m), 1.63 (1H, d, J ) 5.4), 1.5-
1.2 (8H, m), 0.87 (3H, t, J ) 6.2); 13C-NMR (CDCl3)δ 142.44,
128.55, 127.99, 125.51, 84.77, 72.21, 70.10, 49.58, 34.93, 31.67,
24.99, 22.54, 13.98; MS m/ z 163 (7), 133 (12), 115 (12), 108
(13), 107 (92), 105 (48), 103 (13), 99 (17), 91 (20), 86 (19), 85
(24), 84 (42), 79 (75), 77 (59), 72 (80), 67 (12), 57 (100), 55 (58),
51 (23), 43 (71).
(Z)-1-[(4-Meth ylben zyl)oxy]-1-octen -3-ol [(Z)-16a ]: 1H-
NMR (CDCl3)δ 7.2-7.0 (4H, m), 6.08 (1H, d, J ) 5.6), 4.77
(2H, s), 4.53 (1H, m), 4.6-4.4 (1H, m), 2.35 (3H, s), 1.7-1.1
(9H, m), 0.88 (3H, t, J ) 6.2); 13C-NMR (CDCl3)δ 145.86,
137.91, 134.00, 129.23, 127.59, 110.91, 74.06, 66.45, 37.33,
31.80, 30.94, 25.08, 22.65, 21.18, 14.06; MS m/ z 167 (5), 149
(39), 121 (12), 105 (100), 85 (13), 84 (18), 69 (14), 57 (20), 55
(20).
(E)-1-[(4-Meth ylben zyl)oxy]-1-octen -3-ol [(E)-16a ]: 1H-
NMR (CDCl3)δ 7.2-7.0 (4H, m), 6.55 (1H, d, J ) 12.4), 4.92
(1H, dd, J ) 12.4, 8.0), 4.71 (2H, s), 4.2-4.0 (1H, m), 2.35 (1H,
s), 1.7-1.1 (9H, m), 0.88 (3H, J ) 6.2). Anal. Calcd for
C16H24O2: C, 77.38; H, 9.74. Found: C, 77.56; H, 9.71.
Isom er iza tion of (E)-1-[(4-ter t-Bu tylben zyl)oxy]-2,3-
ep oxyocta n e (14b). (a ) Rea ction w ith 1 equ iv of LIDA-
KOR. The general procedure was used, obtaining 96 mg (66%)
of a 63:37 mixture of the two isomeric 1-[(4-tert-butylbenzyl)-
oxy]-1-octen-3-ol (16b) (Z:E ) 48:52) and 2-(4-tert-butylphenyl)-
3-(2-hydroxyhexyl)oxetane (15b). After a further purification
by column chromatography (eluent petroleum ether/ethyl
acetate, 3:1), 16b (32 mg) and 15b (30 mg) were obtained.
2-(4-ter t-Bu tylph en yl)-3-(2-h ydr oxyh exyl)oxetan e (15b):
1H-NMR (CDCl3)δ 7.4-7.2 (4H, m), 5.49 (1H, d, J ) 6.2), 4.70
(2H, app d, J ) 7.8), 4.0-3.9 (1H, m), 2.94 (1H, m), 1.63 (1H,
d, J ) 5.2), 1.5-1.2 (8H, m), 1.33 (9H, s), 0.87 (3H, t, J ) 6.0);
13C-NMR (CDCl3)δ 151.06, 139.40, 125.48, 125.40, 84.70, 72.32,
70.01, 49.41, 34.96, 34.58, 31.69, 31.32, 25.01, 22.54, 13.96;
MS m/ z 290 (0.1, M+), 163 (100), 147 (79), 115 (11), 91 (26),
86 (11), 84 (18), 57 (58), 55 (17). Anal. Calcd for C19H30O2: C,
78.57; H, 10.41. Found: C, 78.33; H, 10.58.
(2S,3R,1′S)-2-P h en yl-3-(1′-h ydr oxyh exyl)oxetan e 8: [R]20
-31.0 (c 0.98, CHCl3).
D
Isom er iza tion of (E)-1-[(4-F lu or oben zyl)oxy]-2,3-ep -
oxyocta n e (10). The general procedure was used obtaining
79 mg (63%) of a 56:44 mixture of the two isomeric 1-[(4-
fluorobenzyl)oxy]-1-octen-3-ol (12) (Z:E ) 30:70) and 2-(4-
fluorophenyl)-3-(2-hydroxyhexyl)oxetane (11). After a further
purification by column chromatography (petroleum ether/ethyl
acetate, 3:2), 12 (42 mg) and 11 (32 mg) were obtained.
2-(4-Flu or oph en yl)-3-(2-h ydr oxyh exyl)oxetan e (11): 1H-
NMR (CDCl3)δ 7.5-7.3 (2H, m), 7.1-7.0 (2H, m), 5.50 (1H, d,
J ) 6.6), 4.70 (2H, app d, J ) 7.6), 4.0-3.9 (1H, m), 2.89 (1H,
m), 1.57 (1H, d, J ) 5.4), 1.5-1.2 (8H, m), 0.87 (3H, t, J )
6.6); 13C-NMR (CDCl3)δ 162.50 (d, J ) 246.7), 138.28 (d, J )
3.0), 127.38 (d, J ) 7.5), 115.45 (d, J ) 21.9), 84.16, 72.08,
69.94, 49.81, 34.96, 31.69, 24.96, 22.53, 13.96; MS m/ z 251
(0.1, M+ - 1), 125 (100), 123 (17), 97 (12), 86 (13), 84 (25), 72
(19), 57 (41), 55 (12), 43 (15). Anal. Calcd for C15H21O2F: C,
71.40; H, 8.39. Found: C, 71.11; H, 8.63.
(E)-1-[(4-F lu or oben zyl)oxy]-1-octen -3-ol [(E)-12]: 1H-
NMR (CDCl3)δ 7.4-7.2 (2H, m), 7.1-7.0 (2H, m), 6.55 (1H, d,
J ) 12.8), 4.93 (1H, dd, J ) 12.8, 8.6), 4.72 (2H, s), 4.1-4.0
(1H, m), 1.6-1.2 (9H, m), 0.89 (3H, t, J ) 6.8); MS m/ z 251
(0.2, M+ - 1), 110 (18), 109 (100), 83 (14), 43 (14), 41 (12).
Anal. Calcd for C15H21O2F: C, 71.40; H, 8.39. Found: C, 71.36;
H, 8.37.
(E)-1-[(4-ter t-Bu tylben zyl)oxy]-1-octen -3-ol [(E)-16b]:
1H-NMR (CDCl3)δ 7.4-7.2 (4H, m), 6.57 (1H, d, J ) 12.4), 4.93
(1H, dd, J ) 12.4, 8.4), 4.72 (2H, s), 4.1-4.0 (1H, m), 1.6-1.2
(9H, m), 1.32 (9H, s), 0.88 (3H, t, J ) 6.2); 13C-NMR (CDCl3)δ
151.12, 145.99, 133.59, 127.53, 125.46, 107.88, 73.98, 71.07,
37.93, 34.56, 31.69, 31.29, 25.34, 22.64, 14.04; MS m/ z 149
(10), 148 (19), 147 (100), 132 (25), 131 (13), 119 (13), 117 (39),
115 (15), 105 (12), 91 (25), 57 (11), 55 (11). Anal. Calcd for
C19H30O2: C, 78.57; H, 10.41. Found: C, 78.77; H, 10.32.
(Z)-1-[(4-ter t-Bu tylben zyl)oxy]-1-octen -3-ol [(Z)-16b]:
1H-NMR (CDCl3)δ 7.4-7.2 (4H, m), 6.10 (1H, d, J ) 5.8), 4.78
(2H, s), 4.7-4.5 (2H, m), 1.6-1.2 (9H, m), 1.32 (9H, s), 0.88
(3H, t, J ) 6.2); 13C-NMR (CDCl3)δ 148.59, 145.99, 134.03,
127.28, 125.46, 110.79, 73.98, 66.45, 37.33, 34.56, 31.78, 31.29,
25.08, 22.64, 14.04.
(Z)-1-[(4-F lu or oben zyl)oxy]-1-octen -3-ol [(Z)-12]: 1H-
NMR (CDCl3)δ 7.4-7.2 (2H, m), 7.1-7.0 (2H, m), 6.07 (2H, d,
J ) 5.4), 4.77 (2H, s), 4.6-4.5 (2H, m), 1.6-1.2 (9H, m), 0.9-
0.8 (3H, m).
Isom er iza tion of (E)-1-[(4-Meth ylben zyl)oxy]-2,3-ep -
oxyocta n e (14a ). A solution of butyllithium in hexane (0.55
mmol), diisopropylamine (56 mg, 0.55 mmol), and potassium
tert-butoxide (62 mg, 0.55 mmol) was mixed together in
pentane (3 mL). After 15 min, 14a (124 mg, 0.50 mmol) was
added and the mixture stirred for 15 h at 25 °C before it was
treated with ether (3 mL) and H2O (2 mL). The aqueous phase
was then extracted with ether (2 × 3 mL) and the organic
solution dried. After evaporation of the solvent 44 mg of a
mixture of (E)-1-[(4-methylbenzyl)oxy]-2,3-epoxyoctane (14a )
Ack n ow led gm en t. Financial support provided by
the Consiglio Nazionale delle Ricerche is gratefully
acknowledged.
J O960226D