Superbase-promoted rearrangement of oxiranes to cyclopropanes

Article abstract of DOI:10.1016/j.tet.2005.01.102

Aryl- and alkenyl substituted oxiranes, when submitted to treatment with superbasic reagents, undergo a highly regio- and stereoselective rearrangement leading to cyclopropylmethanol derivatives. The process can also be applied to mono- and dihydroxy subs

Full text of DOI:10.1016/j.tet.2005.01.102

Tetrahedron 61 (2005) 3349–3360
Superbase-promoted rearrangement of oxiranes to cyclopropanes
*
Alessandro Mordini, Daniela Peruzzi, Francesco Russo, Michela Valacchi, Gianna Reginato
and Alberto Brandi
Istituto di Chimica dei Composti Organometallici, Dipartimento di Chimica Organica ‘U. Schiff’, Via della Lastruccia 13,
50019 Sesto Fiorentino, Firenze, Italy
Received 2 November 2004; revised 6 January 2005; accepted 21 January 2005
Dedicated to Prof. Manfred Schlosser on the occasion of his 70th birthday
Abstract—Aryl- and alkenyl substituted oxiranes, when submitted to treatment with superbasic reagents, undergo a highly regio- and
stereoselective rearrangement leading to cyclopropylmethanol derivatives. The process can also be applied to mono- and dihydroxy
substituted substrates thus leading to polyhydroxylated cyclopropanes.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
efficient in promoting 4-exo and 7-endo ring forming
reactions from substituted oxiranyl ethers and this
encouraged us to investigate additional possible intra-
molecular cyclization processes induced by formation of
carbanions suitably positioned in oxirane derivatives.
The usefulness of superbasic reagents1,2 in promoting small
ring heterocycle rearrangements has been clearly shown in
recent years. We have indeed demonstrated that alkoxyalkyl
oxiranyl-1 (XZO) and aziridinyl ethers 1 (XZNTs) are
efficiently converted into the isomeric hydroxy-3–7 2 (XZ
O) or amino vinylethers 2 (XZNTs),8,9 respectively. In
addition we have shown that benzyl-1 (XZO, YZaryl),
allyl-1 (XZO, YZalkenyl) and propargyl 1 (XZO, YZ
alkynyl) oxiranyl ethers can be conveniently rearranged to
the corresponding di- or trisubstituted oxetanes 3 (XZO)10–14
usually with very high regio- and stereoselectivity. Both the
benzyl oxiranyl ethers 1 (XZO, YZC6H5) and the
rearranged phenyl substituted oxetanes 3 (XZO, YZ
C6H5) can also be further isomerized to unsaturated 1,4-
diols 4 with perfect Z-stereocontrol.13,15 More recently, we
have also reported that monosubstituted oxiranyl allyl ethers
1 (XZO, YZalkenyl, RZH) are regio- and stereo-
selectively converted into the isomeric disubstituted
tetrahydrooxepines 5 (XZO, RZH).16 All these transform-
ations have been carried out making use of superbases1,2
and in particular the equimolar mixtures butyllithium/
potassium tert-butoxide (Schlosser’s base, LICKOR)1 and
butyllithium/diisopropylamine/potassium tert-butoxide
(LIDAKOR)17 (Scheme 1).
Scheme 1.
In this paper, we describe our results on the synthesis of
cyclopropanes 7 through a 3-exo cyclization process
performed on alkenyl- or phenyl substituted oxiranes 6
(YZalkenyl or phenyl) (Scheme 2).
2. Results and discussion
These results clearly show that superbasic reagents are very
It is well known that cyclopropanes can be obtained from
oxiranes through 3-exo cyclizations induced by carbanions.
Usually the formation of the carbanionic species is
Keywords: Superbase; Cyclopropanes; Rearrangement; 3-exo Cyclization.
* Corresponding author. Tel.: C39 055 4573555; fax: C39 055 4573580;
e-mail: alessandro.mordini@unifi.it
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.01.102

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A. Mordini et al. / Tetrahedron 61 (2005) 3349–3360
The use of stoichiometric amounts of the base resulted only
in recovery of starting material and a decrease of the amount
of olefin formed.
On the other hand, the use of the less nucleophilic reagent
LIDAKOR, gave only the expected phenyl cyclopropyl
methanol 11 in good yields and very good stereoselectivity,
the trans-cyclopropane being the only detectable product
(Scheme 5).
Scheme 2.
performed on substrates possessing good activating groups
(nitriles,18–20 esters,21,22 amides,23 ketones,24 sulfones,25–27
sulfides28) while very little is known on similar processes
performed on oxiranes without a heterosubstituent able to
stabilize the carbanionic intermediates. The only known
results in this field date back to the 1970s when it was first
reported29,30 that lithium amides in the presence of HMPT
as a cosolvent were able to convert a few 1-aryl- and
1-alkenyl-3,4-epoxyalkanes into the corresponding cyclo-
propanes. Drawbacks of this reaction are the use of the
highly toxic HMPT, the low stereoselectivity and the quite
limited number of examples. Thus, we decided to see if the
use of the superbasic mixtures, LIDAKOR and LICKOR,
could positively affect the outcome of the 3-exo cyclization
reaction on a variety of suitably substituted oxiranes. For
this purpose, we synthesized a series of arylethyl oxiranes
and we submitted them to reaction with superbasic reagents.
The simplest substrate in the series, the 1,2-epoxy-4-
phenylbutane 8 easily obtained by epoxidation of 4-phenyl-
1-butene, served as a test for finding the best organometallic
base and reaction conditions. When 8 was treated with an
excess of TMEDA-activated sec-butyllithium or with the
superbasic mixture LICKOR, it gave no 3-exo cyclization
products but instead the two olefins 9 and 10, respectively as
the only detected products (Scheme 3).
A similar behaviour was observed also with a representative
series of di- and trisubstituted oxiranes which were prepared
by epoxidation of the corresponding olefins, all synthesized
by Wittig olefination. A 67:33 mixture of cis and trans-3,4-
epoxy-2-methyl-6-phenylhexane 12 gave the corresponding
cyclopropane 15 in 64% yield as a 67:33 anti:syn mixture by
treatment with 2 equiv LIDAKOR in THF at K50 8C; no cis
cyclopropanes were detected in the reaction mixture. When
the oxirane ring has a methyl substituent as in the 2,3-
epoxy-5-phenylpentane 13 and in the 2,3-epoxy-2-methyl-
5-phenylpentane 14 cases, treatment with LIDAKOR
afforded again the desired trans-cyclopropyl derivatives
16 and 17, respectively in good yields but contaminated by
the allylic alcohols 18 and 19. Their formation is clearly
due to a b-elimination process induced by deprotonation of
the methyl groups. Interestingly such pathway became
exclusive when LICKOR was used, showing the higher
efficiency of the metal amide base towards the deprotona-
tion of benzylic positions (Scheme 6).
The LIDAKOR promoted rearrangement leading to cyclo-
propanes works well even when the intermediate metallic
species is of the allylic type.33 Thus, 5,6-epoxy-1-hexene 20
was converted into trans-vinyl cyclopropylmethanol 21 in
75% yield with LIDAKOR in THF at K50 8C (Scheme 7).
Such results can be explained by assuming that an initial
a-metalation of the oxirane ring is then followed by
isomerization to a carbene species which then adds a
second organometallic reagent and eventually leads to the
olefin via lithium oxide elimination (Scheme 4).31,32
In order to extend the scope of the described 3-exo
cyclization process we then turned our attention to
Scheme 3.
Scheme 4.
functionalized 1-aryl-3,4-epoxy substrates. Methoxy sub-
stituted compounds 22, 23 and 24 derived from the
corresponding allylic alcohols via m-CPBA epoxidation,
were first selected to test their reaction with superbases. The
position of the methoxy group is clearly crucial in driving
Scheme 5.

A. Mordini et al. / Tetrahedron 61 (2005) 3349–3360
3351
Scheme 6. Reaction conditions: 2 equiv LIDAKOR, THF, K508C, 16 h; 2 equiv LICKOR, pentane, 258C, 16 h.
allylic alcohol, was treated with LIDAKOR. In this case the
benzylic deprotonation again becomes the predominant
pathway due to the decreased availability of the methine
proton, and then follows the 3-exo cyclization pathway to
the cyclopropyl derivative (Scheme 8).
Scheme 7.
the base-promoted reaction. Oxirane 22 was in fact
converted into the vinyl oxirane 25 via benzylic metalation
followed by elimination of the methoxy group. When the
substituent is instead located on the other side of the oxirane
The reaction is again highly stereoselective leading to the
trans-stereoisomer only, and shows that this can be a
convenient way to access cyclopropyl diols or polyols
starting from oxiranyl ethers derived from secondary allylic
alcohols. In order to further prove this finding and to study
in more details the stereochemical outcome of the
isomerization reaction, we synthesized the 1,2-di-tert-
butyldimethylsilyloxy-3,4-epoxy-6-phenylhexane in its dia-
stereomeric forms syn,cis (28, R,R,R), syn,trans (29, R,R,S)
and anti,trans (30, R,S,R). Compound 28 was prepared by
diastereoselective epoxidation with tert-butylhydro-
peroxide, titanium isopropoxide and (C)-L-diethyl tartrate
of the corresponding cis-olefin 31 which in turn has been
prepared by Wittig olefination of the 2,3-isopropylidene-D-
glyceraldehyde34 with phenylpropyl triphenylphosphonium
bromide (Scheme 9).
The two oxiranes 29 and 30 were obtained as a 50:50
mixture by m-CPBA epoxidation of the corresponding
trans-olefin 32 which was prepared by the same Wittig
olefination as described above, followed by a photo-
chemically induced isomerization of the double bond in
the presence of diphenyl disulfide.34 The two diastereomers
29 and 30 were separated and then used, together with 28, in
the base-promoted rearrangements (Scheme 10).
Scheme 8. Reaction conditions: 2 equiv LIDAKOR, THF, K508C, 16 h.
ring as in 23, treatment with a superbase produced a ring-
opened product 26 derived from deprotonation at the
methylene a to the oxirane ring and the methoxy group,
followed by b-elimination. No 3-exo ring-closure com-
pounds could be detected in both cases while the
cyclopropyl derivative 27 became the only observed
reaction product when oxirane 24, derived from a secondary
Treatment of compounds 28–30 with the superbasic reagent
LIDAKOR, gave the same result: all diastereoisomers were
Scheme 9.

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A. Mordini et al. / Tetrahedron 61 (2005) 3349–3360
Scheme 10.
converted into the corresponding trans-cyclopropanes
33–35a,b with a perfect stereocontrol thus showing that
changes in the configuration of the oxirane ring or in the
relative stereochemistry of the silyloxy substituent did not
affect the outcome of the rearrangement process.
seems to be of a general applicability allowing the synthesis
of functionalized cyclopropanes.
3. Experimental
In all cases the reaction mixture contained actually two
isomers which, upon a careful NMR investigation, turned
out to be those deriving from a tert-butyldimethylsilyl group
migration from one oxygen to the neighbouring one during
the isomerization process. This was then further demon-
strated for the cyclopropane derivatives 34a,b and 35a,b
which by fluoride deprotection of all the silylated
hydroxy groups afforded the triols 36 and 37, respectively
(Scheme 11).
3.1. General procedures
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.
Purifications by flash column chromatography35 were
performed using glass columns (10–50 mm wide); silica
gel 230–400 mesh was chosen as stationary phase (15 cm
high), with an elution rate of 5 cm/min. Nuclear magnetic
resonance spectra of hydrogen nuclei were recorded at 200
or 400 MHz. Chemical shifts were determined relative to
the residual solvent peak (CHCl3: 7.26 ppm). Coupling
constants (J) are measured in Hz. Coupling patterns are
In conclusion, we have found that superbasic mixtures can
be conveniently used for the 3-exo cyclization of suitably
substituted oxiranes lacking strong electron withdrawing
substituents. The reaction is highly stereoselective and
Scheme 11.

A. Mordini et al. / Tetrahedron 61 (2005) 3349–3360
3353
described by abbreviations: s (singlet), d (doublet), t
(triplet), q (quartet), quint (quintet), dd (doublet of a
doublet), m (multiplet), bs (broad singlet), app (apparent).
Nuclear magnetic resonance spectra of carbon-13 nuclei
were recorded at 50.3 or 100 MHz. Chemical shifts were
determined relative to the residual solvent peak (CHCl3:
77.0 ppm). Mass spectra were obtained at a 70 eV ionization
potential.
2.0 mmol, 1 equiv) in 20 mL CH2Cl2. The mixture was
allowed to reach room temperature and then stirred
overnight. The reaction mixture was cooled to K20 8C,
and the m-chlorobenzoic acid was filtered on Celite. The
organic layer was washed twice with satd Na2S2O3, once
with satd NaHCO3 and dried over Na2SO4. The crude
product was purified by flash chromatography (petroleum
ether:ethyl acetate 10:1) giving 215 mg (49% yield) of 12 as
a colourless oil in a 67:33 cis/trans mixture. 1H NMR
(CDCl3, 200 MHz) d cis: 7.32–7.17 (5H, m); 3.07–2.96 (1H,
m); 2.92–2.70 (2H, m); 2.63 (1H, dd, JZ9.2, 4.2 Hz); 1.98–
1.69 (2H, m); 1.63–1.38 (1H, m); 1.13 (3H, d, JZ6.6 Hz);
0.94 (3H, d, JZ6.6 Hz). trans: 7.32–7.17 (5H, m); 3.07–
2.96 (1H, m); 2.92–2.70 (2H, m); 2.47 (1H, dd, JZ6.6,
1.9 Hz); 1.98–1.69 (2H, m); 1.63–1.38 (1H, m); 1.01 (3H, d,
JZ6.4 Hz); 0.91 (3H, d, JZ6.6 Hz).
3.2. Materials
Starting materials were commercially available unless
otherwise stated. All commercial reagents were used
without further purification except diisopropyl amine,
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
diphenylketyl36 was found to persist. Pentane was stored
over lithium aluminum hydride. Methylene chloride was
3.3.3. Preparation of cis-2,3-epoxy-5-phenylpentane
13.37 (Z)-5-Phenylpent-2-ene. A solution 1.6 M of BuLi
(3.2 mL, 1.0 equiv, 5.1 mmol) in hexane was added, at
K78 8C under N2, to a solution of triphenylethyl-
phosphonium bromide (2.00 g, 1.05 equiv, 5.4 mmol) in
15 mL of dry THF. The mixture was stirred at K78 8C for
2 h and then 3-phenylpropionaldehyde (0.76 mL,
1.13 equiv, 5.8 mmol) was added. The mixture was allowed
to reach room temperature and then stirred for 12 h.
Petroleum ether was added and the triphenylphosphinoxide
was filtered on Celite. After evaporation of the solvent the
residue was purified by flash chromatography (petroleum
ether:ethyl acetate 10:1) to give 296 mg of (Z)-5-phenyl-
pent-2-ene (40% yield) as a colourless oil. 1H NMR (CDCl3,
200 MHz) d: 7.39–7.17 (5H, m); 5.49 (2H, appd, JZ
5.4 Hz); 2.83–2.58 (2H, m); 2.46–2.32 (2H, m); 1.60 (3H, d,
JZ4.4 Hz).
˚
dried over calcium chloride and stored over 4 A molecular
sieves. Petroleum ether, unless specified, was the 40–70 8C
boiling fraction.
3.3. Preparation of oxiranes
3.3.1. 1,2-Epoxy-4-phenylbutane 8.37 m-CPBA (1. 035 g,
6.0 mmol, 2 equiv) was added to a cooled (0 8C) solution of
the 4-phenyl-1-butene (400 mg, 3.0 mmol, 1 equiv) in
30 mL CH2Cl2. The mixture was allowed to reach room
temperature and then stirred overnight. The reaction
mixture was cooled to K20 8C, and the m-chlorobenzoic
acid was filtered on Celite. The organic layer was washed
twice with satd Na2S2O3, once with satd NaHCO3 and dried
over Na2SO4. The crude product was purified by flash
chromatography (petroleum ether:ethyl acetate 10:1) giving
1
cis-2,3-Epoxy-5-phenylpentane 13. m-CPBA (0.35 g,
2.0 mmol, 2 equiv) was added to a cooled (0 8C) solution
of the (Z)-5-phenylpent-2-ene (146 mg, 1.0 mmol, 1 equiv)
in 10 mL CH2Cl2. The mixture was allowed to reach room
temperature and then stirred overnight. The reaction
mixture was cooled to K20 8C, and the m-chlorobenzoic
acid was filtered on Celite. The organic layer was washed
twice with satd Na2S2O3, once with satd NaHCO3 and dried
over Na2SO4. After the solvent was evaporated 162 mg
(100% yield) of the crude epoxide 13 were obtained and
173 mg (39% yield) of oxirane 8 as a yellow oil. H NMR
(CDCl3, 200 MHz) d: 7.38–7.18 (5H, m); 3.05–2.94 (1H,
m); 2.93–2.71 (3H, m); 2.51 (1H, dd, JZ4.8, 2.6 Hz); 1.95–
1.80 (2H, m).
3.3.2. Preparation of cis,trans-3,4-epoxy-2-methyl-6-
phenylhexane 12.38 (Z,E)-2-Methyl-6-phenyl-3-hexene.
To a stirred suspension of isobutyltriphenylphosphonium
bromide (1.26 g, 1.05 equiv, 3.15 mmol) in 8 mL of dry
THF a 1.6 M hexane solution of BuLi (1.96 mL, 1.0 equiv,
3.00 mmol) was added dropwise under N2 at K78 8C until
the mixture became homogeneous and deep red coloured.
After 2 h, 3-phenylpropionaldehyde (0.40 mL, 1.0 equiv,
3.00 mmol) was added dropwise. The mixture was allowed
to reach room temperature and then stirred for 6 h.
Petroleum ether was added and the triphenylphosphine
oxide was filtered on Celite. After evaporation of the
solvent, 0.52 g (99% yield) of a 67:33 mixture of (Z,E)-2-
methyl-6-phenyl-3-hexene was obtained and used in the
next step without any further purification. 1H NMR (CDCl3,
200 MHz) d Z: 7.37–7.20 (5H, m); 5.48–5.18 (2H, m); 2.95–
2.67 (4H, m); 2.46–2.35 (1H, appq, JZ6.4 Hz); 0.93 (6H, d,
JZ6.6 Hz). E: 7.37–7.20 (5H, m); 5.48–5.18 (2H, m); 2.95–
2.67 (4H, m); 2.65–2.47 (1H, m); 1.00 (6H, d, JZ7.0 Hz).
1
used in the next step without any further purification. H
NMR (CDCl3, 200 MHz) d: 7.35–7.17 (5H, m); 3.11–2.65
(4H, m); 1.86 (2H, appquint); 1.21 (3H, d, JZ5.6 Hz).
3.3.4. Preparation of 2,3-epoxy-2-methyl-5-phenyl-
pentane 14.37 2-Methyl-5-phenylpent-2-ene. Isopropyl-
triphenylphosphonium bromide/sodium amide mixture
(3.60 g, 8.3 mmol, 1.0 equiv) was poured, under N2, in
20 mL of dry THF. After 30 min, 3-phenylpropionaldehyde
(1.32 mL, 10.0 mmol, 1.2 equiv) was added and the mixture
stirred at 40 8C under N2 overnight. Petroleum ether was
then added and the precipitate was filtered on silica. After
evaporation of the solvent, 1.55 g (97% yield) of 2-methyl-
5-phenylpent-2-ene was obtained as a dark yellow oil and
1
used in the next step without any further purification. H
cis,trans-3,4-Epoxy-2-methyl-6-phenylhexane 12. m-CPBA
(0.69 g, 4.0 mmol, 2 equiv) was added to a cooled (0 8C)
solution of the (E,Z)-2-methyl-6-phenyl-3-hexene (350 mg,
NMR (CDCl3, 200 MHz) d: 7.42–7.18 (5H, m); 5.23 (1H, t,
JZ6.7 Hz); 2.80–2.62 (2H, m); 2.34 (2H, dt, JZ8.8,
6.7 Hz); 1.74 (3H, s); 1.62 (3H, s).

3354
A. Mordini et al. / Tetrahedron 61 (2005) 3349–3360
2,3-Epoxy-2-methyl-5-phenylpentane 14. m-CPBA (1.72 g,
10.0 mmol, 2 equiv) was added to a cooled (0 8C) solution
of the 2-methyl-5-phenylpent-2-ene (1.60 g, 5.0 mmol,
1 equiv) in 40 mL CH2Cl2. The mixture was allowed to
reach room temperature and then stirred overnight. The
reaction mixture was cooled to K20 8C, and the m-chloro-
benzoic acid was filtered on Celite. The organic layer was
washed twice with satd Na2S2O3, once with satd NaHCO3
and dried over Na2SO4. The crude product was purified by
flash chromatography (petroleum ether:ethyl acetate 10:1)
ether:ethyl acetate 4:1) giving 112 mg (52% yield) of a 1:1
syn:anti diastereomeric mixture of 22 as a yellow oil. First
1
diastereoisomer: H NMR (CDCl3, 200 MHz) d: 7.41–7.19
(5H, m); 3.49 (3H, s); 3.32–3.20 (1H, m); 3.18–2.73 (4H,
m); 2.66 (1H, app t, JZ4.4 Hz). Second diastereoisomer: 1H
NMR (CDCl3, 200 MHz) d: 7.41–7.19 (5H, m); 3.36 (3H,
s); 3.32–3.20 (1H, m); 3.18–2.73 (4H, m); 2.25 (1H, dd, JZ
4.7, 2.5 Hz). MS (m/z, %): 178 (0.2, MC); 148 (14); 146 (34,
MCKOMe– 1); 135 (7); 119 (14); 115 (18); 103 (19); 91
(54); 88 (55); 87 (100); 77 (18); 65 (28); 57 (34).
1
giving 436 mg (50% yield) of 14 as a colourless oil. H
NMR (CDCl3, 200 MHz) d: 7.32–7.10 (5H, m); 2.98–2.61
(3H, m); 1.99–1.65 (2H, m); 1.27 (3H, s); 1.12 (3H, s).
3.3.6. Preparation of trans-2,3-epoxy-1-methoxy-5-
phenylpentane 23.39 Ethyl 5-phenyl-(E)-2-pentenoate.
NaH (600 mg, 1.15 equiv, 17.2 mmol) in a 60% dispersion
in mineral oil, was suspended in 25 mL under N2 and the
mixture was cooled to 0 8C. A solution of diisopropyl-
(ethoxycarbonylmethyl)phosphonate (4.1 mL, 1.1 equiv,
16.5 mmol) in 10 mL of dry THF was added slowly; after
stirring at room temperature for 30 min, the mixture was
cooled to 0 8C and 3-phenylpropionaldehyde (1.98 mL,
1.0 equiv, 15 mmol) in 15 mL of THF was added. After
stirring at 0 8C for 1 h, satd NH4Cl was added and the
organic layer was washed twice with satd NaHCO3 and
brine, then dried over Na2SO4. After the solvent was
evaporated 3.0 g (98% yield) of the crude ethyl 5-phenyl-
3.3.5. Preparation of syn,anti-3,4-epoxy-2-methoxy-1-
phenylbutane 22. 1-Phenylbut-3-en-2-ol. Vinylmagnesium
bromide (22.5 mL, 22.5 mmol, 1.5 equiv) was added, at
0 8C under N2, to a solution of phenylacetaldehyde
(1.95 mL, 15 mmol, 1.0 equiv) in 30 mL of dry THF.
After the addition was complete the temperature was
allowed to reach 25 8C and the mixture was stirred for
2.5 h and then cooled to 0 8C. HCl (10 mL of a 1.0 M
solution) was then added and, after 30 min, the precipitate
was filtered through Celite. The aqueous layer was extracted
with Et2O, and the organic layer washed with brine and
dried over Na2SO4. After the solvent was evaporated 2.20 g
1
(E)-2-pentenoate were obtained as a yellow oil. H NMR
1
(100% yield) of 1-phenylbut-3-en-2-ol were obtained. H
(CDCl3, 200 MHz) d: 7.40–7.20 (5H, m); 7.07 (1H, dt, JZ
15.8, 6.8 Hz); 5.91 (1H, dt, JZ15.8, 1.7 Hz); 4.24 (2H, q,
JZ7.1 Hz); 2.84 (2H, t, JZ8.4 Hz); 2.58 (2H, tdd, JZ8.4,
6.8, 1.7 Hz); 1.34 (3H, t, JZ7.1 Hz).
NMR (CDCl3, 200 MHz) d: 7.42–7.05 (5H, m); 5.94 (1H,
ddd, JZ17.0, 10.3, 5.8 Hz); 5.34–4.95 (2H, m); 4.62–4.57
(1H, m); 2.87–2.60 (2H, m); 2.40 (1H, bs).
syn,anti-3,4-Epoxy-1-phenyl-2-butanol. m-CPBA (1.72 g,
10.0 mmol, 2 equiv) was added to a cooled (0 8C) solution
of the 1-phenylbut-3-en-2-ol (740 mg, 5.0 mmol, 1 equiv)
in 40 mL CH2Cl2. The mixture was allowed to reach room
temperature and then stirred overnight. The reaction
mixture was cooled to K20 8C, and the m-chlorobenzoic
acid was filtered on Celite. The organic layer was washed
twice with satd Na2S2O3, once with satd NaHCO3 and dried
over Na2SO4. The crude product was purified by flash
chromatography (petroleum ether:ethyl acetate 4:1) giving
295 mg (36% yield) of a 1:1 syn:anti mixture of 3,4-epoxy-
1-phenyl-2-butanol as a yellow oil. First diastereoisomer:
1H NMR (CDCl3, 200 MHz) d: 7.40–7.17 (5H, m); 4.07–
3.95 (1H, m); 3.08–3.00 (1H, m); 2.99–2.85 (2H, m); 2.83–
2.71 (1H, m); 2.61 (1H, dd, JZ4.8, 2.6 Hz); 2.48 (1H, bs).
(2E)-5-Phenylpent-2-en-1-ol. A solution of 3.06 g
(1.0 equiv, 15 mmol) of 5-phenyl-(E)-2-pentenoate in
35 mL of dry CH2Cl2 was cooled to K78 8C; 37 mL
(2.5 equiv, 37 mmol) of DIBAL-H 1.0 M in CH2Cl2 was
added and the mixture was stirred under N2 for 1 h; then
10 mL of H2O was added and the organic layer was washed
twice with a 10% sodium tartrate solution, once with brine,
and then dried over Na2SO4. Evaporation of the solvent
afforded 2.03 g (83% yield) of the crude (2E)-5-phenylpent-
2-en-1-ol as a pale yellow oil. 1H NMR (CDCl3, 200 MHz)
d: 7.42–7.19 (5H, m); 5.76 (2H, m); 4.13 (2H, bs); 2.77 (2H,
t, JZ7.4 Hz); 2.50–2.40 (2H, m); 1.77 (1H, bs).
trans-2,3-Epoxy-5-phenylpentan-1-ol.39 m-CPBA (3.44 g,
20.0 mmol, 2 equiv) was added to a cooled (0 8C) solution
of the (2E)-5-phenylpent-2-en-1-ol (1.62 g, 10.0 mmol,
1 equiv) in 80 mL CH2Cl2. The mixture was allowed to
reach room temperature and then stirred overnight. The
reaction mixture was cooled to K20 8C, and the m-chloro-
benzoic acid was filtered on Celite. The organic layer was
washed twice with satd Na2S2O3, once with satd NaHCO3 and
dried over Na2SO4. After the solvent was evaporated, 1.48 g
(83% yield) of the crude colourless oil trans-2,3-epoxy-5-
phenylpentan-1-ol were obtained and used in the next step
without any further purification. 1H NMR (CDCl3, 200 MHz)
d: 7.41–7.18 (5H, m); 3.90 (1H, dd, JZ12.6, 2.5 Hz); 3.61
(1H, dd, JZ12.6, 4.3 Hz); 3.33 (1H, bs); 3.05 (1H, td, JZ5.8,
2.5 Hz); 2.95–2.63 (3H, m); 2.00–1.85 (2H, m).
1
Second diastereoisomer: H NMR (CDCl3, 200 MHz) d:
7.40–7.17 (5H, m); 3.71 (1H, td, JZ6.8, 4.8 Hz); 3.08–3.00
(1H, m); 2.99–2.85 (2H, m); 2.83–2.71 (1H, m); 2.61 (1H,
dd, JZ4.8, 2.6 Hz); 2.48 (1H, bs).
syn,anti-3,4-Epoxy-2-methoxy-1-phenylbutane 22. NaH
(29 mg, 1.2 mmol, 1.2 equiv) in a 60% dispersion in mineral
oil, was suspended in dry THF (1 mL) under N2 at 0 8C.
Then a 0.5 M THF solution of the syn,anti-3,4-epoxy-1-
phenyl-2-butanol (164 mg, 1.0 mmol, 1.0 equiv) was added
and the mixture stirred at 0 8C under N2 for 45 min. The
temperature was allowed to rise to room temperature and
methyl iodide (170 mg, 1.2 mmol, 1.2 equiv) was then
added. After stirring for 6 h, ice and Et2O were added and
the aqueous layer extracted with Et2O; the organic layers
were washed with brine and dried over Na2SO4. The crude
product was purified by flash chromatography (petroleum
trans-2,3-Epoxy-1-methoxy-5-phenylpentane 23. NaH
(58 mg, 2.4 mmol, 1.2 equiv) in a 60% dispersion in mineral
oil, was suspended in dry THF (2 mL) under N2 at 0 8C.

A. Mordini et al. / Tetrahedron 61 (2005) 3349–3360
3355
Then a 0.5 M THF solution of the trans-2,3-epoxy-5-
phenylpentan-1-ol (356 mg, 2.0 mmol, 1.0 equiv) was
added and the mixture stirred at 0 8C under N2 for 45 min.
The temperature was allowed to rise to room temperature
and methyl iodide (340 mg, 2.4 mmol, 1.2 equiv) was then
added. After stirring for 6 h, ice and Et2O were added and
the aqueous layer extracted with Et2O; the organic layers
were washed with brine and dried over Na2SO4. Evapor-
ation of the solvent gave 213 mg (55% yield) of the crude 23
as a colourless oil that was used in the next step without any
(36% yield) of a 64:36 syn:anti diastereomeric mixture as a
pale yellow oil. H NMR (CDCl3, 200 MHz) d: syn: 7.38–
1
7.18 (5H, m); 3.46 (3H, s); 3.08 (1H, appquint, JZ6.6 Hz);
3.01–2.67 (4H, m); 1.92 (2H, td, JZ7.0, 6.5 Hz); 1.16 (3H,
d, JZ6.6 Hz). anti: 7.38–7.18 (5H, m); 3.38 (3H, s); 3.20
(1H, appquint, JZ6.2 Hz); 3.01–2.67 (4H, m); 1.92 (2H, td,
JZ7.0, 6.5 Hz); 1.24 (3H, d, JZ6.2 Hz). 13C NMR (CDCl3,
50 MHz) d: syn: 140.9, 128.3, 128.2, 126.0, 77.5, 61.8, 57.0,
53.8, 33.2, 32.1, 16.7. anti: 141.0, 128.3, 128.2, 125.9, 76.1,
60.4, 56.9, 56.8, 33.4, 32.0, 17.0. MS (m/z, %): 187 (1); 175
(2, MCKOMe); 173 (6); 147 (8); 129 (9); 128 (13); 117
(91); 103 (35); 91 (100); 77 (23); 58 (100).
1
further purification. H NMR (CDCl3, 200 MHz) d: 7.34–
7.15 (5H, m); 3.58 (1H, dd, JZ11.4, 2.8 Hz); 3.67 (3H, s);
3.31 (1H, dd, JZ11.4, 5.3 Hz); 2.91–2.61 (4H, m); 1.89
(2H, td, JZ7.7, 5.3 Hz).
3.4. Preparation of oxiranyl ethers from mannitol
3.4.1. Preparation of 2,3-isopropylidene-D-glyceralde-
hyde.34 1,2:5,6-Diisopropylidene-D-mannitol (787 mg,
3 mmol, 1.0 equiv) was dissolved in a mixture of CH2Cl2
(7 mL) and a saturated solution of NaHCO3 (0.4 mL);
NaIO4 (963 mg, 4.5 mmol, 1.5 equiv) was then slowly
added and the mixture stirred at room temperature. After
5 h, Na2SO4 was added with vigorous stirring. The resulting
suspension was filtered and the filtrate washed with CH2Cl2.
The organic layers were evaporated to give 709 mg (91%
yield) of the crude 2,3-isopropylidene-D-glyceraldehyde as
a colourless oil which was immediately used in the next
3.3.7. Preparation of syn,anti-trans-3,4-epoxy-2-meth-
oxy-6-phenylhexane 24. trans-2,3-Epoxy-5-phenylpenta-
nal. trans-2,3-Epoxy-5-phenylpentan-1-ol (270 mg,
1.0 equiv, 1.5 mmol) was dissolved in 15 mL of dry
CH2Cl2, and Dess Martin periodinane (950 mg, 1.5 equiv,
2.3 mmol) was added at room temperature under N2. After
1 h and 30 min Et2O (5 mL) and satd Na2S2O3 (5 mL) were
added and the aqueous layer was extracted with Et2O. The
organic layers were washed with satd NaHCO3 and brine,
then dried over Na2SO4. Evaporation of the solvent gave
260 mg (98% yield) of the crude trans-2,3-epoxy-5-
phenylpentanal as a yellow oil. 1H NMR (CDCl3,
200 MHz) d: 9.02 (1H, d, JZ6.2 Hz); 7.39–7.20 (5H, m);
3.29 (1H, td, JZ5.5, 1.9 Hz); 3.15 (1H, dd, JZ6.2, 1.9 Hz);
2.95–2.77 (2H, m); 2.10–1.92 (2H, m).
1
reaction. H NMR (CDCl3, 400 MHz) d: 9.72 (1H, d, JZ
1.9 Hz); 4.38 (1H, ddd, JZ7.4, 4.7, 1.9 Hz); 4.17 (1H, dd,
JZ8.8, 7.4 Hz); 4.10 (1H, dd, JZ8.8, 4.7 Hz); 1.49 (3H, s);
1.42 (3H, s).
syn,anti-trans-3,4-Epoxy-2-hydroxy-6-phenylhexane. trans-
2,3-Epoxy-5-phenylpentanal (350 mg, 1.0 equiv, 2.0 mmol)
was dissolved in 4 mL of dry THF and then cooled to 0 8C.
A 3.0 M THF solution of methylmagnesium chloride
(0.7 mL, 1.05 equiv, 2.1 mmol) was added and the mixture
stirred at 0 8C under N2 for 1.5 h and for other 45 min at
room temperature. 1 M HCl (4 mL) and Et2O (4 mL) were
added and the organic layer was washed with water and
brine, then dried over Na2SO4. After evaporation of the
solvent, 252 mg (65% yield) of the crude syn,anti-trans-3,4-
epoxy-2-hydroxy-6-phenylhexane were obtained as a
yellow oil in a 62:38 syn:anti ratio. 1H NMR (CDCl3,
200 MHz) d: syn: 7.35–7.15 (5H, m); 3.55 (1H, appquint,
JZ5.5 Hz); 2.91 (1H, td, JZ5.7, 2.3 Hz); 2.84–2.62 (3H,
m); 2.11–2.01 (1H, bs); 2.00–1.81 (2H, m); 1.16 (3H, d, JZ
6.4 Hz) anti: 7.35–7.15 (5H, m); 3.94–3.79 (1H, m); 3.00
(1H, td, JZ5.6, 2.2 Hz); 2.84–2.62 (3H, m); 2.11–2.01 (1H,
bs); 2.00–1.81 (2H, m); 1.14 (3H, d, JZ5.9 Hz).
3.4.2. Preparation of syn-(3,4-cis)-(2R,3R,4R)-1,2-di(tert-
butyldimethylsilyloxy)-3,4-epoxy-6-phenylhexane 28.
(3Z)-(2S)-1,2-Isopropyliden-6-phenylhex-3-enyl-1,2-diol
31.34 To a stirred suspension of 1-phenylpropyltriphenyl-
phosphonium bromide (1.45 g, 3.15 mmol, 1.05 equiv) in
8 mL of dry THF, a 1.6 M hexane solution of BuLi
(1.96 mL, 3.00 mmol, 1.0 equiv) was added dropwise,
under N2 at K78 8C, until the mixture became homo-
geneous and deep red coloured. After 1 h, a solution of 2,3-
isopropylidene-D-glyceraldehyde (390 mg, 3.0 mmol,
1.0 equiv) in 2 mL of dry THF was added and the mixture
stirred at room temperature, under N2 overnight. Petroleum
ether was added, the precipitate filtered through Celite and
the filtrate was washed with petroleum ether. The organic
layer was evaporated to give 366 mg (56% yield) of 31 as a
1
yellow oil. H NMR (CDCl3, 200 MHz) d: 7.34–7.12 (5H,
m); 5.67 (1H, dt, JZ11.0, 7.4 Hz); 5.41 (1H, dd, JZ11.0,
8.5 Hz); 4.70 (1H, ddd, JZ8.5, 8.0, 6.0 Hz); 3.77 (1H, dd,
JZ8.0, 6.0 Hz); 3.35 (1H, appt, JZ8.0 Hz); 2.82–2.34 (4H,
m); 1.40 (3H, s); 1.36 (3H, s).
syn,anti-trans-3,4-Epoxy-2-methoxy-6-phenylhexane 24.
NaH (44 mg, 1.8 mmol, 1.2 equiv) in a 60% dispersion in
mineral oil, was suspended in dry THF (1.5 mL) under N2 at
0 8C. Then a 0.5 M THF solution of the syn,anti-trans-3,4-
epoxy-2-hydroxy-6-phenylhexane (288 mg, 1.5 mmol,
1.0 equiv) was added and the mixture stirred at 0 8C under
N2 for 45 min. Methyl iodide (255 mg, 1.8 mmol, 1.2 equiv)
was then added and the temperature was allowed to rise to
room temperature. After stirring for 6 h, ice and Et2O were
added and the aqueous layer extracted with Et2O; the
organic layers were washed with brine and dried over
Na2SO4. The crude product was purified by flash chroma-
tography (petroleum ether:ethyl acetate 4:1) giving 110 mg
(3Z)-(2S)-6-Phenylhex-3-enyl-1,2-diol. To a solution of 31
(349 mg, 1.50 mmol, 1 equiv) in 8.5 mL of THF, 2 mL of
10% HCl were added and the mixture stirred at room
temperature overnight. Solid NaHCO3 was then added until
CO2 evolution finished; the mixture was dried over Na2SO4.
After evaporation of the solvent 218 mg (75% yield) of
(3Z)-(2S)-6-phenylhex-3-enyl-1,2-diol as a white solid were
1
obtained. H NMR (CDCl3, 200 MHz) d: 7.37–7.10 (5H,
m); 5.68–5.54 (1H, m); 5.36 (1H, td, JZ8.8, 2.2 Hz); 4.37–
4.27 (1H, m); 3.36 (2H, d, JZ5.9 Hz); 2.70 (2H, td, JZ6.6,
2.2 Hz); 2.43 (2H, t, JZ6.6 Hz); 1.76 (2H, bs).

3356
A. Mordini et al. / Tetrahedron 61 (2005) 3349–3360
(3Z)-(2R)-1-(tert-Butyldimethylsilyloxy)-6-phenylhex-3-en-
2-ol. To a stirred solution of (3Z)-(2S)-6-phenylhex-3-enyl-
1,2-diol (200 mg, 1.04 mmol, 1 equiv) in 2 mL of dry
CH2Cl2, tert-butyldimethylsilyl chloride (165 mg,
1.09 mmol, 1.05 equiv) and imidazole (177 mg, 2.6 mmol,
2.5 equiv) were added, under N2, and the mixture stirred for
5 h. The reaction was quenched with H2O; the aqueous layer
washed with CH2Cl2 and the combined organic layers were
washed with brine and dried over Na2SO4. Evaporation of
the solvent gave 320 mg of the crude product that was
purified by flash chromatography (petroleum ether:ethyl
acetate 5:1) to give 151 mg (47% yield) of pure (3Z)-(2R)-1-
(tert-butyldimethylsilyloxy)-6-phenylhex-3-en-2-ol as a
white solid. 1H NMR (CDCl3, 200 MHz) d: 7.10–7.33
(5H, m); 5.68–5.54 (1H, m); 5.35 (1H, td, JZ8.1, 1.5 Hz);
4.43–4.33 (1H, m); 3.42–3.26 (2H, m); 2.77–2.62 (2H,
m); 2.52–2.30 (2H, m); 1.67 (1H, bs); 0.91 (9H, s); 0.07
(6H, s).
m); 3.69–3.52 (3H, m); 3.10–3.00 (1H, m); 2.97–2.73 (3H,
m); 2.15–1.97 (1H, m); 1.81–1.60 (1H, m); 0.94 (9H, s);
0.91 (9H, m); 0.16 (3H, s); 0.11 (3H, s); 0.08 (3H, s); 0.07
(3H, s).
3.4.3. Preparation of syn-(3,4-trans)-(2R,3R,4S)-1,2-
di(tert-butyldimethylsilyloxy)-3,4-epoxy-6-phenylhexane
29 and anti-(3,4-trans)-(2R,3S,4R)-1,2-di(tert-butyl-
dimethylsilyloxy)-3,4-epoxy-6-phenylhexane 30. (3E)-
(2S)-6-Phenylhex-3-enyl-1,2-diol34 To a stirred solution of
31 (835 mg, 3.6 mmol, 1.0 equiv) in 18 mL of dry
cyclohexane, diphenyl sulfide (786 mg, 3.6 mmol,
1.0 equiv) was added under N2. The solution was irradiated
by a water-cooled high-pressure mercury lamp for 11 h at
room temperature. The reaction mixture was then concen-
trated to give 1.6 g of the residue containing 31 and 32 in a
9:91 ratio (by 1H NMR analysis). 1H NMR (CDCl3,
200 MHz) d, 32: 7.30–7.10 (5H, m); 5.79 (1H, dt, JZ
15.4, 6.6 Hz); 5.43 (1H, ddt, JZ15.3, 7.8, 1.4 Hz); 4.42 (1H,
ddd, JZ8.0, 7.8, 6.2 Hz); 4.01 (1H, dd, JZ8.1, 6.1 Hz);
3.49 (1H, appt, JZ8.0 Hz); 2.72–2.62 (2H, m); 2.40–2.26
(2H, m); 1.38 (3H, s); 1.34 (3H, s). The crude was dissolved
in a solution of 18 mL of THF and 4.5 mL of 10% HCl and
the mixture was stirred at room temperature overnight. Solid
NaHCO3 was added until CO2 evolution finished; then the
mixture was dried over Na2SO4. After evaporation of the
solvent, the residue was purified by flash chromatography
(petroleum ether:ethyl acetate 1:1–1:2) to give 421 mg
(61% yield) of (3E)-(2S)-6-phenylhex-3-enyl-1,2-diol as a
white solid. 1H NMR (CDCl3, 200 MHz) d: 7.34–7.13 (5H,
m); 5.81 (1H, dtd, JZ15.5, 6.7, 1.1 Hz); 5.44 (1H, ddt, JZ
15.5, 6.3, 1.4 Hz); 4.18 (1H, ddd, JZ7.0, 6.3, 3.6 Hz); 3.59
(1H, dd, JZ11.1, 3.6 Hz); 3.45 (1H, dd, JZ11.1, 7.0 Hz);
2.76–2.26 (2H, m); 2.45–2.31 (2H, m); 1.98 (1H, bs); 1.81
(1H, bs). 13C NMR (CDCl3, 50 MHz) d: 141.5; 133.1;
129.3; 128.4; 128.3; 125.9; 73.0; 66.5; 35.4; 34.0.
syn-(3,4-cis)-(2S)-1-(tert-Butyldimethylsilyloxy)-3,4-epoxy-
6-phenylhexan-2-ol. (C)-L-Diethyl tartrate (80 mL, 1 equiv,
0.46 mmol), titanium (IV) isopropoxide (140 mL, 1 equiv,
0.46 mmol) and (3Z)-(2S)-1-(tert-butyldimethylsilyloxy)-6-
phenylhex-3-en-2-ol (140 mg, 1 equiv, 0.46 mmol) were
sequentially added to a cooled (K20 8C) suspension of
˚
activated 4 A powdered molecular sieves in 2 mL of dry
CH2Cl2. After stirring at K20 8C for 15 min, tert-butyl-
hydroperoxide (170 mL, 2 equiv, 0.92 mmol), previously
˚
dried on activated 4 A molecular sieves, was added
dropwise. After the mixture was stirred for 15 h under N2
at K20 8C, the reaction was quenched by adding a solution
of 400 mg of citric acid and 1.32 g of FeSO4$7H2O in 4 mL
of H2O at 0 8C. After 10 min the aqueous layer was
extracted twice with Et2O and the combined organic layers
were poured into 4 mL of a precooled (0 8C) solution of
30% NaOH (w/v) in saturated brine and stirred for 1 h. The
aqueous phase was extracted with Et2O and the combined
organic phases were washed with brine and dried over
Na2SO4. After the solvent was evaporated 169 mg of the
crude product were obtained. Purification by flash chroma-
tography (petroleum ether:ethyl acetate 5:1) led to 80 mg
(54% yield) of the pure (3,4-cis)-(2R)-1-(tert-butyl-
dimethylsilyloxy)-3,4-epoxy-6-phenylhexan-2-ol as a
white solid. 1H NMR (CDCl3, 400 MHz) d: 7.33–7.19
(5H, m); 3.61 (2H, appt, JZ5.1 Hz); 3.58–3.53 (1H, m);
3.06 (1H, dt, JZ7.8, 4.4 Hz); 3.00 (1H, dd, JZ6.6, 4.4 Hz);
2.89 (1H, ddd, JZ14.4, 8.9, 5.9 Hz); 2.77 (1H, ddd, JZ
13.9, 8.9, 7.22 Hz); 2.42 (1H, bs); 2.00 (1H, dddd, JZ14.0,
12.1, 7.4, 4.7 Hz); 1.94–1.85 (1H, m); 0.94 (9H, s); 0.11
(6H, s).
(3E)-(2S)-1-(tert-Butyldimethylsilyloxy)-6-phenylhex-3-en-
2-ol. To a stirred solution of (3E)-(2S)-6-phenylhex-3-enyl-
1,2-diol (421 mg, 2.2 mmol, 1 equiv) in 8 mL of dry
CH2Cl2, tert-butyldimethylsilyl chloride (332 mg,
2.2 mmol, 1.0 equiv) and imidazole (373 mg, 5.5 mmol,
2.5 equiv) were added, under N2, and the mixture stirred at
room temperature for 6 h. The reaction was quenched with
H2O; the aqueous layer was washed with CH2Cl2 and the
combined organic layers were washed with brine and dried
over Na2SO4. Evaporation of the solvent gave 629 mg (93%
yield) of (3E)-(2S)-1-(tert-butyldimethylsilyloxy)-6-
1
phenylhex-3-en-2-ol as a white solid. H NMR (CDCl3,
200 MHz) d: 7.30–7.13 (5H, m); 5.81 (1H, dtd, JZ15.5, 6.6,
1.0 Hz); 5.42 (1H, ddt, JZ15.5, 6.6, 1.4 Hz); 4.16–4.05
(1H, m); 3.59 (1H, dd, JZ10.0, 3.6 Hz); 3.38 (1H, dd, JZ
10.0, 8.0 Hz); 2.75–2.64 (2H, m); 2.43–2.28 (2H, m); 1.67
(1H, bs); 0.91 (9H, s); 0.07 (6H, s); 13C–NMR (CDCl3,
50 MHz) d: 141.7; 132.8; 128.8; 128.4; 128.3; 125.8; 72.8;
67.3; 35.5; 34.2; 25.9; 18.3; K5.3.
syn-(3,4-cis)-(2R,3R,4R)-1,2-di(tert-butyldimethylsilyloxy)-
3,4-epoxy-6-phenylhexane 28. To a stirred solution of -(3,4-
cis)-(2S)-1-(tert-butyldimethylsilyloxy)-3,4-epoxy-6-
phenylhexan-2-ol (161 mg, 0.5 mmol, 1 equiv) in 1 mL of
dry CH2Cl2, tert-butyldimethylsilyl chloride (113 mg,
0.75 mmol, 1.05 equiv) and imidazole (85 mg, 1.25 mmol,
2.5 equiv) were added, under N2, and the mixture stirred for
5 h. The reaction was quenched with H2O; the aqueous layer
was washed with CH2Cl2 and the combined organic layers
were washed with brine and dried over Na2SO4. Evapor-
ation of the solvent gave 204 mg (94%, yield) of 28 as a
syn- and anti-(3,4-trans)-(2R)-1-(tert-Butyldimethylsilyl-
oxy)-3,4-epoxy-6-phenylhexan-2-ol. m-CPBA (740 mg,
3.0 mmol, 1.5 equiv) was added to a cooled (0 8C) solution
of (3E)-(2S)-1-(tert-butyldimethylsilyloxy)-6-phenylhex-3-
en-2-ol (610 mg, 2.0 mmol, 1 equiv) in CH2Cl2. The
mixture was allowed to reach room temperature and then
1
yellow oil. H NMR (CDCl3, 200 MHz) d: 7.37–7.20 (5H,

A. Mordini et al. / Tetrahedron 61 (2005) 3349–3360
3357
stirred overnight. The mixture was diluted with CH2Cl2,
3.5. Isomerization of oxiranes with LIDAKOR and
LICKOR
washed twice with satd Na2S2O3, twice with 1 M NaOH
solution and dried over Na2SO4. The crude was purified by
flash chromatography (petroleum ether: dichloromethane
1:1), to afford 231 mg (36% yield) of the syn-epoxide and
215 mg (33% yield) of the anti-epoxide both white solids.
syn-Epoxide: 1H NMR (CDCl3, 200 MHz) d: 7.34–7.16
(5H, m); 3.76–3.69 (1H, A part of ABX spin system); 3.69–
3.61 (1H, B part of ABX spin system); 3.57–3.44 (1H, m);
3.00 (1H, ddd, JZ6.3, 5.1, 2.2 Hz); 2.85–2.69 (2H,m); 2.81
(1H, dd, JZ5.3, 2.2 Hz); 2.35 (1H, bs); 2.01–1.79 (2H, m);
0.90 (9H, s); 0.09 (3H, s); 0.08 (3H, s); 13C NMR (CDCl3,
50 MHz) d: 141.1; 128.5; 128.4; 126.1; 71.0; 64.3; 58.2;
3.5.1. General procedure. Hexane was stripped off from a
solution of BuLi (0.74 mL of a 1.5 M solution, 2 equiv,
1.00 mmol both for LIDAKOR and LICKOR), and
precooled THF (1.0 mL) was added at K78 8C under N2,
followed by diisopropylamine (112 mg, 2 equiv, 1.00 mmol
for LIDAKOR) and potassium tert-butoxide (124 mg,
2 equiv, 1.00 mmol for LIDAKOR, 124 mg, 2 equiv,
1.00 mmol for LICKOR). The mixture was stirred at
K78 8C for 45 min and the oxirane (1 equiv, 0.50 mmol)
was added and allowed to react at K50 8C; after 15 h the
reaction mixture was warmed up to room temperature,
quenched with H2O and extracted twice with Et2O. The
combined organic layers were washed with brine and dried
over Na2SO4. After evaporation of the solvent the residue
was purified.
1
56.1; 33.5; 32.2; 25.8; 18.3; K5.4. anti-Epoxide: H NMR
(CDCl3, 200 MHz) d: 7.32–7.17 (5H, m); 3.65–3.54 (3H,
m); 2.99 (1H, ddd, JZ5.8, 5.8, 2.3 Hz); 2.87–2.68 (2H, m);
2.82 (1H, dd, JZ3.6, 2.3 Hz); 2.21 (1H, d, JZ5.7 Hz);
1.93–1.84 (2H, m); 0.90 (9H, s); 0.07 (6H, s); 13C NMR
(CDCl3, 50 MHz) d: 141.1; 128.5; 128.4; 126.1; 70.5; 64.5;
58.9; 54.9; 33.4; 32.2; 25.8; 18.2; K5.4, K5.4.
3.5.2. (trans-2-Phenylcyclopropyl)methanol 11.30 The
procedure with 2.2 equiv of LIDAKOR was used on the
epoxide 8 obtaining 76 mg of the crude product which was
purified by flash chromatography (petroleum ether:ethyl
acetate 2:1) giving 60 mg (66% yield) of 11 as a yellow oil.
1H NMR (CDCl3, 200 MHz) d: 7.25–6.95 (5H, m); 3.58
(2H, d, JZ6.8 Hz); 1.92 (1H, bs); 1.79 (1H, appdt, JZ8.0,
5.2 Hz); 1.51–1.33 (1H, m); 0.99–0.85 (2H, m). 13C NMR
(CDCl3, 50 MHz) d: 142.3; 128.2; 125.7; 125.5; 66.4; 25.2;
21.2;13.8.
syn-(3,4-trans)-(2R,3R,4S)-1,2-Di(tert-butyldimethylsilyl-
oxy)-3,4-epoxy-6-phenylhexane 29. To a stirred solution of
syn-(3,4-trans)-(2R)-1-(tert-butyldimethylsilyloxy)-3,4-
epoxy-6-phenylhexan-2-ol (231 mg, 0.72 mmol, 1 equiv) in
7 mL of dry CH2Cl2, tert-butyldimethylsilyl chloride
(163 mg, 1.08 mmol, 1.5 equiv) and imidazole (123 mg,
1.8 mmol, 2.5 equiv) were added, under N2, and the mixture
stirred at room temperature for 2 h. The reaction was
quenched with H2O; the aqueous layer was washed with
CH2Cl2 and the combined organic layers were washed with
brine and dried over Na2SO4. Evaporation of the solvent
3.5.3. 1-(trans-2-Phenylcyclopropyl)-2-methylpropan-1-
ol 15.40 The procedure with 2.2 equiv of LIDAKOR was
used on the 67:33 cis:trans diasteromeric mixture of
epoxide 12 obtaining, after purification by flash chroma-
tography (eluent: CH2Cl2), 64 mg (64% yield) of the anti-15
1
gave 325 mg (100% yield) of 29 as a yellow oil. H NMR
(CDCl3, 400 MHz) d: 7.31–7.16 (5H, m); 3.69 (1H, ddd, JZ
5.6, 5.4, 3.8 Hz); 3.61 (1H, dd, JZ10.2, 5.4 Hz); 3.56 (1H,
dd, JZ10.2, 5.6 Hz); 2.97 (1H, ddd, JZ6.7, 4.8, 2.2 Hz);
2.85 (1H, dd, JZ3.8, 2.2 Hz); 2.83–2.67 (2H, m); 1.95–1.75
(2H, m); 0.89 (9H, s); 0.87 (9H, s); 0.05 (9H, s); 0.04 (3H,
s); 13C NMR (CDCl3, 50 MHz) d: 141.3; 128.4; 128.3;
125.9; 71.7; 65.8; 59.1; 54.9; 33.7; 32.3; 25.9; 25.8; 18.4;
18.2; K4.6; K4.7; K5.3; K5.4.
1
as a yellow oil. H NMR (CDCl3, 200 MHz) d: 7.34–7.07
(5H, m); 2.95 (1H, appt, JZ6.2 Hz); 1.98–1.80 (2H, m);
1.51 (1H, bs); 1.35–1.20 (1H, m); 1.04–0.96 (2H, m); 1.03
(6H, d, JZ6.8 Hz). 13C NMR (CDCl3, 50 MHz) d: 142.7;
128.3; 125.8; 125.5; 80.5; 34.3; 27.5; 20.3; 18.7; 18.0; 14.4.
MS (m/z, %): 190 (7, MC); 173 (1, MCKOH); 147 (8); 129
(54); 127 (71); 117 (61); 115 (76); 102 (100); 91 (45); 89
(59); 77 (84).
anti-(3,4-trans)-(2R,3S,4R)-1,2-Di(tert-butyldimethylsilyl-
oxy)-3,4-epoxy-6-phenylhexane 30. To a stirred solution of
anti-(3,4-trans)-(2R)-1-(tert-butyldimethylsilyloxy)-3,4-
epoxy-6-phenylhexan-2-ol (215 mg, 0.67 mmol, 1 equiv) in
7 mL of dry CH2Cl2, tert-butyldimethylsilyl chloride
(152 mg, 1.01 mmol, 1.5 equiv) and imidazole (114 mg,
1.68 mmol, 2.5 equiv) were added, under N2, and the
mixture stirred at room temperature for 2 h. The reaction
was quenched with H2O; the aqueous layer was washed with
CH2Cl2 and the combined organic layers were washed with
brine and dried over Na2SO4. Evaporation of the solvent
3.5.4. 1-(trans-2-Phenylcyclopropyl)ethan-1-ol 16.41 The
procedure with 2.2 equiv of LIDAKOR was used on the
epoxide 13 obtaining 97 mg of the crude product which was
purified by flash chromatography (petroleum ether:ethyl
acetate 5:2) giving 51 mg (60% yield) of 16 as a yellow oil
1
and 13 mg (15% yield) of 18 as a pale yellow oil. 16: H
NMR (CDCl3, 200 MHz) d: 7.36–7.08 (5H, m); 3.41 (1H,
dq, JZ7.4, 6.3 Hz); 2.00–1.87 (1H, m); 1.84 (1H, bs); 1.35
(3H, d, JZ6.3 Hz); 1.34–1.24 (1H, m); 1.00–0.88 (2H, m).
13C NMR (CDCl3, 50 MHz) d: 142.6; 128.3; 125.7; 125.5;
71.6; 30.7; 22.3; 21.2; 13.3.
1
gave 300 mg (100% yield) of 30 as a yellow oil. H NMR
(CDCl3, 400 MHz) d: 7.30–7.15 (5H, m); 3.55 (2H, d, JZ
6.5 Hz); 3.40 (1H, td, JZ6.5, 6.0 Hz); 2.93 (1H, ddd, JZ
6.7, 4.5, 2.2 Hz); 2.80 (1H, dd, JZ6.0, 2.2 Hz); 2.77–2.67
(2H, m); 1.96–1.76 (2H, m); 0.89 (9H, s); 0.88 (9H, s); 0.09
(3H, s); 0.06 (3H, s); 0.05 (3H, s); 0.04 (3H, s); 13C NMR
(CDCl3, 50 MHz) d: 141.3; 128.4; 128.3; 126.0; 74.2; 65.1;
60.8; 55.6; 33.7; 32.2; 25.9; 25.8; 18.3; 18.2; K4.7; K4.8;
K5.4; K5.4.
3.5.5. 5-Phenylpent-1-en-3-ol 18. The procedure with
2.2 equiv of LICKOR was used on the epoxide 13 obtaining
62 mg of the crude product which was purified by flash
chromatography (petroleum ether:ethyl acetate 3:1) giving
42 mg (52% yield) of 18 as a pale yellow oil. H NMR
(CDCl3, 200 MHz) d: 7.38–7.21 (5H, m); 5.95 (1H, ddd, JZ
17.2, 10.4 Hz); 5.28 (1H, appdt, JZ17.2, 1.4 Hz); 5.18 (1H,
1

3358
A. Mordini et al. / Tetrahedron 61 (2005) 3349–3360
appdt, JZ10.4, 1.4 Hz); 4.24–4.10 (1H, m); 2.76 (2H, td,
JZ7.9, 3.5 Hz); 1.97–1.83 (2H, m); 1.61 (1H, d, JZ
4.1 Hz).
a syn/anti diasteromeric mixture of 27 as a pale yellow oil.
Major isomer: H NMR (CDCl3, 200 MHz) d: 7.38–7.04
1
(5H, m); 3.42 (3H, s); 3.38–3.25 (1H, m); 3.09–2.90 (1H,
m); 2.44 (1H, d, JZ4.1 Hz); 1.98–1.81 (1H, m); 1.24 (3H,
bs); 1.18–0.82 (3H, m). 13C NMR (CDCl3, 50 MHz) d:
142.2; 128.3; 125.6; 125.5; 79.6; 78.1; 56.5; 25.7; 21.1;
14.9; 12.8. MS (m/z, %): 206 (1, MC); 188 (5); 175 (10);
147 (21); 131 (52); 129 (100); 118 (72); 103 (69); 91 (100);
77 (84); 59 (100). Anal. Calcd for C13H18O2: C, 75.69; H,
3.5.6. 2-(trans-2-Phenylcyclopropyl)propan-2-ol 17.42
The procedure with 2.2 equiv of LIDAKOR was used on
the epoxide 14 obtaining 136 mg of the crude product which
was purified by flash chromatography (petroleum ether:-
ethyl acetate 3:1) giving 105 mg (67% yield) of 17 and
1
1
8.79. Found: C, 75.59; H, 8.78. Minor isomer: H NMR
12 mg (7% yield) of 19 both as yellow oils. 17: H NMR
(CDCl3, 200 MHz) d: 7.38–7.04 (5H, m); 3.41 (3H, s);
3.38–3.25 (1H, m); 3.09–2.90 (1H, m); 2.56 (1H, d, JZ
3.4 Hz); 1.98–1.81 (1H, m); 1.21 (3H, bs); 1.18–0.82 (3H,
m). 13C NMR (CDCl3, 50 MHz) d: 142.3; 128.2; 125.7;
125.4; 81.1; 76.2; 56.5; 24.4; 20.7; 13.6; 13.2.
(CDCl3, 200 MHz) d: 7.45–7.20 (5H, m); 2.09 (1H, appdt,
JZ8.9, 5.1 Hz); 1.61 (1H, bs); 1.43 (6H, s); 1.42–1.34 (1H,
m); 1.19 (1H, ddd, JZ8.9, 6.0, 5.1 Hz); 0.99 (1H, appdt, JZ
8.9, 5.1 Hz). 13C NMR (CDCl3, 50 MHz) d: 143.1; 128.2;
125.9; 125.3; 69.4; 34.1; 29.1; 28.9; 19.2; 11.7.
3.5.12. (1R,2R,10R,20R)-1-(trans-2-Phenylcyclopropyl)-
2,3-di-tert-butyldimethylsilyloxy-propan-1-ol 33a and
1-(trans-2-phenylcyclopropyl)-1,3-di-tert-butyldimethyl-
silyloxypropan-2-ol 33b. The procedure with 2.0 equiv of
LIDAKOR was used on the syn-epoxide 28 (76 mg,
0.17 mmol) obtaining 66 mg of the crude product which
was purified by flash chromatography (petroleum ether:-
ethyl acetate 3:1) giving 57 mg (75% yield) of a mixture of
33a and 33b as a yellow oil in a 67/33 ratio. 33a: 1H NMR
(CDCl3, 400 MHz) d: 7.26–7.21 (2H, m); 7.16–7.10 (1H,
m); 7.09–7.03 (2H, m); 3.78 (1H, ddd, JZ7.5, 4.8, 2.7 Hz);
3.70 (1H, dd, JZ9.7, 7.5 Hz); 3.56 (1H, dd, JZ9.7, 4.8 Hz);
3.20 (1H, ddd, JZ8.3, 7.9, 2.7 Hz); 2.53 (1H, d, JZ8.3 Hz);
2.03 (1H, ddd, JZ8.4, 5.2, 4.4 Hz); 1.38–1.30 (1H, m);
0.94–0.84 (2H, m); 0.91 (9H, s); 0.89 (9H, s); 0.12 (3H, s);
0.11 (3H, s); 0.09 (6H, s). 13C NMR (CDCl3, 50 MHz) d:
143.0; 128.2; 125.8; 125.4; 75.1; 74.9; 62.2; 26.3; 25.9;
25.8; 21.5; 18.3; 18.1; 13.1; K4.3; K4.8; K5.4; K5.5.
Anal. Calcd for C24H44O3Si2: C, 66.00; H, 10.15. Found: C,
66.19; H, 10.08. 33b: 1H NMR (CDCl3, 400 MHz) d: 7.26–
7.21 (2H, m); 7.16–7.10 (1H, m); 7.09–7.03 (2H, m); 3.68–
3.55 (3H, m); 3.47 (1H, dd, JZ7.4; 2.6 Hz); 2.50 (1H, d,
JZ6.8 Hz); 1.88 (1H, ddd, JZ8.6, 5.2, 4.8 Hz); 1.48 (1H,
m); 0.94–0.84 (2H, m); 0.88 (9H, s); 0.87 (9H, s); 0.06 (3H,
s); 0.05 (3H, s); 0.04 (3H, s); 0.03 (3H, s). 13C NMR
(CDCl3, 50 MHz) d: 142.7; 128.2; 125.7; 125.4; 74.8; 74.4;
63.4; 26.0; 25.9; 25.8; 22.1; 18.2; 18.1; 13.2; K4.0; K4.7;
K5.3; K5.4.
3.5.7. 5-Phenyl-2-methylpent-1-en-3-ol 19. The procedure
with 2.2 equiv of LICKOR was used on the epoxide 14
obtaining 59 mg of the crude product which was purified by
flash chromatography (petroleum ether:ethyl acetate 3:1)
1
giving 46 mg (57% yield) of 19 as a yellow oil. H NMR
(CDCl3, 200 MHz) d: 7.27–7.05 (5H, m); 4.97 (1H, br s);
4.88 (1H, br s); 4.09 (1H, br t, JZ6.4 Hz); 2.69 (2H, appq,
JZ7.6 Hz); 1.89 (2H, appquint, JZ7.6 Hz); 1.74 (1H, bs);
1.29 (3H, s).
3.5.8. (trans-2-Vinylcyclopropyl)methanol 21.30 The pro-
cedure with 2.2 equiv of LIDAKOR was used on the
commercially available epoxide obtaining 186 mg of the
crude product which was purified by flash chromatography
(petroleum ether:ethyl acetate 2:1) giving 150 mg (75%
yield) of 21 as a yellow oil. 1H NMR (CDCl3, 200 MHz) d:
5.41 (1H, ddd, JZ17.2, 10.1, 8.4 Hz); 5.06 (1H, ddd, JZ
17.2, 1.8, 0.5 Hz); 4.88 (1H, ddd, JZ10.1, 1.8, 0.4 Hz); 3.51
(2H, d, JZ6.8 Hz); 1.49 (1H, bs); 1.41–1.26 (1H, m); 1.25–
1.09 (1H, m); 0.72–0.63 (2H, m).
3.5.9. (E)-1-Phenyl-3,4-epoxybut-1-en 25. The procedure
with 2.2 equiv of LIDAKOR was used on the 1:1 syn:anti
diasteromeric mixture of epoxide 22 obtaining, after
purification by flash chromatography (petroleum ether:ethyl
1
acetate 4:1), 40 mg (50% yield) of 25 as a yellow oil. H
NMR (CDCl3, 200 MHz) d: 7.39–7.18 (5H, m); 6.85 (1H, d,
JZ16.0 Hz); 5.90 (1H, dd, JZ16.0, 8.0 Hz); 3.12–3.02
(1H, m); 2.88–2.74 (2H, m). MS (m/z, %): 146 (32, MC);
117 (100); 115 (76); 102 (11); 90 (48); 50 (16).
3.5.13. (1R,2R,10S,20S)-1-(trans-2-Phenylcyclopropyl)-
2,3-di-tert-butyldimethylsilyloxy-propan-1-ol 34a and
1-(trans-2-phenylcyclopropyl)-1,3-di-tert-butyldimethyl-
silyloxypropan-2-ol 34b. The procedure with 2.0 equiv of
LIDAKOR was used on the syn-epoxide 29 (87 mg,
0.2 mmol) obtaining 79 mg of the crude product which
was purified by flash chromatography (petroleum ether:-
ethyl acetate 3:1) giving 50 mg (57% yield) of 34a and
24 mg (28% yield) of 34b both as yellow oils. 34a: 1H NMR
(CDCl3, 400 MHz) d: 7.27–7.22 (2H, m); 7.17–7.11 (1H,
m); 7.07–7.03 (2H, m); 3.75 (1H, ddd, JZ6.7, 5.4, 4.4 Hz);
3.68 (1H, d, JZ5.4 Hz); 3.68 (1H, d, JZ6.7 Hz); 3.45 (1H,
bdd, JZ6.8, 4.4 Hz); 2.88 (1H, bs); 1.94 (1H, ddd, JZ8.8,
5.1, 5.0 Hz); 1.37 (1H, m); 1.11 (1H, ddd, JZ8.8, 5.6,
4.9 Hz); 0.94–0.89 (1H, m); 0.88 (9H, s); 0.87 (9H, s); 0.08
(3H, s); 0.07 (3H, s); 0.04 (3H, s); 0.03 (3H, s). 13C NMR
(CDCl3, 50 MHz) d: 142.9; 128.3; 125.8; 125.4; 76.3; 75.0;
65.5; 25.9; 25.8; 24.4; 20.3; 18.2; 18.1; 12.7; K4.4; K4.8;
3.5.10. (E,Z)-5-Phenyl-1-methoxypent-1-en-3-ol 26. The
procedure with 2.2 equiv of LIDAKOR was used on the
epoxide 23 obtaining 88 mg (83% yield) of a 20:80 Z/E
1
diastereomeric mixture of 26 as a yellow oil. H NMR
(CDCl3, 200 MHz) d: Z-26: 7.44–7.12 (5H, m); 6.08 (1H, d,
JZ5.3 Hz); 4.73–4.58 (2H, m); 3.50 (3H, s); 2.79 (2H, appt,
JZ7.8 Hz); 2.18–1.82 (3H, m); E-26: 7.44–7.12 (5H, m);
6.63 (1H, d, JZ12.7 Hz); 4.93 (1H, dd, JZ12.7, 8.5 Hz);
4.15 (1H, dt, JZ8.5, 6.6 Hz); 3.64 (3H, s); 2.79 (2H, appt,
JZ7.8 Hz); 2.18–1.82 (3H, m).
3.5.11. 1-(trans-2-Phenylcyclopropyl)-2-methoxypropan-
1-ol 27. The procedure with 2.2 equiv of LIDAKOR was
used on the 64:36 diasteromeric mixture of epoxide 24
obtaining, after purification by flash chromatography
(petroleum ether:ethyl acetate 2:1), 66 mg (63% yield) of

A. Mordini et al. / Tetrahedron 61 (2005) 3349–3360
3359
K5.4; K5.5. MS (m/z, %): 247 (8); 155 (18); 147 (20); 129
(24); 117 (19); 101 (19); 91 (18); 89 (30); 75 (43); 73 (100);
59 (14). Anal. Calcd for C24H44O3Si2: C, 66.00; H, 10.15.
Found: C, 66.11; H, 10.19. 34b: 1H NMR (CDCl3,
400 MHz) d: 7.27–7.22 (2H, m); 7.17–7.11 (1H, m); 7.07–
7.04 (2H, m); 3.78–3.70 (2H, m); 3.67–3.60 (1H, m); 3.46
(1H, dd, JZ7.2; 4.0 Hz); 2.51 (1H, bs); 1.91 (1H, ddd, JZ
8.1, 5.9, 4.6 Hz); 1.31 (1H, m); 0.98–0.87 (2H, m); 0.92
(9H, s); 0.89 (9H, s); 0.14 (3H, s); 0.09 (3H, s); 0.05 (3H, s);
0.04 (3H, s). 13C NMR (CDCl3, 50 MHz) d: 142.5; 128.2;
125.7; 125.5; 75.6; 75.5; 63.7; 25.9; 25.9; 25.3; 20.4; 18.3;
18.2; 13.3; K4.0; K4.4; K5.3; K5.3. MS (m/z, %): 287 (2,
MCKH2O -OTBDMS); 261 (18); 247 (7); 155 (15); 129
(21); 117 (27); 91 (16); 89 (34); 75 (52); 73 (100); 59 (15).
Anal. Calcd for C24H44O3Si2: C, 66.00; H, 10.15. Found: C,
66.03; H, 10.10. 35b: 1H NMR (CDCl3, 400 MHz) d: 7.26–
7.22 (2H, m); 7.17–7.11 (1H, m); 7.07–7.03 (2H, m); 3.65–
3.55 (3H, m); 3.43 (1H, dd, JZ7.8, 2.9 Hz); 2.51 (1H, d, JZ
5.9 Hz); 1.81 (1H, ddd, JZ7.1, 6.8, 4.9 Hz); 1.39 (1H, m);
1.00 (2H, appt, JZ7.1 Hz); 0.93 (9H, s); 0.88 (9H, s); 0.15
(3H, s); 0.10 (3H, s); 0.05 (3H, s); 0.04 (3H, s). 13C NMR
(CDCl3, 100 MHz) d: 142.3; 128.3; 125.9; 125.6; 75.1;
74.9; 63.4; 26.1; 25.9; 25.8; 20.4; 18.2; 18.2; 14.9; K3.8;
K4.7; K5.3; K5.4.
3.5.16. (1S,2R,10R,20R)-1-(trans-2-Phenylcyclopropyl)-
1,2,3-propantriol 37. To a stirred solution of 35a (13 mg,
0.03 mmol, 1.0 equiv) in THF (0.5 mL), TBAF$3H2O
(28 mg, 0.09 mmol, 3.0 equiv) and 10 mL of water were
added. After 12 h at room temperature, evaporation of the
solvent gave 25 mg of the crude product that was purified by
flash chromatography (ethyl acetate:methanol 10:1) to
give 5 mg (80% yield) of pure 37 as a colourless solid.
[a]D C52.68 (cZ0.48; methanol) 1H NMR (CD3OD,
400 MHz) d: 7.24–7.19 (2H, m); 7.13–7.06 (3H, m); 3.68
(1H, dd, JZ10.1, 3.7 Hz); 3.61 (1H, ddd, JZ6.0, 4.8,
3.7 Hz); 3.57 (1H, dd, JZ10.1, 6.0 Hz); 3.11 (1H, dd, JZ
8.4, 4.8 Hz); 1.87 (1H, ddd, JZ8.7, 5.1, 4.9 Hz); 1.31 (1H,
m); 1.06 (1H, ddd, JZ8.7, 5.5, 4.9 Hz); 0.98 (1H, ddd, JZ
8.5, 5.1, 4.9 Hz). 13C NMR (CD3OD, 100 MHz) d: 143.9;
129.3; 126.8; 126.5; 76.6; 76.4; 64.4; 27.3; 21.9; 14.4. MS
(m/z, %): 190 (1, MCKH2O); 159 (10); 147 (8); 129 (100);
128 (25); 118 (37); 117 (68); 115 (35); 104 (76); 91 (98,
C7HC7 ); 84 (17); 77 (26); 65 (20); 61 (49); 51 (26). Anal. Calcd
for C12H16O3: C, 69.21; H, 7.74. Found: C, 69.32; H, 7.69.
3.5.14. (1R,2R,10S,20S)-1-(trans-2-Phenylcyclopropyl)-
1,2,3-propantriol 36. To a stirred solution of 34a (26 mg,
0.06 mmol, 1.0 equiv) in THF (1.0 mL), TBAF$3H2O
(57 mg, 0.18 mmol, 3.0 equiv) and 20 mL of water were
added. After 12 h at room temperature, evaporation of the
solvent gave 30 mg of the crude product that was purified
by flash chromatography (ethyl acetate:methanol 10:1) to
give 10 mg (80% yield) of pure 36 as a colorless solid.
[a]DZK98.28 (cZ0.22; methanol) 1H NMR (CD3OD,
400 MHz) d: 7.24–7.19 (2H, m); 7.12–7.06 (3H, m); 3.72
(1H, dd, JZ10.3, 4.2 Hz); 3.68 (1H, ddd, JZ6.2, 4.8,
4.2 Hz); 3.57 (1H, dd, JZ10.3, 6.2 Hz); 3.23 (1H, dd, JZ
7.8, 4.8 Hz); 1.89 (1H, ddd, JZ8.7, 5.0, 4.9 Hz); 1.35 (1H,
m); 1.01 (1H, ddd, JZ8.7, 5.5, 4.8 Hz); 0.91 (1H, ddd, JZ
8.7, 5.5, 4.9 Hz). 13C NMR (CD3OD, 100 MHz) d: 144.1;
129.3; 126.8; 126.5; 76.5; 76.4; 64.6; 26.1; 21.9; 13.2. MS
(m/z, %): 190 (8, MCKH2O); 159 (8); 147 (12); 129 (88);
117 (67); 115 (36); 104 (64); 91 (100, C7HC7 ); 77 (20); 65
(23); 61 (45); 51 (21). Anal. Calcd for C12H16O3: C, 69.21;
H, 7.74. Found: C, 69.11; H, 7.82.
To a stirred solution of 35b (13 mg, 0.03 mmol, 1.0 equiv)
in THF (0.5 mL), TBAF$3H2O (28 mg, 0.09 mmol,
3.0 equiv) and 10 mL of water were added. After 12 h at
room temperature, evaporation of the solvent gave 26 mg of
the crude product that was purified by flash chromatography
(ethyl acetate:methanol 10:1) to give 4 mg (64% yield) of
pure 37, identical to that described above.
To a stirred solution of 34b (13 mg, 0.03 mmol, 1.0 equiv)
in THF (0.5 mL), TBAF$3H2O (28 mg, 0.09 mmol,
3.0 equiv) and 10 mL of water were added. After 12h at
room temperature, evaporation of the solvent gave 20 mg of
the crude product that was purified by flash chromatography
(ethyl acetate:methanol 10:1) to give 5 mg (80% yield) of
pure 36, identical to that described above.
Acknowledgements
3.5.15. (1S,2R,10R,20R)-1-(trans-2-Phenylcyclopropyl)-
2,3-di-tert-butyldimethylsilyloxy-propan-1-ol 35a and
1-(trans-2-phenylcyclopropyl)-1,3-di-tert-butyldimethyl-
silyloxypropan-2-ol 35b. The procedure with 2.0 equiv of
LIDAKOR was used on the anti-epoxide 30 (87 mg,
0.2 mmol) obtaining 82 mg of the crude product which
was purified by flash chromatography (petroleum ether:-
ethyl acetate 3:1) giving 52 mg (59% yield) of 35a and
25 mg (29% yield) of 35b both as yellow oils. 35a: 1H NMR
(CDCl3, 400 MHz) d: 7.26–7.21 (2H, m); 7.16–7.11 (1H,
m); 7.05–7.01 (2H, m); 3.77 (1H, ddd, JZ7.3, 4.8, 2.7 Hz);
3.69 (1H, dd, JZ9.7, 7.3 Hz); 3.55 (1H, dd, JZ9.7, 4.8 Hz);
3.27 (1H, ddd, JZ7.9, 7.7, 2.7 Hz); 2.62 (1H, d, JZ7.9 Hz);
1.81 (1H, ddd, JZ8.7, 5.0, 4.3 Hz); 1.30 (1H, m); 1.14 (1H,
ddd, JZ8.7, 5.3, 5.3 Hz); 1.02 (1H, ddd, JZ8.4, 5.3,
5.0 Hz); 0.89 (9H, s); 0.86 (9H, s); 0.05 (3H, s); 0.04 (3H, s);
0.03 (3H, s); K0.08 (3H, s). 13C NMR (CDCl3, 100 MHz) d:
142.6; 128.2; 125.5; 125.4; 75.3; 74.3; 64.2; 26.5; 25.9;
25.8; 20.1; 18.3; 18.0; 14.0; K4.3; K5.1; K5.4; K5.5.
Ente Cassa di Risparmio di Firenze (Italy) is acknowledged
for granting a 400 MHz NMR spectrometer. CINMPIS
(Consorzio Interuniversitario Nazionale ‘Metodologie e
Processi Innovativi di Sintesi’) is gratefully acknowledged
for the research award to D.P.
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