Useful base promoted elaborations of oxiranyl ethers

Article abstract of DOI:10.1016/S0040-4020(01)00790-6

Functionalized oxiranyl ethers can be regio- and stereoselectively converted into hydroxy oxetanes or cis-diols by treatment with organometallic bases. These two rearrangements can be conveniently carried out either using different reaction conditions sta

Full text of DOI:10.1016/S0040-4020(01)00790-6

TETRAHEDRON
Pergamon
Tetrahedron 57 82001) 8173±8180
Useful base promoted elaborations of oxiranyl ethers
a
a,p
a
b
Angelika Thurner, Ferenc Faigl, Laszlo Toke, Alessandro Mordini, Michela Valacchi,
b
Â
Gianna Reginato and Gabor Czira
 Í
b
c
Â
a
È
Department of Organic Chemical Technology, Budapest University of Technology and Economics, Muegyetem rkp. 3,
H-1111 Budapest, Hungary
bDipartimento di Chimica Organica `U. Schiff', Centro CNR Composti Eterociclici, via G. Capponi 9, I-50121 Firenze, Italy
c
È
Í Â
Richter Gedeon Co., H-1103Budapest, Gyo mroi ut 19-21, Hungary
Received 29December 2000; revised 4 July 2001; accepted 26 July 2001
AbstractÐFunctionalized oxiranyl ethers can be regio- and stereoselectively converted into hydroxy oxetanes or cis-diols by treatment with
organometallic bases. These two rearrangements can be conveniently carried out either using different reaction conditions starting from the
oxirane or in two consecutive steps from the oxirane via the oxetane. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
We have shown in the last few years that oxiranyl ethers 1
can be conveniently elaborated in a number of ways, to
afford useful building blocks such as hydroxyvinyl ethers
2,1±4 hydroxyoxetanes 3,5±7 diols 4,8 allylic alcohols 59 and
hydroxytetrahydrooxepines 610 8Scheme 1, routes a±f,
respectively).
Due to the synthetic utility of oxetanes,18,19 their preparation
is still of interest. Furthermore, the recently reported novel
stereoselective rearrangement of oxiranes 81) or oxetanes
83) into Z-2-alkene-1,4-diols 84) worked only in those
cases when R and Y were alkyl and phenyl groups, respec-
tively.8 The phenyl group is a requisite of the rearrangement
process. However, this new reaction would be a convenient
route to practically useful building blocks 8type 4) of bio-
logically active sugar and azasugar derivatives20 if we could
extend the method to a series of compounds 81 and 3) in
which R would be an alkoxymethyl, dialkylaminomethyl or
alkenyl group. Therefore, we have undertaken a further
study with the aim of extending the scope of the rearrange-
ment sequences. A series of alkyl, alkoxymethyl and
All these transformations have been carried out making use
of superbases11,12 and in particular an equimolar mixture of
butyllithium, diisopropylamine and potassium tert-butoxide
8LIDAKOR)13 except for the preparation of allylic alcohols
which occurs by reductive lithiation14 of the thiophenyl
substituted epoxy ether with the radical anion LDBB15 via
Grob-type fragmentation.16,17
Scheme 1. Rˆalkyl group, Yˆmethoxymethyl or phenyl group.
Keywords: oxirane; oxetane; superbase; rearrangement; diol.
Corresponding author. Tel.: 136-1-463-3652; fax: 136-1-463-3648; e-mail: faigl.oct@chem.bme.hu
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020801)00790-6

8174
A. Thurner et al. / Tetrahedron 57 92001) 8173±8180
Scheme 2. R and R0 in compounds 7±9 are as follows. a: RˆH, R0ˆbutyl; b: RˆH, R0ˆethyl; c: Rˆmethyl, R0ˆ3-methylbut-2-en-1-yl; d: RˆH, R0ˆtert-
butyl-diphenylsilyloxy; e: RˆH, R0ˆbenzyloxy; f: RˆH, R0ˆmethoxy; g: RˆH, R0ˆtriphenylmethyloxy; h: RˆH, R0ˆdibenzylamino; i: RˆH,
R0ˆdiethylamino; l: RˆH, R0ˆpiperidyl.
dialkylaminomethyl group containing oxiranylmethyl
benzyl ethers have been synthesized 8compounds 7a±l)
and then submitted to treatment with the LIDAKOR reagent
8Scheme 2).
reported in Table 1, the results of these experiments show
that the conversion to diols is possible and/or synthetically
useful only for a limited number of substrates under these
reaction conditions. This behaviour can be attributed mainly
to the very strongly basic conditions used that are not suit-
able for highly functionalised substrates. By changing the
base from LIDAKOR to butyllithium alone in a large excess
84 equiv.), we have been able to convert most of oxetanes 8
to diols 9 again with a perfect stereocontrol 8Scheme 2). The
yields of this transformation were signi®cantly better than
those obtained via direct superbase isomerisation of the
oxiranes 8see in Table 1) and in one case 8entry 8) the
new experimental procedure allowed us to get 9h while
superbase treatment was not effective. The yields of isolated
9 are not always satisfactory and this can be attributed to
their low stability at room temperature when trace amount
of acids are present, for example in CDCl3 solution or silica
gel columns. We have observed that yields can be improved
by using ¯orisil instead of silica gel 8entry 10).
The benzyl protected octenol- 87a), hexenol- 87b), geraniol
87c) oxides have been obtained via alkene epoxidation and
benzylation. The silyl protected diol 7d has been prepared
from 2-buten-1,4-diol via monosilylation21 followed by
epoxidation and benzylation and, similarly, 7e±g via
suitable alkylation and epoxidation. 2-Buten-1,4-diol has
also been used for the preparation of the three new, amino
substituted oxiranyl ethers 7h, 7i and 7l via monobenzyl-
ation followed by epoxidation, tosylation and nucleophilic
displacement of the tosyl group by the required secondary
amine.
All benzyl oxiranyl ethers 7a±l have been clearly converted
into the corresponding oxetanes 8a±l 8Scheme 2) in good
yields and selectivities, as shown in Table 1.
All the ole®ns 9 were obtained as pure Z-isomers probably
owing to a strong interaction between the two O±metal
groups in the course of the isomerisation process. The Z
con®guration has been con®rmed by NMR 8COSY and
NOESY) experiments.8 The free hydroxyl group in oxetane
8 is essential for the diol formation as shown by an
attempted isomerisation of 3-81-methoxybutyl)-2-phenyl-
oxetane 8m 8the O-methylated derivative of 8b) which
failed under both superbase and butyllithium treatment.
The cis/trans ratio of the newly formed oxetanes 8c±l is
always strongly in favour of the trans isomer. The isomeric
ratios could be determined on the basis of the H NMR
1
spectra as already found in the cases of 8a and 8b.5±7 The
transition state for a cis-mode 4-exo ring closure is indeed
clearly more crowded than the transition state for a trans-
mode and the difference is strikingly higher when a bulky
substituent is present on the oxirane in the cis-position with
respect to the benzyl group.
In conclusion we have found that a series of benzyl oxiranyl
ethers 8containing dialkylaminomethyl or alkoxymethyl
groups) can be conveniently converted into disubstituted
trans-oxetanes or new Z-2-alkene-1,4-diols. Moreover, we
In order to test the feasibility of the sequence leading to
diols 9 8Scheme 2), we have then submitted oxiranes 7 to
treatment with the LIDAKOR base in a threefold excess. As
Table 1. Base induced isomerization of oxiranes
Entry
Oxirane
Transformation of
7 to 8 with LIDAKOR
8yielda; cis/trans)
7 to 9 with LIDAKOR
8yielda; Z/E)
8 to 9 with BuLi 8yielda; Z/E)
1
2
3
4
5
6
7
8
9
10
78a
7
7
7
7
7
7
7
7
870%; 0:100)
868%; 0:1080b)
869%; 0:1080c)
864%; 0:1080d)
850%; 13:887e)
850%; 0:1008)f
866%; 3:978)g
864%; 5:958)h
875%; 5:95)8i
859%; 0:1008)l
9a 855%; 100:0)
9b 852%; 100:0)
±
9d 813%; 100:0)
±
9f 810%; 100:0)
9g 86%; 100:0)
±
9i 839%; 100:0)
9l 820%; 100:0)
9a 855%; 100:0)
9b 864%; 100:0)
±
b
c
d
e
f
g
h
i
9d 819%b; 100:0)
±
9f 822%; 100:0)
9g 835%; 100:0)
9h 824%; 100:0)
9i 835%; 100:0)
9l 839%c; 100:0)
7
l
Structures of 8a±l and 9a±l are given in Scheme 2.
Yields of isolated products.
a
b
38% Yield was achieved when the alcoholate of 9d was quenched with methyl iodide before hydrolysis and workup.
Puri®cation on Florisil; the yield dropped to 20% when Silica gel was used for column chromatography.
c

A. Thurner et al. / Tetrahedron 57 92001) 8173±8180
8175
have developed a novel, two-step method for the prepara-
3.3. Preparation of oxiranyl ethers 7a±l
tion of 9. In this case the second step is a simple treatment of
trans-oxetane 8 with an excess of butyllithium. This method
provided us 9a and 9b in similar yields to those obtained by
the one step superbase method. However, the rearrangement
process served series of highly functionalized new Z-2-
alkene-1,4-diols 89d±l) in signi®cantly better yields than
the LIDAKOR induced reaction. Due to the perfect Z
selectivity of the reaction, these diols can serve as starting
materials for the stereoselective synthesis of sugar and
azasugar derivatives.20
Epoxidation. General procedure. m-Chloro-perbenzoic acid
81.5 equiv.) in CH2Cl2 was added, during a period of 20 min,
to a solution of the alkene 81.0 equiv.) in CH2Cl2 8total
amount to make a 0.5 M solution) at 08C. The reaction
mixture was stirred for 15 h at 258C then cooled to 08C.
The precipitated m-chlorobenzoic acid was rapidly ®ltered
off and washed with cold CH2Cl2. The organic solution was
washed with saturated aqueous NaHCO3, saturated aqueous
Na2S2O3, brine and dried. After evaporation of the solvent,
the residue was puri®ed by column chromatography 833%
ethyl acetate/hexane).
3. Experimental
3.1. General
3.4. Preparation of the benzyl ethers
General procedure. NaH 81 equiv., 60% in oil) was washed
with pentane and vacuum-dried then dry DMF was added.
The resulting suspension was added to a precooled 808C)
solution of the alcohol 81 equiv.; 2.2 equiv. of the diol) in
dry DMF 8total amount to make a 1.0 M solution). After
stirring for 2 h at 258C the mixture was cooled to 08C and
a solution of benzyl bromide 81 equiv.) in DMF was added
during a period of 15 min. The reaction mixture was stirred
for 16 h at 258C, then cautiously poured into ice and
extracted with ether. The organic phase was washed with
brine. After drying and evaporation of the solvent the
residue was puri®ed by ¯ash chromatography 825±33%
ethyl acetate/hexane).
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 2788C, that of ice bath as 08C and `room
temperature' as 258C. If no reduced pressure is speci®ed,
boiling ranges were determined under ordinary atmospheric
conditions 8720^35 mmHg). Puri®cations by ¯ash column
chromatography were performed using glass columns 810±
50 mm wide); silica gel 8230±400 mesh) or Florisil 860±100
mesh) was chosen as stationary phase 815 cm high), with an
elution rate of 5 cm/min. All products 87±9) were obtained
as colourless oils after evaporating of the eluent except 8g,
3.4.1. +E)-1-+Benzyloxy)-2,3-epoxyoctane 7a.7 Compound
7a 860%, oil) was prepared according to the general pro-
cedure; dH 8CDCl3): 7.4±7.2 85H, m, Ph), 4.63 81H, d,
Jˆ11.5 Hz, CHaHbPh), 4.55 81H, d, Jˆ11.5 Hz, CHaHbPh),
3.72 81H, dd, Jˆ11.4, 3.4 Hz, CHaHbO), 3.47 81H, dd,
Jˆ11.4, 5.8 Hz, CHaHbO), 2.95 81H, ddd, Jˆ5.8, 3.4,
2.6 Hz, oxirane CH), 2.82 81H, m, oxirane CH), 1.6±1.2
88H, m, CH2), 0.8983H, t, Jˆ6.6 Hz, Me).
3.4.2. +E)-1-+Benzyloxy)-2,3-epoxyhexane 7b.8 Compound
7b 865%, oil) was prepared according to the general pro-
cedure; dH 8CDCl3): 7.35±7.22 85H, m, Ph), 4.65 81H, d,
Jˆ12.0 Hz, CHaHbPh), 4.50 81H, d, Jˆ12.0 Hz, CHaHbPh),
3.70 81H, dd, Jˆ11.5, 3.5 Hz, CHaHbO), 3.45 81H, dd,
Jˆ11.5, 5.5 Hz, CHaHbO), 2.93 81H, m, oxirane CH), 2.82
81H, m, oxirane CH), 1.6±1.3 84H, m, CH2), 0.95 83H, t,
Jˆ6.8 Hz, Me).
1
8m and 9g which are white solids. H NMR spectra were
recorded at 250 or 500 MHz. Chemical shifts were deter-
mined relative to the residual solvent peak 8CHCl3 d:
7.26 ppm) or to tetramethyl silane 8TMS d: 0.00 ppm).
Coupling constants 8J) are measured in Hz. Coupling
patterns are described by abbreviations: s 8singlet), d
8doublet), t 8triplet), q 8quartet), quint 8quintet), dd 8doublet
of a doublet), m 8multiplet), bs 8broad singlet), bt 8broad
triplet), bq 8broad quartet). All mass spectra were recorded
on a Finnigan MAT 95SQ hybrid-tandem mass spectro-
meter. The electron ionization 8EI) spectra were obtained
at 70 eV using a heated direct inlet system. A Cs ion gun
was used for FAB experiments and the energy of the
bombarding Cs1 beam was 30 keV. The matrix was
glycerol. The exact mass determinations were performed
at the resolving power of 5000 and using PFK 8per¯uoro-
kerosene) and glycerol adduct ions as references for EI and
FAB measurements, respectively.
3.4.3. +E)-1-Benzyloxy-2,3-epoxy-3,7-dimethyl-6-octene
7c.22 Compound 7c 840%, oil) was prepared according to
the general procedure; dH 8CDCl3): 7.36±7.25 85H, m, Ph),
5.08 81H, bt, Jˆ7.0 Hz, vCH), 4.64 81H, d, Jˆ11.9Hz,
CHaHbPh), 4.52 81H, d, Jˆ11.9Hz, CH aHbPh), 3.68 81H,
dd, Jˆ11.2, 4.5 Hz, CHaHbO), 3.54 81H, dd, Jˆ11.2,
6.1 Hz, CHaHbO), 3.01 81H, app t, Jˆ5.4 Hz, oxirane
CH), 2.08 82H, m, CH2), 1.71 83H, s, Me±Cv), 1.60 83H,
s, Me±Cv), 1.54 82H, m, CH2), 1.46 83H, s, Me).
3.2. Materials
Starting materials were commercially available unless
otherwise stated. All commercial reagents were used with-
out further puri®cation except diisopropylamine, which was
distilled over calcium hydride. Anhydrous tetrahydrofuran
was distilled from sodium diphenylketyl. Dimethylforma-
mide was distilled over calcium hydride and then stored
3.5. Synthesis of 7d
Ê
over 4-A molecular sieves. Methylene chloride was dried
Ê
over calcium chloride and stored over 4-A molecular sieves.
3.5.1. +Z)-4-+tert-Butyldiphenylsilyloxy)-2-buten-1-ol.23
Butyllithium 81.6 M in hexane, 10.7 mL, 17.3 mmol) was
slowly added to cis-2-buten-1,4-diol 81.57 g, 18.2 mmol) in
Petroleum ether, unless speci®ed, was the 40±708C boiling
fraction.

8176
A. Thurner et al. / Tetrahedron 57 92001) 8173±8180
THF 825 mL) at 2788C. After 10 min, tert-butyldiphenyl-
silyl chloride 84.74 g, 17.3 mmol) was added and the solu-
tion warmed to 258C. After re¯uxing 7 h, the solvent was
evaporated giving 9.8 g of residue which was then puri®ed
by column chromatography 825% ethyl acetate/petroleum
ether) to 5.0 g 884%, oil) of pure 8Z)-4-8tert-butyldiphenyl-
silyloxymethyl)-2-buten-1-ol; dH 8CDCl3): 7.68 84H, m,
Ph), 7.41 86H, m, Ph), 5.66 82H, m, vCH), 4.25 82H, d,
Jˆ4.8 Hz, CH2OH), 4.01 82H, d, Jˆ4.8 Hz, CH2OSi), 1.57
81H, bs, OH), 1.05 89H, s, Me3C); m/z 8EI): 26982.4,
[M2C4H9]1), 200 811), 1998100), 181 810), 139810), 77
815), 57 811).
3.7. Synthesis of 7f
3.7.1. +Z)-4-Benzyloxy-2-buten-1-ol.26 The general pro-
cedure was used on 8Z)-2-buten-1,4-diol 87.93 g,
90 mmol) affording 6.48 g of a raw material which was
puri®ed by ¯ash chromatography 830% ethyl acetate/
petroleum ether) yielding 4.79g 890%, oil) of 8 Z)-4-
8benzyloxy)-2-buten-1-ol; dH 8CDCl3): 7.41±7.24 85H, m,
Ph), 5.75 82H, m, vCH), 4.51 82H, s, CH2Ph), 4.13 82H, d,
Jˆ5.6 Hz, CH2OH), 4.07 82H, d, Jˆ5.7 Hz, CH2OBn), 2.36
81H, bs, OH).
3.7.2.
+Z)-1-Benzyloxy-4-methoxy-2-butene.27
NaH
3.5.2. +Z)-4-+tert-Butyldiphenylsilyloxy)-2,3-epoxy-1-buta-
nol.23 The general epoxidation procedure was used giving
8Z)-4-8tert-butyldiphenylsilyloxy)-2,3-epoxy-1-butanol 872%,
oil) after puri®cation 825% ethyl acetate/petroleum ether);
dH 8CDCl3): 7.70±7.30 810H, m, Ph), 3.96±3.67 84H, m,
CH2OH1CH2OSi), 3.23 82H, m, oxirane CH), 1.981H,
app t, Jˆ5.6 Hz, OH), 1.05 89H, s, Me3C).
80.22 g, 5 mmol, 55% in oil) was washed with hexane
83£5 mL) and vacuum-dried then dry THF 88 mL) was
added. The resulting suspension was added to a precooled
808C) solution of 8Z)-4-8benzyloxy)-2-buten-1-ol 80.75 g,
4.2 mmol) in THF 810 mL). After stirring 1 h at 08C methyl
iodide 81,41 g, 10 mmol) was added, and the reaction
mixture was stirred for 16 h at 258C then quenched with
ice-water 820 mL) and extracted with ether 83£15 mL).
The organic phase was washed with saturated NH4Cl
82£10 mL) and brine 810 mL). After drying and evaporation
of the solvent 0.76 g 894%, oil) of 8Z)-1-benzyloxy-4-
methoxy-2-butene was obtained, which was used without
further puri®cation; dH 8CDCl3): 7.43±7.25 85H, m, Ph),
5.76 82H, m, vCH), 4.51 82H, s, CH2Ph), 4.0982H, d,
Jˆ5.0 Hz, CH2OBn), 3.96 82H, d, Jˆ5.2 Hz, CH2OCH3),
3.23 83H, s, OCH3).
3.5.3. +Z)-1-Benzyloxy-4-+tert-butyldiphenylsilyloxy)-2,3-
epoxy-butane 7d. Compound 7d 864%, oil) was prepared
according to the general benzylation procedure, [Found: C,
75.04; H, 7.53. C27H32O3Si requires C, 74.96; H, 7.46%];
nmax 8liquid ®lm) 3063, 3030, 2972, 1452, 1274 cm21; dH
8CDCl3): 7.68±7.27 815H, m, Ph2Si1Ph±CH2), 4.57 81H, d,
Jˆ11.0 Hz, CHaHbPh), 4.43 81H, d, Jˆ11.0 Hz, CHaHbPh),
3.78 82H, d, Jˆ5.2 Hz, OCH2), 3.5981H, dd, Jˆ4.5,
11.2 Hz, OCHaHb), 3.40 81H, m, OCHaHb), 3.21 82H, m,
oxirane CH), 1.05 89H, s, Me3C); m/z 8FAB): 455 88,
[M1Na]1), 197 818), 163 811), 135 836), 91 8100).
3.7.3. +Z)-1-Benzyloxy-4-methoxy-2,3-epoxybutane 7f.26,27
The general epoxidation procedure was used giving oxirane
7f 872%, oil) after puri®cation by column chromatography
833% ethyl acetate/hexane); dH 8CDCl3): 7.43±7.25 85H, m,
Ph), 4.62 81H, d, Jˆ11.9Hz, C HaHbPh), 4.53 81H, d, Jˆ
11.9Hz, CH aHbPh), 3.73±3.54 83H, m, CH2O1CHaHbO),
3.40 83H, s, Me), 3.28±3.05 83H, m, CHaHbO1oxirane CH).
3.6. Synthesis of 7e
3.6.1. +Z)-1,4-Bis+benzyloxy)-2-butene.24 NaH 81.92 g,
44 mmol, 55% in oil) was washed with hexane 83£5 mL)
and vacuum-dried, then dry THF 810 mL) was added. The
resulting suspension was added to a precooled 8258C)
solution of cis-2-buten-1,4-diol 81.76 g, 20 mmol) in THF
830 mL). After addition of triethylbutylammonium chloride
80.06 g, 0.4 mmol) the mixture was stirred 1 h at 258C.
Benzyl bromide 88.23 g, 48 mmol) was then added, and
the reaction mixture was stirred for 16 h at 258C. The
reaction was quenched with ice-water 820 mL) and
extracted with diethyl ether 83£15 mL). The organic phase
was washed with saturated NH4Cl 82£15 mL) and brine
815 mL). After drying and evaporation of the solvent and
the excess of benzyl bromide, the residue 85.53 g) was puri-
®ed by column chromatography 825% ethyl acetate/hexane)
affording 4.53 g 884%, oil) of pure 8Z)-1,4-bis8benzyloxy)-
2-butene; dH 8CDCl3): 7.33±7.21 810H, m, Ph), 5.78 82H,
m, vCH), 4.47 84H, s, CH2Ph), 4.05 84H, d, Jˆ5.0 Hz,
CH2).
3.8. Synthesis of 7g
3.8.1. +Z)-4-Triphenylmethyloxy-2-buten-1-ol.28 NaH
80.96 g, 22 mmol, 55% in oil) was washed with pentane
83£5 mL) and vacuum-dried, then dry DMF 815 mL) was
added. The resulting suspension was added to a precooled
808C) solution of cis-2-buten-1,4-diol 85.29g, 60 mmol) in
dry DMF 850 mL). After stirring for 2 h at 258C the mixture
was cooled to 08C and a solution of trityl chloride 85.58 g,
20 mmol) in DMF 812 mL) was added during a period of
20 min. The reaction mixture was stirred for 16 h at 258C,
then cautiously poured into 300 g of ice and extracted with
ether 83£100 mL). The organic phase was washed with
brine 850 mL). After drying and evaporation of the solvent
the residue 86.32 g) was puri®ed by column chromatography
833% ethyl acetate/hexane) affording 3.70 g 856%, oil) of
8Z)-4-triphenylmethyloxy-2-buten-1-ol; dH 8CDCl3): 7.46±
7.19815H, m, Ph), 5.74 82H, m, vCH), 3.98 82H, d,
Jˆ5.3 Hz, CH2OH), 3.68 82H, d, Jˆ5.3 Hz, CH2OCPh3),
1.6981H, bs, O H).
3.6.2. +Z)-1,4-Dibenzyloxy-2,3-epoxybutane 7e.25 The
general epoxidation procedure was used giving oxirane 7e
874%, oil) after puri®cation of the crude product by column
chromatography 825% ethyl acetate/hexane); dH 8CDCl3):
7.41±7.23 810H, m, Ph), 4.5982H, d, Jˆ15.5 Hz, CH2Ph),
4.50 82H, d, Jˆ15.5 Hz, CH2Ph), 3.67 82H, dd, Jˆ3.5,
11.3 Hz, CH2O), 3.51 82H, dd, Jˆ6.1, 11.3 Hz, CH2O),
3.26 82H, m, oxirane CH).
3.8.2. +Z)-4-Triphenylmethyloxy-2,3-epoxybutan-1-ol.29
The general epoxidation procedure was used giving
the epoxy alcohol 892%, solid) after puri®cation by
column chromatography 833% ethyl acetate/hexane).

A. Thurner et al. / Tetrahedron 57 92001) 8173±8180
8177
Crystallization from ethyl acetate afforded 2.84 g of white
crystals, mp 115.7±116.88C; dH 8CDCl3): 7.46±7.20 815H,
m, Ph), 3.57 83H, m, CH2O1CHaHbO), 3.23 82H, m,
oxirane CH), 3.03 81H, m, CHaHbO), 1.92 81H, bs, OH).
80.40; H, 7.29; N, 3.75%]; nmax 8liquid ®lm) 3060, 3001,
2923, 2860, 1251 cm21; dH 8CDCl3): 7.38±7.20 815H, m,
Ph), 4.5981H, d, Jˆ11.2 Hz, CHaHbPh), 4.47 81H, d,
Jˆ11.2 Hz, CHaHbPh), 3.83 82H, d, Jˆ13.6 Hz, NCH2Ph),
3.60 81H, m, CHaHbO), 3.50 82H, d, Jˆ13.6 Hz, NCH2Ph),
3.3981H, m, CH aHbO), 3.1982H, m, oxirane C H), 2.76 81H,
dd, Jˆ4.0, 13.0 Hz, CHaHbN), 2.44 81H, dd, Jˆ4.0,
13.0 Hz, CHaHbN).
3.8.3. +Z)-1-Benzyloxy-4-triphenylmethyloxy-2,3-epoxy-
butane 7g.30 The general epoxidation procedure was used
on 8Z)-4-triphenylmethyloxy-2-buten-1-ol 82.5 g, 7.22 mmol)
affording 3.55 g of a crude product which was puri®ed by
column chromatography 825% ethyl acetate/hexane) yield-
ing 2.77 g 888%, oil) of 7g; dH 8CDCl3): 7.46±7.15 820H, m,
Ph), 4.53 81H, d, Jˆ12.0 Hz, CHaHbPh), 4.42 81H, d,
Jˆ12.0 Hz, CHaHbPh), 3.57 81H, dd, Jˆ3.8, 9.5 Hz,
CHaHbO), 3.39±3.20 84H, m, CH2O1oxirane CH), 3.11
81H, dd, Jˆ3.8, 9.5 Hz, CHaHbO).
3.10.2. +Z)-1-Benzyloxy-4-diethylamino-2,3-epoxybutane
7i. Puri®cation by column chromatography 830%
petroleum ether/ethyl acetate) afforded 7i 874%, oil); nmax
8liquid ®lm) 3063, 2963, 2933, 2872, 1203 cm21; dH
8CDCl3): 7.36±7.28 85H, m, Ph), 4.64 81H, d, Jˆ11.6 Hz,
CHaHbPh), 4.53 81H, d, Jˆ11.6 Hz, CHaHbPh), 3.71 81H,
dd, Jˆ4.2, 11.2 Hz, CHaHbO), 3.54 81H, dd, Jˆ6.4,
11.2 Hz, CHaHbO), 3.18 82H, m, oxirane CH), 2.81±2.38
86H, m, NCH2), 1.03 86H, t, Jˆ6.8 Hz, Me); m/z 8EI): 248
81, [M2H]1), 234 82), 158 83), 128 83), 91 825), 86 8100);
HRMS 8EI): [M2H]1, found 248.1652. C15H22NO2 requires
248.16505.
3.9. Synthesis of 7h±l
3.9.1. +Z)-4-Benzyloxy-2,3-epoxybutan-1-ol.26,30 The
general epoxidation procedure was used giving the epoxy-
alcohol 892%, oil) after puri®cation by column chromato-
graphy 833% ethyl acetate/hexane); dH 8CDCl3): 7.39±7.25
85H, m, Ph), 4.61 81H, d, Jˆ11.8 Hz, CHaHbPh), 4.46 81H,
d, Jˆ11.8 Hz, CHaHbPh), 3.70 84H, m, CH2O), 3.25 82H, m,
oxirane CH), 2.30 81H, bs, OH).
3.10.3. +Z)-1-Benzyloxy-4-piperidino-2,3-epoxybutane
7l. Puri®cation by column chromatography 820% petroleum
ether/ethyl acetate) afforded 7l 854%, oil); nmax 8liquid ®lm)
3062, 2933, 2853, 2788, 1206 cm21; dH 8CDCl3): 7.36±7.26
85H, m, Ph), 4.65 81H, d, Jˆ11.8 Hz, CHaHbPh), 4.52 81H,
d, Jˆ11.8 Hz, CHaHbPh), 3.70 81H, dd, Jˆ4.1, 11.2 Hz,
CHaHbO), 3.54 81H, dd, Jˆ6.4, 11.2 Hz, CHaHbO), 3.19
82H, m, oxirane CH), 2.66 81H, dd, Jˆ3.3, 13.3 Hz,
CHaHbN), 2.42 84H, m, CH2N), 2.2981H, dd, Jˆ6.6,
13.3 Hz, CHaHbN), 1.60 84H, m, CH2), 1.44 82H, m,
CH2); m/z 8EI): 260 81.2, [M2H]1), 170 83), 98 8100), 91
815); HRMS 8EI): [M2H]1, found 260.1647. C16H22NO2
requires 260.16505.
3.9.2. +Z)-1-Benzyloxy-2,3-epoxy-4-p-toluenesulfonylox-
85.55 g,
ybutane.31
p-Toluene-sulfonyl
chloride
29.1 mmol) in dry pyridine 815 mL) was added under
nitrogen at 2108C to a solution of 4-benzyloxy-2,3-epoxy-
butane-1-ol 84.71 g, 24.2 mmol) in dry pyridine 815 mL).
The mixture was stirred for 18 h at 2108C and then poured
into a mixture of 1 M sulfuric acid 8100 mL) and ice 850 g).
After stirring for 20 min the mixture was extracted with
ether 84£40 mL) and dried. After evaporation of the solvent
7.9g 894%, oil) of 8 Z)-1-benzyloxy-2,3-epoxy-4-p-toluene-
sulfonyloxybutane was obtained, which was used without
further puri®cation; dH 8CDCl3): 7.78 82H, d, Jˆ8.3 Hz,
Ph), 7.34±7.28 87H, m, Ph), 4.54 81H, d, Jˆ11.8 Hz,
CHaHbPh), 4.48 81H, d, Jˆ11.8 Hz, CHaHbPh), 4.24 81H,
dd, Jˆ3.8, 11.5 Hz, CHaHbOSO2), 4.05 81H, dd, Jˆ6.6,
11.5 Hz, CHaHbOSO2), 3.58 81H, d, Jˆ3.6, 11.4 Hz,
CHaHbO), 3.53 81H, dd, Jˆ5.4, 11.4 Hz, CHaHbO), 3.24
82H, m, oxirane CH), 2.44 83H, s, Me±Ph).
3.11. LIDAKOR induced isomerisation
General procedure. A solution of potassium tert-butoxide in
THF was cooled to 2788C then diisopropylamine and a
solution of butyllithium in hexane were added and the
mixture was stirred for 30 min. After addition of the oxirane
derivative 7 the reaction mixture was stirred for 2±16 h at
the desired temperature before being diluted with diethyl
ether 810 mL) and treated with a saturated aqueous solution
of ammonium chloride 810 mL). The aqueous phase was
then extracted with ether 83£15 mL) and the organic
phase was washed with brine 83£15 mL) and dried. After
removal of the solvent either oxetane 8 or 2-penten-1,4-diol
9 was obtained. The crude products were puri®ed by column
chromatography.
3.10. Substitution of tosyl group with amines. General
procedure
A
solution of 8Z)-1-benzyloxy-2,3-epoxy-4-p-toluene-
sulfonyloxy-butane 83.48 g, 10 mmol) and potassium iodide
80.83 g, 0.5 mmol) in DMF 840 mL) was cooled to 08C.
Then the amine 820 mmol) was added. The resulting
mixture was stirred for 3 days at room temperature then
poured into a saturated aqueous solution of NaHCO3
8300 mL). The aqueous phase was extracted with ether
84£50 mL) and the organic phase was washed with brine
850 mL). After drying and evaporation of the solvent the
residue was puri®ed by column chromatography.
3.11.1. 3-+1-Hydroxyhexyl)-2-phenyloxetane 8a.7 The
general procedure with LIDAKOR was used leading to 8a
870%, oil, cis/trans 0:100) after column chromatography
833% petroleum ether/ether); dH 8CDCl3): 7.5±7.2 85H, m,
Ph), 5.52 81H, d, Jˆ6.6 Hz, OCHPh), 4.72 82H, d,
Jˆ7.6 Hz, CH2O), 4.0±3.981H, m, C HOH), 2.91 81H, m,
oxetane CH), 1.63 81H, d, Jˆ5.4 Hz, OH), 1.5±1.2 88H, m,
CH2), 0.87 83H, t, Jˆ6.2 Hz, Me); m/z 8EI): 163 87), 133
812), 115 812), 108 813), 107 892), 105 848), 99 817), 91 820),
85 824), 84 842), 79875), 77 859), 57 8100), 55 858), 43 871).
3.10.1.
+Z)-1-Benzyloxy-4-dibenzylamino-2,3-epoxy-
butane 7h. Puri®cation by column chromatography 817%
ethyl acetate/petroleum ether) afforded 7h 885%, oil),
[Found: C, 80.04; H, 7.33; N, 3.69. C25H27NO2 requires C,

8178
A. Thurner et al. / Tetrahedron 57 92001) 8173±8180
3.11.2. 3-+1-Hydroxybutyl)-2-phenyloxetane 8b.8 The
general procedure with LIDAKOR was used leading to 8b
868%, oil, cis/trans 0:100) after puri®cation by column
chromatography 833% ethyl acetate/hexane); dH 8CDCl3):
7.5±7.2 85H, m, Ph), 5.50 81H, d, Jˆ6.8 Hz, OCHPh), 4.68
82H, d, Jˆ7.8 Hz, CH2O), 4.0±3.981H, m, C HOH), 2.90
81H, m, oxetane CH), 1.98 81H, br s, OH), 1.5±1.2 84H, m,
CH2), 0.87 83H, t, Jˆ6.6 Hz, Me); m/z 8EI): 163 87), 133
821), 115 815), 107 881), 105 842), 91 875); 84 843), 79 844),
77 8100), 57 876).
d, Jˆ6.2 Hz, CHPh), 4.65 82H, m, oxetane CH2O), 4.16
81H, m, CHOH), 3.34 83H, s, OMe), 3.40±3.20 82H, m,
OCH2), 2.94 81H, quint, Jˆ7.5 Hz, oxetane CH), 2.71
81H, bs, OH); m/z 8EI): 163 85), 133 851), 121 827), 115
837), 107 866), 105 855), 91 841), 77 8100), 70 844), 57 852).
3.11.7.
3-[1-Hydroxy-2-+triphenylmethyloxy)ethyl]-2-
phenyloxetane 8g. The general procedure with LIDAKOR
was used leading to 8g+ 866%, white solid, cis/trans 3:97)
after puri®cation by column chromatography 833% ethyl
acetate/hexane), mp 48.5±49.98C; nmax 8®lm) 3440, 3058,
3031, 2878, 1073, 1032, 972 cm21; dH 8CDCl3): 7.40±7.21
820H, m, Ph), 5.66 81H, d, Jˆ6.3 Hz, oxetane CHPh), 4.52
82H, m, oxetane CH2O), 4.18 81H, m, CHOH), 3.12 81H, dd,
Jˆ3.8, 9.5 Hz, OCHaHb), 3.02±2.83 82H, m, OCHaHb1
oxetane CH), 2.40 81H, bs, OH). m/z 8FAB): 45981,
[M1Na]1), 197 818), 163 811), 135 836), 91 8100); HRMS
8FAB): [M1Na]1, found 459.1927. C30H28O3Na requires
459.19355.
3.11.3. 3-+2-Hydroxy-6-methyl-hept-5-en-2-yl)-2-phenyl-
oxetane 8c. The general procedure with LIDAKOR was
used leading to 8c 869%, oil, cis/trans 0: 100) after puri®ca-
tion by column chromatography 833% ethyl acetate/
hexane), [Found: C, 78.34; H, 9.33; C17H24O2 requires C,
78.42; H, 9.29%]; nmax 8in CHCl3) 3585±3295, 3021, 1665,
1557, 1254 cm21; dH 8CDCl3): 7.54±7.27 85H, m, Ph), 5.69
81H, d, Jˆ6.7 Hz, OCHPh), 5.06 81H, bt, Jˆ6.5 Hz, vCH),
4.78 81H, dd, Jˆ6.0, 7.2 Hz, CHaHbO), 4.63 81H, dd, Jˆ6.0,
8.6 Hz, CHaHbO), 2.94 81H, app q, Jˆ7.2 Hz, oxetane CH),
2.0982H, m, C H2), 1.67 83H, s, Me), 1.58 83H, s, Me), 1.37
82H, m, CH2), 1.26 83H, s, Me). m/z 8EI): 195 80.4); 169
810); 134 841); 131 812); 115 845); 107 811); 105 875); 103
832); 102 812); 92 880); 91 8100); 78 844); 77 862).
3.11.8. 3-+2-Dibenzylamino-1-hydroxyethyl)-2-phenyl-
oxetane 8h. The general procedure with LIDAKOR was
used leading to 8h 864%, oil, cis/trans 5:95) after puri®ca-
tion by column chromatography 833% ethyl acetate/
hexane), [Found: C, 80.51; H, 7.35; N, 3.81. C25H27NO2
requires C, 80.40; H, 7.29; N 3.75%]; nmax 8®lm) 3432,
3084, 2939, 1120, 1072, 975 cm21; dH 8CDCl3): 7.36±
7.23 815H, m, Ph), 5.56 81H, d, Jˆ6.2 Hz, oxetane
CHPh), 4.61 82H, d, Jˆ8.0 Hz, oxetane CH2O), 4.10 81H,
m, CHOH), 3.8982H, d, Jˆ13.2 Hz, NCH2Ph), 3.34 82H, d,
Jˆ13.2 Hz, NCH2Ph), 2.78 81H, m, oxetane CH), 2.30 82H,
m, NCH2), 1.57 81H, bs, OH); m/z, 8EI): 145 82), 134 82),
117 85), 105 85), 91 8100), 77 810), 65 819).
3.11.4. 3-[2-+tert-Butyldiphenylsilyloxy)-1-hydroxyethyl]-
2-phenyloxetane 8d. The general procedure with LIDA-
KOR was used leading to 8d 864%, oil, cis/trans 0:100)
after puri®cation by column chromatography 833% ethyl
acetate/hexane), [Found: C, 75.01; H, 7.51; C27H32O3Si
requires C, 74.96; H, 7.46%]; nmax 8in CHCl3) 3416,
3069±3030, 2997, 1115, 977 cm21; dH 8CDCl3): 7.63±
7.35 815H, m, Ph), 5.74 81H, d, Jˆ6.5 Hz, CHPh), 4.49
82H, m, CH2O), 4.16 81H, m, CHOH), 3.60 81H, dd,
Jˆ4.5 Hz, 11.0, CHaHbO), 3.43 81H, dd, Jˆ7.5, 11.0 Hz,
CHaHbO), 2.86 81H, quint, Jˆ7.5 Hz, oxetane CH), 2.55
81H, bs, OH), 1.04 89H, s, Me); m/z 8EI): 241 861), 223
830), 197 88), 183 811), 181 817), 163 8100), 105 838), 91
827), 77 826).
3.11.9.
3-+2-Diethylamino-1-hydroxyethyl)-2-phenyl-
oxetane 8i. The general procedure with LIDAKOR was
used leading to 8i 875%, oil, cis/trans 5:95) after puri®cation
by column chromatography 89% methanol/dichloro-
methane), [Found: C, 72.11; H, 9.35; N, 5.71. C15H23NO2
requires C, 72.25; H, 9.30; N 5.62%]; nmax 8®lm) 3418,
3060, 2968, 1065, 976 cm21; dH 8CDCl3): 7.50±7.27 85H,
m, Ph), 5.7981H, d, Jˆ6.2 Hz, oxetane CHPh), 4.65 82H, m,
oxetane CH2O), 3.99 81H, m, CHOH), 2.90±2.08 87H, m,
oxetane CH1CH2N), 1.01 86H, t, Jˆ7.2 Hz, Me). m/z 8EI):
200 821), 199 8100), 181 85), 115 83), 105 811), 86 842), 77
825).
3.11.5. 3-+2-Benzyloxy-1-hydroxyethyl)-2-phenyloxetane
8e. The general procedure with LIDAKOR was used leading
to 8e 850%, oil, cis/trans 13:87) after puri®cation by column
chromatography 833% ethyl acetate/hexane), [Found: C,
76.01; H, 7.19; C18H20O3 requires C, 76.03; H, 7.09%];
nmax 8®lm) 3418, 3061±3029, 2882, 1095, 976 cm21; dH
8CDCl3) trans-88e): 7.47±7.24 810H, m, Ph), 5.74 81H, d,
Jˆ6.5 Hz, oxetane CHPh), 4.72±4.35 84H, m, CH2Ph1
oxetane CH2O), 4.16 81H, m, CHOH), 3.42 81H, dd,
Jˆ3.4, 9.4 Hz, OCHaHb), 3.28 81H, dd, Jˆ6.8, 9.4 Hz,
OCHaHb), 2.94 81H, quint, Jˆ7.3 Hz, oxetane CH), 2.54
81H, bs); cis-88e): 5.96 81H, d, Jˆ8.2 Hz, oxetane CHPh);
m/z 8EI): 207 84), 145 86.6), 117 851), 115 822), 107 811),
105 818), 91 8100), 77 821).
3.11.10.
3-[+1-Hydroxy-2-piperidino)ethyl]-2-phenyl-
oxetane 8l. The general procedure with LIDAKOR was
used leading to 8l 859%, oil, cis/trans 0:100) after puri®ca-
tion by column chromatography 89% methanol/dichloro-
methane); nmax 8®lm) 3417, 3060, 2935, 1119, 978 cm21
;
dH 8CDCl3): 7.48±7.25 85H, m, Ph), 5.78 81H, d, Jˆ6.3 Hz,
oxetane CHPh), 4.64 82H, m, oxetane CH2O), 4.06 81H, m,
CHOH), 3.50 81H, bs, OH), 2.81 81H, m, oxetane CH),
2.60±2.08 86H, m, 8CH2N)3), 1.63±1.42 86H, m, 8CH2)3);
m/z 8EI): 261 80.2, M1), 260 80.3), 158 82.8), 128 84), 93
838), 91 830), 86 8100). HRMS 8EI): M1, found 261.1721.
C16H23NO2 requires 261.17288.
3.11.6. 3-+1-Hydroxy-2-methoxyethyl)-2-phenyloxetane
8f. The general procedure with LIDAKOR was used leading
to 8f 850%, oil, cis/trans 0:100) after puri®cation by column
chromatography 833% ethyl acetate/hexane), [Found: C,
69.11; H, 7.79; C12H16O3 requires C, 69.21; H, 7.74%];
nmax 8®lm) 3394, 3061, 2927, 2850, 1099, 1066,
968 cm21; dH 8CDCl3): 7.45±7.25 85H, m, Ph), 5.75 81H,
3.11.11. 3-+1-Methoxybutyl)-2-phenyloxetane 8m. This
compound was prepared from 8b 864%, white solid, cis/
trans 4:96) by the methylation method described for the

A. Thurner et al. / Tetrahedron 57 92001) 8173±8180
8179
synthesis of 8Z)-1-Benzyloxy-4-methoxy-2-butene,
a
103 817), 91 8100), 79 829), 78 822), 77 857), 65 836), 63
821), 33 869), 51 843).
precursor of 7f after puri®cation by column chromatography
833% ethyl acetate/petroleum ether), mp 48.5±49.98C; nmax
8®lm) 3061, 2958, 2874, 1092, 963 cm21; dH 8CDCl3):
7.46±7.2985H, m, Ph), 5.50 81H, d, Jˆ6.8 Hz, oxetane
CHPh), 4.70 82H, d, Jˆ7.8 Hz, oxetane CH2O), 3.56 81H,
m, CHOMe), 3.41 83H, s, OMe), 2.98 81H, quint, Jˆ6.9Hz,
oxetane CH), 1.80±1.24 84H, m, CH2), 0.87 83H, t,
Jˆ6.6 Hz, Me); m/z 8FAB): 219820, [M 2H]1), 105 880),
87 8100); HRMS 8FAB): [M2H]1, found 219.1364.
C14H19O2 requires 219.1385.
3.12.4. +Z)-5-Methoxy-2-phenyl-2-penten-1,4-diol 9f. The
general procedure was used obtaining 9f 822%, oil, cis/trans
0:100) after puri®cation by column chromatography 850%
hexane/ethyl acetate), [Found: C, 69.25; H, 7.76. C12H16O3
requires C, 69.21; H, 7.74%]; nmax 8®lm) 3396, 3058, 2850,
1718, 1194 cm21; dH 8CDCl3): 7.48±7.30 85H, m, Ph), 5.82
81H, d, Jˆ7.9Hz, vCH), 4.7981H, q, Jˆ7.0 Hz, CHOH),
4.55 81H, d, Jˆ12.0 Hz, CHaHbOH), 4.47 81H, d,
Jˆ12.0 Hz, CHaHbOH), 3.46 82H, m, CH2), 3.41 83H, s,
Me), 2.83 81H, bs, OH), 1.55 81H, bs, OH); m/z 8FAB):
231 855, [M1Na]1), 173 8100), 129833), 115 836), 105
840), 91 875).
3.12. Butyllithium induced isomerization
General procedure. A solution of the oxetane 8 in THF was
cooled to 08C and a solution of butyllithium in hexane
84 equiv.) was added. The mixture was allowed to warm
up to room temperature and stirred for 3 h at this tempera-
ture. After being diluted with diethyl ether 810 mL) the
mixture was treated with a saturated aqueous solution of
ammonium chloride 810 mL). The aqueous phase was then
extracted with ether 83£15 mL) and the organic phase was
washed with brine 83£15 mL) and dried. After removal of
the solvent the residue was puri®ed by column chromato-
graphy.
3.12.5. +Z)-2 Phenyl-5-trityloxy-2-penten-1,4-diol 9g. The
general procedure was used obtaining 9g 835%, white solid,
cis/trans 0:100) after puri®cation by column chromato-
graphy 833% ethyl acetate/hexane), mp 125.5±127.28C;
nmax 8®lm) 3406, 3058, 2920, 1636, 1093 cm21; dH
8CDCl3): 7.46±7.21 820H, m, Ph), 5.72 81H, d, Jˆ7.6 Hz,
vCH), 4.70 81H, q, Jˆ7.0 Hz, CHOH), 4.53 81H, d,
Jˆ12.0 Hz, CHaHbOH), 4.3981H, d, Jˆ12.0 Hz, CHaH
OH). m/z 8FAB): 45983, [M 1Na]1), 357 816), 318 84),
243 8100), 165 825), 115 830); HRMS 8FAB): [M1Na]1,
found 459.1889. C30H28O3Na requires 459.19355.
-
2O), 2.91 81H, bs, OH), 2.45 81H, bs,
OH), 3.2982H, m, C H
b
3.12.1. +Z)-2-Phenyl-2-nonen-1,4-diol 9a.8 The general
procedure was used obtaining 9a 855%, oil) after puri®ca-
tion 833% ethyl acetate/hexane), [Found: C 76.79; H 9.42.
C15H22O2 requires C 76.88; H 9.46%]; dH 8CDCl3): 7.5±7.2
85H, m, Ph); 5.85 81H, d, Jˆ8.0 Hz, vCH); 4.65 81H, d,
Jˆ12.0 Hz, CHaHbOH); 4.57 81H, m, CHOH); 4.46 81H, d,
Jˆ12.0 Hz, CHaHbOH); 3.62 82H, bs, OH); 1.8±1.2 88H, m,
CH2); 0.87 83H, t, Jˆ6.6 Hz, Me); m/z 8EI): 217 83), 203
813), 163 827), 133 835), 101 8100), 77 842).
3.12.6. +Z)-5-Dibenzylamino-2-phenyl-2-penten-1,4-diol
9h. The general procedure was used obtaining 9h 814%,
oil cis/trans 0:100) after puri®cation by column chromato-
graphy 833% ethyl acetate/hexane); nmax 8®lm) 3379, 3027,
2929, 1650, 1070 cm21; dH 8CDCl3): 7.42±7.24 815H, m,
Ph), 5.61 81H, d, Jˆ8.0 Hz, vCH), 4.64 81H, m, CHOH),
4.48 81H, d, Jˆ12.0 Hz, CHaHbOH), 4.37 81H, d,
Jˆ12.0 Hz, CHaHbOH), 3.84 82H, d, Jˆ13.0 Hz, CH2Ph),
3.53 82H, d, Jˆ13.0 Hz, CH2Ph), 2.75 81H, bs, OH), 2.62
82H, m, CH2N), 1.60 81H, bs, OH); m/z 8FAB): 374 890,
[M1H]1), 210 814), 147 816), 106 815), 98 8100); HRMS
8FAB): [M1H]1, found 374.2091. C25H28NO2 requires
374.21201.
3.12.2. +Z)-1,4-Dimethoxy-2-phenyl-2-heptene +O,O0-
dimethyl 9b). The general procedure was used obtaining
9b8 as a crude product. Then it was treated with 2 equiv.
of NaH in dry THF and consecutively with a large excess of
iodomethane to get O,O0-dimethyl 9b 864%, oil, cis/trans
0:100) after puri®cation by column chromatography 833%
ethyl acetate/hexane); nmax 8®lm) 3058, 2959, 2872, 1724,
1095 cm21; dH 8CDCl3): 7.47±7.25 85H, m, Ph), 5.81 81H,
d, Jˆ9.5 Hz, vCH), 4.36 82H, s, OCH2), 4.1981H, m,
OCH), 3.33 83H, s, OMe), 3.32 83H, s, OMe), 1.79±1.20
84H, m, CH2), 0.93 83H, t, Jˆ6.7 Hz, Me); m/z 8EI): 233
823), 219822), 206 837), 147 835), 129836), 121 877), 105
8100), 91 861), 87 894), 77 842), 45 876); HRMS 8EI):
[M2H]1, found 233.1504. C15H21O2 requires 233.15416.
3.12.7. +Z)-5-Diethylamino-2-phenyl-2-penten-1,4-diol
9i. The general procedure was used obtaining 9i 835%, oil,
cis/trans 0:100) after puri®cation by column chromato-
graphy 8Florisil; 33% hexane/ethyl acetate), [Found: C,
72.31; H, 9.33; N, 5.69. C15H23NO2 requires C, 72.25; H,
9.30; N 5.62%]; nmax 8®lm) 3356, 2970, 2871, 1650,
1070 cm21; dH 8CDCl3): 7.52±7.28 85H, m, Ph), 5.75 81H,
d, Jˆ8.0 Hz, vCH), 4.60 81H, q, Jˆ7.4 Hz, CHOH), 4.48
81H, d, Jˆ12.4 Hz, CHaHbOH), 4.38 81H, d, Jˆ12.4 Hz,
CHaHbOH), 2.64 81H, bs, OH), 2.5986H, m, C H2), 1.45
81H, bs, OH), 1.05 86H, t, Jˆ7.0, Me). m/z 8EI): 177 813),
163 815), 133 825), 103 811), 77 8100).
3.12.3. +Z)-5-[+tert-Butyldiphenyl)silyloxy]-2-phenyl-2-
penten-1,4-diol 9d. The general procedure was used obtain-
ing 9d 819%, oil, cis/trans 0:100) after puri®cation by
column chromatography 833% ethyl acetate/hexane),
[Found: C, 75.04; H, 7.49. C27H32O3Si requires C, 74.96;
H, 7.46%]; nmax 8®lm) 3383, 3070, 2857, 1684, 1080 cm21
;
3.12.8. +Z)-2-Phenyl-5-piperidino-2-penten-1,4-diol 9l.
The general procedure was used obtaining 9l 839%, oil,
cis/trans 0:100) after puri®cation by column chromato-
graphy 8Florisil; 33% hexane/ethyl acetate); nmax 8®lm)
3361, 3057, 2935, 1653, 1115 cm21; dH 8CDCl3): 7.50±
7.27 85H, m, Ph), 5.77 81H, d, Jˆ7.6 Hz, vCH), 4.67 81H,
q, Jˆ7.0 Hz, CHOH), 4.4981H, d, Jˆ12.3 Hz, CHaHbOH),
dH 8CDCl3): 7.68±7.38 815H, m, Ph), 5.76 81H, d,
Jˆ7.4 Hz, vCH), 4.6981H, q, Jˆ6.2 Hz, CHOH), 4.53
81H, d, Jˆ12.0 Hz, CHaHbOH), 4.41 81H, d, Jˆ12.0 Hz,
CHaHbOH), 3.72 82H, m, CH2), 2.95 81H, bs, OH), 1.70
81H, bs, OH), 1.08 89H, s, Me); m/z 8EI): 160 85); 145 85),
133 863), 129 813), 128 813), 115 849), 107 839), 105 816),

8180
A. Thurner et al. / Tetrahedron 57 92001) 8173±8180
11. Schlosser, M. J. Organomet. Chem. 1967, 8, 9 .
12. Mordini, A. Comprehensive Organometallic Chemistry II;
Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon:
Oxford, 1995; Vol. 11, p. 93.
4.40 81H, d, Jˆ12.3 Hz, CHaHbOH), 2.56±2.38 87H, m,
CH2N1OH), 1.60±1.23 87H, m, CH21OH); m/z 8EI): 261
80.1, M1), 252 80.1), 243 80.1), 230 80.2), 141 85), 98 8100);
HRMS 8EI): M1, found 261.1717. C16H23NO2 requires
261.17288.
13. Margot, C.; Schlosser, M. Tetrahedron Lett. 1985, 26, 1035.
14. Cohen, T.; Bhupathy, M. Acc. Chem. Res. 1989, 22, 152.
15. Freeman, P. K.; Hutchinson, L. L. J. Org. Chem. 1983, 48,
4705.
Acknowledgements
16. Grob, C. A. Angew. Chem., Int. Ed. Engl. 1969, 8, 535.
17. Grob, C. A.; Schiess, P. W. Angew. Chem., Int. Ed. Engl.
1967, 6, 1.
The authors are indebted to the CNR 8Italy) and the
Hungarian Academy of Sciences for promotion of the
scienti®c cooperation in the framework of the bilateral
cooperation agreement between the two institutions. This
research work was supported by the National Research
Foundation of Hungary 8OTKA Grant No. T-030803).
18. Linderman, R. J. Comprehensive Heterocyclic Chemistry II;
Padwa, A., Ed.; Pergamon: Oxford, 1996; Vol. 1B, pp. 755±
771.
19. Linderman, R. J. Comprehensive Heterocyclic Chemistry II;
Padwa, A., Ed.; Pergamon: Oxford, 1996; Vol. 1B, pp. 721±
753.
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