Carotenoids and related polyenes. Part 4. Synthesis of carotenoid analogues containing a conjugated carbonyl group and their fluorescence properties

Article abstract of DOI:10.1039/a702815f

Fluorescence properties of several synthetic carotenoid analogues have been investigated in order to assess the relationship between molecular structures and function as a photosynthetic antenna. The origin of fluorescence is determined by two factors; th

Full text of DOI:10.1039/a702815f

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Carotenoids and related polyenes. Part 4.1 Synthesis of carotenoid
analogues containing a conjugated carbonyl group and their
fluorescence properties
Yumiko Yamano,a Mamoru Mimurob and Masayoshi Ito*,a
a
Kobe Pharmaceutical University, Motoyamakita-machi, Higashinada-ku, Kobe 658, Japan
b Department of Information Science, Faculty of Science, Yamaguchi University,
Yamaguchi 753, Japan
Fluorescence properties of several synthetic carotenoid analogues have been investigated in order to
assess the relationship between molecular structures and function as a photosynthetic antenna. The
origin of fluorescence is determined by two factors; the length of the conjugated double bond system
and the presence of a carbonyl group. For efficient energy transfer to chlorophyll a, eight conjugated
double bonds and an associated carbonyl group are required, which ensures that fluorescence occurs
from the S1 state.
in which a carbonyl group of fucoxanthin 1 was replaced with a
Introduction
normal double bond, showed its origin from the S2 state. How-
ever, in the case of spheroidenone 5, even though the carbonyl
group was contained in the conjugated system, its main emis-
sion originated from the S2 state (Fig. 1). This suggests that the
origin of fluorescence is determined not only by the presence of
a carbonyl group but also by the molecular structure of the
carotenoids. Thus we investigated this point by using several
synthetic carotenoid analogues.
In photosynthesis of algae, three carotenoids, fucoxanthin 1,
peridinin 2 and siphonaxanthin 3, function as efficient light-
harvesting antennas in pigment systems;2,3 their energy-transfer
efficiency to an acceptor molecule, chlorophyll (Chl) a, was
estimated to be very high. These carotenoids show a stronger
emission from the forbidden S1 state than that from the allowed
S2 state and their S1 lifetimes were longer than those of the
unsubstituted carotenoids.4,5 Their S1 fluorescence spectra
exhibit a greater overlap with the absorption spectrum of Chl a
and thus a higher transition probability from the S1 state takes
place in the energy-transfer sequence. These are of the utmost
importance for the antenna function in algal photosynthetic
pigment systems.3
Results and discussion
Effect of â-ionone rings on the fluorescence properties
A characteristic molecular structure of antenna carotenoids is
Previously, our group reported that the fluorescence spectra
of carbonyl-containing carotenoids were characterized by dual
emissive properties.4–7 The origin of fluorescence is determined
by the presence of a carbonyl group; for example, neoxanthin 4,
the presence of β-ionone rings and a carbonyl group in a chain
of eight conjugated C᎐C double bonds. First, in order to study
᎐
the effect of β-ionone rings on the fluorescence properties, we
synthesized four analogues 6,7 7, 8 and 97 of fucoxanthin 1.
HO
OAc
OH
CH2OH
O
O
P
O
Siphonaxanthin 3
P
HO
HO
Fucoxanthin 1
HO
OH
HO
OAc
O
O
P
O
O
HO
HO
Peridinin 2
Neoxanthin 4
MeO
P
O
Spheroidenone 5
Structure of carotenoids of interest
J. Chem. Soc., Perkin Trans. 1, 1997
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Fig. 1 Absorption spectra (smooth curves; left side) and fluorescence spectra (noisy curves; right side) of fucoxanthin 1, neoxanthin 4, spheroid-
enone 5 and analogues 6–13, for solutions in CS2
Analogues 6 and 7 were derived from the oxo pentaenal 14,
which was previously prepared 1 for the first total synthesis of
fucoxanthin 1 (Scheme 1). Wittig condensation of the phos-
phonium salt 158 with the aldehyde 14 in the presence of
sodium methoxide as base, followed by acetylation, afforded an
isomeric mixture [50% from 14; all-E (analogue 6):13Z ~1:1]
of the condensed products, which was cleanly separated by pre-
parative HPLC (PHPLC) in the dark. The stereochemistry of
the newly formed 13,14-double bonds of these isomers was
determined from the coupling constants (E: 15 Hz; Z: 12 Hz)
between 13- and 14-H in the 1H NMR spectra. The analogue 7
was also synthesized [64% from 15; all-E :11Z ~1:1] using the
Wittig salt 16, which was derived from the formyl ester 179 in 3
steps (64%) as shown in Scheme 1.
Analogues 8 and 9, not possessing a β-ionone ring on the left
side of the polyene chain, were prepared by reaction of the
Wittig salt 15 or 16 with the oxo pentaenal 24a. Condensed
products (8: 74%; 9: 87%; as isomeric mixtures) were purified by
PHPLC to give each pure analogue. The aldehyde 24a was
derived from the formyl ester 17. Introduction of a methyl
group into aldehyde 17 and subsequent protection of the result-
ing hydroxy group gave the tert-butyldimethylsilyl (TBS) ether
20 (80%). Reduction of the ester group in compound 20 with
lithium aluminium hydride (LAH) provided the alcohol 21
(83%), which was treated with lithium chloride and methane-
sulfonyl chloride (MsCl) followed by treatment with triphenyl-
phosphine in chloroform under reflux to afford the Wittig salt
22 (73% from 21). Wittig condensation of the phosphonium
salt 22 with the C10-dialdehyde 23 gave a mixture of the con-
densed products, which was desilylated using tetrabutyl-
ammonium fluoride (TBAF ), oxidized with MnO2, and sub-
sequently separated by PHPLC to provide the all-E-oxo pen-
taenal 24a (42% from 23) and its 8Z-isomer 24b (8% from 23).
The steady-state fluorescence spectra of these analogues 6–9
in CS2 are shown in Fig. 1. The main emissions from these
analogues were all observed at around 750 nm, indicating their
origin from the S1 state as in the case of antenna carotenoids
1–3. These results show that β-ionone rings on both sides of a
polyene chain do not affect its fluorescence properties.
Effect of the direction of a carbonyl group with respect to a
polyene chain on the fluorescence properties
The carbonyl group in antenna carotenoids 1,10 2 and 311 is
arranged in s-trans form. The s-trans configuration of fucoxan-
1
thin 1 was confirmed 10 by H NMR spectroscopy, including
nuclear Overhauser enhancement (NOE) experiments. In
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J. Chem. Soc., Perkin Trans. 1, 1997

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siphonaxanthin 3, the oxygen atom of the carbonyl group is
fixed in the same plane as that of conjugated double bonds by
intramolecular hydrogen bonding with the alcohol.11 This is
also the case in peridinin 2, which has an ylidene butenolide
ring structure. The carbonyl group in analogues 6–9 was also
confirmed to be s-trans from H NMR spectroscopy including
NOE experiments (cross-peaks between 1-H2 or 1-H3 and 4-H).
On the other hand, the carbonyl group in spheroidenone 5
(emission from S2 state is dominant) is known 12 to be in the
s-cis form. Therefore, it is expected 7 that coplanarity of a car-
bonyl group with a polyene chain in the ground state is correl-
ated with the origin of fluorescence. Thus, in order to study the
effect of a carbonyl group on the fluorescence properties, we
synthesized analogues 10–12, whose configuration of the carb-
onyl group with respect to the eight conjugated double bonds
is fixed in s-cis or s-trans form by the terminal ring structure.
The analogue 10, possessing an s-trans carbonyl group,
was synthesized starting from 2-methylcyclohexane-1,3-dione
25 (Scheme 2). Treatment of dione 25 with 1 mol equiv. of
N-phenyltrifluoromethanesulfonimide (Tf2NPh) in the presence
of sodium hydride as a base gave the oxo enol triflate 26 (98%).
Reduction of the carbonyl group of compound 26 with sodium
borohydride followed by protection of the resulting hydroxy
group gave the TBS ether 27 (68%), which underwent a
coupling reaction 13 with methyl vinyl ketone in the presence of
palladium catalyst to afford the dienone 28 (91%). Peterson
olefination of compound 28 with ethyl (trimethylsilyl)(TMS)-
acetate and lithium diisopropylamide (LDA) at Ϫ78 ЊC
afforded the trienoate 29 (2E :2Z = 4:3) (95%), which without
separation was transformed into the trienal 30 (2E :2Z = 3:2) in
3 steps (63%) as shown in Scheme 2. Wittig condensation of the
phosphonium salt 3114 with aldehyde 30 and subsequent acid
hydrolysis gave a crude isomeric mixture of the oxo pentaenal
32, which without separation was treated with a palladium
catalyst 1,15 and then purified by PHPLC to give the all-E-oxo
pentaenal 32a (76% from 30) and its 6Z-isomer 32b (13%
from 30). Finally, compound 32a was condensed with the
phosphonium salt 16 (Scheme 1) to give the analogue 10 (62%;
all-E :9ЈZ ~1:1).
1
13
O
R2
2
4
14
R1
P
6′
6 R1 = A, R2 = B ; 8 R1 = Me, R2 = B
7 R1 = A, R2 = Me ; 9 R1 = R2 = Me
A =
B =
2′
4′
AcO
2′′
6′′
11′
13′
14′
12′
O
P
1
P
3
O
10
11
12′
14′
P
The analogue 11 was derived from cyclohexane-1,2-dione 33
as shown in Scheme 2. Treatment of the dione 33 with methoxy-
trimethylsilane at 0 ЊC in the presence of a catalytic amount of
trifluoromethanesulfonic acid (TfOH) gave the dione mono-
ketal 37 as the major initial product, which was converted into
the diosphenol methyl ether 34 by keeping the reaction mixture
at room temperature for several hours.16 Emmons–Horner reac-
tion of enone 34 with the phosphonate 35 provided an isomeric
O
12
17
19
2
O
P
13
Structure of synthetic carotenoid analogues
+
Br– Ph3P
analogue 6
15
O
CHO
i, ii
i, ii
+
Br– Ph3P
analogue 7
HO
14
16
v
R
iii
CO2Me
OHC
17
vi, vii
18 R = CO2Me
19 R = CH2OH
iv
23
9
15
16
analogue 8
analogue 9
TBSO
R
O
CHO
i
i, x, xi
8
i
24a
20 R = CO2Me
8Z-isomer 24b
CHO
iv
21 R = CH2OH
+
viii, ix
22 R = CH2PPh3Cl–
OHC
23
Scheme 1 Reagents: i, 15, 16 or 23, NaOMe; ii, Ac2O, Py; iii, EtPPh3Br, nBuLi; iv, LAH; v, PPh3ؒHBr; vi, MeMgBr; vii, TBSOTf, γ-collidine; viii,
LiCl, MsCl, γ-collidine; ix, PPh3; x, TBAF; xi, MnO2
J. Chem. Soc., Perkin Trans. 1, 1997
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O
O
O
1
OTf
3
TBSO
OTf
TBSO
3
1
3′
O
ii, iii
iv
i
3
25
26
27
28
v
TBSO
CO2Et
3′
3′
O
CHO
vi, vii, viii
2
2
29
30
O
+
Cl– Ph3P
ix, x, xi
O
3′
O
CHO
16
31
6
4
analogue 10
ix
32a
6Z-isomer 32b
6′
ref. 16
xii
2′
+
CO2Et
O
O
2
O
OMe
OMe
OMe CO2Et
ref. 16
33
34
36a
36b
ref. 16
6′
xii
xiv
+
2
R
2′
+
+
PPh3 Cl–
PPh3 Cl–
O
MeO
OMe
MeO
OMe
MeO
OMe
OMe
42
41
38 R = CO2Et
39 R = CH2OH
40 R = CH2Cl
37
vi
xiii
5
:
1
23 ix, x, xi
6′
CHO
2′
16
analogue 11
ix
O
43
5′
O
O
xii
xv, xvi, xvii, x
5
CHO
2′
OHC
O
R
O
O
44
45 R = CO2Et
46 R = CHO
47
vi, viii
ix, x, xi
31
16
CHO
2′
analogue 12
ix
6
O
48a
6Z-isomer 48b
O
CHO
31
16
24a
analogue 13
ix, x, xi
ix
49
Scheme 2 Reagents: i, NaH, Tf2NPh; ii, NaBH4; iii, TBSCl, Et3N, DMAP; iv, methyl vinyl ketone, cat. PdCl2(PPh3)2, Et3N; v, TMSCH2CO2Et,
LDA; vi, LAH; vii, TBAF; viii, MnO2; ix, 31, 16 or 23, NaOMe; x, p-TsOH; xi, cat. PdCl2(MeCN)2, Et3N; xii, (EtO)2P(O)CH2CO2Et 35, nBuLi; xiii,
LiCl, MsCl, γ-collidine; xiv, PPh3; xv, cyclopentanone, LDA; xvi, Ac2O, DMAP; xvii, DBU
mixture of ylidene-esters 36a (31%) and 36b (36%), while the
same reaction of ketal 37 afforded the E-ylidene-ester 38 (95%)
as a single isomer. Therefore, the ester 38 was used for further
reaction. Stereochemistry of those isomers was confirmed by
1H NMR spectroscopy including 2D NOE and exchange
spectroscopy (NOESY) experiments: in E-isomers 36a and 38,
cross-peaks between 2-H and 2Ј-OMe were observed, whereas
cross-peaks between 2-H and 6Ј-H2 appeared in the Z-isomer
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J. Chem. Soc., Perkin Trans. 1, 1997

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36b. Similar treatment of the ester 38 as in the case of the
preparation of the Wittig salt 22 from 20 (Scheme 1) gave a
mixture of Wittig salts 41 and 42, which without purification
group associated with the conjugated double-bond system,
might be necessary for these carotenoids to function as efficient
light-harvesting antennas in pigment systems.
Ϫ
was allowed to react with the C10 -dialdehyde 23. The result-
ing condensed products were deprotected by acid hydrolysis
and subsequently treated with palladium catalyst and then
purified by PHPLC to give the all-E-oxo pentaenal 43 (81%
from 23). Finally, aldehyde 43 was condensed with the
phosphonium salt 16 to furnish the analogue 11 (79%; all-
E :10ЈZ ~1:1).
Experimental
UV–VIS spectra were recorded on a JASCO Ubest-55 instru-
ment. IR spectra were measured on a Shimadzu IR-27G
spectrometer, a Shimadzu FT-IR 4000 spectrometer or a
Perkin-Elmer FT-IR spectrometer, model Paragon 1000, for
chloroform solutions unless otherwise stated. 1H NMR spectra
at 200, 300 or 500 MHz were determined on a Varian XL-200, a
Varian Gemini-200, a Varian Gemini-300 or a Varian VXR-500
superconducting Fourier-transform (FT)-NMR spectrometer,
respectively, for deuteriochloroform solutions (tetramethyl-
silane as internal reference). 13C NMR spectrum at 75 MHz was
measured on a Varian Gemini-300 superconducting FT-NMR
spectrometer for samples in deuteriochloroform solution with
tetramethylsilane as internal standard. J-Values are given in
Hz. Mass spectra were taken on a Hitachi M-80 or a Hitachi
M-4100 spectrometer.
Absorption and fluorescence spectra shown in Fig. 1 were
measured with a Hitachi 330 spectrophotometer and a Hitachi
850 spectrofluorometer, respectively, at 20 ЊC for solutions in
carbon disulfide. For the fluorescence spectra, the maximum
absorbance of sample solutions was kept <0.3. Measurements
were repeated several times to increase the signal-to-noise ratio.
The excitation wavelength was between 410 and 460 nm
depending on the sample. The bandwidths for fluorescence
analysis were 5 nm for excitation and 3 nm for emission. Data
were transferred to a microcomputer for processing and to
correct the spectral sensitivity of the fluorometer numerically.
Short-column chromatography (SCC) was performed on
silica gel (Merck Art. 7739) under reduced pressure, and open
column chromatography (CC) on silica gel (Merck Art. 7734).
Preparative TLC (PLC) was performed on silica gel plates
(Merck silica gel 60F254 precoated plates, 0.5 mm thickness).
Analytical and preparative HPLC was carried out on Shimadzu
LC-3A, 5A, 6A and Waters Model 510 instruments with a
UV–VIS detector.
The analogue 12 was synthesized through reaction of
cyclopentanone with the dienal 46, which was prepared from
the enal 4414 by Emmons–Horner reaction with the phos-
phonate 35 (98%) and subsequent reduction with LAH and
oxidation with MnO2 (50% from 45). Treatment of the dienal 46
with the lithium enolate of cyclopentanone gave the aldol,
which was acetylated, treated with 1,8-diazabicyclo[5.4.0]-
undec-7-ene (DBU), and then hydrolysed to provide the all-E-
oxo trienal 47 (64% from 46). The newly formed ylidene double
1
bond in compound 47 was determined to be E from H NMR
spectroscopy including NOE experiments (cross-peaks between
5Ј-H2 and 5-H). The oxo trienal 47 was transformed into the
analogue 12 in the same manner as in the case of synthesis of
the analogue 10, as shown in Scheme 2.
The steady-state fluorescence spectra of analogues 10–12
(Fig. 1) were similar to those of antenna carotenoids 1–3
and analogues 6–9; the main emission originated from the
S1 state (~750 nm). This shows that coplanarity of a carb-
onyl group with a polyene chain is not significant for the S1
emission.
Effect of length of conjugated double-bond system on the
fluorescence properties
The number of conjugated double bonds (n) in antenna caro-
tenoids 1–3 and synthetic analogues 6–12 is nine [C᎐C (or
᎐
C᎐C᎐C) × 8 ϩ C᎐O × 1]† and show, preferentially, S emission,
᎐ ᎐
᎐
1
whereas the emission from the S2 state is dominant in spheroid-
enone 5 (n = 11; C᎐C × 10 ϩ C᎐O × 1). Therefore, in order to
᎐
᎐
study the effect of the length of the conjugated double-
bond system on the fluorescence properties, we synthesized the
analogue 13 as shown in Scheme 2 and measured its fluores-
cence spectrum (Fig. 1). The main emission from analogue 13
was observed at ~600 nm, indicating S2 emission. This clearly
shows that the origin of fluorescence is affected by the length of
the conjugated double-bond system.
Previously, our group reported that the presence of a
carbonyl group had a large effect on the origin of fluorescence
of polyenes.4–7 For example, in the case of fucoxanthin 1,
replacement of a carbonyl group with a normal double bond
(neoxanthin 4) changed the origin of fluorescence from the S1
state to the S2 state (Fig. 1), even though the number n was the
same in the two carotenoids.5 From the above results, it appears
that the origin of fluorescence is determined not only by the
presence of a carbonyl group but also by the length of the
conjugated double-bond system. However, neither the substitu-
ent group (for example, β-ionone ring) nor the direction of a
carbonyl group with respect to a polyene chain is so significant
for the S1 emission.
Standard work-up means that the organic layers were finally
washed with brine, dried over anhydrous sodium sulfate
(Na2SO4), filtered and concentrated in vacuo below 30 ЊC, using
a rotary evaporator. All operations were carried out under
nitrogen or argon. Ether refers to diethyl ether and hexane to
n-hexane.
Preparation of the analogue 6
A solution of NaOMe (1.0 mol dmϪ3 in MeOH; 1.54 cm3, 1.54
mmol) was added to an ice-cooled solution of the Wittig salt
158 (690 mg, 1.28 mmol) and the aldehyde 141 (98 mg, 0.26
mmol) in CH2Cl2 (10 cm3). After being stirred at 0 ЊC for 1.5 h,
the reaction mixture was diluted with ether. The organic layer
was followed by standard work-up to give a residue, which was
purified by SCC (acetone–hexane, 2:8) to afford an isomeric
mixture of condensed products. Without separation, this was
dissolved in a mixture of pyridine (Py) (6 cm3) and acetic an-
hydride (2 cm3). The mixture was stirred at room temp. for 16 h,
poured into ice–water and extracted with ether. The extracts
were washed successively with aq. 3% HCl, saturated aq.
NaHCO3 and brine. Evaporation of the dried extracts gave a
residue, which was purified by SCC (ether–hexane, 1:3) to pro-
vide an isomeric mixture [78 mg, 50% from 14; all-E (analogue
6):13Z ~1:1]. PHPLC separation [LiChrosorb Si 60 (5 µm)
1.0 × 30 cm; tetrahydrofuran (THF )–hexane, 5:95] of the mix-
ture in the dark gave the analogue 6 and its 13Z-isomer as red
solids. Analogue 6: λmax(EtOH)/nm 267, 449 and 464sh;
λmax(hexane)/nm 264, 424, 446 and 474; νmax(KBr)/cmϪ1 1730
As pointed out by one of us,17 a main determinant for the
origin of fluorescence is assigned to the energy gap between the
S2 and S1 states (∆E21). On the other hand, the direction of a
carbonyl group with respect to a polyene chain is known to be a
major determinant in some aspects in the excited S2 state;18 this
might be additional to the relaxation processes from the S2
state.
In summary, it is expected that a common molecular struc-
ture, viz. eight conjugated double bonds, with one carbonyl
(OAc), 1659 (conj. CO) and 1607 (C᎐C); δ (500 MHz) 0.82 and
᎐
H
† One of the eight double bonds in peridinin is cross-conjugated with
the carbonyl group.
0.91 (each 3 H, s, 6Љ-gem-Me), 0.93 (3 H, s, 6Ј-Meeq), 1.03 (3 H,
J. Chem. Soc., Perkin Trans. 1, 1997
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s, 6Ј-Meax), 1.48 (3 H, s , 2Ј-Me), 1.59 (3 H, d, J 1.5, 2Љ-Me), 1.65
(1 H, t, J 12, 5Ј-Hax), 1.74 (1 H, ddd, J 12, 3.5 and 2, 5Ј-Heq),
1.92 (3 H, s, 16-Me), 1.97 (3 H, s, 3-Me), 1.99 (3 H, s, 12-Me),
2.00 (3 H, s, 7-Me), 2.05 (3 H, s, OAc), 2.19 (1 H, d, J 10, 1Љ-H),
2.19 (1 H, br dd, J 16 and 10, 3Ј-Hax), 2.39 (1 H, br dd, J 16 and
6, 3Ј-Heq), 3.44 and 3.48 (each 1 H, d, J 18, 1-H2), 5.07 (1 H, m,
4Ј-H), 5.42 (1 H, br s, 3Љ-H), 5.55 (1 H, dd, J 15 and 10, 18-H),
6.12 (1 H, d, J 15, 17-H), 6.13 (1 H, br d, J 11, 15-H), 6.26 (1 H,
br d, J 11.5, 11-H), 6.35 (1 H, d, J 15, 13-H), 6.40 (1 H, br d, J
12, 8-H), 6.60 (1 H, dd, J 15 and 11, 5-H), 6.64 (1 H, dd, J 15
and 12, 9-H), 6.67 (1 H, dd, J 15 and 11, 14-H), 6.68 (1 H, d, J
15, 6-H), 6.74 (1 H, dd, J 15 and 11.5, 10-H) and 7.24 (1 H, br d,
J 11, 4-H) (Found: Mϩ, 610.440. Calc. for C42H58O3: M,
610.438).
Preparation of the phosphonium salt 16
A solution of the alcohol 19 (2.94 g, 26.3 mmol) and triphenyl-
phosphine hydrobromide (9.01 g, 26.3 mmol) in methanol (100
cm3) was stirred at room temp. for 48 h. Evaporation of the
methanol gave a residue, which was washed with ether to pro-
vide crude phosphonium salt 16 (10.69 g, 93%) as a foam,
δH (200 MHz) 1.35 (3 H, d, J 4, 3-Me), 1.71 (3 H, m, 5-Me), 4.71
(2 H, dd, J 15.5 and 8, 1-H2), 5.21 (1 H, m, 2-H), 5.75 (1 H, m,
5-H), 5.94 (1 H, br d, J 15, 4-H) and 7.60–7.90 (15 H, m, ArH).
Preparation of the analogue 7
In the same manner as described for the preparation of the
analogue 6, the Wittig reaction between the phosphonium salt
16 (192 mg, 0.44 mmol) and the aldehyde 14 (56 mg, 0.15 mmol)
followed by acetylation gave a residue, which was purified by
SCC (ether–hexane, 1:3) to afford an isomeric mixture [47 mg,
64% from 14; all-E (analogue 7):13Z ~1:1]. PHPLC separation
[LiChrosorb Si 60 (5 µm) 1.0 × 30 cm; THF–hexane, 4:96] of
the mixture in the dark provided the analogue 7 and its 13Z-
isomer as red solids.
13Z-Isomer: λmax(EtOH)/nm 269, 333 and 446; λmax(hexane)/
nm 266, 316, 425, 444 and 472; νmax(KBr)/cmϪ1 1730 (OAc),
1665 and 1659 (split) (conj. CO) and 1609 (C᎐C); δ (500 MHz)
᎐
H
0.83 and 0.91 (each 3 H, s, 6Љ-gem-Me), 0.93 (3 H, s, 6Ј-Meeq),
1.03 (3 H, s, 6Ј-Meax), 1.48 (3 H, s , 2Ј-Me), 1.59 (3 H, d, J 1.5,
2Љ-Me), 1.65 (1 H, t, J 12, 5Ј-Hax), 1.74 (1 H, ddd, J 12, 3.5 and
2, 5Ј-Heq), 1.89 (3 H, s, 16-Me), 1.97 (3 H, s, 3-Me), 2.00 (3 H, s,
7-Me), 2.05 (3 H, s, OAc), 2.13 (3 H, s, 12-Me), 2.19 (1 H, br dd,
J 16 and 10, 3Ј-Hax), 2.19 (1 H, d, J 10, 1Љ-H), 2.39 (1 H, br dd, J
16 and 6, 3Ј-Heq), 3.44 and 3.48 (each 1 H, d, J 18, 1-H2), 5.07
(1 H, m, 4Ј-H), 5.42 (1 H, br s, 3Љ-H), 5.58 (1 H, dd, J 15 and 10,
18-H), 5.97 (1 H, d, J 12, 13-H), 6.14 (1 H, d, J 15, 17-H), 6.32
(1 H, br d, J 11, 11-H), 6.34 (1 H, t, J 12, 14-H), 6.41 (1 H, br d,
J 11, 8-H), 6.60 (1 H, dd, J 15 and 11, 5-H), 6.63 (1 H, br d, J
12, 15-H), 6.64 (1 H, dd, J 14.5 and 11, 9-H), 6.68 (1 H, d, J 15,
6-H), 6.72 (1 H, dd, J 14.5 and 11, 10-H) and 7.24 (1 H, br d, J
11, 4-H) (Found: Mϩ, 610.439).
Analogue 7: λmax(EtOH)/nm 265, 447 and 462sh; λmax(hexane)/
nm 262, 420, 443 and 471; νmax(KBr)/cmϪ1 1730 (OAc), 1659
(conj. CO) and 1607 (C᎐C); δ (500 MHz) 0.93 (3 H, s, 6Ј-Meeq),
᎐
H
1.03 (3 H, s, 6Ј-Meax), 1.48 (3 H, s, 2Ј-Me), 1.65 (1 H, t, J 12, 5Ј-
Hax), 1.74 (1 H, ddd, J 12, 3.5 and 2, 5Ј-Heq), 1.83 (3 H, br d, J 7,
18-Me), 1.91 (3 H, s, 16-Me), 1.97 (3 H, s, 3-Me), 1.99 (3 H, s,
12-Me), 2.00 (3 H, s, 7-Me), 2.05 (3 H, s, OAc), 2.18 (1 H, br dd,
J 16 and 10, 3Ј-Hax), 2.39 (1 H, br dd, J 16 and 6, 3Ј-Heq), 3.44
and 3.48 (each 1 H, d, J 18, 1-H2), 5.07 (1 H, m, 4Ј-H), 5.77 (1
H, dq, J 15.5 and 7, 18-H), 6.09 (1 H, br d, J 11, 15-H), 6.16 (1
H, dd-like, J 15.5 and 1, 17-H), 6.26 (1 H, br d, J 12, 11-H), 6.34
(1 H, d, J 15, 13-H), 6.40 (1 H, br d, J 11, 8-H), 6.60 (1 H, dd, J
15 and 11, 5-H), 6.63 (1 H, dd, J 14 and 11, 9-H), 6.66 (1 H, dd,
J 15 and 11, 14-H), 6.68 (1 H, d, J 15, 6-H), 6.74 (1 H, dd, J 14
and 12, 10-H) and 7.24 (1 H, dd-like, J 11 and 1, 4-H) (Found:
Mϩ, 502.343. C34H46O3 requires M, 502.344).
Methyl (2E,4E/Z)-3-methylhexa-2,4-dienoate 18
A solution of butyllithium (1.68 mol dmϪ3 in hexane; 18.5 cm3,
31 mmol) was added to a stirred suspension of ethyltriphenyl-
phosphonium bromide (11.50 g, 31 mmol) in dry THF (50 cm3)
at 0 ЊC. The mixture was stirred for a further 40 min, after
which a solution of the aldehyde 179 (3.84 g, 30 mmol) in dry
THF (20 cm3) was added, and stirring was continued at room
temp. for 15 min. After being quenched with saturated aq.
NH4Cl, the mixture was extracted with ether followed by
standard work-up to give a residue, which was purified by CC
(ether–hexane, 2:8) to afford an isomeric mixture of the ester
18 (3.16 g, 75%; 4E :4Z = 2:3) as an oil, λmax(EtOH)/nm 260;
νmax/cmϪ1 1712 (conj. CO Me) and 1640 and 1612 (C᎐C);
13Z-Isomer: λmax(EtOH)/nm 267, 330 and 443; λmax(hexane)/
nm 264, 314, 327, 423, 441 and 469; νmax(KBr)/cmϪ1 1730
(OAc), 1659 (conj. CO) and 1607 (C᎐C); δH (500 MHz) 0.93 (3
᎐
H, s, 6Ј-Meeq), 1.03 (3 H, s, 6Ј-Meax), 1.48 (3 H, s, 2Ј-Me), 1.65
(1 H, t, J 12, 5Ј-Hax), 1.74 (1 H, ddd, J 12, 3.5 and 2, 5Ј-Heq),
1.83 (3 H, br d, J 7, 18-Me), 1.89 (3 H, s, 16-Me), 1.97 (3 H, s,
3-Me), 2.00 (3 H, s, 7-Me), 2.05 (3 H, s, OAc), 2.11 (3 H, s,
12-Me), 2.19 (1 H, br dd, J 16 and 9.5, 3Ј-Hax), 2.39 (1 H, br dd,
J 16 and 6, 3Ј-Heq), 3.44 and 3.48 (each 1 H, d, J 18, 1-H2), 5.07
(1 H, m, 4Ј-H), 5.80 (1 H, dq, J 15.5 and 7, 18-H), 5.96 (1 H, d, J
11.5, 13-H), 6.19 (1 H, dd-like, J 15.5 and 1.5, 17-H), 6.31 (1 H,
br d, J 11.5, 11-H), 6.33 (1 H, t, J 11.5, 14-H), 6.40 (1 H, br d, J
11, 8-H), 6.58 (1 H, br d, J 11.5, 15-H), 6.60 (1 H, dd, J 15 and
11, 5-H), 6.64 (1 H, dd, J 14.5 and 11, 9-H), 6.68 (1 H, d, J 15,
6-H), 6.71 (1 H, dd, J 14.5 and 11.5, 10-H) and 7.24 (1 H, br d, J
11, 4-H) (Found: Mϩ, 502.343).
᎐
2
δH (300 MHz) 1.83 (3 H, d-like, J 7, 5-Me), 2.27 (3 H, s-like,
3-Me), 3.70 (6/5 H) and 3.71 (9/5 H) (each s, CO2Me), 5.69 (2/5
H) and 5.73 (3/5 H) (each br s, 2-H), 5.72 (3/5 H, dq, J 12 and 7)
and 6.12–6.23 (2/5 H, m) (together 5-H) and 5.91 (3/5 H, br d, J
12) and 6.11 (2/5 H, d, J 15) (together 4-H) (Found: Mϩ,
140.085. C8H12O2 requires M, 140.084).
(2E,4E/Z)-3-Methylhexa-2,4-dien-1-ol 19
Methyl (E)-4-(tert-butyldimethylsiloxy)-3-methylpent-2-enoate
20
A solution of the ester 18 (4.00 g, 28.6 mmol) in dry ether (30
cm3) was added dropwise to a stirred suspension of LAH (0.81
g, 21.3 mmol) in dry ether (100 cm3) at 0 ЊC and the mixture
was stirred for a further 15 min. The excess of LAH was
decomposed by dropwise addition of water. The mixture was
extracted with ether followed by standard work-up to provide
a residue, which was purified by SCC (ether–hexane, 2:8) to
afford an isomeric mixture of the alcohol 19 (2.94 g, 92%;
4E :4Z = 2:3) as an oil, νmax/cmϪ1 3630 and 3460 (OH); δH (300
MHz) 1.68 (1 H, br s, OH), 1.77 (9/5 H) and 1.82 (6/5 H) (each
s, 3-Me), 1.81 (9/5 H, d, J 7.2) and 1.81 (6/5 H, d, J 6.7)
(together 5-Me), 4.25 (2 H, d, J 6.5, 1-H2), 5.51 (3/5 H, dq, J 12
and 7.2) and 5.72 (2/5 H, dq, J 15.5 and 6.7) (together 5-H),
5.52–5.58 (1 H, m, 2-H), 5.83 (3/5 H, br d, J 12) and 6.09 (2/5 H,
dd-like, J 15.5 and 1) (together 4-H) (Found: Mϩ, 112.090.
C7H12O requires M, 112.089).
A solution of methylmagnesium bromide (0.92 mol dmϪ3 in
THF; 94.5 cm3, 86.9 mmol) was added dropwise to a stirred
solution of the formyl ester 179 (10.60 g, 82.8 mmol) in dry
THF (50 cm3) at 0 ЊC and the mixture was stirred for a further
30 min. After the reaction had been quenched with saturated
aq. NH4Cl, the organics were extracted with ether followed by
standard work-up to give a residue, which was purified by SCC
(ether–hexane, 2:8) to afford the corresponding alcohol (11.63
g, 98% from 17) as an oil, νmax/cmϪ1 3608 and 3482 (OH), 1715
(conj. CO Me) and 1655 (C᎐C); δ (300 MHz) 1.32 (3 H, d, J
᎐
2
H
6.5, 5-H3), 2.12 (3 H, d, J 1, 3-Me), 3.70 (3 H, s, CO2Me), 4.27 (1
H, qd, J 6.5 and 1, 4-H) and 5.98 (1 H, quint, J 1, 2-H).
Subsequently, tert-butyldimethylsilyl trifluoromethanesul-
fonate (TBSOTf) (20.4 cm3, 88.8 mmol) was added to a stirred
solution of this alcohol (11.63 g, 80.8 mmol) and 2,4,6-
2718
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
trimethylpyridine (γ-collidine) (16.0 cm3, 121 mmol) in dry
ether (50 cm3) at 0 ЊC. After being stirred at 0 ЊC for 1.5 h, the
reaction mixture was poured into ice–water and extracted with
ether. The organic layer was washed successively with aq. 3%
HCl, saturated aq. NaHCO3 and brine. Evaporation of the
dried extracts provided a residue, which was purified by CC
(ether–hexane, 2:8) to yield the TBS ether 20 (17.08 g, 80%
from 17) as an oil, νmax/cmϪ1 1712 (conj. CO2Me) and 1657
(C᎐C); δ (300 MHz) 0.03 and 0.05 (each 3 H, s, SiMe × 2), 0.90
hexane, 2:8). The resulting hydroxy compound was dissolved in
a mixture of ether–hexane (1:1) and shaken with active MnO2
(4.0 g) at room temp. for 5 h. The mixture was filtered through
Celite. Evaporation of the filtrate gave a residue, which was
purified by SCC (acetone–hexane, 2:8) and then PHPLC
[LiChrosorb CN 60 (7 µm) 1.0 × 25 cm; THF–hexane, 15:85]
to afford the all-E-oxo pentaenal 24a (125 mg, 42% from 23)
and the 8Z-isomer 24b (23 mg, 8% from 23) as yellow solids.
Compound 24a: λmax(EtOH)/nm 393 and 413; νmax/cmϪ1 1660
(conj. CO and conj. CHO) and 1606 (C᎐C); δ (500 MHz) 1.91
᎐
H
(9 H, s, But), 1.24 (3 H, d, J 6.5, 5-H3), 2.10 (3 H, s, 3-Me), 3.70
(3 H, s, CO2Me), 4.19 (1 H, qd, J 6.5 and 1, 4-H) and 5.94 (1 H,
J 1, 2-H) (Found: Mϩ, 258.163. C13H26O3Si requires M,
258.165).
᎐
H
(3 H, d, J 0.5, 2-Me), 1.96 (3 H, d, J 1.5, 11-Me), 2.07 (3 H, br s,
7-Me), 2.38 (3 H, s, MeCO), 6.43 (1 H, br d, J 11.5, 6-H), 6.67
(1 H, d, J 14.5, 8-H), 6.74 (1 H, dd, J 14.5 and 10.5, 9-H), 6.79
(1 H, dd, J 14.5 and 11.5, 4-H), 6.97 (1 H, br d, J 11.5, 3-H),
7.03 (1 H, dd, J 14.5 and 11.5, 5-H), 7.14 (1 H, dd-like, J 10.5
and 1.5, 10-H) and 9.49 (1 H, s, CHO) (Found: Mϩ, 244.147.
C16H20O2 requires M, 244.146).
(E)-4-(tert-Butyldimethylsiloxy)-3-methylpent-2-en-1-ol 21
According to the procedure described for the preparation of the
alcohol 19 from the ester 18, reduction of the ester 20 (4.91 g)
with LAH followed by purification by SCC (ether–hexane, 3:7)
afforded the alcohol 21 (3.63 g, 83%) as an oil, νmax/cmϪ1 3613
and 3460 (OH); δH (300 MHz) 0.02 and 0.05 (each 3 H, s,
SiMe × 2), 0.89 (9 H, s, But), 1.20 (3 H, d, J 6.5, 5-H3), 1.47 (1
H, br s, OH), 1.64 (3 H, br s, 3-Me), 4.18 (2 H, d, J 6.5, 1-H2),
4.18 (1 H, br q, J 6.5, 4-H) and 5.60 (1 H, tquint, J 6.5 and 1.5,
2-H) [Found: (M Ϫ Me)ϩ, 215.146. C11H23O2Si requires m/z,
215.147].
Compound 24b: λmax(EtOH)/nm 231, 288, 389 and 409; νmax
/
cmϪ1 1655 (conj. CO and conj. CHO) and 1605 (C᎐C); δ (500
᎐
H
MHz) 1.90 (3 H, br s, 2-Me), 1.93 (3 H, d, J 1, 11-Me), 2.18 (3
H, br s, 7-Me), 2.36 (3 H, s, MeCO), 6.34 (1 H, d, J 12, 8-H),
6.40 (1 H, br d, J 12, 6-H), 6.44 (1 H, t, J 12, 9-H), 6.77 (1 H, dd,
J 14.5 and 11.5, 4-H), 6.98 (1 H, br d, J 11.5, 3-H), 7.00 (1 H,
dd, J 14.5 and 11.5, 5-H), 7.62 (1 H, br d, J 12, 10-H) and 9.49
(1 H, s, CHO) (Found: Mϩ, 244.147).
Preparation of the phosphonium salt 22
Preparation of the analogue 8
A solution of LiCl (738 mg, 17.4 mmol) in dry dimethyl-
formamide (DMF ) (15 cm3) was added to a stirred mixture of
the alcohol 21 (3.63 g, 15.8 mmol) in γ-collidine (2.55 cm3, 19.0
mmol) at 0 ЊC and the mixture was stirred at 0 ЊC for 15 min. To
this reaction mixture was added MsCl (1.34 cm3, 17.3 mmol)
and stirring of the mixture was continued at 0 ЊC for 1 h and at
room temp. for 3 h. The mixture was poured into ice–water and
extracted with ether. The organic layer was washed successively
with aq. 3% HCl, saturated aq. NaHCO3 and brine. Evapor-
ation of the dried extracts provided a residue, which was puri-
fied by SCC (ether–hexane, 5:95) to afford the corresponding
chloride (3.38 g, 86% from 21) as an oil, δH (300 MHz) 0.02 and
0.05 (each 3 H, s, SiMe × 2), 0.89 (9 H, s, But), 1.20 (3 H, d, J
A solution of NaOMe (1.0 mol dmϪ3 in MeOH; 1.3 cm3, 1.3
mmol) was added to an ice-cooled solution of the Wittig salt
158 (560 mg, 1.04 mmol) and the aldehyde 24a (63 mg, 0.26
mmol) in CH2Cl2 (10 cm3). After being stirred at 0 ЊC for 1.5 h,
the reaction mixture was diluted with ether. The organic layer
was followed by standard work-up to provide a residue, which
was purified by SCC (ether–hexane, 1:3) followed by PLC
(ether–hexane, 1:3) to afford an isomeric mixture [82 mg, 74%
from 24a; all-E (analogue 8):13Z ~1:1]. PHPLC separation
[LiChrosorb Si 60 (5 µm) 1.0 × 25 cm; THF–hexane, 4:96] of
the mixture provided the analogue 8 and its 13Z-isomer as red
solids. Analogue 8: λmax(EtOH)/nm 267, 447 and 460sh; λmax
-
(hexane)/nm 263, 421, 444 and 472; νmax(KBr)/cmϪ1 1649 (conj.
6.5, CHMe), 1.68 (3 H, d, J 1.5, ᎐CMe), 4.10 (2 H, d, J 8,
CO) and 1613 (C᎐C); δ (500 MHz) 0.82 and 0.91 (each 3 H, s,
᎐
᎐
H
CH2Cl), 4.17 (1 H, br q, J 6.5, CHOTBS) and 5.64 (1 H, tquint,
6Ј-gem-Me), 1.59 (3 H, d, J 1.5, 2Ј-Me), 1.92 (3 H, s, 16-Me),
1.94 (3 H, s, 3-Me), 1.99 (6 H, s, 7- and 12-Me), 2.19 (1 H, d, J
9.5, 1Ј-H), 2.37 (3 H, s, MeCO), 5.42 (1 H, br s, 3Ј-H), 5.56 (1 H,
dd, J 15.5 and 9.5, 18-H), 6.11 (1 H, d, J 15.5, 17-H), 6.13 (1 H,
br d, J 11.5, 15-H), 6.26 (1 H, br d, J 11.5, 11-H), 6.35 (1 H, d, J
15, 13-H), 6.40 (1 H, br d, J 11.5, 8-H), 6.58 (1 H, dd, J 15 and
10.5, 5-H), 6.63 (1 H, dd, J 14 and 11.5, 9-H), 6.67 (1 H, dd, J
15 and 11.5, 14-H), 6.67 (1 H, d, J 15, 6-H), 6.74 (1 H, dd, J 14
and 11.5, 10-H) and 7.14 (1 H, dd-like, J 10.5 and 1.5, 4-H)
(Found: Mϩ, 430.323. C31H42O requires M, 430.323).
J 8 and 1.5, ᎐CH).
᎐
Subsequently, triphenylphosphine (4.28 g, 16.3 mmol) and
triethylamine (0.1 cm3) were added to a solution of the above
chloride (3.38 g, 13.6 mmol) in CHCl3 (15 cm3) and the mixture
was refluxed for 20 h. Evaporation off of the solvent gave a
residue, which was washed with ether to provide the phos-
phonium salt 22 (5.88 g, 73% from 21) as a solid, δH (300 MHz)
Ϫ0.14 and Ϫ0.04 (each 3 H, s, SiMe × 2), 0.74 (9 H, s, But), 1.08
(3 H, d, J 6, CHMe), 1.42 (3 H, br d, J 3, ᎐CMe), 4.04 (1 H, br
᎐
quint, J 6, CHOTBS), 4.53 and 4.71 (each 1 H, td, J 15.5 and
13Z-Isomer: λmax(EtOH)/nm 268, 332 and 445; λmax(hexane)/
7.5, CH P), 5.47 (1 H, br q, J 7.5, ᎐CH) and 7.65–7.89 (15 H, m,
nm 265, 319, 328, 421, 442 and 470; νmax(KBr)/cmϪ1 1659 and
᎐
2
ArH).
1649 (split) (conj. CO) and 1609 (C᎐C); δ (500 MHz) 0.83 and
᎐
H
0.91 (each 3 H, s, 6Ј-gem-Me), 1.59 (3 H, d, J 1.5, 2Ј-Me), 1.89
(3 H, d, J 1, 16-Me), 1.94 (3 H, s, 3-Me), 1.99 (3 H, s, 7-Me),
2.13 (3 H, s, 12-Me), 2.19 (1 H, br d, J 9.5, 1Ј-H), 2.37 (3 H, s,
MeCO), 5.42 (1 H, br s, 3Ј-H), 5.58 (1 H, dd, J 15.5 and 9.5,
18-H), 5.97 (1 H, d, J 12, 13-H), 6.14 (1 H, d, J 15.5, 17-H), 6.32
(1 H, br d, J 11.5, 11-H), 6.34 (1 H, t, J 12, 14-H), 6.41 (1 H, br
d, J 11.5, 8-H), 6.58 (1 H, dd, J 15 and 10.5, 5-H), 6.63 (1 H, br
d, J 12, 15-H), 6.64 (1 H, dd, J 14 and 11.5, 9-H), 6.67 (1 H, d, J
15, 6-H), 6.72 (1 H, dd, J 14 and 11.5, 10-H) and 7.14 (1 H,
dd-like, J 10.5 and 1, 4-H) (Found: Mϩ, 430.323).
(2E,4E,6E,8E/Z,10E)-2,7,11-Trimethyl-12-oxotrideca-
2,4,6,8,10-pentaenal 24a and 24b
A solution of NaOMe (1.0 mol dmϪ3 in MeOH; 3.10 cm3, 3.10
mmol) was added to an ice-cooled solution of the phos-
phonium salt 22 (1.06 g, 2.08 mmol) and the C10-dialdehyde 23
(200 mg, 1.22 mmol) in CH2Cl2 (20 cm3). After being stirred at
room temp. for 30 min, the reaction mixture was diluted with
ether. The organic layer was treated by standard work-up to
give a residue, which was purified by SCC (acetone–hexane,
15:85) to afford an isomeric mixture of condensed products.
This was dissolved in THF (20 cm3) and a solution of TBAF (1.0
mol dmϪ3 in THF; 2.5 cm3, 2.5 mmol) was added. After being
stirred at room temp. for 3 h, the reaction mixture was diluted
with ether. The organic layer was followed by standard work-up
to provide a residue, which was purified by SCC (acetone–
Preparation of the analogue 9
Following the procedure described for the preparation of the
analogue 8, Wittig reaction between the phosphonium salt
16 (242 mg, 0.55 mmol) and the aldehyde 24a (54 mg, 0.22
mmol) followed by purification by SCC (ether–hexane, 2:3)
J. Chem. Soc., Perkin Trans. 1, 1997
2719

View Article Online
gave an isomeric mixture [62 mg, 87% from 24a; all-E (analogue
9):13Z ~1:1]. PHPLC separation [LiChrosorb Si 60 (5 µm)
1.0 × 30 cm; THF–hexane, 4:96] of the mixture in the dark
provided the analogue 9 and its 13Z-isomer as red solids.
Analogue 9: λmax(EtOH)/nm 265, 447 and 460sh; λmax(hexane)/
nm 261, 418, 441 and 469; νmax(KBr)/cmϪ1 1655 and 1645 (split)
(E)-4-[3Ј-(tert-Butyldimethylsiloxy)-2Ј-methylcyclohex-1Ј-enyl]-
but-3-en-2-one 28
PdCl2(PPh3)2 (273 mg, 0.39 mmol) was added to a solution of
the vinyl triflate 27 (4.84 g, 12.9 mmol), methyl vinyl ketone
(5.24 cm3, 64.7 mmol) and triethylamine (6.32 cm3, 45.2 mmol)
in dry DMF (50 cm3). The mixture was heated and stirred at
75 ЊC for 7 h. After cooling, the reaction mixture was diluted
with ether and washed successively with aq. 3% HCl, saturated
aq. NaHCO3 and brine. Evaporation of the dried solution pro-
vided a residue, which was purified by SCC (ether–hexane, 1:9)
to furnish the dienone 28 (3.47 g, 91%) as an oil, λmax(EtOH)/nm
(conj. CO) and 1611 (C᎐C); νmax/cmϪ1 1647, 1607, 1574 and
᎐
1530 (conj. CO and C᎐C); δ (500 MHz) 1.83 (3 H, dd, J 7 and
᎐
H
1, 18-Me), 1.91 (3 H, s, 16-Me), 1.94 (3 H, d, J 1, 3-Me), 1.99
(6 H, s, 7-Me and 12-Me), 2.37 (3 H, s, MeCO), 5.77 (1 H, dq,
J 15.5 and 7, 18-H), 6.09 (1 H, br d, J 11, 15-H), 6.16 (1 H,
dd-like, J 15.5 and 1, 17-H), 6.26 (1 H, br d, J 12, 11-H), 6.34
(1 H, d, J 15, 13-H), 6.39 (1 H, br d, J 11.5, 8-H), 6.58 (1 H, dd,
J 15 and 10.5, 5-H), 6.62 (1 H, dd, J 14 and 11.5, 9-H), 6.65
(1 H, dd, J 15 and 11, 14-H), 6.66 (1 H, d, J 15, 6-H), 6.73
(1 H, dd, J 14 and 12, 10-H) and 7.14 (1 H, dd-like, J 10.5 and
1, 4-H) (Found: Mϩ, 322.230. Calc. for C23H30O: M, 322.230).
13Z-Isomer: λmax(EtOH)/nm 266, 329 and 442; λmax(hexane)/
nm 262, 312, 325, 418, 439 and 468; νmax(KBr)/cmϪ1 1644 (conj.
291; νmax/cmϪ1 1660 (conj. CO) and 1613 and 1585 (C᎐C);
᎐
δH (200 MHz) 0.11 and 0.13 (each 3 H, s, SiMe × 2), 0.91 (9 H, s,
SitBu), 1.5–1.9 (4 H, m, 4Ј- and 5Ј-H2), 1.96 (3 H, br s, 2Ј-Me),
2.1–2.4 (2 H, m, 6Ј-H2), 2.30 (3 H, s, MeCO), 4.13 (1 H, br t, J 5,
3Ј-H), 6.15 (1 H, d, J 16, 3-H) and 7.66 (1 H, d, J 16, 4-H)
(Found: Mϩ, 294.202. C17H30O2Si requires M, 294.202).
Ethyl (2E/Z,4E)-5-[3Ј-(tert-butyldimethylsiloxy)-2Ј-methyl-
cyclohex-1Ј-enyl]-3-methylpenta-2,4-dienoate 29
CO) and 1611 (C᎐C); δ (500 MHz) 1.83 (3 H, dd, J 7 and 1,
᎐
H
18-Me), 1.88 (3 H, s, 16-Me), 1.94 (3 H, d, J 1, 3-Me), 1.99 (3 H,
s, 7-Me), 2.10 (3 H, s, 12-Me), 2.37 (3 H, s, MeCO), 5.80 (1 H,
dq, J 16 and 7, 18-H), 5.96 (1 H, d, J 12, 13-H), 6.19 (1 H, dd-
like, J 16 and 1, 17-H), 6.30 (1 H, br d, J 11, 11-H), 6.33 (1 H, t,
J 12, 14-H), 6.40 (1 H, br d, J 11.5, 8-H), 6.58 (1 H, br d, J 12,
15-H), 6.59 (1 H, dd, J 15 and 11, 5-H), 6.63 (1 H, dd, J 14.5
and 11.5, 9-H), 6.66 (1 H, d, J 15, 6-H), 6.71 (1 H, dd, J 14.5
and 11, 10-H) and 7.15 (1 H, dd-like, J 11 and 1, 4-H) (Found:
Mϩ, 322.230).
A solution of BuLi (1.71 mol dmϪ3 in hexane; 7.02 cm3, 12
mmol) was added to a stirred solution of diisopropylamine
(1.68 cm3, 12 mmol) in dry THF (10 cm3) at Ϫ78 ЊC and the
mixture was stirred for a further 30 min. To this LDA solution
was added dropwise a solution of ethyl TMSacetate (1.92 g, 12
mmol) in dry THF (15 cm3). The mixture was stirred for 30 min
at Ϫ78 ЊC, after which a solution of the ketone 28 (2.94 g, 10
mmol) in dry THF (15 cm3) was added dropwise at the same
temp. and stirring was continued for a further 15 min. After
being quenched with saturated aq. NH4Cl, the mixture was
extracted with ether followed by standard work-up to give a
residue, which was purified by SCC (ether–hexane, 5:95) to
afford an isomeric mixture of the trienoate 29 (3.44 g, 95%;
2E :2Z = 4:3) as a solid, λmax(EtOH)/nm 310; νmax/cmϪ1 1700
2-Methyl-3-(trifluoromethylsulfonyloxy)cyclohex-2-enone 26
A suspension of sodium hydride (60% oil dispersion; 1.80 g, 45
mmol) was added to a stirred, dry solution of 2-methyl-
cyclohexane-1,3-dione 25 (3.78 g, 30 mmol) in THF (20 cm3)–
DMF (20 cm3) at 0 ЊC. The mixture was stirred at 0 ЊC for 30
min, after which a solution of Tf2NPh (11.25 g, 31.5 mmol) in
dry THF (50 cm3) was added dropwise at the same temperature.
The mixture was stirred at room temp. for 30 min. After the
reaction had been quenched with saturated aq. NH4Cl, the mix-
ture was extracted with ether. The extracts were followed by
standard work-up to give a residue, which was purified by CC
(acetone–hexane, 1:3) to provide the oxo enol triflate 26 (7.58
g, 98%) as an oil, νmax/cmϪ1 1680 (conj. CO) and 1414 and 1132
(OSO2); δH (300 MHz) 1.86 (3 H, s, 2-Me), 2.09 (2 H, quint-like,
J 6.5, 5-H2), 2.49 (2 H, dd, J 6.5 and 7.5, 4-H2) and 2.75 (2 H, m,
6-H2); δC(75 MHz) 9.19 (CH3), 20.71, 28.83 and 36.66 (CH2 ×
3), 118.36 (q, J 318, CF3), 128.14 (2-C), 162.11 (3-C) and 197.66
(CO) (Found: Mϩ, 258.016. C8H9F3O4S requires M, 258.017).
(conj. CO Et) and 1607 (C᎐C); δ (200 MHz) 0.10 and 0.12
᎐
2
H
(each 3 H, s, SiMe × 2), 0.91 (9 H, s, SitBu), 1.28 (3 H, t, J 7,
OCH2CH3), 1.45–1.90 (4 H, m, 4Ј- and 5Ј-H2), 1.90 (3 H, br s,
2Ј-Me), 2.05–2.38 (2 H, m, 6Ј-H2), 2.06 (9/7 H) and 2.35 (12/7
H) (each d, J 1, 3-Me), 4.12 (1 H, m, 3Ј-H), 4.17 (2 H, q, J 7,
OCH2CH3), 5.66 (3/7 H) and 5.80 (4/7 H) (each s, 2-H), 6.26
(4/7 H) and 7.84 (3/7 H) (each d, J 16, 4-H) and 7.06 (1 H, d,
J 16, 5-H) (Found: Mϩ, 364.242. C21H36O3Si requires M,
364.244).
(2E/Z,4E)-3-Methyl-5-(2Ј-methyl-3Ј-oxocyclohex-1Ј-enyl)penta-
2,4-dienal 30
According to the procedure for the preparation of the alcohol
19 from the ester 18, reduction of the trienoate 29 (750 mg, 2.06
mmol) with LAH produced a crude alcohol, which without
purification was dissolved in THF (20 cm3) and a solution of
TBAF (1.0 mol dmϪ3 in THF; 4.3 cm3, 4.3 mmol) was added.
After being stirred at room temp. for 24 h, the reaction mixture
was diluted with ether followed by standard work-up to give an
oil, which was purified by SCC (acetone–hexane, 2:3) to afford
an isomeric mixture of the corresponding diol (375 mg, 87%
from 29; 2E :2Z = 3:2) as an oil, νmax/cmϪ1 3606 and 3444 (OH)
and 1624 (C᎐C); δ (300 MHz) 1.85 (9/5 H, s) and 1.94 (21/5 H,
3-(tert-Butyldimethylsiloxy)-2-methylcyclohex-1-enyl
trifluoromethanesulfonate 27
NaBH4 (380 mg, 10.0 mmol) was added to a stirred solution of
the oxo enol triflate 26 (2.58 g, 10.0 mmol) in MeOH (20 cm3)
0 ЊC. After being stirred for a further 15 min, the reaction mix-
ture was poured into ice–water. The organics were extracted
with ether followed by standard work-up to give the crude alco-
hol, which was dissolved in CH2Cl2 (20 cm3). To this solution
was added triethylamine (1.54 cm3, 11.0 mmol), 4-(dimethyl-
amino)pyridine (DMAP) (1.34 g, 11.0 mmol) followed by
TBSCl (1.58 g, 10.5 mmol). The mixture was stirred at room
temp. for 5 h, poured into chilled water and extracted with
ether. The extracts were washed successively with aq. 3% HCl,
saturated aq. NaHCO3 and brine. Evaporation of the dried
extracts gave a residue, which was purified by SCC (ether–
hexane, 5:95) to afford the TBS ether 27 (2.54 g, 68% from 26)
as an oil, νmax/cmϪ1 1402 and 1133 (OSO2); δH (200 MHz) 0.09
and 0.10 (each 3 H, s, SiMe × 2), 0.90 (9 H, s, SitBu), 1.6–2.0 (6
H, m, 4-, 5- and 6-H2), 1.79 (3 H, t, J 2, 2-Me) and 4.21 (1 H, br
t-like, J 5, 3-H) (Found: Mϩ, 374.119. C14H25F3O4SSi requires
M, 374.120).
᎐
H
br s) (2Ј- and 3-Me), 4.07 (1 H, br s, 3Ј-H), 4.30 (6/5 H) and 4.32
(4/5 H) (each d, J 7, 1-H2), 5.58 (2/5 H) and 5.70 (3/5 H) (each br
t, J 7, 2-H) and 6.30 (3/5 H), 6.62 (2/5 H), 6.71 (2/5 H) and 6.64
(3/5 H) (each d, J 16, 4- and 5-H).
Subsequently, a solution of the diol (375 mg, 1.80 mmol) in
CH2Cl2 was shaken with active MnO2 (7.5 g) at room temp. for
4 h. The mixture was filtered through Celite. Evaporation of the
filtrate followed by purification by SCC (MeOH–CH2Cl2, 2:98)
provided the oxo trienal 30 (265 mg, 63% from 29) as an orange
solid, λmax(EtOH)/nm 329; νmax/cmϪ1 1656 (conj. CO and conj.
CHO) and 1599 (C᎐C); δ (300 MHz) 1.98 (3 H, s, 2Ј-Me), 2.05
᎐
H
(2 H, m, 5Ј-H2), 2.19 (6/5 H) and 2.37 (9/5 H) (each s, 3-Me),
2.49 (2 H, m, 4Ј-H2), 2.58 (2 H, m, 6Ј-H2), 6.03 (2/5 H, d, J 7.5)
2720
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
and 6.09 (3/5 H, d, J 8) (together 2-H), 6.71 (3/5 H) and 7.66
(2/5 H) (each d, J 16, 4-H), 7.17 (2/5 H) and 7.26 (3/5 H) (each
d, J 16, 5-H) and 10.18 (3/5 H, d, J 8) and 10.22 (2/5 H, d, J 7.5)
(CHO) (Found: Mϩ, 204.115. C13H16O2 requires M, 204.115).
1566 and 1532 (conj. CO and C᎐C); δ (500 MHz) 1.83 (3 H, dd,
᎐
H
J 7 and 1, 14Ј-Me), 1.88 (3 H, s, 12Ј-Me), 1.96 (3 H, t, J 1.5,
2-Me), 1.97–2.02 (2 H, m, 5-H2), 2.00 (3 H, s, 3Ј-Me), 2.10 (3 H,
s, 8Ј-Me), 2.45 (2 H, dd, J 7.5 and 6, 6-H2), 2.56 (2 H, br t, J 6,
4-H2), 5.80 (1 H, dq, J 15.5 and 7, 14Ј-H), 5.96 (1 H, d, J 12,
9Ј-H), 6.19 (1 H, dd-like, J 15.5 and 1, 13Ј-H), 6.30 (1 H, br d,
J 10.5, 7Ј-H), 6.33 (1 H, t, J 12, 10Ј-H), 6.43 (1 H, br d, J 10.5,
4Ј-H), 6.57 (1 H, br d, J 12, 11Ј-H), 6.64 (1 H, dd, J 14 and 10.5,
5Ј-H), 6.70 (1 H, dd, J 14 and 10.5, 6Ј-H), 6.73 (1 H, d, J 16,
2Ј-H) and 6.77 (1 H, d, J 16, 1Ј-H) (Found: Mϩ, 348.246).
(2E,4E,6E/Z,8E)-2,7-Dimethyl-9-(2Ј-methyl-3Ј-oxocyclohex-1Ј-
enyl)nona-2,4,6,8-tetraenal 32a and 32b
In the same manner as described for the preparation of the
analogue 8, Wittig reaction between the phosphonium salt 3114
(1.21 g, 2.59 mmol) and the aldehyde 30 (265 mg, 1.30 mmol)
followed by purification by SCC (acetone–hexane, 1:4) pro-
vided condensed products, which were dissolved in THF (30
cm3). To this solution were added water (1.5 cm3) and a solution
of toluene-p-sulfonic acid (p-TsOH) (0.1 mol dmϪ3 in THF; 10
cm3, 1.0 mmol) and the mixture was stirred at room temp. for 30
min, before being diluted with ether. The organic layer was
washed successively with saturated aq. NaHCO3 and brine.
Evaporation of the dried solution gave crude products, which
without purification were dissolved in CH3CN (40 cm3). To this
solution was added a solution (10 cm3) prepared from
PdCl2(CH3CN)2 (65 mg), triethylamine (0.035 cm3) and water
(6 cm3) in CH3CN (50 cm3) and the mixture was stirred at room
temp. for 3 h. The solvent was evaporated off to give a residue,
which was purified by SCC (acetone–hexane, 1:3) and then
PHPLC [LiChrosorb Si 60 (5 µm) 1.0 × 30 cm; THF–hexane,
13:87] to afford the all-E-oxo pentaenal 32a (265 mg, 76% from
30) and the 6Z-isomer 32b (47 mg, 13% from 30) as orange
solids. Compound 32a: λmax(EtOH)/nm 395 and 413; νmax/cmϪ1
Ethyl 2-[2-methoxycyclohex-2-en-(E/Z)-ylidene]acetate 36a and
36b
A solution of BuLi (1.62 mol dmϪ3 in hexane; 1.62 cm3, 2.62
mmol) was added to a stirred solution of ethyl (diethoxy-
phosphoryl)acetate 35 (587 mg, 2.62 mmol) in dry THF (3 cm3)
at 0 ЊC and the mixture was stirred for a further 30 min. To this
mixture was added dropwise a solution of the ketone 3416 (110
mg, 0.87 mmol) in dry THF (3 cm3) at 0 ЊC, and the mixture
was refluxed for 1 h. After cooling, the reaction was quenched
with saturated aq. NH4Cl. The mixture was extracted with ether
followed by standard work-up to give an oil, which was purified
by SCC (ether–hexane, 1:4) to furnish the E-isomer 36a (53 mg,
31%) and the Z-isomer 36b (61 mg, 36%) as pale yellow oils.
Compound 36a: λmax(EtOH)/nm 221 and 285; νmax/cmϪ1 1700
(conj. CO Et) and 1625 and 1610 (C᎐C); δ (200 MHz) 1.28 (3
᎐
2
H
H, t, J 7, OCH2CH3), 1.67 (2 H, quint-like, J 6.5, 5Ј-H2), 2.25 (2
H, q-like, J 5, 4Ј-H2), 3.01 (2 H, ddd, J 6.5, 5 and 1.5, 6Ј-H2),
3.58 (3 H, s, OMe), 4.16 (2 H, q, J 7, OCH2CH3), 5.26 (1 H, t, J
5, 3Ј-H) and 6.19 (1 H, br s, 2-H) (Found: Mϩ, 196.110.
C11H16O3 requires M, 196.110).
1655 (conj. CO and conj. CHO) and 1600 (C᎐C); δ (500 MHz)
᎐
H
1.91 (3 H, d, J 1, 2-Me), 1.97 (3 H, t, J 1.5, 2Ј-Me), 2.02 (2 H,
quint-like, J 6.5, 5Ј-H2), 2.08 (3 H, d, J 0.5, 7-Me), 2.47 (2 H,
dd, J 7.5 and 6, 4Ј-H2), 2.56 (2 H, br t, J 6, 6Ј-H2), 6.46 (1 H, br
d, J 12, 6-H), 6.73 (1 H, d, J 16, 8-H), 6.78 (1 H, dd, J 14.5 and
11.5, 4-H), 6.91 (1 H, d, J 16, 9-H), 6.98 (1 H, br d, J 11.5, 3-H),
7.05 (1 H, dd, J 14.5 and 12, 5-H) and 9.49 (1 H, s, CHO)
(Found: Mϩ, 270.161. C18H22O2 requires M, 270.162).
Compound 36b: λmax(EtOH)/nm 210 and 256; νmax/cmϪ1 1708
(conj. CO Et) and 1610 (C᎐C); δ (200 MHz) 1.31 (3 H, t, J 7,
᎐
2
H
OCH2CH3), 1.73 (2 H, quint, J 6, 5Ј-H2), 2.24 (2 H, td, J 6 and
4, 4Ј-H2), 2.37 (2 H, ddd, J 6, 4 and 1.5, 6Ј-H2), 3.52 (3 H, s,
OMe), 4.20 (2 H, q, J 7, OCH2CH3), 5.02 (1 H, td, J 4 and 1.5,
3Ј-H) and 5.54 (1 H, br s, 2-H) (Found: Mϩ, 196.110).
Compound 32b: λmax(EtOH)/nm 238, 295, 389 and 407sh;
νmax/cmϪ1 1655 (conj. CO and conj. CHO) and 1600 (C᎐C);
᎐
δH (500 MHz) 1.90 (3 H, d, J 1, 2-Me), 1.97 (3 H, t, J 1.5, 2Ј-
Me), 2.04 (2 H, quint-like, J 6.5, 5Ј-H2), 2.09 (3 H, s, 7-Me), 2.49
(2 H, dd, J 7.5 and 6, 4Ј-H2), 2.63 (2 H, br t, J 6, 6Ј-H2), 6.35 (1
H, br d, J 11.5, 6-H), 6.71 (1 H, dd, J 14.5 and 11.5, 4-H), 6.92
(1 H, d, J 16, 9-H), 6.98 (1 H, br d, J 11.5, 3-H), 7.19 (1 H, dd, J
14.5 and 11.5, 5-H), 7.26 (1 H, d, J 16, 8-H) and 9.48 (1 H, s,
CHO) (Found: Mϩ, 270.162).
Ethyl (E)-2-[2,2-dimethoxycyclohexylidene]acetate 38
Following the procedure described for the preparation of the
ylidene esters 36ab, Emmons–Horner reaction between the
phosphonate 35 (9.82 g, 43.8 mmol) and the ketone 3716 (2.31 g,
14.6 mmol) followed by purification by CC (ether–hexane,
1:4) provided the E-ylidene ester 38 (3.16 g, 95%) as an oil, νmax
/
cmϪ1 1704 (conj. CO Et) and 1652 (C᎐C); δ (200 MHz) 1.29 (3
᎐
2
H
H, t, J 7.5, OCH2CH3), 1.53–1.86 (6 H, m, CH2 × 3), 2.82 (2 H,
Preparation of the analogue 10
t-like, J 6, CH2), 3.14 (6 H, s, OMe × 2), 4.17 (2 H, q, J 7.5,
In the same manner as described for the preparation of the
analogue 8, Wittig reaction between the phosphonium salt 16
(675 mg, 1.54 mmol) and the aldehyde 32a (104 mg, 0.39
mmol) followed by purification by SCC (MeOH–CH2Cl2, 3:97)
furnished an isomeric mixture [83 mg, 62% from 32a; all-E
(analogue 10):9ЈZ ~1:1]. PHPLC separation [LiChrosorb Si 60
(5 µm) 1.0 × 30 cm; THF–hexane, 4:96] of the mixture in the
dark provided the analogue 10 and its 9ЈZ-isomer as red solids.
Analogue 10: λmax(EtOH)/nm 268, 445 and 460sh; λmax(hexane)/
nm 264, 416, 439 and 467; νmax/cmϪ1 1643, 1600, 1574 and 1532
OCH CH ) and 6.18 (1 H, s, ᎐CH) (Found: Mϩ, 228.134.
᎐
2
3
C12H20O4 requires M, 228.136).
(E)-2-[2,2-Dimethoxycyclohexylidene]ethanol 39
According to the procedure for the preparation of the alcohol
19 from the ester 18, reduction of the ester 38 (3.00 g, 13.2
mmol) with LAH produced a crude product, which was purified
by SCC (acetone–hexane, 35:65) to yield the alcohol 39 (2.36 g,
96%) as an oil, νmax/cmϪ1 3600 and 3400 (OH); δH (200 MHz)
1.42–1.80 (6 H, m, CH2 × 3), 2.16 (3 H, t-like, J 6, CH2 and
OH), 3.13 (6 H, s, OMe × 2), 4.24 (2 H, dd, J 6.5 and 5,
CH OH) and 5.94 (1 H, t, J 6.5, ᎐CH) (Found: Mϩ, 186.124.
(conj. CO and C᎐C); δ (500 MHz) 1.82 (3 H, dd, J 7 and 1,
᎐
H
14Ј-Me), 1.91 (3 H, s, 12Ј-Me), 1.95 (3 H, t, J 1, 2-Me), 1.97–
2.02 (2 H, m, 5-H2), 1.98 (3 H, s, 8Ј-Me), 2.00 (3 H, s, 3Ј-Me),
2.45 (2 H, dd, J 7.5 and 6, 6-H2), 2.56 (2 H, br t, J 6, 4-H2), 5.76
(1 H, dq, J 15.5 and 7, 14Ј-H), 6.08 (1 H, br d, J 11.5, 11Ј-H),
6.16 (1 H, dd-like, J 15.5 and 1, 13Ј-H), 6.26 (1 H, br d, J 11.5,
7Ј-H), 6.34 (1 H, d, J 15, 9Ј-H), 6.42 (1 H, br d, J 11.5, 4Ј-H),
6.64 (1 H, dd, J 14 and 11.5, 5Ј-H), 6.65 (1 H, dd, J 15 and 11.5,
10Ј-H), 6.72 (1 H, d, J 16, 2Ј-H), 6.73 (1 H, dd, J 14 and 11.5,
6Ј-H) and 6.76 (1 H, d, J 16, 1Ј-H) (Found: Mϩ, 348.246.
C25H32O requires M, 348.245).
᎐
2
C10H18O3 requires M, 186.126).
Preparation of the phosphonium salts 41 and 42
A solution of LiCl (180 mg, 4.24 mmol) in dry DMF (4 cm3)
was added to a stirred mixture of the alcohol 39 (750 mg, 4.03
mmol) in γ-collidine (0.60 cm3, 4.46 mmol) at 0 ЊC and the
mixture was stirred at 0 ЊC for 15 min. To this reaction mixture
was added MsCl (0.33 cm3, 4.26 mmol) and stirring of the mix-
ture was continued for a further 1.5 h. The mixture was poured
into ice–water and extracted with ether. The organic layer was
washed successively with aq. 3% HCl, saturated aq. NaHCO3
9ЈZ-Isomer: λmax(EtOH)/nm 269, 332 and 442; λmax(hexane)/
nm 265, 314sh, 327, 417sh, 437 and 465; νmax/cmϪ1 1642, 1600,
J. Chem. Soc., Perkin Trans. 1, 1997
2721

View Article Online
and brine. Evaporation of the dried extracts provided a residue,
which was purified by SCC (ether–hexane, 3:97) to afford the
chloride 40 (810 mg, 98%) as an oil, δH (300 MHz) 1.48–1.80 (6
H, m, CH2 × 3), 2.22 (2 H, t, J 6, CH2), 3.12 (6 H, s, OMe × 2),
4.13 (2 H, d, J 8, CH Cl) and 6.03 (1 H, t, J 8, ᎐CH).
Subsequently, triphenylphosphine (1.13 g, 5.12 mmol) and
triethylamine (0.05 cm3) were added to a solution of the
chloride 40 (810 mg, 3.95 mmol) in CHCl3 (30 cm3) and the
mixture was refluxed for 15 h. Evaporation of the solvent gave
a residue, which was washed with ether to give a mixture of
the phosphonium salts 41 and 42 (1.77 g; 41:42 ~5:1) as a
foam, δH (200 MHz) (inter alia) 3.42 (s, gem-OMe) and 3.63 (s,
Ethyl (2E,4E)-5-(5,5-dimethyl-1,3-dioxolan-2-yl)-4-methyl-
penta-2,4-dienoate 45
A solution of BuLi (1.63 mol dmϪ3 in hexane; 13.0 cm3, 21.2
mmol) was added to a stirred solution of the phosphonate 35
(4.65 g, 20.8 mmol) in dry THF (35 cm3) at 0 ЊC and the mixture
was stirred for a further 30 min. To this mixture was added
dropwise a solution of the aldehyde 4414 (3.00 g, 16.3 mmol) in
dry THF (50 cm3) at 0 ЊC and stirring was continued at room
temp. for 1 h. After being quenched with saturated aq. NH4Cl,
the mixture was extracted with ether followed by standard
work-up to give an oil, which was purified by CC (ether–
hexane, 1:3) to furnish the dienoate 45 (4.06 g, 98%) as an oil,
᎐
2
᎐COMe).
᎐
νmax/cmϪ1 1707 (conj. CO Et) and 1626 (C᎐C); δ (300 MHz)
᎐
2
H
0.76 and 1.23 (each 3 H, s, gem-Me), 1.30 (3 H, t, J 7,
OCH2CH3), 1.88 (3 H, s, 4-Me), 3.53 and 3.67 (each 2 H, d, J
11, OCH2 × 2), 4.21 (2 H, q, J 7, OCH2CH3), 5.20 (1 H, d, J 6,
OCHO), 5.86 (1 H, br d, J 6, 5-H), 5.95 (1 H, d, J 16, 2-H) and
7.30 (1 H, d, J 16, 3-H) (Found: Mϩ, 254.151. C14H22O4 requires
M, 254.152).
(2E,4E,6E,8E)-2,7-Dimethyl-10-[2Ј-oxocyclohex-(E)-ylidene]-
deca-2,4,6,8-tetraenal 43
In the same manner as described for the preparation of the oxo
pentaenals 32ab, Wittig reaction between a mixture of the
phosphonium salts 41 and 42 (880 mg, ~2 mmol) and the C10-
dialdehyde 23 (164 mg, 1.0 mmol) and successive hydrolysis
with p-TsOH followed by treatment with the palladium com-
plex catalyst gave a crude product. This was purified by SCC
(THF–CH2Cl2, 5:95) and then PHPLC [LiChrosorb Si 60 (5
µm) 1.0 × 30 cm; THF–hexane, 13:87] to afford the all-E-oxo
pentaenal 43 (220 mg, 81% from 23) as an orange solid,
λmax(EtOH)/nm 403 and 420; νmax/cmϪ1 1668 (conj. CO and
(2E,4E)-5-(5,5-Dimethyl-1,3-dioxolan-2-yl)-4-methylpenta-2,4-
dienal 46
According to the procedure for the preparation of the alco-
hol 19 from the ester 18, reduction of the dienoate 45 (6.71 g,
26.4 mmol) with LAH produced a crude alcohol, which
without purification was dissolved in ether–hexane (1:3) and
shaken with active MnO2 (48 g) at room temp. for 6 h. The
mixture was filtered through Celite. Evaporation of the fil-
trate gave a residue, which was purified by SCC (ether–
hexane, 1:4) to provide the dienal 46 (2.79 g, 50%) as a solid,
conj. CHO) and 1596 and 1573 (C᎐C); δ (300 MHz) 1.76–1.93
᎐
H
(4 H, m, 4Ј- and 5Ј-H2), 1.90 (3 H, s, 2-Me), 2.04 (3 H, s, 7-Me),
2.48 (2 H, t, J 7, 3Ј-H2), 2.70 (2 H, br t, J 6.5, 6Ј-H2), 6.42 (1 H,
br d, J 11.5, 6-H), 6.59 (1 H, dd, J 15 and 11, 9-H), 6.71 (1 H, d,
J 15, 8-H), 6.78 (1 H, dd, J 14.5 and 11.5, 4-H), 6.96 (1 H, br d,
J 11.5, 3-H), 7.02 (1 H, dd, J 14.5 and 11.5, 5-H), 7.20 (1 H, dt,
J 11 and 2, 10-H) and 9.48 (1 H, s, CHO) (Found: Mϩ, 270.163.
C18H22O2 requires M, 270.162).
νmax/cmϪ1 1681 (conj. CHO) and 1643 and 1608 (C᎐C);
᎐
δH (300 MHz) 0.77 and 1.24 (each 3 H, s, gem-Me), 1.92 (3 H,
s, 4-Me), 3.55 and 3.68 (each 2 H, d, J 11, OCH2 × 2), 5.22 (1 H,
d, J 6, OCHO), 5.97 (1 H, br d, J 6, 5-H), 6.23 (1 H, dd, J 16
and 7.5, 2-H), 7.11 (1 H, d, J 16, 3-H) and 9.60 (1 H, d, J 7.5,
CHO) (Found: Mϩ, 210.127. C12H18O3 requires M, 210.125).
Preparation of the analogue 11
In the same manner as described for the preparation of the
analogue 8, Wittig reaction between the phosphonium salt 16
(300 mg, 0.69 mmol) and the aldehyde 43 (54 mg, 0.20 mmol)
followed by purification by SCC (ether–hexane, 2:3) gave an
isomeric mixture [55 mg, 79% from 43; all-E (analogue
11):10ЈZ ~1:1]. PHPLC separation [LiChrosorb Si 60 (5 µm)
1.0 × 30 cm; THF–hexane, 4:96] of the mixture in the dark
provided the analogue 11 and its 10ЈZ-isomer as red solids.
Analogue 11: λmax(EtOH)/nm 270 and 459; λmax(hexane)/nm
267, 425sh, 447 and 475; νmax/cmϪ1 1661, 1597, 1558 and 1520
(conj. CO and C᎐C); δ (500 MHz) 1.76–1.89 (4 H, m, 4- and
5-H2), 1.82 (3 H, dd, J 7 and 1, 15Ј-Me), 1.91 (3 H, s, 13Ј-Me),
1.96 (3 H, s, 4Ј-Me), 1.98 (3 H, s, 9Ј-Me), 2.46 (2 H, t, J 6.5,
6-H2), 2.67 (2 H, td, J 7 and 2, 3-H2), 5.76 (1 H, dq, J 15.5 and 7,
15Ј-H), 6.08 (1 H, br d, J 11.5, 12Ј-H), 6.16 (1 H, dd-like, J 15.5
and 1, 14Ј-H), 6.25 (1 H, br d, J 11.5, 8Ј-H), 6.33 (1 H, d, J 14.5,
10Ј-H), 6.39 (1 H, br d, J 12, 5Ј-H), 6.50 (1 H, dd, J 15 and 12,
2Ј-H), 6.61 (1 H, dd, J 14.5 and 12, 6Ј-H), 6.65 (1 H, dd, J 14.5
and 11.5, 11Ј-H), 6.70 (1 H, d, J 15, 3Ј-H), 6.73 (1 H, dd, J 14.5
and 11.5, 7Ј-H) and 7.23 (1 H, dt, J 12 and 2, 1Ј-H) (Found:
Mϩ, 348.244. C25H32O requires M, 348.245).
(2E,4E)-3-Methyl-6-[2Ј-oxocyclopent-(E)-ylidene]hexa-2,4-
dienal 47
A solution of BuLi (1.63 mol dmϪ3 in hexane; 3.86 cm3, 6.29
mmol) was added to a stirred solution of diisopropylamine
(0.88 cm3, 6.29 mmol) in dry THF (20 cm3) at Ϫ78 ЊC and the
mixture was stirred for a further 30 min. To this LDA solution
was added dropwise a solution of cyclopentanone (480 mg, 5.71
mmol) in dry THF (10 cm3). The mixture was stirred for 30 min
at Ϫ78 ЊC, after which a solution of the aldehyde 46 (1.00 g,
47.6 mmol) in dry THF (20 cm3) was added dropwise at the
same temperature and stirring was continued for a further 45
min. After being quenched with saturated aq. NH4Cl, the mix-
ture was extracted with ether followed by standard work-up to
give a residue, which was purified by SCC (acetone–hexane, 1:4)
to afford the adduct (1.24 g, 89%) as an oil, νmax/cmϪ1 3493
᎐
H
(OH), 1722 (CO) and 1635 (C᎐C).
᎐
Subsequently, acetic anhydride (0.68 cm3, 7.2 mmol) was
added to a stirred solution of this adduct (1.24 g, 4.2 mmol) and
DMAP (930 mg, 7.62 mmol) in dry benzene (30 cm3). The
mixture was stirred at room temp. for 1.5 h, after which DBU
(0.63 cm3, 4.2 mmol) was added. After being stirred at room
temp. for 2 h, the mixture was diluted with ether and washed
successively with aq. 3% HCl, saturated aq. NaHCO3 and brine.
Evaporation of the dried solution provided the crude product,
which without purification was dissolved in a mixture of
acetone (15 cm3) and THF (40 cm3). To this solution were
added water (5 cm3) and a solution of p-TsOH (0.1 mol dmϪ3 in
THF; 10 cm3, 1.0 mmol) and the mixture was stirred at room
temp. for 2.5 h, before being diluted with ether. The organic
layer was washed successively with saturated aq. NaHCO3 and
brine. Evaporation of the dried solution gave a residue, which
was purified by SCC (acetone–hexane, 1:3) to provide the oxo
trienal 47 (578 mg, 64% from 46) as a yellow solid, νmax/cmϪ1
10ЈZ-Isomer: λmax(EtOH)/nm 272, 336, 447 and 455sh; λmax
-
(hexane)/nm 260sh, 268, 320sh, 333, 425sh, 445 and 475; νmax
/
cmϪ1 1660, 1597, 1558 and 1523 (conj. CO and C᎐C); δ (500
᎐
H
MHz) 1.76–1.90 (4 H, m, 4- and 5-H2), 1.83 (3 H, dd, J 7 and
1.5, 15Ј-Me), 1.88 (3 H, s, 13Ј-Me), 1.97 (3 H, s, 4Ј-Me), 2.10
(3 H, s, 9Ј-Me), 2.46 (2 H, t, J 6.5, 6-H2), 2.67 (2 H, td, J 7 and 2,
3-H2), 5.80 (1 H, dq, J 15.5 and 7, 15Ј-H), 5.95 (1 H, d, J 12,
10Ј-H), 6.19 (1 H, dd-like, J 15.5 and 1.5, 14Ј-H), 6.29 (1 H, br
d, J 11.5, 8Ј-H), 6.32 (1 H, t, J 12, 11Ј-H), 6.39 (1 H, br d, J 11.5,
5Ј-H), 6.45 (1 H, dd, J 15 and 12, 2Ј-H), 6.57 (1 H, br d, J 12,
12Ј-H), 6.61 (1 H, dd, J 14.5 and 11.5, 6Ј-H), 6.70 (1 H, d, J 15,
3Ј-H), 6.71 (1 H, dd, J 14.5 and 11.5, 7Ј-H) and 7.23 (1 H, dt, J
12 and 2, 1Ј-H) (Found: Mϩ, 348.245).
2722
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
1707 (conj. CO and conj. CHO) and 1634 and 1618 (split)
(C᎐C); δ (300 MHz) 2.03 (2 H, quint, J 7.5, 4Ј-H ), 2.34 (3 H, s,
6.33 (1 H, t, J 11.5, 11Ј-H), 6.34 (1 H, dd, J 14.5 and 12, 2Ј-H),
6.41 (1 H, br d, J 11.5, 5Ј-H), 6.58 (1 H, br d, J 11.5, 12Ј-H),
6.61 (1 H, dd, J 14.5 and 11.5, 6Ј-H), 6.71 (1 H, d, J 14.5, 3Ј-H),
6.72 (1 H, dd, J 14.5 and 11.5, 7Ј-H) and 7.04 (1 H, dt, J 12 and
2, 1Ј-H) (Found: Mϩ, 334.230).
᎐
H
2
3-Me), 2.41 (2 H, t, J 7.5, 3Ј-H2), 2.81 (2 H, td, J 7.5 and 2.5,
5Ј-H2), 6.06 (1 H, d, J 7.5, 2-H), 6.70 (1 H, d, J 15, 4-H), 6.82 (1
H, dd, J 15 and 11, 5-H), 7.00 (1 H, dt, J 11 and 2.5, 6-H) and
10.16 (1 H, d, J 7.5, CHO) (Found: Mϩ, 190.099. C12H14O2
requires M, 190.099).
(2E,4E,6E,8E,10E,12E,14E)-2,6,11,15-Tetramethyl-16-oxo-
heptadeca-2,4,6,8,10,12,14-heptaenal 49
In the same manner as described for the preparation of the oxo
pentaenals 32ab, Wittig reaction between the phosphonium salt
3114 (1.03 g, 2.21 mmol) and the aldehyde 24a (216 mg, 0.89
mmol) followed by acid hydrolysis and successive treatment
with the palladium complex catalyst gave a crude product,
which was purified by SCC (acetone–hexane, 2:8) and then
PHPLC [LiChrosorb CN 60 (7 µm) 2.5 × 30 cm; THF–hexane,
13:87] to provide the all-E-oxo heptaenal 49 (159 mg, 58% from
24a) as an orange solid, λmax(EtOH)/nm 264, 420sh, 442 and
467; νmax/cmϪ1 1721, 1662, 1611 and 1576 (conj. CO, conj. CHO
(2E,4E,6E/Z,8E)-2,7-Dimethyl-10-[2Ј-oxocyclopent-(E)-
ylidene]deca-2,4,6,8-tetraenal 48a and 48b
In the same manner as described for the preparation of the oxo
pentaenals 32ab, Wittig reaction between the phosphonium salt
3114 (1.10 g, 2.35 mmol) and the aldehyde 47 (224 mg, 1.78
mmol) followed by acid hydrolysis and then treatment with the
palladium complex catalyst gave a crude product, which was
purified by SCC (acetone–hexane, 3:7) and then PHPLC
[LiChrosorb Si 60 (5 µm) 1.0 × 30 cm; THF–hexane, 13:87] to
provide the all-E-oxo pentaenal 48a (130 mg, 43% from 47) and
the 6Z-isomer 48b (26 mg, 9% from 47) as orange solids. Com-
pound 48a: λmax(EtOH)/nm 296, 401 and 421; νmax/cmϪ1 1698
and C᎐C); δ (500 MHz) 1.91 (3 H, s, 2-Me), 1.95 (3 H, d, J 1,
᎐
H
15-Me), 2.02 and 2.03 (each 3 H, s, 6- and 11-Me), 2.37 (3 H, s,
MeCO), 6.40 (1 H, br d, J 10.5, 10-H), 6.46 (1 H, br d, J 10,
7-H), 6.64 (1 H, dd, J 15 and 8.5, 13-H), 6.68 (1 H, d, J 15,
12-H), 6.73 (1 H, dd, J 14.5 and 9, 4-H), 6.72–6.80 (3 H, m,
5-, 8- and 9-H), 6.95 (1 H, br d, J 9, 3-H), 7.14 (1 H, br d, J 8.5,
14-H) and 9.47 (1 H, s, CHO) (Found: Mϩ, 310.195. C21H26O2
requires M, 310.193).
(conj. CO), 1665 (conj. CHO) and 1601 and 1557 (C᎐C); δ (300
᎐
H
MHz) 1.90 (3 H, s, 2-Me), 2.00 (2 H, quint, J 7.5, 4Ј-H2), 2.04
(3 H, s, 7-Me), 2.38 (2 H, t, J 7.5, 3Ј-H2), 2.78 (2 H, td, J 7.5 and
2, 5Ј-H2), 6.44 (1 H, br d, J 11.5, 6-H), 6.48 (1 H, dd, J 15 and
11.5, 9-H), 6.71 (1 H, d, J 15, 8-H), 6.79 (1 H, dd, J 14.5 and
11.5, 4-H), 6.97 (1 H, dd-like, J 11.5 and 1, 3-H), 7.01 (1 H, dt,
J 11.5 and 2, 10-H), 7.02 (1 H, dd, J 14.5 and 11.5, 5-H) and
9.48 (1 H, s, CHO) (Found: Mϩ, 256.146. C17H20O2 requires M,
256.146).
Preparation of the analogue 13
According to the procedure described for the preparation of
the analogue 8, Wittig reaction between the phosphonium salt
16 (350 mg, 0.80 mmol) and the aldehyde 49 (82 mg, 0.26 mmol)
gave a residue, which was purified by SCC (acetone–hexane,
1:3) and then PLC (acetone–hexane, 1:3) to afford an isomeric
mixture (92 mg, 90%). PHPLC separation [LiChrosorb Si 60
(5 µm) 1.0 × 30 cm; THF–hexane, 7:93] of the mixture in the
dark provided the analogue 10 as a red solid, λmax(EtOH)/nm
292, 446sh, 471 and 494sh; λmax(hexane)/nm 277sh, 289, 340,
357, 443, 470 and 502; νmax/cmϪ1 1647, 1607, 1584, 1558 and
Compound 48b: λmax(EtOH)/nm 297, 397 and 416; νmax/cmϪ1
1699 (conj. CO), 1663 (conj. CHO) and 1603 and 1571 (C᎐C);
᎐
δH (300 MHz) 1.89 (3 H, s, 2-Me), 2.01 (2 H, quint, J 7.5, 4Ј-H2),
2.06 (3 H, s, 7-Me), 2.40 (2 H, t, J 7.5, 3Ј-H2), 2.78 (2 H, td, J 7.5
and 2, 5Ј-H2), 6.31 (1 H, br d, J 12, 6-H), 6.48 (1 H, dd, J 15 and
12, 9-H), 6.70 (1 H, dd, J 14 and 11.5, 4-H), 6.97 (1 H, br d, J
11.5, 3-H), 7.06 (1 H, dt, J 12 and 2, 10-H), 7.16 (1 H, dd, J 14
and 12, 5-H), 7.25 (1 H, d, J 15, 8-H) and 9.49 (1 H, s, CHO)
(Found: Mϩ, 256.147).
1515 (conj. CO and C᎐C); δ (500 MHz) 1.83 (3 H, br d, J 5.5,
᎐
H
22-Me), 1.91 (3 H, s, 20-Me), 1.94 (3 H, d, J 1, 3-Me), 1.99 (3 H)
and 2.00 (6 H) (each s, 7-, 12- and 16-Me), 2.37 (3 H, s, MeCO),
5.75 (1 H, dq, J 15.5 and 7, 22-H), 6.08 (1 H, br d, J 11, 19-H),
6.16 (1 H, dd-like, J 15.5 and 1.5, 21-H), 6.23 (1 H, br d, J 11.5,
15-H), 6.28 (1 H, br d, J 11.5, 11-H), 6.34 (1 H, d, J 15, 17-H),
6.38 (1 H, d, J 15, 13-H), 6.40 (1 H, br d, J 11.5, 8-H), 6.59 (1 H,
dd, J 15 and 11, 5-H), 6.62 (1 H, dd, J 15 and 11, 18-H), 6.64
(1 H, dd, J 14 and 11.5, 9-H), 6.66 (1 H, d, J 15, 6-H), 6.69 (1 H,
dd, J 15 and 11.5, 14-H), 6.74 (1 H, dd, J 14 and 11.5, 10-H)
and 7.14 (1 H, dd-like, J 11 and 1, 4-H) (Found: Mϩ, 388.278.
C28H36O requires M, 388.276).
Preparation of the analogue 12
Following the procedure described for the preparation of the
analogue 8, Wittig reaction between the phosphonium salt 16
(850 mg, 1.95 mmol) and the aldehyde 48a (200 mg, 0.78 mmol)
followed by purification by SCC (ether–hexane, 2:3) afforded
an isomeric mixture [130 mg, 50% from 48a; all-E (analogue
12):10ЈZ ~1:1]. PHPLC separation [LiChrosorb Si 60 (5 µm)
1.0 × 30 cm; THF–hexane, 5:95] of the mixture in the dark
provided the analogue 12 and its 10ЈZ-isomer as red solids.
Analogue 12: λmax(EtOH)/nm 260sh, 269 and 462; λmax
-
(hexane)/nm 257sh, 266, 425, 449 and 447; νmax/cmϪ1 1694,
1604, 1571 and 1523 (conj. CO and C᎐C); δ (500 MHz) 1.82
᎐
H
(3 H, br d, J 6, 15Ј-Me), 1.91 (3 H, s, 13Ј-Me), 1.97 (3 H, s,
4Ј-Me), 1.98 (3 H, s, 9Ј-Me), 1.98 (2 H, quint, J 7.5, 4-H2),
2.37 (2 H, t, J 7.5, 5-H2), 2.75 (2 H, td, J 7.5 and 2, 3-H2),
5.76 (1 H, dq, J 15.5 and 6, 15Ј-H), 6.08 (1 H, br d, J 11.5,
12Ј-H), 6.16 (1 H, dd-like, J 15.5 and 1.5, 14Ј-H), 6.25 (1 H,
br d, J 11.5, 8Ј-H), 6.33 (1 H, d, J 15, 10Ј-H), 6.34 (1 H, dd,
J 15 and 12, 2Ј-H), 6.40 (1 H, br d, J 11.5, 5Ј-H), 6.61 (1 H,
dd, J 14.5 and 11.5, 6Ј-H), 6.65 (1 H, dd, J 15 and 11.5, 11Ј-
H), 6.70 (1 H, d, J 15, 3Ј-H), 6.73 (1 H, dd, J 14.5 and 11.5,
7Ј-H) and 7.04 (1 H, dt, J 12 and 2, 1Ј-H) (Found: Mϩ,
334.231. C24H30O requires M, 334.230).
Acknowledgements
We appreciate Kuraray Co., Ltd. Japan, Dr U. Hengartner,
Hoffmann-La Roche Ltd. in Basel and Dr J. Paust, BASF
Aktiegesellschaft in Ludwigshafen for the chemical support.
We thank Misses Y. Konishi, K. Ono, H. Yao, T. Inoue and M.
Yokota for technical assistance. This work was partly supported
by Kobe Pharmaceutical University Collaboration Fund.
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-
(hexane)/nm 257sh, 267, 318, 332, 426, 448 and 477; νmax/cmϪ1
1695, 1604, 1560 and 1523 (conj. CO and C᎐C); δ (500 MHz)
᎐
H
1.83 (3 H, br d, J 6.5, 15Ј-Me), 1.88 (3 H, s, 13Ј-Me), 1.97 (3 H,
s, 4Ј-Me), 1.99 (2 H, quint, J 7.5, 4-H2), 2.10 (3 H, s, 9Ј-Me),
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(1 H, dd-like, J 15 and 1, 14Ј-H), 6.30 (1 H, br d, J 11.5, 8Ј-H),
J. Chem. Soc., Perkin Trans. 1, 1997
2723

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Paper 7/02815F
Received 24th April 1997
Accepted 23rd May 1997
2724
J. Chem. Soc., Perkin Trans. 1, 1997