Formal synthesis of strobilurins A and X

Article abstract of DOI:10.1007/s11172-010-0359-x

Known synthetic precursors of strobilurins A and X, i.e., methyl (3Z,5E)-6-aryl-3-methylhexa-3,5-dienoates (aryl is phenyl, 4-methoxyphenyl), were synthesized by highly stereospecific reactions from 2-(2-tert- butyldimethylsilyloxyethyl)- and 2-[2-(4-methoxybenzyloxy)-ethyl]-5-arylpenta- 2E,4E-dien-1-ols. These dienols were efficiently dehydroxylated to (1E,3Z)-4-methyl-6-(4-methoxybenzyloxy)hexa-1,3-dienylarenes with their subsequent demethoxyben-zylation to (3Z,5E)-6-aryl-3-methylhexa-3,5-dien-1-ols. The latter through the step of corresponding aryldienals and aryldienoic acids were transformed to the target methyl (3Z,5E)-6-aryl-3-methylhexa-3,5-dienoates, which completes a formal synthesis of strobilurins A and X. Configuration of the C=C bonds of the conjugated aryldiene system is preserved in the considered transformations by 95-97%.

Full text of DOI:10.1007/s11172-010-0359-x

Russian Chemical Bulletin, International Edition, Vol. 59, No. 11, pp. 2086—2093, November, 2010
2086
Formal synthesis of strobilurins A and X
N. Ya. Grigorieva, V. A. Popovsky, A. V. Stepanov, and E. D. Lubuzh
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: ves@ioc.ac.ru
Known synthetic precursors of strobilurins A and X, i.e., methyl (3Z,5E)ꢀ6ꢀarylꢀ3ꢀmethylꢀ
hexaꢀ3,5ꢀdienoates (aryl is phenyl, 4ꢀmethoxyphenyl), were synthesized by highly stereospeꢀ
cific reactions from 2ꢀ(2ꢀtertꢀbutyldimethylsilyloxyethyl)ꢀ and 2ꢀ[2ꢀ(4ꢀmethoxybenzyloxy)ꢀ
ethyl]ꢀ5ꢀarylpentaꢀ2E,4Eꢀdiеnꢀ1ꢀols. These dienols were efficiently dehydroxylated to (1E,3Z)ꢀ
4ꢀmethylꢀ6ꢀ(4ꢀmethoxybenzyloxy)hexaꢀ1,3ꢀdienylarenes with their subsequent demethoxybenꢀ
zylation to (3Z,5E)ꢀ6ꢀarylꢀ3ꢀmethylhexaꢀ3,5ꢀdiеnꢀ1ꢀols. The latter through the step of correꢀ
sponding aryldienals and aryldienoic acids were transformed to the target methyl (3Z,5E)ꢀ6ꢀ
arylꢀ3ꢀmethylhexaꢀ3,5ꢀdienoates, which completes a formal synthesis of strobilurins A and X.
Configuration of the C=C bonds of the conjugated aryldiene system is preserved in the considꢀ
ered transformations by 95—97%.
Key words: stereocontrolled synthesis, strobilurins, dienes, dienals, aryldiеnoic acids, dehydrꢀ
oxylation, debenzylation, oxidation.
Strobilurins are biologically active compounds proꢀ
Retrosynthetic analysis of molecule 1 (Scheme 1) toꢀ
gether with the method developed by us earlier5 for the
creation of internal (Z)ꢀtrisubstituted C=C bond allowed
us to expect success in development of highly stereoselecꢀ
tive pathway for the construction of (3Z,5E)ꢀesters 2, the
known6,7 precursors of 1 and, thus, in accomplishment of
formal total synthesis of compounds 1.8
duced by bazidomicetes.1 At present, there are known
15 representatives of this group of natural compounds of
general formula 1 with different substituents in the benꢀ
zene ring.2,3 The structures of some of them are given
below.
To check a plausibility of such an approach, for the
synthesis of esters 2a (R1 = R2 = H) and 2b (R1 = H,
R2 = OMe), precursors of simple strobilurins A (1A) and
X (1X), earlier9 we have accomplished the syntheses of
(2E,4E)ꢀdienals 5a—c,e,f in high yields and stereoselecꢀ
tivity ~100% (Scheme 2). The latter are the key intermeꢀ
diates in the approach under consideration, since they
contain a required aryldiene fragment.
The present work is aimed on the development of highly
stereoselective methods for the transformation of dienals
5a—d through the steps of dienols 8a—d, dienols 3a,b, and
dienoic acids 13a,b (see below) to esters 2a,b.
1A: R1 = R2 = H
1X: R1 = H, R2 = OMe
1C: R1 = Me2C=CHCH2O, R2 = H
1B: R1 = OMe, R2 = Cl
1D: R1 + R2
=
Dienals 5a—d (see Scheme 2), like dienals 5e,f,10 are
smoothly and stereospecifically reduced with NaBH4 unꢀ
der standard conditions to give (2E,4E)ꢀdienols 8a—d.
The structure of the latter was confirmed by elemental
analysis and combination of physicoꢀchemical methods,
first of all, NOE 1H NMR. Thus, the olefinic region in the
1H NMR spectrum of dienol 8a shows the presence of two
doublets at δ 6.31 and 6.59, as well as a doublet of doublets
at δ 6.99, and only the first of these signals (δ 6.31) reveals
the NOE (5.3%) with the protons of the CH2OH group,
whereas the doublet of doublets gives the NOE (7.5%)
All the known strobilurins are capable of inhibiting the
respiratory cycle in mitochondria and due to this exhibit
high fungicide activity.
The structure of strobilurins is characterized by the
presence of a (E,Z,E)ꢀaryltriene fragment, whose stereoꢀ
selective construction is poorly investigated. It is known
from the literature that syntheses of strobilurins, except of
one of them,4 are based on the Wittig—Horner reaction
and are not stereoselective.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2033—2040, November, 2010.
1066ꢀ5285/10/5911ꢀ2086 © 2010 Springer Science+Business Media, Inc.

Strobilurins
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 11, November, 2010 2087
Scheme 1
with the protons of the allylic CH2 group. These data
allowed us, first, to assign the doublet at δ 6.31 to the
HC(3), and, second, to draw conclusion on the (E)ꢀconꢀ
figuration of the C(2)=C(3) bond. The second doublet
signal in the H NMR spectrum of dienol 8a (δ 6.59) is
assigned to the HC(5). Its spinꢀspin coupling constant
with HC(4) (15.5 Hz) evidences the (E)ꢀconfiguration of
the C(4)=C(5) bond. The (E,E)ꢀconfiguration of dienols
8b—d was established similarly.
It was more difficult to preserve configuration of the
diene system of C=C bonds during dehydroxylation of the
free CH2OH group of dienols 8a—d. Transformation of
1
Scheme 2
a: R1 = H, R2 = SiMe2But
b: R1 = OMe, R2 = SiMe2But
c: R1 = H, R2 = 4ꢀMeOC6H4CH2
d: R1 = OMe, R2 = 4ꢀMeOC6H4CH2
e: R1 = H, R2 = Bn
f: R1 = OMe, R2 = Bn
Reagents and conditions: i. NaBH4/EtOH, 20 °C, 2 h; ii. Py•SO3/THF, 0 °C, 2.5 h; iii. LiAlH4, 20 °C, 20 h; iv. BuLi/Et2O—HMPA,
0 °C; v. TsCl/HMPA, 0 °C, 2.5 h; vi. Bu4NF/THF, 20 °C, 30 min; vii. PhNMe2, then, AlCl3, 0 °C, 1.5 h.

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Grigorieva et al.
alcohol using a Py•SO3 complex to sulfonic ester and
reduction of the latter (without isolation) with LiAlH4,
was good in dehydroxylation of allylic alcohols (see, for
example, Refs 11 and 12). However, its extension on diꢀ
enols gave satisfactory results only in the case of dienol 8c,
which was successfully converted to (1E,3Z)ꢀdiene 4c in
more than 95% purity (1H NMR data). Analytically pure
sample of 4c was isolated by HPLC in 50% yield calculatꢀ
ed on two steps. Its structure, as well as structures of dienes
4a,b,d described below, were confirmed by high resolution
mass spectrometry (HRMS) and NOE 1H NMR similarly
to that described above for dienol 8a.
cally pure samples of 4b,d,c were isolated by flashꢀchromꢀ
atography.
Formation of (1E,3E)ꢀdienes 11 during preparation of
(1E,3Z)ꢀdienes 4 was inferred from the NMR spectroꢀ
1
scopic data. Thus, the H NMR spectrum of diene 4a,
together with signals for its H2C(5) (t, δ 2.53), HC(3) (d,
δ 6.09), and HC(1) (d, δ 6.45) groups, exhibits additional
signals close to each of them: a triplet at δ 2.34 and two
doublets at δ 6.05 and 6.43, respectively. The 13C NMR
spectrum, together with the signal for the MeC(4) of
Zꢀisomer (δ 24.72), shows the signal for the MeC(4) of
(E)ꢀisomer (δ 17.34). Similarly, admixture isomers 11b—d
were found in dienes 4b—d.
Dehydroxylation of dienols 8a,b bearing tertꢀbutylꢀ
dimethylsilyl (TBS) Oꢀprotecting group and dienol 8d
bearing 4ꢀmethoxybenzyl protecting group through the
step of their sulfonic esters is less selective. For instance,
(2E,4E)ꢀdienol 8a gives in the best experiment of this seꢀ
ries (1E,3Z)ꢀdiene 4a containing totally 11% of dienes 9a
and 10a in the ratio 8 : 3 as an admixture. The structure
and content of the latter in the mixture were established by
NMR spectroscopy. In fact, in the 1H NMR spectra of the
mixture of products of dehydroxylation of dienol 8a, in
addition to the signals for diene 4a, there are two minor
doublet signals for the terminal methylene group at δ 5.0
and 4.96 and the ratio of integral intensities ~8 : 3. In
addition, the spectra contain a doublet signal for the CH2
group placed between the Ph ring and the C=C bond
(δ 3.46), as well as a signal for the CH2 group placed
between two C=C bonds (δ 2.98).13 The ratio of their
integral intensities is also ~8 : 3, while the ratio of integral
intensities of the first of them and the signal for the H2C(5)
group of diene 4a is 11 : 1. These results, as well as the fact
that the high resolution mass spectrum of the mixture of
products of dehydroxylation of dienol 8a exhibits only ions
[M + H]+, [M + Na]+, and [M + K]+, allowed us to
assign the structure 9a to the major product in the admixꢀ
ture, while the minor admixture product has the structure
10a. Similar situation is also observed in the reduction of
sulfonic esters of dienols 8b and 8d. However, here in the
first case the total content and the ratio of isomers 9b and
10b in the mixture are ~33% and 4 : 1, in the second case,
the total content and the ratio of isomers 9d and 10d are
~38% and 5 : 1 (1H NMR spectroscopic data).
Analysis of considered transformations of dienals
5a—d, as well as recently described10 transformations of
dienals 5e,f to diens 4aꢀf, allows us to conclude that stereoꢀ
chemistry of formation of dienals 5a—f, determined by
a thermodynamic factor,5 depends little on both the presꢀ
ence of a substituent in the benzene ring and the nature of
the Oꢀprotecting group. This regularity also operates in
the transformation of dienals 5a—f to (2E,4E)ꢀdienols
8a—f. At the same time, the stereoselectivity of dehydrꢀ
oxylation processes of the latter significantly depends on
their structure. Dienols 8b,d,f with a MeO substituent in
the benzene ring can be converted to the desired dienes
with high stereoselectivity starting from their tosylates. In
the case of dienols 8a,e unsubstituted in the benzene ring,
it is reasonable to use their sulfonic esters. The high (98%)
stereospecificity of dehydroxylation of both sulfonic esters
and tosylates was reached only in the case of dienol 8c
with Oꢀmethoxybenzyl protection.
Deprotection of dienes 4a,b with OꢀTBSꢀprotection
was accomplished with Bu4NF in aqueous THF and gave
dienols 3a,b in 78—80% yield with full preservation of
configuration of the C=C bonds. Removal of Oꢀmethoxyꢀ
benzyl protection from diene 4c was successfully accomꢀ
plished by their treatment with AlCl3 at 0 °C in the presꢀ
ence of PhNMe2 (80—82% yield, see similar10 deproꢀ
14
tection of benzyloxydienes 4e,f). In this case, the dienol
3a obtained contains totally no more than 2% of correꢀ
sponding isomers 9a, 10a, and 11a (1H NMR spectroꢀ
scopic data). However, deprotection in diene 4d under
these conditions is accompanied by isomerization and gives
a mixture of dienol 3b and its (3E,5E)ꢀisomer in the
ratio 4 : 1.
Note that according to the data published earlier,15,16
dienol 3a is a metabolite of ascomicete Bolinea lutea, the
only known by now strobilurins producer other than
bazidomicete. The authors of the work15 assumed that
dienol 3a is a biosynthetic precursor of strobilurin A; physꢀ
icoꢀchemical parameters of the sample of 3a isolated by
them are in good correlation with those described earlier10
and in the present work.
To find an alternative method for the preparation of
dienes 4a—d from dienols 8a—d, we studied the LiAlH4
reduction of their crude tosylates. Dienols 8b,d are thus
converted in two steps to dienes 4b,d in ~60% yield,
which contain no admixtures of 9b,d and 10b,d. However,
dienes 4b and 4d in such a case contained ~5 and ~8%
of (1E,3E)ꢀdienes 11b and 11d, respectively. At the
same time, tosylate of dienol 8c is reduced with LiAlH4
to diene 4c containing totally ~2% of isomers 9c and 10c
1
and containing no isomer 11c (the data of H NMR
spectrum). Reduction of tosylate of dienol 8a leads to
a mixture of dienes 4a and 11a in the ratio ~3 : 1. Analytiꢀ
A search for the method of clean oxidation of diꢀ
enols 3a,b to acids 13a,b turned out to be difficult, too

Strobilurins
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 11, November, 2010 2089
(Scheme 3). Attempted direct transformation of dienol 3b
to acid 13b with PDC in DMF (see Ref. 17) or NaIO4 in
the presence of catalytic amounts of Na2Cr2O7 and HNO3
(see Ref. 18) did not give the desired result: complex mixꢀ
tures of isomerization and destruction products were obꢀ
tained in both cases (NMR spectroscopic data).
was unsuccessful. A mixture of ethoxydienal 15 (δCHO 10.10)
(see Scheme 3) and its 2Zꢀisomer (δCHO 9.66) in the ratio
~7 : 1 (1H NMR spectroscopic data) was isolated from the
reaction products in ~30% yield instead of expected acid
13b or its ester. The structure of compound 15 was estabꢀ
1
lished by HRMS and H NMR using the double resoꢀ
nance and NOE techniques.
Dienals 12a,b were successfully oxidized with full presꢀ
ervation of configuration of the C=C bonds by treatment
with NaClO2 in the presence of DMSO at pH 9 using
modified by us procedure.23 The obtained acids 13a,b were
quantitatively converted to methyl esters 2a and 2b, that
formally finishes the total synthesis of strobilurins A and
X, respectively.
Scheme 3
The structure of compounds 2a,b, 3a,b, 12a,b, and
13a,b was established by physicoꢀchemical methods, first
1
of all by HRMS and H NMR spectroscopy using the
NOE procedure, as it was described above taken dienol 8a
as an example.
In conclusion, we have developed a new efficient eightꢀ
step formal synthesis of strobilurins A and X. The configuꢀ
ration of aryldiene system of conjugate C=C bonds, creatꢀ
ed by crossꢀcondensation of aldimines 7 with (E)ꢀcinꢀ
namic aldehydes, remained intact during the synthesis by
95—97%.
Experimental
UV spectra were recorded on a Specord UV—Vis spectroꢀ
meter in ethanol, IR spectra were recorded on a Specord Mꢀ80
spectrometer for neat samples or (for alcohols) for solutions in
1
CHCl3. H and 13C NMR spectra were recorded on a Bruker
ACꢀ200 spectrometer in CDCl3 relatively to the signal of the
solvent (δ 7.27 and 77.0, respectively). Assignment of signals for
1
the vinylic protons in the H NMR spectra was made based on
the NOE experiment. Mass spectra (EI, 70 eV) were recorded
on a Kratos MSꢀ30 instrument with exhibiting peaks of >10%
relative intensities, except peaks of molecular ions. High resoluꢀ
tion mass spectra (HRMS) were recorded on a micrOTOF II
instrument (Bruker Daltonics) using electrospray ionization
(ESI), the scanning range from m/z 50 to m/z 3000, positive ions
(the voltage on a capillary was 4500 V). Compounds were injectꢀ
ed with a syringe. Acetonitrile was a solvent, the solution flow
rate was 3 μL min–1, the interface temperature was 180 °C,
nitrogen was the spray gas (4.0 L min–1). Melting points were
measured on a Kofler heating stage. Column chromatography
was performed on Silica gеl 60 (0.04—0.06 mm, Fluka); TLC,
unless indicated otherwise, was performed in the systems 1
(TBME—hexane (1 : 1)) or 2 (acetone—hexane (2 : 3)). Analytꢀ
ical and preparative HPLC was performed on a Armofer Sil 10
column (10 μm, 150×24 mm); a RIDKꢀ102 detector, using a 5%
(vol.) solution of ethyl acetate in heptane as an eluent (the flow
rate was 6 mL min–1). Solvents were purified as follows: diethyl
ether and THF were kept over KOH, sequentially distilled over
Na and LiAlH4, then refluxed with benzophenone Naꢀketyl until
blue color was persistent and distilled directly into the reaction
vessel; hexane was distilled over Na. Hexane solution of BuLi
was obtained according to the standard procedure. Experiments
R = H (a), OMe (b)
Reagents and conditions: i. IBX (14)/DMF, 20 °C, 2 h;
ii. NaClO2—DMSO/H2O—THF, phosphate buffer with pH 9,
0 °C, 2.5 h; iii. CH2N2/Et2O, 0 °C.
Dienols 3a,b were smoothly converted to acids 13a,b
through the step of preparation of the corresponding dienals
12a,b. The best oxidant for obtaining the latter was found
to be oꢀiodoxybenzoic acid (IBX, 14),19,20 which gave diꢀ
enals 12a,b chemoꢀ and stereospecifically in high yields.
Note that both the Swern and Corey (using РCC or PDC
in CH2Cl2) procedures, as well as oxidation with iodosucꢀ
cinimide in methanol in the presence of K2CO3 (see
Ref. 21), led to complex mixtures (1H NMR spectroꢀ
scopic data).
Attempted oxidation of dienal 12b with Ag2O, generꢀ
ated in situ in aqueous ethanol from AgNO3 with KOH,22

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Russ.Chem.Bull., Int.Ed., Vol. 59, No. 11, November, 2010
Grigorieva et al.
with unstable compound were performed under argon; chemical
glassware used was heated at 160 °C for 12 h and cooled in the
flow of argon.
Usual treatment of organic extracts included their washing
to pH ~7, drying with Na2SO4, and concentration in vacuo on
a rotary evaporator.
1364, 1304, 1248, 1172, 1088, 1036, 1004, 964, 824. 1H NMR, δ:
2.67 (t, 2 H, H2C(1´), J = 6.10 Hz); 2.89 (br.s, 1 H, OH); 3.63
(t, 2 H, H2C(2´), J = 6.10 Hz); 3.79 (s, 3 H, MeO); 4.14 (s, 2 H,
H2C(1)); 4.49 (s, 2 H, H2CPh); 6.30 (d, 1 H, HC(3), J = 11.2 Hz);
6.59 (d, 1 H, HC(5), J = 15.7 Hz); 6.87 (d, 2 H, Ar, J = 8.4 Hz);
6.97 (dd, 1 H, HC(4), J1 = 11.2 Hz, J2 = 15.7 Hz); 7.34 (m, 7 H,
Ar). 13C NMR, δ: 29.85 (C(1´)); 55.15 (MeO); 67.87 (C(1));
69.33 C(2´); 72.83 (CH2Ph); 113.81 (Ar), 124.15 (C(4)); 126.36
(C(3)); 127.48, 127.85, 128.10, 128.54, 129.25 (Ar); 133.19
(C(5)); 137.40 (Ar); 139.49 (C(2)); 159.23 (Ar). MS, m/z
(Irel (%)): 324 [M]+ (1), 203 (3), 137 (14), 122 (8.5), 121 (100),
91 (10).
Dienals 5a—c were obtained as described in the work.9
(2E,4E)ꢀ2ꢀ(2ꢀtertꢀButyldimethylsilyloxyethyl)ꢀ5ꢀphenylpenꢀ
taꢀ2,4ꢀdiеnꢀ1ꢀol (8a) was obtained by reduction of dienal 5a (see
Ref. 9) with NaBH4 according to the standard procedure. The
yield was ~100%, Rf 0.49 (system 1). HRMS (m/z): found:
341.1890 [M + Na]+. C19H30O2NaSi. Calculated: 341.1901
[M + Na]+. UV, λmax/nm (ε): 239 (7950), 298.5 (27380), 320
(15900). IR, ν/cm–1: 3600, 3392, 3080, 3064, 3048, 3008, 2952,
2856, 2256, 1792, 1676, 1620, 1592, 1520, 1492, 1468, 1392,
1376, 1256, 1188, 1148, 1080, 1008, 960, 912, 840, 696. 1H NMR,
δ: 0.11 (s, 6 H, Me2Si); 0.93 (s, 9 H, But); 2.62 (t, 2 H, H2C(1´),
J = 6.1 Hz); 3.81 (t, 2 H, H2C(2´), J = 6.1 Hz); 4.16 (s, 2 H,
H2C(1)); 6.31 (d, 1 H, HC(3), J = 11.0 Hz); 6.59 (d, 1 H,
HC(5), J = 15.5 Hz); 6.99 (dd, 1 H, HC(4), J1 = 11.0 Hz, J2 =
= 15.5 Hz); 7.35 (m, 5 H, Ph). 13C NMR, δ: –5.50 (Me2Si);
18.26 (CMe3); 25.84 (CMe3); 32.62(C(1´)); 63.06 (C(2´)); 67.91
(C(1)); 124.11 (C(4)); 126.33 (C(3)); 127.46, 127.86, 128.55 (Ar);
133.11 (C(5)); 137.39 (Ar); 139.36 (C(2)). MS, m/z (Irel (%)):
318 [M]+ (8), 261 (23), 259 (14), 243 (13), 186 (30), 185 (15),
171 (14), 170 (15), 169 (45), 167 (17), 158 (14), 157 (32), 156 (17),
155 (53), 154 (41.5), 153 (22), 143 (32), 142 (21), 141 (57),
129 (37), 128 (36), 118 (27), 117 (81), 116 (10), 115 (46), 106 (24),
105 (88), 103 (13), 101 (17), 99 (14), 95 (14), 92 (15.5), 91 (52),
90 (15.5), 89 (100), 83 (10), 77 (29), 76 (39), 75 (93), 74 (51),
73 (84.5), 61 (14), 57 (23), 43 (14), 38 (14).
(2E,4E)ꢀ2ꢀ[2ꢀ(4ꢀMethoxybenzyloxy)ethyl]ꢀ5ꢀ(4ꢀmethoxyꢀ
phenyl)pentaꢀ2,4ꢀdiеnꢀ1ꢀal (5d) was obtained by condensation
of (E)ꢀ4ꢀmethoxycinnamaldehyde with 4ꢀ(4ꢀmethoxybenzylꢀ
oxy)butanal Nꢀtertꢀbutylimine according to the procedure deꢀ
scribed earlier,9 yellow crystals, m.p. 74—76 °C (from benzꢀ
ene—hexane (1 : 1)). Found (%): C, 74.70; H, 6.72. C22H24O4.
Calculated (%): C, 74.97; H, 6.86. UV, λmax/nm (ε): 203 (17000),
226 (16000), 351 (37000). IR, ν/cm–1: 3000, 2850, 2836, 1656,
1592, 1512, 1464, 1440, 1424, 1376, 1360, 1332, 1316, 1252,
1172, 1112, 1096, 1052, 1032, 984, 968, 884, 840, 808, 764, 640.
1H NMR, δ: 2.78 (t, 2 H, H2C(1´), J = 6.8 Hz); 3.55 (t, 2 H,
H2C(2´), J = 6.8 Hz); 3.75, 3.85 (both s, 3 H each, MeO); 4.44
(s, 2 H, H2CPh); 6.79 (d, 2 H, Ar, J = 8.6 Hz); 6.90 (d, 2 H, Ar,
J = 8.8 Hz); 6.96 (d, 1 H, HC(5), J = 15.2 Hz); 7.06 (d, 1 H,
HC(3), J = 11.2 Hz); 7.18 (dd, 1 H, HC(4), J1 = 15.2 Hz,
J2 = 11.2 Hz); 7.23 (d, 2 H, Ar, J = 8.6 Hz); 7.43 (d, 2 H, Ar,
J = 8.7 Hz); 9.47 (s, 1 H, HC(1)). 13C NMR, δ: 25.18 (C(1´));
55.17, 55.35 (MeO); 68.75 (C(2´)); 72.57 (CH2Ph); 113.72,
114.36 (Ar); 121.93 (C(4)); 129.03, 129.12 (Ar); 137.71 (C(2));
141.55 (C(5)); 151.23 (C(3)); 159.05, 160.78 (Ar); 194.22 (C(1)).
(2E,4E)ꢀ2ꢀ[2ꢀ(4ꢀMethoxybenzyloxy)ethyl]ꢀ5ꢀ(4ꢀmethoxyꢀ
phenyl)pentaꢀ2,4ꢀdiеnꢀ1ꢀol (8d) was obtained similarly to dienols
8a—c from 5d. The yield was ~100%, m.p. 75—76 °C. Found (%):
C, 74.72; H, 7.13. C22H26O4. Calculated (%): C, 74.55; H, 7.39.
UV, λmax/nm (ε): 229 (23400), 303 (46700). IR, ν/cm–1: 3608,
3400, 3032, 3008, 2936, 2912, 2840, 1604, 1508, 1464, 1436,
1420, 1356, 1304, 1248, 1176, 1088, 1060, 1036, 1004, 964, 820,
664. 1H NMR, δ: 2.65 (t, 2 H, H2C(1´), J = 6.2 Hz); 2.90 (br.s,
1 H, OH); 3.62 (t, 2 H, H2C(2´), J = 6.2 Hz); 3.79, 3.82 (both s,
3 H each, MeO); 4.12 (s, 2 H, H2C(1)); 4.48 (s, 2 H, H2CPh);
6.27 (d, 1 H, HC(3), J = 10.9 Hz); 6.53 (d, 1 H, HC(5), J = 15.4 Hz);
6.84 (dd, 1 H, HC(4), J1 = 10.9 Hz, J2 = 15.4 Hz); 6.87 (d, 4 H,
Ar, J = 8.7 Hz); 7.26 (d, 2 H, Ar, J = 8.6 Hz); 7.34 (d, 2 H, Ar,
J = 8.7 Hz). 13C NMR, δ: 29.90 (C(1´)); 55.17, 55.23 (MeO);
68.07 (C(1)); 69.39 (C(2´)); 72.85 (CH2Ph); 113.04, 113.81 (Ar);
122.14 (C(4)); 127.58 (C(3)); 128.17, 129.25 (Ar); 132.85 (C(5));
138.18 (C(2)); 159.24 (COMe).
(2E,4E)ꢀ2ꢀ(2ꢀtertꢀButyldimethylsilyloxyethyl)ꢀ5ꢀ(4ꢀmethꢀ
oxyphenyl)pentaꢀ2,4ꢀdiеnꢀ1ꢀol (8b) was obtained similarly to diꢀ
enol 8a from dienal 5b (see Ref. 9). The yield was 90%, b.p.
170 °C (7•10–2 Torr) (bath). Found (%): C, 68.95; H, 9.30;
Si, 7.70. C20H32O3Si. Calculated (%): C, 68.92; H, 9.25; Si, 8.06.
UV, λmaх/nm (ε): 226 (7700), 304 (25100). IR, ν/cm–1: 3612,
3400, 3040, 3000, 2930, 2860, 1600, 1580, 1512, 1472, 1440,
1392, 1364, 1300, 1260, 1176, 1076, 1036, 1000, 960, 920, 888,
1
836, 660. H NMR, δ: 0.01 (s, 6 H, Me2Si); 0.92 (s, 9 H, But);
2.60 (t, 2 H, H2C(1´), J = 6.1 Hz); 3.00 (br.s, 1 H, OH); 3.79
(t, 2 H, H2C(2´), J = 6.1 Hz); 3.82 (s, 3 H, MеO); 4.14 (s, 2 H,
H2C(1); 6.27 (d, 1 H, HC(3), J = 10.5 Hz); 6.53 (d, 1 H, HC(5),
J = 15.4 Hz); 6.84 (dd, 1 H, HC(4), J1 = 10.5 Hz, J2 = 15.4 Hz);
6.87 (d, 2 H, Ar, J = 8.7 Hz); 7.35 (d, 2 H, Ar, J = 8.7 Hz).
13C NMR, δ: –5.56 (Me2Si); 18.19 (CMe3); 25.78 (Me3C); 32.61
(C(1´)); 55.16 (MeO); 62.97 (C(2´)); 68.00 (C(1)); 113.99 (Ar);
122.16 (C(4)); 127.47 (Ar); 128.06 (C(3)); 132.64 (C(5)); 138.36
(C(2)); 159.17 (COMe). MS, m/z (Irel (%)): 348 [M]+ (12),
289 (20), 200 (10), 199 (20), 187 (16), 185 (32), 173 (15), 171 (16),
165 (10), 158 (14), 147 (25), 145 (12), 141 (15), 134 (36), 129 (17),
121 (13), 115 (50), 105 (21), 112 (14), 91 (21), 89 (11), 77 (28),
75 (100), 74 (86), 57 (13), 55 (15).
(2E,4E)ꢀ2ꢀ[2ꢀ(4ꢀMethoxybenzyloxy)ethyl]ꢀ5ꢀphenylpentaꢀ
2,4ꢀdiеnꢀ1ꢀol (8c) was obtained similarly to dienols 8a,b from 5c
(see Ref. 9). The yield was ~100%, m.p. 43—45 °C (from hexꢀ
ane—diethyl ether (1 : 1)). HRMS (m/z), found: 347.1624
[M + Na]+; 363.1360 [M + K]+. C21H24O3. Calculated (%):
347.1618 [M + Na]+; 363.1357 [M + K]+. UV, λmax/nm (ε): 234
(21380), 301 (30560). IR, ν/cm–1: 3608, 3420, 3036, 3008, 2950,
2930, 2910, 2864, 2835, 1612, 1588, 1520, 1512, 1464, 1448,
(1E,3Z)ꢀ6ꢀtertꢀButyldimethylsilyloxyꢀ4ꢀmethylꢀ1ꢀphenylꢀ
hexaꢀ1,3ꢀdiene (4a). A. A solution of dienol 8a (180 mg, 0.61 mmol)
in THF (5 mL) was added dropwise to a vigorously stirred susꢀ
pension of Py•SO3 (159 mg, 1 mmol) in THF (10 mL) at –15 °C.
The reaction mixture was heated to 0 °C and stirred at this temꢀ
perature for 2.5 h, then cooled to –10 °C, followed by a dropwise
addition of a solution of LiAlH4 (3.4 mmol) in THF (2 mL),
then the mixture was slowly heated to ~20 °C and stirred at this
temperature for 20 h. The mixture again was cooled to –10 °C,
followed by sequential dropwise addition of water (0.12 mL),
15% aqueous NaOH (0.12 mL), and water (0.36 mL). A precipꢀ
itate formed was filtered off and thoroughly washed with TBME.

Strobilurins
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 11, November, 2010 2091
The residue after usual treatment of the filtrate was subjected to
chromatography on SiO2 (20 g). The gradient elution from benꢀ
zene to TBME (to 10% of the latter) yielded a mixture of dienes
4a, 9a, and 10a (100 mg, 59%) in the ratio 89 : 8 : 3 (1H NMR
spectroscopic data). Analytically pure diene 4a was isolated by
HPLC, Rf 0.63 (10% TBME in hexane). HRMS (m/z), found:
303.2116 [M + H]+; 325.1939 [M + Na]+; 341.1696 [M + K]+.
C19H30OSi. Calculated: 303.2139 [M + H]+; 325.1958 [M + Na]+;
341.1696 [M + K]+. UV, λmax/nm (ε): 297 (24470), 316.5
(17180). IR, ν/cm–1: 3080, 3060, 3028, 2960, 2932, 2856, 1684,
1640, 1596, 1496, 1472, 1464, 1436, 1384, 1360, 1256, 1096,
211 (51), 201 (47), 200 (47), 199 (43), 189 (15), 188 (58), 184 (15),
173 (19), 172 (52), 169 (16), 165 (26), 159 (56), 158 (47), 145 (26),
159 (55), 158 (47), 145 (26), 141 (25), 138 (19), 121 (22), 89 (12),
75 (22), 73 (40).
(1E,3Z)ꢀ6ꢀ(4ꢀMethoxybenzyloxy)ꢀ4ꢀmethylꢀ1ꢀphenylhexaꢀ
1,3ꢀdiene (4c). Dehydroxylation of dienol 8c by method A simiꢀ
larly to that described above for dienols 8a,b gave diene 4c in
55% yield, the total admixtures of dienes 9c and 10c in which did
not exceed 3% (1H NMR spectroscopic data). Dehydroxylation
of diene 4c by method B gave a mixture of dienes 4c and 11c in
62% yield in the ratio 96 : 4 (1H NMR spectroscopic data). Anaꢀ
lytically pure diene 4c was isolated by flashꢀchromatography as
colorless oil, which crystallizes on standing in refrigerator; m.p.
25—27 °C. HRMS (m/z), found: 309.1847 [M + H]+; 326.2111
[M + NH4]+; 331.1666 [M + Na]+; 347.1419 [M + K]+.
C21H24O2. Calculated: 309.1849 [M + H]+; 326.2115 [M + NH4]+;
331.1669 [M + Na]+; 347.1408 [M + K]+. UV, λmax/nm (ε): 234
(21560), 301 (32030). IR, ν/cm–1: 3028, 3000, 2960, 2936, 2904,
2852, 1640, 1616, 1596, 1516, 1464, 1452, 1360, 1348, 1304,
1
1008, 960, 912, 872, 836, 776, 748, 692, 664. H NMR, δ: 0.08
(s, 6 H, Me2Si); 0.91 (s, 9 H, But); 1.89 (s, 3 H, MeC(4)); 2.53
(t, 2 H, H2C(5), J = 7.1 Hz); 3.74 (t, 2 H, H2C(6), J = 7.1 Hz);
6.09 (d, 1 H, HC(3), J = 10.9 Hz); 6.45 (d, 1 H, HC(1),
J = 15.45 Hz); 7.02 (dd, 1 H, HC(2), J1 = 10.9 Hz, J2 = 15.45 Hz);
7.30 (m, 5 H, Ph). 13C NMR, δ: –5.30 (Me2Si); 18.33 (Me3C);
24.72 (MeC(4)); 25.93 (Me3C); 36.35 (C(5)); 61.97 (C(6));
125.42 (C(2)); 126.09 (C(3)); 126.94, 127.36, 128.49 (Ar); 130.14
(C(1)); 136.95 (C(4)); 137.95 (Ar).
1
1248, 1172, 1096, 1036, 960, 820, 748, 692. H NMR, δ: 1.88
B. A solution of BuLi (2.8 mL, 4.76 mmol) in hexane and
after 10 min a solution of TsCl (0.95 g, 5 mmol) in HMPA
(5 mL) were sequentially added to a vigorously stirred solution of
dienol 8a (1.20 g, 4.08 mmol) in the mixture of Et2O (30 mL)
and HMPA (5 mL) at 0 °C (Ar). The reaction mixture was stirred
for 2.5 h at 0 °C, then cooled to –15 °C, followed by a dropwise
addition of a solution of LiAlH4 (20.4 mmol) in THF (12 mL).
The mixture was slowly heated to ~20 °C and stirred at this
temperature for 20 h. Then, the mixture was again cooled to
–15 °C, followed by a sequential dropwise addition of H2O
(0.8 mL), 15% aq. NaOH (0.8 mL), and H2O (2.4 mL). A preꢀ
cipitate formed was filtered off, thoroughly washed with TBME.
The residue (1.30 g) after usual treatment of the filtrate was
subjected to chromatography on SiO2 (50 g). The gradient eluꢀ
tion from hexane to benzene (to 40% of the latter) yielded
a mixture of dienes 4a and 11a (0.6 g, 52%) in the ratio 3 : 1
(1H NMR spectroscopic data).
(1E,3Z)ꢀ6ꢀtertꢀButyldimethylsilyloxyꢀ4ꢀmethylꢀ1ꢀ(4ꢀmethꢀ
oxyphenyl)hexaꢀ1,3ꢀdiene (4b). A mixture of dienes 4b, 9b, and
10b (52% yield) in the ratio 10 : 4 : 1 (1H NMR spectroscopic
data) was obtained by dehydroxylation of dienol 8b by method A
similarly to the described above for dienol 8a. Dehydroxylation
of dienol 8b by method B and flashꢀchromatography of the reacꢀ
tion products led to the isolation of pure (NMR data) diene 4b in
58% yield as colorless light oil with b.p. 150 °C (0.1 Torr) (bath).
Found (%): C, 71.99; H, 9.73; Si, 8,45. C20H32O2Si. Calculatꢀ
ed (%): C, 72.23; H, 9.70; Si, 8.45. UV, λmaх/nm (ε): 226 (10600),
304 (33200). IR, ν/cm–1: 3032, 2952, 2928, 2856, 1640, 1604,
1512, 1470, 1450, 1440, 1400, 1384, 1304, 1288, 1256, 1176,
1096, 1040, 1008, 960, 912, 836, 824, 812, 792, 776, 750, 664.
1H NMR, δ: 0.09 (s, 6 H, Me2Si); 0.92 (s, 9 H, But); 1.87 (s, 3 H,
CH3C(4)); 2.52 (t, 2 H, H2C(5), J = 7.2 Hz); 3.74 (t, 2 H,
H2C(6), J = 7.2 Hz); 3.82 (s, 3 H, MеO); 6.06 (d, 1 H, HC(3),
J = 10.8 Hz); 6.40 (d, 1 H, HC(6), J = 15.3 Hz); 6.86 (d, 2 H, Ar,
J = 8.7 Hz); 6.88 (dd, 1 H, HC(2), J1 = 10.8 Hz, J2 = 15.3 Hz);
7.34 (d, 2 H, Ar, J = 8.7 Hz). 13C NMR, δ: –5.27 (Me2Si); 18.37
(CMe3); 24.64 (CH3C(4)); 25.96 (Me3C); 36.40 (C(5)); 55.28
(CH3O); 62.02 (C(6)); 114.04 (Ar); 123.56 (C(2)); 127.27 (Ar);
127.49 (C(3)); 129.75 (C(1)); 130.89 (Ar); 135.64 (C(4)); 158.87
(COMe). MS, m/z (Irel (%)): 332 [M]+ (95), 334 (11), 277 (18),
276 (100), 260 (22), 245 (14), 230 (11), 215 (10), 212 (15),
(s, 3 H, MeC(4)); 2.61 (t, 2 H, H2C(5), J = 7.1 Hz); 3.58 (t, 2 H,
H2C(6), J = 7.1 Hz); 3.80 (s, 3 H, MeO); 4.49 (s, 2 H, CH2Ph);
6.09 (d, 1 H, HC(3), J = 11.0 Hz); 6.46 (d, 1 H, HC(1), J = 15.4 Hz);
6.86 (d, 2 H, Ar, J = 8.7 Hz); 7.02 (dd, 1 H, HC(2), J1 = 11.0 Hz,
J2 = 15.4 Hz); 7.35 (m, 7 H, Ar). 13C NMR, δ: 24.54 (MeC(4));
33.21 (C(5)); 55.26 (MeO); 68.60 (C(6)); 72.63 (CH2Ph); 113.81
(Ar); 125.30 (C(2)); 126.21 (Ar); 127.05 (C(3)); 128.55, 129.17
(Ar); 130.46 (C(1)); 136.82 (C(4)); 137.99 (Ar); 159.17 (COMe).
(1E,3Z)ꢀ6ꢀ(4ꢀMethoxybenzyloxy)ꢀ1ꢀ(4ꢀmethoxyphenyl)ꢀ4ꢀ
methylhexaꢀ1,3ꢀdiene (4d). Dehydroxylation of dienol 8d by
method A similarly to that described for dienols 8a—c gave
a mixture of dienes 4d, 9d, and 10d in ~50% yield in the ratio
~10 : 5 : 1. Dehydroxylation of dienol 8d by method B gave diene
4d containing ~8% of E,Eꢀisomer 11d. Analytically pure 4c was
isolated by flashꢀchromatography as colorless viscous oil with
Rf 0.60 (system 1). HRMS (m/z), found: 339.1956 [M + H]+;
356.2219 [M + NH4]+; 361.1771 [M + Na]+. C22H26O3. Calcuꢀ
lated: 339.1955 [M + H]+; 356.2220 [M + NH4]+; 361.1774
[M + Na]+. UV, λmax/nm (ε): 228 (22000), 303 (45300). IR,
ν/cm–1: 3028, 3000, 2952, 2836, 1748, 1684, 1652, 1604, 1584,
1508, 1484, 1456, 1440, 1420, 1360, 1300, 1248, 1176, 1096,
1036, 960, 848, 816, 756, 668. 1H NMR, δ: 1.89 (s, 3 H, MeC(4));
2.62 (t, 2 H, H2C(5), J = 7.2 Hz); 3.59 (t, 2 H, H2C(6),
J = 7.2 Hz); 3.80, 3.83 (both s, 3 H each, MeO); 4.50 (s, 2 H,
CH2Ph); 6.05 (d, 1 H, HC(3), J = 10.9 Hz); 6.43 (d, 1 H,
HC(1), J = 15.4 Hz); 6.88 (d, 4 H, Ar, J = 8.4 Hz); 6.90 (dd, 1 H,
HC(2), J1 = 10.9 Hz, J2 = 15.4 Hz); 7.30 (d, 2 H, Ar, J = 8.3 Hz);
7.34 (d, 2 H, Ar, J = 8.3 Hz). 13C NMR, δ: 24.35 (MeC(4));
33.05 (C(5)); 55.12, 55.15 (MeO); 68.50 (C(6)); 72.48 (CH2Ph);
113.68, 113.94 (Ar); 123.28 (C(2)); 127.24, 127.42 (Ar); 129.05
(C(3)); 129.90 (C(1)); 130.47, 130.71 (Ar); 135.33 (C(4)); 158.22,
159.05 (COMe).
(3Z,5E)ꢀ3ꢀMethylꢀ6ꢀphenylhexaꢀ3,5ꢀdiеnꢀ1ꢀol (3a). A. A soluꢀ
tion of Bu4NF in THF (1 M, 2 mL) was added to a solution
of diene 4a (0.15 g, 0.496 mmol) in THF (10 mL) and the mixꢀ
ture was stirred for 50 min at ~20 °C (TLC monitoring). Then,
H2O (5 mL) was added to the mixture, which was extracted
with TBME. After usual treatment of combined extracts, the
residue was subjected to chromatography on SiO2 (10 g). The
gradient elution from hexane to TBME (to 60% of the latter)
gives pure (NMR data) dienol 3a in 80% yield, physicoꢀchemꢀ

2092
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 11, November, 2010
Grigorieva et al.
ical parameters agree with those for the samples described
earlier.10,15
(2E,4E)ꢀ6ꢀEthoxyꢀ6ꢀ(4ꢀmethoxyphenyl)ꢀ3ꢀmethylhexaꢀ2,4ꢀ
dienal (15). A solution of freshly prepared dienal 12b (0.11 g,
0.5 mmol) in 95% aq. EtOH (5 mL) was added to a stirred
solution of AgNO3 (0.17 g, 1 mmol) in H2O (0.5 mL) at ~20 °C.
The reaction mixture was cooled to –15 °C, followed by a dropꢀ
wise addition of a solution of KOH (56 mg, 1 mmol) in H2O
(2 mL). A suspension formed was stirred for 30 h at ~20 °C,
a precipitate formed was filtered off, a solution of KOH (0.5 M)
was added to the filtrate to pH 9, and a suspension formed was
again filtered off. The filtrate was diluted with H2O (7 mL) and
extracted with TBME (3×7 mL). The aqueous layer was acidiꢀ
fied with dilute (1 : 4) HCl to pH 2 and extracted with TBME
(3×10 mL). Usual treatment of combined extracts from the acidꢀ
ic solution gave a complex mixture (10 mg) of the reaction prodꢀ
ucts (1H NMR spectroscopic data), which was discarded. Usual
treatment of combined extracts from the alkaline solution and
chromatography of the residue (94 mg) on SiO2 (5 g) with the
gradient elution from hexane to TBME (to 50% of the latter)
yielded dienal 15 (33 mg) containing ~12% of (2Z)ꢀisomer
(1H NMR spectroscopic data). Dienal 15, HRMS (m/z), found:
283.1277 [M + Na]+. C16H20O3. Calculated: 283.1305 [M + Na]+.
B. N,NꢀDimethylaniline (1.51 mL, 11.92 mmol) and anꢀ
hydrous AlCl3 (1.19 g, 8.94 mmol) were sequentially added to
a vigorously stirred solution of diene 4c (0.9 g, 2.98 mmol) in
CH2Cl2 (14 mL) at 0 °C (Ar). The reaction mixture was stirred
for 1 h, followed by a dropwise addition of dilute (1 : 10) HCl
(25 mL), the layers formed were separated after 10 min. The
aqueous layer was extracted with CH2Cl2 (3×15 mL). The resiꢀ
due after usual treatment of combined extracts contained a mixꢀ
ture of dienol 3a and its isomer (E,E)ꢀ11a in the ratio ~97 : 3
(1H NMR spectroscopic data). Flashꢀchromatography of this
mixture on SiO2 (25 g) with the gradient elution from hexane to
TBME (to 60% of the latter) gives analytically pure (NMR data)
dienol 3a in 81% yield, physicoꢀchemical parameters agree with
those described above.
(3Z,5E)ꢀ6ꢀ(4ꢀMethoxyphenyl)ꢀ3ꢀmethylhexaꢀ3,5ꢀdiеnꢀ1ꢀol
(3b) was obtained similarly to dienol 3a from diene 4b by method
A. The yield after flashꢀchromatography was 80%, physicoꢀchemꢀ
ical parameters agree with those for the samples described
earlier.10 Deprotection of diene 4d by method B similarly to
that described above for diene 4a gave a mixture of dienol 3b
and its (3E,5E)ꢀisomer in the ratio 4 : 1 (1H NMR spectroꢀ
scopic data).
(3Z,5E)ꢀ3ꢀMethylꢀ6ꢀphenylhexaꢀ3,5ꢀdienal (12a). The oxiꢀ
dant IBX (14)19,20 (867 mg, 3.12 mmol) was added in one porꢀ
tion to a stirred solution of dienol 3a (387 mg, 2.06 mmol) in
DMF (15 mL) at ∼20 °C under argon and with protection from
light and the mixture was stirred for 2 h (TLC monitoring),
followed by addition of TBME (50 mL). The mixture was filꢀ
tered through SiO2 (10 g) and the adsorbent was washed with
TBME (75 mL). Combined filtrates were washed with saturated
aq. Na2SO4 (3×50 mL), dried with anhydrous Na2SO4, concenꢀ
trated on a rotary evaporator, dried in vacuum at 1 Torr at ~20 °C
until the weight was constant to obtain dienal 12a (390 mg,
~100%) as a light yellow light oil; the admixture of (E,E)ꢀisomer
in the sample formed did not exceed 1—2% (1H NMR spectroꢀ
scopic data). Dienal 12a is unstable on heating. HRMS (m/z),
found: 209.0941 [M + Na]+. C13H14O. Calculated: 209.0937
[M + Na]+. UV, λmax/nm (ε): 297 (25960), 317 (20150). IR,
ν/cm–1: 3028, 2968, 2924, 2852, 2728, 2368, 2328, 1720, 1668,
1616, 1596, 1496, 1448, 1436, 1384, 1356, 1300, 1208, 1124,
1072, 1048, 1016, 960, 748, 692. 1H NMR, δ: 1.94 (s, 3 H,
MeC(3)); 3.37 (d, 2 H, H2C(2), J = 2.35 Hz); 6.31 (d, 1 H,
HC(4), J = 10.9 Hz); 6.56 (d, 1 H, HC(6), J = 15.4 Hz); 6.90
(dd, 1 H, HC(5), J1 = 10.9 Hz, J2 = 15.4 Hz); 7.38 (m, 5 H, Ph);
9.66 (t, 1 H, HC(1), J = 2.35 Hz). 13C NMR, δ: 24.88 (MeC(3));
47.80 (C(2)); 123.93 (C(5)); 126.27, 127.49, 128.55 (Ar); 129.06
(C(3)); 129.99 (C(4)); 132.46 (C(6)); 137.28 (Ar); 198.38 (C(1)).
(3Z,5E)ꢀ6ꢀ(4ꢀMethoxyphenyl)ꢀ3ꢀmethylhexaꢀ3,5ꢀdienal (12b)
was obtained similarly to dienal 12a from dienol 3b, the yield
was ~100%, Rf 0.55 (system 1). 1H NMR, δ: 1.92 (s, 3 H,
MeC(3)); 3.35 (d, 2 H, H2C(2), J = 2.2 Hz); 3.83 (s, 3 H, MeO);
6.28 (d, 1 H, HC(4), J = 10.9 Hz); 6.50 (d, 1 H, HC(6), J = 15.5 Hz);
6.76 (dd, 1 H, HC(5), J1 = 10.9 Hz, J2 = 15.5 Hz); 6.87 (d, 2 H,
Ar, J = 8.7 Hz); 7.34 (d, 2 H, Ar, J = 8.7 Hz); 9.65 (t, 1 H,
HC(1), J = 2.2 Hz). 13C NMR, δ: 24.90 (MeC(3)); 47.89 (C(2));
55.29 (MeO); 114.13 (Ar); 122.06 (C(5)); 127.57, 127.76 (Ar);
130.19 (C(4)); 130.24 (C(3)); 130.99 (C(6)); 159.31 (COMe);
198.61 (C(1)). Unstable dienal 12b was immediately used in
subsequent oxidation.
1
UV, λmax/nm (ε): 226 (12100), 278 (15130). H NMR, δ: 1.23
(t, 3 H, CH2CH3, J = 7.0 Hz); 2.24 (s, 3 H, MeC(3)); 3.46
(m, 2 H, CH2CH3); 3.81 (s, MeO); 4.86 (d, 1 H, HC(6),
J = 4.9 Hz); 5.96 (d, 1 H, HC(2), J = 8.1 Hz); 6.35 (dd, 1 H,
HC(5), J1 = 15.1 Hz, J2 = 4.9 Hz); 6.42 (d, 1 H, HC(4),
J = 15.1 Hz); 6.91 (d, 2 H, Ar, J = 8.7 Hz); 7.26 (d, 2 H, Ar,
J = 8.7 Hz); 10.10 (d, 1 H, HC(1), J = 8.1 Hz). 13C NMR, δ:
13.09 (CH3CH2); 15.24 (MeC(3)); 55.28 (MeO); 64.05 (CH3CH2);
81.45 (C(6)); 114.11, 128.18 (Ar); 129.95, 133.03 (C(2), C(5));
138.60 (C(4)); 153.87 (C(3)); 159.45 (COMe); 191.34 (C(1)).
(3Z,5E)ꢀ3ꢀMethylꢀ6ꢀphenylhexaꢀ3,5ꢀdienoic acid (13a).
Dimethyl sulfoxide (11 mL) and a solution of NaH2PO4•2 H2O
(839 mg, 5.38 mmol) in H2O (6.64 mL) were sequentially added
to a solution of freshly prepared dienal 12a (360 mg, 1.93 mmol)
in THF (13 mL). The mixture was cooled to 0 °C, followed by
a dropwise addition of NaClO2 (318.6 mg, 5.52 mmol) solution
in H2O (6.64 mL), and the mixture was stirred for 2.5 h at 0 °C
(TLC monitoring) with protection from light. After addition of
TBME (100 mL), the layers were separated. The organic layer
was extracted with 10% aq NaOH (2×50 mL). The combined
alkaline extracts were acidified at 0 °C with dilute (1 : 3) HCl to
pH 2, then, they were extracted with TBME (3×50 mL). Usual
treatment of combined extracts yielded acid 13a (264 mg, 69%)
containing less than 2% of (E,E)ꢀisomer (1H NMR spectroscopꢀ
ic data). Acid 13a is a light yellow crystalline compound, m.p.
105—107 °C (from hexane—TBME (3 : 1)); Rf 0.48 (system 1),
0.42 (hexane—acetone (3 : 1)). HRMS (m/z), found: 225.0882
[M + Na]+. C13H14O2. Calculated: 225.0886 [M + Na]+. UV,
λ
max/nm (ε): 301.4 (44190). IR, ν/cm–1: 3028, 3012, 2968, 2924,
2900,2400, 1708, 1596, 1540, 1520, 1492, 1448, 1412, 1296, 1228,
964, 928, 800, 692, 624. 1H NMR, δ: 2.01 (s, 3 H, MeC(3)); 3.33
(s, 2 H, H2C(2)); 6.22 (d, 1 H, HC(4), J = 10.8 Hz); 6.54 (d, 1 H,
HC(6), J = 15.4 Hz); 6.95 (dd, 1 H, HC(5), J1 = 10.8 Hz,
J2 = 15.4 Hz); 7.32 (m, 5 H, Ph). 13C NMR, δ: 24.55 (MeC(3));
37.92 (C(2)); 124.28 (C(5)); 126.39; 127.48, 128.60 (Ar);
129.48 (C(4)); 130.67 (C(3)); 132.34 (C(6)); 137.49 (COMe);
177.24 (C(1)).
(3Z,5E)ꢀ6ꢀ(4ꢀMethoxyphenyl)ꢀ3ꢀmethylhexaꢀ3,5ꢀdienoic
acid (13b) was obtained similarly to acid 13a from dienal 12b,
the yield was 45%, the content of (E,E)ꢀisomer in the sample

Strobilurins
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 11, November, 2010 2093
was <3% (1H NMR spectroscopic data), Rf 0.62 (system 1), 0.42
(system 2). HRMS (m/z), found: 233.1172 [M + H]+; 255.0997
[M + Na]+. C14H16O3. Calculated: 233.1175 [M + H]+; 255.0992
[M + Na]+. UV, λmax/nm (ε): 201 (13000), 297 (23000). IR,
ν/cm–1: 3028, 3012, 2936, 2840, 2400, 1708, 1604, 1576, 1508,
1464, 1440, 1420, 1304 1248, 1228, 1176, 1032, 964, 932, 848,
800, 676, 624. 1H NMR, δ: 1.96 (s, 3 H, MeC(3)); 3.32 (s, 2 H,
H2C(2)); 3.82 (MeO); 6.19 (d, 1 H, HC(4), J = 10.0 Hz); 6.49
(d, 1 H, HC(6), J = 15.2 Hz); 6.82 (dd, 1 H, HC(5), J1 = 10.0 Hz,
J2 = 15.2 Hz); 6.86 (d, 2 H, Ar, J = 10.3 Hz); 7.30 (d, 2 H, Ar,
J = 10.3 Hz). 13C NMR, δ: 24.48 (MeC(3)); 37.84 (C(2)); 55.29
(MeO); 114.08 (Ar); 122.33 (C(5)); 127.58 (Ar); 129.63 (C(3));
129.82 (C(4)); 131.91 (C(6)); 159.20 (COMe); 177.28 (C(1)).
Methyl (3Z,5E)ꢀ3ꢀmethylꢀ6ꢀphenylhexaꢀ3,5ꢀdienoate (2a)
was obtained by treatment of acid 13a with an ethereal solution
of CH2N2 at 0 °C according to the standard procedure. The yield
was ~100%, stereochemical purity was 98% (1H NMR spectroꢀ
scopic data), light yellow viscous oil solidified at –18 °C; Rf 0.57
(system 1), 0.55 (hexane—acetone, 3 : 1). HRMS (m/z), found:
239.1041 [M + Na]+. C14H16O2. Calculated: 239.1043 [M + Na]+.
UV, λmax/nm (ε): 308.5 (33750). IR, ν/cm–1: 3028, 2952, 2916,
2848, 2328, 1732, 1644, 1596, 1520, 1492, 1448, 1436, 1328,
1256, 1192, 1164, 1108, 1028, 1008, 960, 876, 748, 692. 1H NMR,
δ: 1.96 (s, 3 H, MeC(3)); 3.31 (s, 2 H, H2C(2)); 3.72 (s, 3 H,
COOMe); 6.20 (d, 1 H, HC(4), J = 10.9 Hz); 6.53 (d, 1 H,
HC(6), J = 15.4 Hz); 6.98 (dd, 1 H, HC(5), J1 = 10.9 Hz,
J2 = 15.4 Hz); 7.30 (m, 5 H, Ph). 13C NMR, δ: 24.51 (MeC(3));
38.04 (C(2)); 51.96 (OMe); 124.49 (C(5)); 126.33, 127.39, 128.58
(Ar); 129.02 (C(4)); 131.37 (C(3)); 132.00 (C(6)); 137.60 (Ar);
171.39 (C(1)).
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Methyl (3Z,5E)ꢀ6ꢀ(4ꢀmethoxyphenyl)ꢀ3ꢀmethylhexaꢀ3,5ꢀdiꢀ
enoate (2b) was obtained by treatment of acid 13b with an etheꢀ
real solution of CH2N2 at 0 °C according to the standard proceꢀ
dure. The yield was ~100%, stereochemical purity was >98%,
Rf 0.53 (system 1). HRMS (m/z), found: 247.1334 [M + H]+;
269.1151 [M + Na]+; 285.0901 [M + K]+. C15H18O3. Calculatꢀ
ed: 247.1340 [M + H]+; 269.1159 [M + Na]+; 285.0898 [M + K]+.
UV, λmax/nm (ε): 213 (46700), 297 (48000). IR, ν/cm–1
3015, 2968, 2840, 1760, 1732, 1720, 1640, 1604, 1572, 1508,
1460, 1440, 1380, 1364, 1320, 1304, 1280, 1252, 1192,
:
1
1176, 1160, 1112, 1032, 996, 972, 820, 748. H NMR, δ: 1.94
(s, 3 H, MeC(3)); 3.29 (s, 2 H, H2C(2)); 3.72, 3.82 (both s,
3 H each, MeO); 6.16 (d, 1 H, HC(4), J = 10.3 Hz); 6.18
(d, 1 H, HC(6), J = 15.4 Hz); 6.83 (dd, 1 H, HC(5), J1 = 10.3 Hz,
J2 = 15.4 Hz); 6.87 (d, 2 H, Ar, J = 8.7 Hz); 7.36 (d, 2 H, Ar,
J = 8.7 Hz). 13C NMR, δ: 24.41 (MeC(3)); 37.98 (C(2));
51.89, 55.25 (OMe); 114.04 (Ar); 122.52 (C(5)); 127.49 (Ar);
129.18 (C(4)); 130.03 (C(3)); 131.51 (C(6)); 159.13 (COMe);
171.47 (C(1)).
23. E. Dalcanale, F. Montanari, J. Org. Chem., 1986, 51, 567.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 07ꢀ03ꢀ00454).
Received September 23, 2010