Synthetic Strategy for Tetraphenyl-Substituted All-E-Carotenoids with Improved Molecular Properties

Article abstract of DOI:10.1002/ejoc.202000130

The synthetic method of tetraphenyl-substituted all-E-carotenes 1 with improved properties of antioxidant and molecular electronic conductance was developed through the formation of tetraphenyl-substituted all-E-apocarotenedial 4. The synthesis highlighted the preparation of novel subunits containing phenyl substituent(s) with E-configuration starting from the key (E)-4-chloro-2-phenylbut-2-enal (10), utilizing conjugation effect with formyl group or easy recrystallization of sulfone compounds. Sulfone-mediated coupling methods of Julia and modified Julia–Kocienski olefinations utilizing the subunits were demonstrated to produce tetraphenyl-substituted apocarotenedials 4. The major all-E-forms (73–85 % selectivity) were easily purified by SiO₂ chromatography and trituration with Et₂O due to the presence of the polar formyl groups. The olefination of all-E-apocarotenedials 4 and Wittig salt 5 provided all-E-9,9',13,13'-tetraphenylcarotenes 1.

Full text of DOI:10.1002/ejoc.202000130

A Journal of
Accepted Article
Title: Synthetic strategy for tetraphenyl-substituted all-E-carotenoids
with improved molecular properties
Authors: Boram Lim, Hyunuk Jung, Hyebin Yoo, Myeongnam Park,
Huijeong Yang, Wook-Jin Chung, and Sangho Koo
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202000130
Link to VoR: http://dx.doi.org/10.1002/ejoc.202000130
Supported by

10.1002/ejoc.202000130
European Journal of Organic Chemistry
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Synthetic strategy for tetraphenyl-substituted all-E-carotenoids
with improved molecular properties
Boram Lim,[a] Hyunuk Jung,[b] Hyebin Yoo,[b] Myeongnam Park,[b] Huijeong Yang,[b] Wook-Jin Chung,[b]
,
and Sangho Koo*[a] [b]
[a]
[b]
Dr. B. Lim, Prof. Dr. S, Koo*
Department of Chemistry
Myongji University
Myongji-Ro 116, Cheoin-Gu, Yongin, Gyeonggi-Do, 17058, Korea
E-mail: sangkoo@mju.ac.kr
Homepage: http://www.kooslab.org
H. Jung, H. Yoo, M. Park, H. Yang, Prof. Dr. W.-J. Chung
Department of Energy Science and Technology
Myongji University
Myongji-Ro 116, Cheoin-Gu, Yongin, Gyeonggi-Do, 17058, Korea
Supporting information for this article is given via a link at the end of the document.
Abstract: The synthetic method of tetraphenyl-substituted all-E-
carotenes 1 with improved properties of antioxidant and molecular
electronic conductance was developed through the formation of
tetraphenyl-substituted all-E-apocarotenedial 4. The synthesis
highlighted the preparation of novel subunits containing phenyl
substituent(s) with E-configuration starting from the key (E)-4-chloro-
2-phenylbut-2-enal (10), utilizing conjugation effect with formyl group
or easy recrystallization of sulfone compounds. Sulfone-mediated
coupling methods of Julia and modified Julia-Kocienski olefinations
utilizing the subunits were demonstrated to produce tetraphenyl-
substituted apocarotenedials 4. The major all-E-forms (73~85%
selectivity) were easily purified by SiO2 chromatography and
trituration with Et2O due to the presence of the polar formyl groups.
The olefination of all-E-apocarotenedials 4 and Wittig salt 5 provided
all-E-9,9´,13,13´-tetraphenylcarotenes 1.
Introduction
Carotenoids are characterized by extensive conjugation of
carbon-carbon double bonds, which affords visible transition
between HOMO and LUMO levels of -electrons with small
energy gap.[1] It also allows delocalization of -electrons to offer
improved electronic conductance.[2] Carotenoids are thus utilized
as natural red dyes for foodstuffs and may serve as efficient
organic molecular wires as demonstrated by the energy-
transferring efficiency in photosynthetic system.[3] Instability of
carotenoids under aerobic condition, which inversely explains the
antioxidant activity of carotenoids,[4] was a major problem in
utilization of these valuable natural compounds for organic
electronic materials. However, the instability was proven to be
mitigated by replacement of the methyl groups along the polyene
chain by phenyl substituents,[5] which not only improved the
antioxidant activity in scavenging reactive oxygen species,[6] but
also diversified the conducting ability of the chain by differing
electronic nature of the substituent group in the phenyl rings.[7]
Scheme 1. Synthetic plan for 9,9´,13,13´-tetraphneyl substituted carotene 1.
The conductance of single molecular wires, which can be
measured by a STM (scanning tunneling microscopy) break
junction method,[8] is largely dependent on the intrinsic decay
constant as well as the length of the chain.[9] We demonstrated
that the conductance can be modulated for 9,9´,13,13´-
tetraphenyl carotene 1 (Scheme 1) by changing the substituent
groups for improving intrinsic decay constant, while maintaining
the same chain length.[10] It was thus anticipated that carotenoid 1
would serve as efficient organic molecular wires with variable
conductance, which may find wide applications in the areas of
bioelectronics and photovoltaic cells etc.
1
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Scheme 2. Disconnection approaches to diacetal 6 of fully conjugated all-(E)- polyenedial 4.
The synthesis of 9,9´,13,13´-tetraphenyl carotene 1 was not
easy especially in controlling all-E configuration of the carbon-
carbon double bonds. It seemed that steric interactions between
bulky phenyl-substituents and polyene chain enforced not only
high dihedral angles for the phenyl-substituents,[10] but also
various Z-configurations of the carbon-carbon double bonds. We
herein report our strategy for synthesizing 9,9´,13,13´-tetraphenyl
carotene 1 with the para-phenyl substituent X of different
electronic nature. Special focus was on the controlling all-E
configuration of the carotenoid by utilizing conjugation effect with
carbonyl groups and easy purification by the polar end groups.
carotene 1 was thus revised through the formation of tetraphenyl-
substituted all-E-polyenedial 4 (Scheme 1). The Wittig olefination
between 4 and 4-(methylthio)benzyl phosphonium bromide 5 was
conceived to produce all-(E)-9,9´,13,13´-tetraphenylcarotene 1.
The synthesis of diacetal 6 of all-E polyenedial 4 was designed
based on the sulfone-mediated coupling and olefination strategy
(Scheme 2). Allylic phenyl sulfone 7 now became the key building
block, which would couple with dialdehyde 3.[14] Diacetal 6 was
also planned to be synthesized by the “one-pot” Julia-Kocienski
olefination between allylic benzothiazolyl (BT) sulfone 8 and 2,7-
diphenyl-2,4,6-octatrienedial (9).[15] These newly devised building
blocks 7, 8, and 9 were all planned to be synthesized from the
common intermediate, 4-chloro-2-phenylbut-2-enal (10), which
was proposed to be prepared by CuCl2-mediated oxidative
opening reaction of vinyl epoxide 11 with phenyl substitution.
Results and Discussion
The
synthesis
commenced
from
para-substituted
The synthesis of 9,9´,13,13´-tetraphenyl-substituted carotene 1
was initially designed based on the sulfone-mediated olefination
method[11] between allylic sulfone 2 with a phenyl substitution and
2,7-diphenyloct-4-enedial 3 (Scheme 1). The key building block 2
was prepared in a stereo-selective manner and purified by facile
crystallization.[12] As an extension of biomimetic approach utilizing
the basic C5 isopentenyl building block,[13] the corresponding unit
with phenyl substitution was prepared and transformed to dienyl
sulfone 2.[12] The 2:1 coupling between 2 and 3, and protection of
the resulting hydroxyl groups, followed by olefination through the
double elimination of sulfone and protected hydroxyl groups
produced the conjugated polyene compound.[11] It was, however,
unfortunate that carotene 1 was not able to be clearly identified
acetophenones of different electronic nature (X = MeO, Me, H, Cl).
Alpha-bromination was efficiently carried out using N-
bromosuccinimide with catalytic TMS·OTf.[16] Vinyl Grignard
addition to the carbonyl group produced bromohydrins 12 in 42–
65% yields (Table 1), which were then treated with base to lead
to vinyl epoxide 11. CuCl2-promoted regioselective oxidative ring
opening of vinyl epoxides 11 was the key reaction for the
preparation of chloro-aldehydes 10.
The reaction was best carried out in the presence of LiCl at 80 °C
for 1.5 h (entries 2, 5, and 9). Unlike to the case of vinyl epoxide
with methyl substitution,[17] oxidation of the ring opening product
was sluggish at 25 °C and allylic alcohols 13 were obtained
exclusively as a mixture of E/Z isomers (entries 1, 4, and 8). The
oxidation was progressed at 25 °C in the case of electron-rich
MeO-substitution, and the reaction was better performed at 25 °C
to reduce the amount of dechlorination product 14 (entry 6). The
rate of oxidation was also dependent on the presence of LiCl, and
a mixture of allylic alcohol 13 and conjugated aldehyde 10 was
obtained in the absence of LiCl even at 80 °C (entry 3). It was
unavoidable to obtain dechlorinated products 14. Nevertheless, it
was satisfactory that conjugated aldehydes 10 were exclusively E
form by effective conjugation and obtained in the yield ranges of
54~64%.
1
due to the presence of multiple stereoisomers (see H NMR in
page S-110 of Supporting Information). Unlike to the synthesis of
carotene with 13,13´-diphenyl substitution,[7] the carotene with
9,9′,13,13′-tetraphenyl substitution was difficult in producing all-E
configuration, presumably due to the steric interactions with the
phenyl substituents.
It was envisioned that conjugated polyenedials
4 with
tetraphenyl substitution might be obtained in all-E configuration
by effective conjugation with terminal formyl groups. The polar
end groups would at least allow purification of the all-E-isomer by
silica gel chromatographic separation. The synthetic plan for
2
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Table 1. Synthesis of chloro-aldehydes 10 through preparation and oxidative chlorination of phenyl-substituted vinyl epoxides 11.
Entry
Compound
X
H
%Yield 12[a]
Condition (Temp, time)
25 °C, 2 d
%Yield 13 (E:Z)[b]
% Yield E-10[b]
%Yield E-14[b]
1
a
58
77 (3:2)
-
-
2
80 °C, 1.5 h
80 °C, 1.5 h
25 °C, 2 d
-
59
22
-
8
3[c]
4
28 (3:2)
16
-
b
c
d
Me
MeO
Cl
62
42
65
48 (3:2)
5
80 °C, 1.5 h
25 °C, 2 d
-
58
54
40
-
8
6
-
14
20
-
7
80 °C, 1.5 h
25 °C, 2 d
-
8
66 (2:1)
-
9
80 °C, 1.5 h
64
13
[a] Purified (by SiO2 chromatography) yield 12 of vinyl Grignard addition to -bromoacetophenone. [b] Purified (by SiO2 chromatography) yields after formation and
oxidative chlorination of vinyl epoxides 11 from vinyl carbinols 12. Compounds 10 and 14 were isolated as a mixture and the yields were calculated based on the
1H NMR ratio. [c] LiCl (1 equiv.) was not added.
(E)-4-Chloro-2-phenylbut-2-enals
(10)
being
prepared
yield (X = Me). Deprotection of neopentyl glycol by aqueous HCl
with oxalic acid produced all-(E)-2,7-diphenylocta-2,4,6-
trienedials 9 in 90% (X = H) and 74% yields (X = Me), which
establishes conjugation of the formyl groups by means of the
polyene.
successfully, their acetals 15 were utilized for the preparation of
the key building blocks 7, 8, and 9 (Scheme 3). Sulfonylation by
NaSO2Ph in DMF produced the corresponding (E)-allylic
benzenesulfones 7 (X = H, Me, MeO, Cl) in 35–46% yields from
chloro-aldehydes 10 in 2 steps (Table 2). The solid products 7
were easily purified by recrystallization with EtOAc/hexane to give
E-configuration. We also demonstrated one-pot Julia-Kocienski
olefination for two cases (X = H, Me) for comparison with double
elimination of the original Julia olefination (entries 1 and 2). Allylic
BT-sulfones 8 were prepared in 60% yield (X = H) and 75% yield
(X = Me) by sufurylation of 2-mercaptobenzothiazole in acetone
with K2CO3 as base, followed by sulfur oxidation using mono
peroxyphthalic acid, generated in situ by the reaction of urea-H2O2
(UHP) and phthalic anhydride in MeCN.[18] Allylic BT-sulfones 8
were consisted of a 3~4:1 mixture of E/Z-isomers, but the E-form
can be easily purified by trituration with MeOH.
Novel 2,7-diphenyl-2,4,6-octatrienedials 9 are useful building
blocks for the preparation of 13,13'-diphenyl carotenes not only
by Julia-Kocienski olefination, but also by Wittig reaction.
Dimerization of acetal-protected allylic chlorides 15 by Na2S in
DMF, followed by sulfur oxidation using mono peroxyphthalic acid
(UHP and phthalic anhydride in MeCN) produced the
corresponding allylic sulfones 16 in 29% (X = H) and 22% yields
(X = Me) in 3 steps from chloro-aldehydes 10. The 4:1 (E,E:E,Z)
stereoisomeric ratio of 16 was believed to be sterically controlled
by the substituents, but all-E form can be easily purified by
trituration with MeOH as white solid. Ramberg-Bäcklund reaction
of allylic sulfones 16 under the modified Meyers’ condition (KOH
[20]
and t-BuOH)[19] with chlorinating agent C2Cl6
in CH2Cl2
Scheme 3. Preparation of allylic sulfones 7, 8 and conjugated trienedials 9 from
acetal 15.
produced conjugated trienes 17 in 85% yield (X = H) and 76%
3
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10.1002/ejoc.202000130
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configuration as the major product. The yields of all-E-
heptaenedial 4 were notified in Table 4 (inside the parentheses).
It was noticeable that non-all-E-configurations were still obtained
in the fully conjugated polyenedials, which were not isomerized to
all-E form, but decomposed under forcing thermal or acidic
conditions. Nevertheless, all-E-products were separable by SiO2
chromatography and further purified by trituration from Et2O
Table 2. Reaction yields (%) of the compounds according to Scheme 3.
Entry
X
E-7[a]
8 (E:Z)[a]
16 (E,E:E,Z)[a]
17
19
1
2
3
4
a: H
42
35
46
43
60 (4:1)
75 (3:1)
29 (4:1)
22 (4:1)
85
76
90
74
b: Me
c: MeO
d: Cl
[a] Yields starting from chloro-aldehydes 10.
The synthesis of 2,7-diphenyloct-4-enedials 3 (Z = CHO, X = H,
Me, MeO) has been reported.[14] Its p-chlorophenyl analogue 3d
(Z, CHO, X = Cl) was prepared uneventfully according to the
above procedure as demonstrated in Scheme 4. The LDA-
promoted 2:1 coupling between ethyl p-chlorophenylacetate and
1,4-dibromobut-2-ene at -78 °C produced diester 18d in 90% yield.
LAH reduction to diol 19d (75% yield) and Swern oxidation (oxalyl
chloride, DMSO, and Et3N) provided dial 3d in 84% yield.
Scheme 4. Preparation of 2,7-di(p-chlorophenyl)oct-4-enedial 3d.
Scheme 5. Synthesis of conjugated polyenedial 4 by sulfone-mediated coupling
and double elimination.
All the required building blocks were ready to assemble
tetraphenyl-substituted conjugated polyenedials 4. Scheme 5 and
Table 3 respectively delineated the sulfone olefination strategy
utilizing the double elimination method[11] and the yield of each
Table 3. %Yield of the compounds according to the scheme 5.
Entry
X
20
6
4[a]
reaction
for
the
preparation
of
all-(E)-2,6,11,15-
tetraphenylhexadeca-2,4,6,8,10,12,14-heptaenedials 4 (X = H,
Me, MeO, Cl). Coupling was initiated from allylic sulfone 7 by
deprotonation with n-BuLi, and reaction with dial 3 produced diols
20 in 58~84% yields. The reaction was carried out at -78 °C for
several hours and quenched with water to prevent both possible
retro-reaction at higher temperature and hydrolysis of the acetal
groups under acidic condition. The hydroxyl groups in the
coupling product 20 was protected with ethyl vinyl ether in CH2Cl2
by catalytic pyridinium p-toluene sulfonate (PPTS) to give 1-
ethoxyethyl ethers (EE) 21, which upon the elimination condition
(KOMe, benzene reflux) for benzenesulfonyl (PhSO2) and 1-
ethoxyethoxy (EEO) groups produced fully conjugated polyene
diacetal 6 in 76~90% yields (2 steps from diol 20). The all-E-
isomer was the major product from this reaction sequence. Pars
pro toto, the stereo-isomeric ratio was analyzed by HPLC for 6b.
Three peaks were observed in the ratio of 6.4: 1.0: 0.1 with all-E-
configuration as the major product (85%, calculated by the ratio).
Hydrolysis of the acetal groups was effective by addition of
oxalic acid in aqueous acidic THF solution. Tetraphenyl-
substituted heptaenedials 4 were obtained in 73~88% yields.
Three stereo-isomers were generally obtained with all-E-
1
2
3
4
a: H
84
72
71
58
81
88 (37)
75 (41)
73 (48)
77 (40)
b: Me
c: MeO
d: Cl
76[b]
90
80
[a] The recrystallization yield of all-(E)-apocarotenedial 4 in parenthesis. [b] The
stereo-isomeric ratio was measured by HPLC as 6.4: 1.0: 0.1 with the all-E
major.
2,6,11,15-Tetraphenylhexadeca-2,4,6,8,10,12,14-
heptaenedials 4 (X = H, Me) were also prepared by the Julia-
Kocienski olefination between allylic BT-sulfone 8 and trienedial 9
as described in Scheme 6. Table 4 reported the isolated yield of
each reaction product and its E/Z stereoisomeric ratio by HPLC.
Julia-Kocienski olefination was carried out with KHMDS base at –
78 °C for 2 h and then at room temperature for overnight to
produce fully conjugated polyene diacetal 6a (X = H) in 33% yield
and 6b (X = Me) in 42% yield with all-E product as the major
product. The all-E selectivity was compared with that of the
previous double elimination method in the case of 6b (85% vide
4
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supra). Three peaks were observed in the ratio of 11: 1: 3 with 73% CH2Cl2/MeOH or even acetone) due to lower solubility than the Z-
all-E-configuration for 6b by Julia-Kocienski olefination. The
double elimination method was slightly better in producing more
all-E product 6b than the Julia-Kocienski olefination.
isomers. The isolated yields were reported in Table 5, and
analytical samples were prepared after several trituration
procedures.
Deprotection of acetal was carried out by addition of oxalic acid
in aqueous acidic (1M HCl) THF solution to provide tetraphenyl-
substituted heptaenedials 4a (X = H) in 60% yield and 4b (X = Me)
in 38% yield. Three stereoisomers were obtained again with all-
E-configuration as the major product. The E/Z-isomeric ratio was
measured by HPLC for 4b as 4: 1: 0.2. The all-E selectivity for 4b
was calculated to be 77%, which was almost same as that for 6b
(73%) within experimental errors. It seemed that aldehyde groups
did not practically improve the all-E selectivity for the
poly(hepta)ene chain by conjugation upon hydrolysis of the acetal
groups. The polar aldehyde groups rather allowed facile
separation of the all-E product by SiO2 chromatography and
further purification by trituration from Et2O.
The UV absorption wave lengths for 9,9´,13,13´-tetraphenyl all-
E-apocarotenedials 4 and all-E-carotenes 1 were listed according
to the group X of the benzene substituents in Table 5. It is
noteworthy that the polar effect of the methoxy substituent
narrowed the energy gap between HOMO and LUMO of -
electrons to give higher UV absorption wave length for 4c and
1c.[7] The trend in UV absorption values for carotene 1, which can
be correlated with the energy gaps between HOMO and LUMO,
coincides exactly with that of the conductance values of the
molecular wire 1, measured by STM break junction method.
Scheme 7. Synthesis of tetraphenyl-substituted all-(E)-carotenes 1 from all-(E)-
polyenedial 4.
Table 5. Yield of carotenes 1 from polyenedials 4 according to the scheme 7
and their UV (max) values.
Entry
X
1 (%)[a]
46
UV (max) 4
473 nm
478 nm
491 nm
475 nm
UV (max) 1
504 nm
508 nm
513 nm
501 nm
Conductance[b]
2.99×10-4 G0
4.50×10-4 G0
4.84×10-4 G0
2.17×10-4 G0
1
2
3
4
a: H
Scheme 6. Synthesis of conjugated polyenedial 4 by Julia-Kocienski olefination.
b: Me
c: MeO
d: Cl
21
15
Table 4. %Yield and stereoisomeric ratio (HPLC) of the compounds according
to the scheme 6.
26
Entry
X
6 (all-E:Zs’)
4 (all-E:Zs’)
[a] The isolated yield of all-(E)-carotene 1 after SiO2 chromatography and
trituration with THF/MeOH (CH2Cl2/MeOH or acetone). [b] The conductance
values were taken from the reference No. [10].
1
2
a: H
33 (3: 1)
60 (11: 1: 2)
38 (4: 1: 0.2)
b: Me
42 (11: 1: 3)
Conclusion
The synthetic method of 9,9´,13,13´-tetraphenyl all-E-carotenes 1
has been developed through the formation of tetraphenyl-
substituted all-E-apocarotenedials 4. A terminal formyl group
allowed E-configuration for short (up to three) carbon-carbon
double bonds by conjugation and for long (up to seven) carbon-
carbon double bonds by easy purification using SiO2
chromatography and trituration with Et2O. The novel building
blocks 7, 8, and 9 containing phenyl substituent(s) were devised
and synthesized from the key intermediate, (E)-4-chloro-2-
phenylbut-2-enal (10), which was prepared by CuCl2/LiCl-
mediated oxidative ring opening of 2-phenyl-2-vinyloxirane (11).
The E-configuration was obtained exclusively for 9 and 10 by
The final synthesis of 9,9´,13,13´-tetraphenyl carotene 1 was
carried out by the Wittig reaction of the above tetraphenyl-
substituted all-E-apocarotenedials 4 and the phosphonium salt 5
containing a methylthio group for the application to the molecular
wires (Scheme 7). The olefination was carried out using NaH as
base at room temperature. The Wittig reaction products were
initially purified by SiO2 flash column chromatography to give an
inseparable mixture of E/Z-isomers of carotene 1. All-E-carotene
1 can be separated and purified from the above mixture by
trituration with
a proper solvent system (THF/MeOH or
5
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To a stirred solution of epoxide 11a (0.49 g, 3.35 mmol) in EtOAc (30 mL)
were added CuCl2·2H2O (0.70 g, 4.11 mmol) and LiCl (0.17 g, 4.11 mmol).
The mixture was then heated to reflux for 1.5 h and cooled to room
temperature. The mixture was diluted with hexane (100 mL), filtered
through a short pad of SiO2, and rinsed with a 1:1 solution of EtOAc and
hexane (100 mL). The filtrate was concentrated under reduced pressure
and purified by SiO2 flash chromatography to give a 7.4:1 mixture (0.40 g)
of chloroaldehyde 10a (calcd 0.36 g, 1.98 mmol, 59%) and dechlorinated
aldehyde 14a (calcd 0.04 g, 0.27 mmol, 8%) as brown oils. Data for 10a:
Rf = 0.52 (8:2 hexane:EtOAc); 1H NMR δ = 4.26 (d, J = 7.6 Hz, 2H), 6.76
(t, J = 7.6 Hz, 1H), 7.18–7.22 (m, 2H), 7.37–7.44 (m, 3H), 9.71 (s, 1H)
ppm; 13C NMR δ = 39.7, 128.5, 128.8, 129.2, 130.6, 144.6, 146.5, 192.7
ppm; IR (KBr) 3069, 2993, 2830, 2722, 1773, 1695, 1643, 1503, 1440,
1376, 1241, 1074, 974, 920, 835, 776, 694, 672 cm-1; HRMS (CI+) calcd
for C10H9ClO 181.0420, found 181.0415.
conjugation with the formyl group and for 7 and 8 by facile
recrystallization of the sulfone compound.
Diacetal 6 of tetraphenyl-substituted all-E-apocarotenedials 4
were synthesized by the sulfone-mediate coupling between allylic
sulfone 7 and dial 3 with phenyl substituent(s), followed by double
eliminations of sulfones and the protected hydroxyl groups. The
Julia-Kocienski olefination between allylic BT-sulfone 8 and
trienedial 9 with phenyl substituent(s) was also demonstrated for
the synthesis of diacetal 6. The all-E-isomer was the major
product from these reaction sequences (85~73% selectivity).
Hydrolysis of the acetal groups provided three E/Z-stereoisomeric
apocarotenedials 4, among which the major all-E-isomers were
easily purified by SiO2 chromatography and trituration with Et2O.
The olefination of all-E-apocarotenedials 4 with phosphonium salt
5 provided 9,9´,13,13´-tetraphenyl carotenes 1, from which all-E-
isomers were obtained by purification using SiO2 chromatography
and trituration with an appropriate solvent system. Tetraphenyl-
substituted all-E-carotenes 1 are stabilized molecular wires which
may find wide applications in the area of bioelectronics and
photovoltaic cells.
(E)-4-Chloro-2-phenylbut-2-en-1-ol (13a). To
a stirred solution of
epoxide 11a (0.50 g, 3.42 mmol) in EtOAc (10 mL) were added
CuCl2·2H2O (0.70 g, 4.10 mmol) and LiCl (0.17 g, 4.10 mmol). The mixture
was stirred vigorously at room temperature for 2 d and quenched with 1M
HCl solution. The mixture was extracted with Et2O, dried over anhydrous
Na2SO4, filtered and concentrated under reduced pressure. The crude was
purified by SiO2 flash column chromatography to give a 3:2 (E:Z) mixture
of chloroallylic alcohol 13a (0.48 g, 2.63 mmol) in 77% yield as yellow liquid.
Data for 13a: 1H NMR (major E-isomer) δ = 1.92 (br s, 1H), 4.01 (d, J = 7.6
Hz, 2H), 4.35 (s, 2H), 5.96 (t, J = 8.0 Hz, 1H), 7.21–7.26 (m, 2H), 7.30–
7.40 (m, 3H) ppm; (minor Z-isomer) δ = 1.92 (br s, 1H), 4.33 (d, J = 8.0 Hz,
2H), 4.61 (s, 2H), 6.06 (t, J = 8.0 Hz, 1H), 7.31–7.47 (m, 5H) ppm; 13C
NMR (major E-isomer) δ = 41.3, 66.4, 122.1, 126.5, 128.1, 128.5, 136.3,
145.2 ppm; (minor Z-isomer) δ = 39.9, 59.3, 126.1, 128.0, 128.0, 128.5,
139.4, 143.4 ppm; IR (KBr) 3369, 3070, 3037, 2935, 2868, 1702, 1499,
1452, 1222, 1113, 1018, 782, 714 cm-1; HRMS (EI) calcd for C10H11ClO
182.0498, found 182.0500.
Experimental Section
General Experimental. Reactions were performed in a well-dried flask
under Argon atmosphere unless noted otherwise. Solvents used as
reaction media were dried over pre-dried molecular sieve (4 Å) by
microwave oven. Solvents for extraction and chromatography were
reagent grade and used as received. The column chromatography was
performed with silica gel 60 (70-230 mesh) using
a mixture of
EtOAc/hexane as eluent. 1H and 13C NMR spectra were respectively
recorded on a 400 MHz and 100 MHz NMR spectrometer in deuterated
chloroform (CDCl3) with tetramethylsilane (TMS) as an internal reference
unless noted otherwise. High resolution mass spectroscopy was
performed using magnetic sector analyzer. All the new compounds were
identified by 1H and 13C NMR, IR, and High-Resolution Mass Spectroscopy.
Identity of the known compounds was established by the comparison of
their 1H and 13C NMR peaks with the authentic values
(E)-5,5-Dimethyl-2-(1-phenyl-3-(phenylsulfonyl)prop-1-en-1-yl)-1,3-
dioxane (7a). An 8:1 mixture (2.47 g) of 10a (calcd 2.24 g, 12.4 mmol) and
dechlorinated aldehyde 14a, neopentyl glycol (1.92 g, 18.5 mmol), and p-
TsOH (117 mg, 0.62 mmol) in benzene was heated to reflux for 3 h under
a reflux condenser equipped with a Dean-Stark column. The mixture was
cooled to room temperature, diluted with Et2O, washed with 1M NaOH (50
mL×3) and with brine. The aqueous layer was extracted with Et2O again.
The combined organic layer was dried over anhydrous Na2SO4, filtered,
and concentrated under reduced pressure to give the crude acetal product
(3.30 g), which was an 8:1 mixture of chloro-acetal 15a and dechlorinated
1-Bromo-2-phenylbut-3-en-2-ol (12a). To
a stirred solution of α-
bromoacetophenone (7.00 g, 35.2 mmol) in THF (70 mL) at -78 ºC was
added 1M THF solution of vinyl magnesium bromide (52.8 mL, 52.8 mmol).
The mixture was stirred vigorously at that temperature for 2.5 h and
quenched with 1M HCl solution. The mixture was extracted with Et2O,
dried over anhydrous Na2SO4, filtered and concentrated under reduced
pressure. The crude product (7.30 g) was purified by SiO2 flash column
chromatography to give vinyl carbinol 12a (4.66 g, 20.5 mmol) in 58% yield
as yellow oil. Data for 12a: Rf = 0.59 (8:2 hexane:EtOAc); 1H NMR δ = 2.70
(br s, 1H), 3.79 (A of ABq, J = 10.6 Hz, 1H), 3.81 (B of ABq, J = 10.6 Hz,
1H), 5.31 (dd, J = 10.7, 0.8 Hz, 1H), 5.41 (dd, J = 17.1, 0.8 Hz, 1H), 6.17
(dd, J = 17.1, 10.7 Hz, 1H), 7.27–7.42 (m, 3H), 7.45–7.50 (m, 2H) ppm;
13C NMR δ = 44.2, 75.6, 115.9, 125.6, 127.8, 128.5, 140.6, 142.2 ppm; IR
(KBr) 3446, 3026, 2970, 1447, 1366, 1217 cm-1; HRMS (CI+) calcd for
C10H12OBr 227.0071, found 227.0069.
acetal as yellow oil. Data for chloro-acetal 15a: Rf
= 0.72 (8:2
1
hexane:EtOAc); H NMR δ = 0.72 (s, 3H), 1.17 (s, 3H), 3.50 (d, J = 10.8
Hz, 2H), 3.68 (d, J = 10.8 Hz, 2H), 4.20 (d, J = 8.0 Hz, 2H), 5.02 (s, 1H),
6.21 (t, J = 8.0 Hz, 1H), 7.28–7.41 (m, 5H) ppm.
To a stirred solution of the above crude acetal (3.30 g) in DMF was added
benzenesulfinic acid sodium salt (2.43 g, 18.4 mmol). The mixture was
stirred at room temperature for 20 h, and then 60 ºC for 2 h. Most of solvent
was removed under reduced pressure. The crude product was dissolved
in CH2Cl2, washed with brine and with H2O, dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure. The crude product
(4.70 g) was solidified upon addition of a 1:9 mixture of EtOAc:hexane.
The product was filtered, rinsed with a 1:9 solution of EtOAc:hexane, and
air-dried to give (E)-sulfone 7a (1.93 g, 5.20 mmol) in 42% yield as light-
brown solid. Data for 7a: m.p.: 131–133 ºC; 1H NMR δ = 0.71 (s, 3H), 1.11
(s, 3H), 3.44 (d, J = 10.8 Hz, 2H), 3.62 (d, J = 10.8 Hz, 2H), 3.78 (d, J =
8.0 Hz, 2H), 4.91 (s, 1H), 6.13 (t, J = 8.0 Hz, 1H), 6.76–6.82 (m, 2H), 7.16–
7.24 (m, 3H), 7.49–7.55 (m, 2H), 7.63–7.68 (m, 1H), 7.76–7.81 (m, 2H)
ppm; 13C NMR δ = 21.7, 22.9, 30.2, 56.3, 77.4, 102.1, 117.2, 127.7, 128.0,
128.6, 128.6, 129.0, 133.6, 135.0, 138.4, 136.5 ppm; IR (KBr) 2956, 2919,
2900, 2852, 1740, 1449, 1395, 1306, 1145, 1128, 1081, 1017, 991 cm-1;
HRMS (CI+) calcd for C21H25O4S 373.1474, found 373.1469.
(E)-4-Chloro-2-phenylbut-2-enal (10a). To
a stirred solution of
bromohydrin 12a (4.66 g, 20.5 mmol) in THF (20 mL) was added aqueous
solution (5 mL) of NaOH (1.92 g, 41.0 mmol). The reaction mixture was
stirred vigorously at room temperature for 3 h, extracted with EtOAc (25
mL×3), dried over anhydrous Na2SO4, filtered, and concentrated to give
vinyl epoxide 11a (3.00 g). Data for 11a: 1H NMR δ = 3.03 (A of ABq, J =
5.6 Hz, 1H), 3.10 (B of ABq, J = 5.6 Hz), 5.26 (d, J = 17.2 Hz, 1H), 5.34 (d,
J = 10.8 Hz, 1H), 6.05 (dd, J = 17.2, 10.8 Hz, 1H), 7.29–7.42 (m, 5H) ppm.
6
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000130
European Journal of Organic Chemistry
FULL PAPER
(E)-2-((3-(5,5-Dimethyl-1,3-dioxan-2-yl)-3-
0.66 (3:2 hexane:EtOAc); 1H NMR δ = 0.72 (s, 6H), 1.12 (s, 6H), 3.45 (d,
J = 10.8 Hz, 4H), 3.62 (d, J = 8.0 Hz, 4H), 3.64 (d, J = 10.8 Hz, 4H), 4.94
(s, 2H), 6.00 (t, J = 8.0 Hz, 2H), 7.23–7.27 (m, 4H), 7.31–7.37 (m, 6H)
ppm; 13C NMR δ = 21.8, 23.0, 30.2, 52.5, 77.5, 102.4, 116.8, 128.0, 128.3,
128.9, 135.0, 146.6 ppm; IR (KBr) 3012, 2956, 2844, 1469, 1394, 1364,
1308, 1230, 1215, 1118, 1088, 1014, 988, 969, 909, 854, 749, 700, 667
cm-1; HRMS (FAB) calcd for C30H39O6S 527.2467, found 527.2473.
phenylallyl)sulfonyl)benzo[d]thiazole (8a). To a stirred solution of
chloro-acetal 15a (5.00 g, 18.74 mmol) in acetone (60 mL) were added 2-
mercaptobenzothiazole (2.51 g, 14.99 mmol) and anhydrous K2CO3 (3.89
g, 28.11 mmol). The mixture was stirred at room temperature for 21 h
under argon atmosphere, and most of solvent was removed under reduced
pressure. The crude product was dissolved in EtOAc, washed with H2O.
The aqueous layer was extracted with EtOAc, and the combined organic
layer was dried over anhydrous Na2SO4, filtered, and concentrated under
reduced pressure to give yellow brown oil, which was purified by SiO2 flash
column chromatography (5–40% EtOAc in hexane) to give a 4:1 E:Z
mixture of benzothiazolyl sulfide (6.91 g, 17.38 mmol) in 60% yield as
sticky solid. The E-isomer was further purified by trituration with Et2O as
white solid [Rf = 0.71 (4:1 hexane:EtOAc)]; 1H NMR δ = 0.71 (s, 3H), 1.14
(s, 3H), 3.48 (d, J = 11.2 Hz, 2H), 3.66 (d, J = 11.2 Hz, 2H), 4.00 (d, J =
7.6 Hz, 2H), 5.02 (s, 1H), 6.29 (t, J = 7.6 Hz, 1H), 7.25–7.31 (m, 1H), 7.31–
7.39 (m, 5H), 7.37–7.43 (m, 1H), 7.72–7.76 (m, 1H), 7.82–7.86 (m, 1H)
ppm.
(1E,3E,5E)-1,6-Bis(5,5-dimethyl-1,3-dioxan-2-yl)-1,6-diphenylhexa-
1,3,5-triene (17a). To a stirred solution of allylic sulfone 16a (1.52 g, 2.89
mmol) in t-BuOH (25 mL) and CH2Cl2 (50 mL) were added C2Cl6 (1.37 g,
5.78 mmol) and pulverized KOH (1.62 g, 28.90 mmol). The mixture was
stirred at room temperature for 1 d under argon atmosphere and quenched
with 10% NaHCO3 solution. The mixture was extracted with CH2Cl2, dried
over anhydrous Na2SO4, filtered, and concentrated under reduced
pressure to give crude trienedial acetal as yellow-brown solid, which was
further purified by trituration with MeOH to give 17a (1.13 g, 2.45 mmol) in
85% overall yield as white solid. Data for 17a: Rf
= 0.62 (4:1
1
hexane:EtOAc); H NMR δ = 0.71 (s, 6H), 1.18 (s, 6H), 3.49 (d, J = 10.4
Hz, 4H), 3.66 (d, J = 10.4 Hz, 4H), 5.03 (s, 2H), 6.45–6.52 (m, 2H), 6.52–
6.58 (m, 2H), 7.28–7.39 (m, 10H) ppm; 13C NMR δ = 21.8, 23.1, 30.2, 77.7,
103.4, 127.4, 128.0, 129.5, 129.9, 132.3, 137.0, 139.2 ppm; IR (KBr) 3012,
2956, 2844, 1469, 1390, 1364, 1305, 1215, 1107, 1085, 1014, 980, 962,
928, 891, 749, 697, 667 cm-1; HRMS (ESI) calcd for C30H36O4Na 483.2506,
found 483.2504.
The mixture of Urea-H2O2 (1.07 g, 11.34 mmol) and phthalic anhydride
(0.84 g, 5.67 mmol) in MeCN (40 mL) was stirred vigorously at room
temperature for 1.5 h to give a clear solution. A solution of the above allylic
sulfide (0.75 g, 1.89 mmol) in CH2Cl2 (10 mL) was added to the above
solution. The mixture was stirred at room temperature under argon
atmosphere for 20 h. Most of solvent was removed under reduced
pressure, and the crude product was dissolved in CH2Cl2. The solid
residue was filtered off, and the filtrate was concentrated under reduced
pressure to give a 4:1 E:Z mixture of the corresponding sulfone 8a (0.91
g, 2.12 mmol) in 100% yield as sticky solid. The E isomer was purified by
trituration with MeOH in 83% yield (0.67g, 1.56mmol) as white solid. The
mother liquor was concentrated under reduced pressure to give the Z-
isomer exclusively. Data for 8a: Rf = 0.27 (4:1 hexane:EtOAc); m.p.: 135–
137 ºC; 1H NMR δ = 0.69 (s, 3H), 1.08 (s, 3H), 3.42 (d, J = 10.4 Hz, 2H),
3.60 (d, J = 10.4 Hz, 2H), 4.22 (d, J = 7.6 Hz, 2H), 4.94 (s, 1H), 6.18 (t, J
= 7.6 Hz, 1H), 6.96–7.00 (m, 2H), 7.16–7.22 (m, 2H), 7.23–7.28 (m, 1H),
7.58–7.67 (m, 2H), 8.00–8.04 (m, 1H), 8.16–8.18 (m, 1H) ppm; 13C NMR
δ = 21.7, 22.9, 30.1, 54.9, 77.4, 102.1, 115.6, 122.2, 125.6, 127.5, 128.0,
128.2, 128.7, 134.7, 137.1, 147.7, 152.6, 165.0 ppm; IR (KBr) 2956, 2848,
1472, 1394, 1331, 1215, 1144, 1122, 1085, 1018, 992, 969, 906, 854, 757,
705, 667, 664 cm-1; HRMS (ESI) calcd for C22H23NO4S2Na 452.0961,
found 452.0960.
(2E,4E,6E)-2,7-diphenylocta-2,4,6-trienedial (9a). To a stirred solution
of diacetal 17a (0.67 g, 1.45 mmol) in THF (5 mL) were added 1 M HCl
solution (10 mL) and oxalic acid (366 mg, 4.06 mmol). The mixture was
stirred vigorously at room temperature for 1 d. Light yellow oil was formed
in the lower phase upon standing, which was extracted with CH2Cl2,
washed with H2O, dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure to give yellow solid. The crude
product was purified by SiO2 flash column chromatography (10–25%
EtOAc in hexane) to give all-E-dialdehyde 9a (374 mg, 1.30 mmol) in 90%
yield as light yellow solid. Data for 9a: m.p.: 165–168 ºC; Rf = 0.30 (4:1
hexane:EtOAc); 1H NMR δ = 7.03–7.13 (m, 4H), 7.24–7.28 (m, 4H), 7.40–
7.50 (m, 6H), 9.70 (s, 2H) ppm; 13C NMR δ = 128.5, 128.8, 129.8, 131.9,
136.9, 144.1, 146.4, 192.8 ppm; IR (KBr) 3012, 2926, 2848, 2714, 1674,
1595, 1495, 1442, 1416, 1372, 1267, 1196, 1085, 1025, 1006, 980, 749,
716, 667 cm-1; HRMS (ESI) calcd for C20H16O2Na 311.1043, found
311.1044.
2,2'-((1E,1'E)-Sulfonylbis(1-phenylprop-1-ene-3,1-diyl))bis(5,5-
dimethyl-1,3-dioxane) (16a). To a stirred solution of chloro-acetal 15a
(3.09 g, 11.58 mmol) in DMF (25 mL) was added Na2S·9H2O (1.39 g, 5.79
mmol). The mixture was stirred vigorously at room temperature for 22 h,
diluted with EtOAc, washed with 10% NaHCO3 solution, dried over
anhydrous Na2SO4, filtered, and concentrated under reduced pressure to
give a crude product as yellow oil, which was purified by SiO2 flash column
chromatography (3–10% EtOAc in hexane) to give disulfide (2.38 g,
(1E,7E,13E)-1,14-Bis(5,5-dimethyl-1,3-dioxan-2-yl)-1,5,10,14-
tetraphenyl-3,12-bis(phenylsulfonyl)tetradeca-1,7,13-triene-4,11-diol
(20a). To a stirred solution of allylic sulfone 7a (3.50 g, 9.63 mmol) in THF
(30 mL) at -78 ºC was added 1.6M hexane solution of n-BuLi (6.6 mL, 10.6
mmol). The mixture was stirred vigorously at that temperature for 15 min,
and a solution of 2,7-diphenyloct-4-endial (3a) (1.28 g, 4.38 mmol) in THF
(10 mL) was added. The reaction mixture was stirred at -78 ºC for 1.5 h
and quenched with H2O (20 mL). The mixture was extracted with Et2O,
washed with brine, dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. The crude product (4.91 g) was
purified by SiO2 flash column chromatography to give the coupling diol 20a
(3.80 g, 3.67 mmol) in 84% yield as clumsy white solid. Data for coupling
diol 20a: Rf = 0.34~0.47 (6:4 hexane:EtOAc); 1H NMR δ = 0.71 (s, 6H),
1.12 (s, 6H), 1.86–2.43 (m, 8H), 3.50–3.70 (m, 8H), 3.55–3.96 (m, 2H),
4.14–4.30 (m, 2H), 4.78 (br s, 2H), 4.90–5.08 (m, 2H), 5.84–6.38 (m, 2H),
6.38–7.76 (m, 30H) ppm; IR (KBr) 3505, 3058, 2957, 2848, 1735, 1696,
1600, 1502, 1444, 1395, 1365, 1306, 1211, 1143, 1123, 1080, 1017 985,
906 cm-1; HRMS (FAB+) calcd for C62H69O10S2 1037.4332, found
1037.4324.
4.81mmol) in 42% overall yield as yellow oil [Rf
= 0.58 (4:1
1
hexane:EtOAc)]; H NMR δ = 0.71 (s, 6H), 1.13 (s, 6H), 3.06 (d, J = 8.0
Hz, 4H), 3.46 (d, J = 10.8 Hz, 4H), 3.64 (d, J = 10.8 Hz, 4H), 4.92 (s, 2H),
5.95 (t, J = 8.0 Hz, 2H), 7.24–7.40 (m, 10H) ppm.
The mixture of UHP (4.21 g, 44.76 mmol) and phthalic anhydride (3.31g,
22.38 mmol) in MeCN (70 mL) was stirred vigorously at room temperature
for 2 h, and a solution of the above disulfide (3.69 g, 7.46 mmol) in CH2Cl2
(20 mL) was slowly added. The mixture was stirred at room temperature
for 18 h, and most of solvent was removed under reduced pressure. The
crude product was dissolved in CH2Cl2, and undissolved solid was filtered
off by a filter paper. The filtrate was diluted with CH2Cl2, washed H2O, dried
over anhydrous Na2SO4, filtered, and concentrated under reduced
pressure to give a crude product as yellow oil, which was purified by SiO2
flash column chromatography (20–70% EtOAc in hexane) to give a 4:1
E,E:E,Z mixture of the corresponding sulfone 16a (2.67 g, 5.07 mmol) in
68% overall yield as sticky solid. The E,E-isomer was further purified by
trituration with MeOH as white solid. Data for 16a: m.p.: 163–165 ºC; Rf =
2,2'-((1E,3E,5Z,7E,9Z,11E,13E)-1,5,10,14-tetraphenyltetradeca-
1,3,5,7,9,11,13-heptaene-1,14-diyl)bis(5,5-dimethyl-1,3-dioxane) (6a).
[Method A: double elimination] To a stirred solution of the coupled diol
20a (3.77 g, 3.63 mmol) in CH2Cl2 (50 mL) at 0 ºC were added ethyl vinyl
7
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000130
European Journal of Organic Chemistry
FULL PAPER
ether (7.0 mL, 72.7 mmol) and pyridinium para-toluenesulfonate (182 mg,
0.73 mol). The mixture was stirred vigorously at 0 ºC to room temperature
for 11.5 h. The reaction mixture was cooled to 0 ºC again, and ethyl vinyl
ether (7.0 mL) was added. Stirring for 3 h, the mixture was diluted with
CH2Cl2, washed with 10% NaHCO3 solution, dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure to give crude bis(1-
etoxyethyl ether) 21a (5.40 g) as bright yellow oil. Rf = 0.56 (6:4
hexane:EtOAc).
filtered, and concentrated to give red solid, which was purified by SiO2 flash
chromatography (0–15% EtOAc in hexane) to give the coupling product 6a
(90.2 mg, 0.13 mmol) in 33% yield as red solid [Rf = 0.54–0.49 in 4:1
EtOAc:hexane]. The E/Z isomeric ratio was analyzed as 3: 1 by HPLC.
To a stirred solution of acetal coupling product 6a (75.0 mg, 0.10 mmol) in
THF (5 mL) were added 1M HCl (15 mL) solution and oxalic acid (27.0 mg,
0.30mmol). The mixture was stirred at room temperature for 12 h. The
mixture was extracted with CH2Cl2, dried over anhydrous Na2SO4, filtered,
and concentrated under reduced pressure to give red solid, which was
purified by SiO2 flash column chromatography (7–30% EtOAc in hexane)
to give dialdehydes 4a (total 31.7 mg, 0.06 mmol) in 60% yield. The E/Z
isomeric ratio was analyzed as 11: 1: 2 by HPLC.
To a stirred solution of 1-ethoxyethyl protected sulfone 21a (5.40 g) in
benzene (50 mL) and cyclohexane (50 mL) was added KOMe (6.41 g, 91.4
mmol). The mixture was heated at reflux for 15 h and cooled to room
temperature. The mixture was quenched with H2O and extracted with Et2O.
The aqueous layer was extracted again with Et2O, and the combined
organic layer was dried over anhydrous Na2SO4, filtered, and concentrated
under reduced pressure to give the crude product (4.05 g), which was
purified by SiO2 flash column chromatography to provide 6a (2.11 g, 2.94
mmol) in 81% yield as dark reddish solid. Data for 6a: Rf = 0.49 (8:2
hexane:EtOAc); m.p.: 158–161 ºC; 1H NMR δ = 0.72 (s, 6H), 1.20 (s, 6H),
3.51 (d, J = 10.8 Hz, 4H), 3.67 (d, J = 10.8 Hz, 4H), 5.05 (s, 2H), 6.06 (dd,
J = 15.2, 11.6 Hz, 2H), 6.18–6.30 (m, 4H), 6.55 (d, J = 15.2 Hz, 2H), 6.64
(d, J = 11.6 Hz, 2H), 7.03–7.10 (m, 4H), 7.12–7.33 (m, 16 H) ppm; 13C
NMR δ = 21.8, 23.1, 30.2, 77.7, 103.7, 127.2, 127.2, 127.7, 128.0, 128.6,
129.2, 129.7, 130.2, 132.2, 133.1, 136.8, 137.2, 138.3, 139.3, 143.1 ppm;
IR (KBr) 3030, 2971, 2924, 2849, 1741, 1651, 1556, 1542, 1459, 1363,
1220, 1128, 1097, 1014, 960, 695 cm-1; HRMS (FAB+) calcd for C50H52O4
716.3866, found 716.3871.
(((1E,3Z,5E,7Z,9E,11Z,13E,15Z,17E)-3,7,12,16-Tetraphenyloctadeca-
1,3,5,7,9,11,13,15,17-nonaene-1,18-diyl)bis(4,1-
phenylene))bis(methylsulfane) (1a). To a stirred suspension of NaH
(60% oil suspension, 115 mg, 2.88 mmol) in THF (20 mL) was added 4-
methylthiobenzyl triphenylphosphonium bromide (5) (690 mg, 1.44 mmol).
The mixture was stirred at room temperature for 15 min, a solution of dial
4a (256 mg, 0.48 mmol) in THF (20 mL) was added. The reaction mixture
was stirred at room temperature overnight, diluted with Et2O, washed with
1M HCl, 10% NaHCO3 solution, and with brine. The aqueous layer was
extracted with CH2Cl2, and the combined organic layer was dried over
Na2SO4, filtered, and concentrated. The crude product (992 mg) was
purified by SiO2 chromatography (Rf = 0.68 at 8:2 EtOAc:hexane), followed
by trituration with CH3OH/CH2Cl2 to give all-E-polyene 1a (153 mg, 0.19
mmol) as red-purple solid. The mother liquor was concentrated and
purified by SiO2 flash column chromatography to give 1a (192 mg, 0.24
mmol). The SiO2 in the column was flushed again with 9:1 CH2Cl2:acetone
(300 mL) and was concentrated to give all-E-1a (21 mg, 0.027 mmol). The
combined total yield of all-E-1a was 174 mg (0.22 mmol) in 46% yield. Data
for 1a (X = H): 1H NMR δ = 2.46 (s, 6H), 5.86 (dd, J = 15.0, 12.0 Hz, 2H;
H11), 6.14 (d, J = 15.8 Hz, 2H; H7), 6.18–6.23 (m, 2H; H15), 6.23–6.29 (m,
4H; H14), 6.47 (d, J = 12.0 Hz, 2H; H10), 6.48 (d, J = 15.0 Hz, 2H; H12), 6.97
(d, J = 15.8 Hz, 2H; H8), 7.02 (d, J = 8.0 Hz, 4H), 7.07 (d, J = 8.0 Hz, 4H),
7.14 (d, J = 8.4 Hz, 4H), 7.20–7.27 (m, 12H), 7.25 (d, J = 8.4 Hz, 4H) ppm;
UV (c = 4.55×10-6 M in CH2Cl2) λ (ε) 477 (182,000), 504 (200,000), 538
(142,000) nm; IR (KBr) 3027, 2972, 2920, 2853, 1738, 1653, 1558, 1487,
1437, 1372, 1229, 1213, 1090, 968 cm-1; HRMS (FAB+) calcd for C56H48S2
784.3197, found 784.3212.
(2E,4E,6Z,8E,10Z,12E,14E)-2,6,11,15-Tetraphenylhexadeca-
2,4,6,8,10,12,14-heptaenedial (4a). To
a
stirred solution of
polyenediacetal 6a (2.62 g, 3.65 mmol) in THF (35 mL) were added oxalic
acid (823 mg, 9.14 mmol) and 1M HCl solution (35 mL). The mixture was
stirred vigorously at room temperature for 22 h, and then extracted with
Et2O. The etheral extract was washed with 10% NaHCO3 solution, dried
over anhydrous Na2SO4, filtered, and concentrated under reduced
pressure to give the crude product (2.61 g) as dark red solid.
The aqueous layer together with red emulsion was extracted with CH2Cl2.
The CH2Cl2 layer was dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure to give mostly all-E-polyene
compound 4a (567 mg) as dark red solid, which was further purified by
trituration with diethyl ether to give pure all-E-4a (222 mg). The crude
product (2.61 g) obtained from etheral extraction was purified by SiO2 flash
column chromatography (4:1 hexane:EtOAc) to give the mono-
deprotected aldehyde (259 mg, Rf = 0.44) and three stereoisomers of
polyenedial in the following amounts: 478 mg (0.88 mmol, 24% yield, Rf =
0.35), 427 mg (Rf = 0.25, all-trans), and 531 mg (0.97 mmol, 27% yield, Rf
= 0.16). The SiO2 in the column was flushed again with 300 mL of 9:1
CH2Cl2:acetone to give all-E-4a (86 mg, Rf = 0.25). The total amount of the
combined all-E-4a (Rf = 0.25) was 735 mg (1.35 mmol, 37% yield). The
total yield of the polyenedial was 1.74 g (3.20 mmol) in 88% yield. Data for
Acknowledgements
This work was supported by the National Research Foundation of
Korea through the Basic Science Research Program (No. NRF-
2016R1A2B4007684) and partly by 2019 Research Fund of
Myongji University.
all-E-hexadecahepta-2,4,6,8,10,12,14-enedial (4a): Rf
= 0.25 (4:1
Keywords: carotenoids • conducting material • olefination •
synthesis design • total synthesis
hexane:EtOAc); 1H NMR δ = 6.35 (dd, J = 14.8, 11.8 Hz, 2H), 6.32–6.42
(m, 2H), 6.44–6.54 (m, 2H), 6.91 (d, J = 14.8 Hz, 2H), 7.07–7.15 (m, 4H)
7.10 (d, J = 11.8 Hz, 2H), 7,20–7.40 (m, 6H) 9.63 (s, 2H) ppm; 13C NMR δ
= 127.9, 127.9, 128.1, 128.1, 128.3, 129.5, 129.7, 132.3, 134.2, 136.0,
137.0, 140.6, 143.8, 145.5, 148.9, 192.9 ppm; IR (KBr) 2922, 2853, 1672,
1648, 1598, 1549, 1457, 1384, 1267, 1103, 1022, 803 cm-1; UV (c =
1.18×10-6 M in CH2Cl2) λ (ε) 444 (65,600), 473 (102,000), 503 (95,000)
nm ; HRMS (FAB+) calcd for C40H33O2 545.2481, found 545.2493.
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Entry for the Table of Contents
Carotenoid Wires
Tetraphenyl-substituted carotenoids with improved antioxidant and electronic conducting properties than natural carotenoids
were synthesized through the formation of all-E-apocarotenedials (4), which were prepared by the sulfone-mediated olefinations
of the novel building blocks 7 and 3, or 8 and 9 with E-configurations. (E)-4-Chloro-2-phenylbut-2-enal (10) was the key
material for the syntheses.
10
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