Systematic Synthesis of Diphenyl-Substituted Carotenoids as Molecular Wires

Article abstract of DOI:10.1002/ejoc.201701229

A general method for the construction of diphenyl-substituted carotenoids has been developed through the stereoselective synthesis of dienyl sulfones with a phenyl substituent. Systematic synthetic pathways to the dienyl sulfones were delineated starting from readily available acetophenones with para-substituent X of various electronic natures, which provided the carotenoids with diverse physicochemical characteristics. The sulfone olefination method together with the Ramberg–B?cklund reaction produced a 9,9′-cis-10,10′-diphenylcarotene and all-trans-9,9′-diphenylcarotenes. Conductance measurements of the all-trans carotenoids by the scanning tunnelling microscopy break-junction method revealed a positional effect of the phenyl groups as well as a polar effect of the phenyl substituent X according to the electronic nature.

Full text of DOI:10.1002/ejoc.201701229

A Journal of
Accepted Article
Title: Systematic synthesis of diphenyl-substituted carotenoids as
molecular wires
Authors: Boram Lim, Eun-Taek Oh, JongOne Im, Kyu Sang Lee,
Hyunuk Jung, Minsoo Kim, Dahye Kim, Jung Taek Oh, Sung-
Hee Bae, Wook-Jin Chung, Kwang-Hyun Ahn, and Sangho
Koo
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201701229
Link to VoR: http://dx.doi.org/10.1002/ejoc.201701229
Supported by

10.1002/ejoc.201701229
European Journal of Organic Chemistry
FULL PAPER
Systematic synthesis of diphenyl-substituted carotenoids as
molecular wires
Boram Lim,[a,b,c] Eun-Taek Oh,[b] JongOne Im,[d] Kyu Sang Lee,[c] Hyunuk Jung,[c] Minsoo Kim,[c] Dahye
Kim,[c] Jung Taek Oh,[b] Sung-Hee Bae,[b] Wook-Jin Chung,[c] Kwang-Hyun Ahn,[e] and Sangho Koo*[a,b,c]
This paper is dedicated to the late Mr. Eun-Taek Oh with unforgettable memories, who was a sincere and responsible person.
Abstract: A general construction method of diphenyl-substituted
carotenoids has been developed through the stereoselective
synthesis of dienyl sulfones with a phenyl substituent. Systematic
synthetic pathways to the dienyl sulfones were delineated starting
from readily available acetophenone with para substituent X of
various electronic natures, which would eventually provide diverse
physiochemical characteristics to the carotenoids. The sulfone
olefination method together with Ramberg-Bäcklund reaction
produced 9,9′-cis-10,10′-diphenyl-carotene and all-trans-9,9′-
diphenyl-carotene. Conductance measurement of all-trans-
carotenoids by STM break junction method revealed a positional
effect of the phenyl groups as well as a polar effect of the phenyl
substituent X according to the electronic nature.
chlorophylls in photosynthesis.[1c,5] It is thus desirable to develop
an efficient synthetic method of diversely phenyl-substituted
carotenoids for wider biological and physiochemical applications.
Versatile building blocks would allow efficient construction of
such carotenoids. We demonstrated an efficient synthesis of all-
trans-13,13′-diphenyl-carotene 1[6] from 2-methyl-substituted
dienyl sulfone 4 and 2,7-diphenyl-substituted 4-octenedial 7a by
the sulfone-mediated coupling and olefination method (Scheme
1).[7] A polar effect of substituent X in the phenyl groups was
clear in the diverse conductance values of carotene 1,[8] which
were measured by forming junctions between the methylthio
groups in the terminal benzene rings and gold electrodes using
STM (Scanning Tunnelling Microscopy).[9] It was also
demonstrated that 13,13′-diphenyl-carotene 1 provides improved
in vivo and in vitro antioxidant activity compared to natural -
carotene.[10]
Introduction
A question comes next whether there is a positional effect of
phenyl substituents along the polyene chain in the conductance
of carotenoids. To answer this question it was necessary to
construct diverse diphenyl-substituted carotenoids such as all-
Carotenoids are structurally characterized by the conjugated
polyene chain, which exhibits their unique reddish color and
antioxidant activity by reacting with ROS (reactive oxygen
species).[1] Instability of carotenoids under aerobic condition can
be attributed to irreversible oxidation of the polyene chain.[2]
Phenyl substituents attached to the polyene chain provides not
only improved stability,[3] but also diverse physiochemical
characteristics depending on the electronic nature of the
substituent.[4] Carotenoids are also known as light-harvesting
and energy-transferring agents working together with
trans-10,10′-diphenyl-carotene
2
or all-trans-9,9′-diphenyl-
carotene 3 (Scheme 1).[6] A general synthetic method of such
carotenoids would provide diverse carotenoids with any possible
phenyl substituents. Dienyl sulfones 5 and 6 containing a phenyl
substituent would be valuable building blocks through the
sulfone-mediated olefination for the syntheses of 10,10′- or 9,9′-
diphenyl-carotenoids 2 and 3, which may as well serve as
improved antioxidants or as stabilized conducting molecular
wires. Coupling of dienyl sulfone 5 or 6 (2 equiv) with C10 4-
octenedial 7b (1 equiv), followed by dehydro-desulfonation
would produce the desired carotenoids 2 and 3.[7] Alternatively,
[a]
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
E.-T. Oh, J. T. Oh, S.-H. Bae
coupling of dienyl sulfone
bis(chloroallylic) sulfone
5
or
6 (2 equiv) with C10
8
(1 equiv),[11] Ramberg-Bäcklund
reaction,[12] and dehydro-desulfonation can possibly produce the
desired carotenoids 2 and 3.
[b]
[c]
[d]
[e]
Department of Nano Science and Engineering
Myongji University
Myongji-Ro 116, Cheoin-Gu, Yongin, Gyeonggi-Do, 17058, Korea
K. S. Lee, H. Jung, M. Kim, D. Kim, Prof. Dr. W.-J. Chung
Department of Energy Science and Technology
Myongji University
Myongji-Ro 116, Cheoin-Gu, Yongin, Gyeonggi-Do, 17058, Korea
J.O. Im
Biodesign Institute, Department of Physics
Arizona State University
Tempe, Arizona, 85287, USA
K.-H. Ahn
Department of Applied Chemistry
Kyung Hee University
Yongin, Gyeonggi-Do, 17104, Korea
Stereoselective construction of dienyl sulfone 5 and 6 could
be the key to success for the stereoselective synthesis of all-
trans-carotenoids
chloroallylic sulfones 11 or 12 containing a phenyl substituent to
p-(methylthio)benzaldehyde 9a, and oxonia-Cope
2
and 3. Indium-mediated addition of
rearrangement of the resulting homo-allylic alcohol would be a
perfect reaction sequence for the synthesis of dienyl sulfones 5
or 6, as was the synthesis of dienyl sulfone 4 from chloroallylic
sulfone 10 containing 2-methyl substituent and p-
(methylthio)benzaldehyde 9a.[7] Detailed studies for the
systematic synthesis of dienyl sulfones 5 and 6, the efficient
construction of diphenyl-substituted carotenoids 2 and 3, and
their conductance measurements by STM are presented in this
work.
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701229
European Journal of Organic Chemistry
FULL PAPER
S
containing 2-phenyl substituent in reasonable yields (41–89%)
with high Z selectivity (5–8:1). The stereochemistry was
R3
9
R1
13
R2
10'
1
9'
10
13'
confirmed by N.O.E. experiment and the 1H NMR chemical shifts
of allylic hydrogens: those from Z-isomer are down-field shifted
and the chemical shift difference is small (~0.1 ppm) compared
to those from E-isomer (>0.2 ppm; see 1H NMR spectra for 11b,
11c, 11g, and 11h in Supporting Information-2).
R2
R1
R3
S
R1 = C6H4-p-X, R2 = Me, R3 = H
1
2
3
R1 = Me, R2 = C6H4- -X, R3 = H
X = OMe, Me, H, Br
p
R
1 = Me, R2 = H, R3 = C6H4-p-X
R1
O
O
1
R3
7a
p
R1
R = C6H4- -X
X
X
+
SO2Ph
7b R1 = Me
R2
S
4 R2 = Me, R3 = H
Cl
Cl
NaSO2Ph
S
O2
5 R2 = C6H4-p-X, R3 = H
SO2Ph
Br
R2 = H, R3 = C6H4-p-X
8
6
16
15
PhO2S
Cl
R2
SOCl2
SO2Ph
O
+
O
Cl
HO
MgBr
R3
Br
S
10 R2 = Me, R3 = H
9a
Br
R2 = C6H4-p-X, R3 = H
X
X
11
13
14
12 R2 = H, R3 = C6H4-p-X
HO
1. NaOH
2. PhSH
Et3N
Scheme 1. Disconnection approach to the synthesis of 10,10′- and 9,9′-
diphenyl-carotenoids and
X
SO2Ph
2
3.
X
18
oxone
or
H2O2
(COCl)2
SO2Ph
HO
Results and Discussion
SPh
X
11
17
Cl
Preparation of chloro-allylic sulfones 11 and 12
Scheme 2. Preparation of chloroallylic sulfones 11 from
bromoacetophenones 13
-
Chloroallylic sulfones 11 were prepared from acetophenone with
a substituent X (H, F, Cl, CN, NO2) at para-position (Scheme 2
and Table 1). Bromination of in situ generated silyl enol ether
using catalytic TMS·OTf and stoichiometric NBS produced 13 in
reasonable yields (60–77%) after recrystallization from
EtOAc/hexane.[13] Unreacted starting material and dibromination
product were removed at this stage. Chemo-selective addition of
vinylmagnesium bromide to the carbonyl group of 13 was carried
out at -78 °C to give tertiary vinyl alcohol 14 (81–93%). Initial
synthetic plan for chloroallylic sulfones 11 was selective
sulfonation by NaSO2Ph at the allylic bromide site of two-sided
allylic halide 15, which was prepared by chlorination (SOCl2)
with allylic migration from vinyl alcohol 14. Unfortunately, there
was no selectivity for sulfonation in the allylic bromide site of 15.
Advantageous electronic effect by bromine (over chlorine) could
not overcome the steric bias generated by the nearby phenyl
group, producing cis-disulfone 16 as the major product.
Table 1. The yields and stereo-isomeric ratios (where applicable) of products
from each step in the reaction sequence of Scheme 2.
Entry
X
13 (%)[a]
73
14 (%)
81
17 (%)
82
18 (%)
80[b]
89[c]
11 (%, Z:E)
1
2
3
4
5
a: H
81 (8:1)
55 (6:1)
89 (8:1)
51 (6:1)
41 (5:1)
b
: F
: Cl
75
76
72
c
77
93
83
93[b]
42[b]
96[c]
g: CN
72
89
85
h: NO2
60
88
85
[a] Yield after recrystallization from EtOAc/Hexane. [b] Oxone was used for
oxidation. [c] H2O2 was used with LiNbMoO6 catalyst for oxidation.
The synthetic plan had to be modified to perform sulfonation
at the homoallylic bromide site of bromohydrin 14 to produce
sulfone 18, which was carried out by epoxide formation and then
opening with benzenethiolate to give sulfides 17 (72–85%),[14]
followed by oxidation to sulfone 18 (42–96%). This oxidation
was typically carried out using oxone or H2O2 under LiNbMoO6
as an efficient metal oxide catalyst.[15] Allylic chlorination using
oxallyl chloride eventually produced chloroallylic sulfone 11
Direct sulfonation by NaSO2Ph to produce chloroallylic
sulfones 12 worked well for two-sided allylic halides 21, in which
electronic effect paired with steric effect to give exclusive
substitution at the allylic bromide site. Reasonable yields (62–
91%) were obtained and marginal selectivity for Z-isomer (1.5–
5:1) were maintained (Scheme 3 and Table 2). The reaction can
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701229
European Journal of Organic Chemistry
FULL PAPER
be performed either in DMF or in MeOH. Allylic halides 21 were
similarly synthesized by the initial sequence of reactions
demonstrated for chloroallylic sulfones 11.
hydrogens with small chemical shift difference for the Z-isomer
in their 1H NMR spectra.
Synthesis of dienyl sulfones 5 and 6 from chloro-
allylic sulfones 11 and 12
O
HO
Cl
MgBr
Indium-mediated addition[18] of chloroallylic sulfone 11a (R2 = Ph,
R3 = H) to benzaldehyde produced homoallylic alcohol 22ã (X =
H) with high syn (OH and CH2SO2Ph) selectivity (>11:1),[19]
which underwent the oxonia-Cope rearrangement[20,21] at 80 °C
in the presence of stoichiometric camphorsulfonic acid (CSA)
and benzaldehyde, as was previously reported (Scheme 4).[22] 2-
(Z)-4(E)-Dienyl sulfone 5ã (X = H) with phenyl substituent at C-2
was obtained in a reasonable yield (~70%). High correlation of
the stereochemistry in the oxonia-Cope rearrangement (syn to Z
at C-2) can be explained by the cyclic transition state model (A
to B),[23] where all the bulky phenyl substituents are located in
equatorial positions. The axial disposition of the benzenesulfonyl
group and the (anti) elimination of benzaldehyde afford (2Z,4E)-
dienyl sulfone 5, which unfortunately does not match with the
desired stereochemistry for all-trans-10,10′-diphenyl-carotene 2.
Cl
X
X
19
20
PBr3
X
X
NaSO2Ph
Cl
Cl
12
21
PhO2S
Br
Scheme 3. Preparation of chloroallylic sulfones 12 from
chloroacetophenones 19
-
.
Table 2. The yields and stereo-isomeric ratios (where applicable) of products
from each step in the reaction sequence of Scheme 3.
OH
4
2
C6H4-p-X
CSA
Ph
Ph
PhO2S
E
Z
Entry
X
19 (%)[a]
85
20 (%)
83
21 (%,
Z
:
E)
12 (%, Z:E)
PhCHO
C6H4-p-X
SO2Ph
5
22
1
2
3
4
5
6
7
8
a: H
90 (3:1)
96 (4:1)
91 (3:1)[b]
80 (5:1)[c]
80 (2:1)[b]
77 (3:1)[b]
b
: F
: Cl
: Br
: OMe
: Me
85
80
c
88
75
83 (2.5:1)
80 (3:1)
H
H
C6H4-p-X
C6H4-p-X
Heq
[3.3]
Ph
Ph
d
78
85
O
O
Ph
Ph
76 (2.5:1)[c]
62 (4.4:1)[b]
70 (1.5:1)[c]
75 (5:1)[c]
SO2Ph
SO2Ph
e
80
91
81 (2.5:1)
95 (4.3:1)
84 (2.5:1)
82 (1.6:1)
A
B
f
85
90
Scheme 4. Stereochemistry in the oxonia-Cope rearrangement of homoallylic
alcohol 22
g: CN
65
95
h: NO2
75
62
The oxonia-Cope rearrangement of homoallylic alcohol 23ã
(X = H, syn:anti = 4:1), which was prepared by the addition of
chloroallylic sulfone 12a (R2 = H, R3 = Ph) to benzaldehyde, was
complicated under the above CSA condition by the lowered Z/E
ratio (3:2) at C-2 of dienyl sulfone 6ã (Y = H) (Scheme 5; Entry 1,
Table 3).[22] The transition state model C for the syn isomer
would be destabilized by the pseudo-axial Ph and the axial
benzenesulfonyl group. It may equilibrate to model D, in which
all other bulky groups are located in equatorial positions except
the C6H4-p-X group. The oxonia-Cope rearrangement of D may
produce E, which undergoes (anti) elimination of aldehyde (p-X-
C6H4CHO) to produce dienyl sulfone 6 (Scheme 5). This
rearrangement scenario predicts (2Z,4E)-dienyl sulfone 6 as the
major stereoisomer, which is the right geometry for all-trans-9,9′-
diphenyl-carotene 3.
[a] Yield after recrystallization from EtOAc/Hexane. [b] DMF was used as
solvent at 0 ºC for 2.5–4 h. [c] MeOH was used as solvent at 0 ºC for 18–20 h.
Chlorination of acetophenone (X = H, F, Cl, Br, OMe, Me,
CN, NO2) using NCS under acidic condition produced the
corresponding
-chloroacetophenone
19
(65–88%).[16]
Recrystallization was necessary to remove unreacted starting
material and dichlorination product. Selective addition of
vinylmagnesium bromide to the carbonyl group of 19 was carried
out at -78 °C to produce chlorohydrin 20 (62–95%). Allylic
bromination using PBr3 produced allylic halide 21 (80–96%), in
which the Z/E ratio (1.6–4.3:1) seems to reflect the
thermodynamics by the steric and electronic effect of the allylic
substituents.[17] The same rationale was applied for the
stereochemical assignment of compounds 21 and 12 as the
isomeric chloroallylic sulfones 11: down-filed shifted allylic
The oxonia-Cope rearrangement of 23 was carefully
investigated in order to obtain better Z/E ratio (at C-2) of 6 for
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701229
European Journal of Organic Chemistry
FULL PAPER
the stereoselective synthesis of all-trans-carotene 3 (Table 3).
Losing stereoselectivity could be explained by scrambling the
less-hindered carbinol chiral center of 23ã (compared to 22a) by
added aldehyde in the formation of oxonium ion C or D under
the harsh condition (stoichiometric CSA at 80 °C). The
rearrangement was thus studied without additional aldehyde, but
the yield of 6ã (20%) was decreased dramatically due to
extensive decomposition of homoallylic alcohol 23ã, which was
confirmed by the formation of fragmentation product 24 (45%)
(Entry 2, Table 3).
Lewis acid, Sn(OTf)2 can induce this rearrangement using a
catalytic amount (10 mol%) at 40 °C.[20] The stereoselectivity
(Z:E = 3.5:1) was not deteriorated in the absence of added
aldehyde under this condition, but the decrease of yield 6ã
(49%) by the fragmentation (21% of 24) was still noticed (Entry
4). Because benzaldehyde is regenerated after the
rearrangement, it is not necessary to add it. Extensive formation
of fragmentation product 24, however, suggests that the rate of
fragmentation is faster than that of rearrangement for
homoallylic alcohol 23ã derived from benzaldehyde. We found
that an electron-releasing group X (MeS) facilitates the oxonia-
Cope rearrangement of homoallylic alcohol 23a, presumably by
speeding up the formation of oxonium ion C, to give higher
yields and better Z/E ratio of 6a (Entries 5–8). This effect was
evident in the absence of added aldehyde under the mild
Sn(OTf)2 catalyst condition, where the desired dienyl sulfone 6a
(Y = MeS) was obtained in 88% yield with non-deteriorated Z/E
ratio of 4:1 (Entry 8). No fragmentation product 24 was observed
for homoallylic alcohol 23a from electron-rich aldehyde 9a.
Ph
H
SO2Ph
+
O
24
Acid
Ph
Ph
O
2
4
X
SO2Ph
H
SO2Ph
E
Z
23
9
Y
6
Y
9
Preparations of dienyl sulfones 5 and 6 with a (p-X-C6H4)
substituent of diverse electronic natures (X = H, F, Cl, Br, OMe,
Me) were illustrated in Scheme 6 by the reaction from
chloroallylic sulfones 11 or 12 and p-(methylthio)benzaldehyde
9a. The two-step protocol of the indium-mediated addition,
followed by the oxonia-Cope rearrangement has been exercised.
The yields and stereo-isomeric ratios of each reaction product
were summarized in Table 4.[24] Indium-mediated addition of
chloroallylic sulfones 11 or 12 to aldehyde 9a was carried out at
70 °C in a 4:1 mixture of H2O/THF.
H
H
Ph
H
H
SO2Ph
Ph
O
p-X-C6H4
p-Y-C6H4
O
p-Y-C6H4
C6H4-p-X
SO2Ph
C
E
[3.3]
H
H
O
p-Y-C6H4
SO2Ph
Ph
C6H4-p-X
D
The initial Z/E ratio of chloroallylic sulfones 11 and 12 was
not important in the control of stereo-isomeric ratio (syn/anti) of
homoallylic alcohols 22 and 23. A new Z/E ratio was established
during the formation of allyl indium species according to the
thermodynamic stability based on the steric interactions between
the allylic substituent groups.[17] It seemed that high Z/E ratio
(>11:1) was attained for allyl indium reagents from 11, but
marginal Z/E ratio of 2–3.5:1 was estimated for allyl indium
reagents from 12, which was explained by the syn:anti ratio of
the resulting homoallylic alcohols 22 and 23 following the
correlation of (Z to syn) and (E to anti) by the cyclic transition
state model. This idea was supported by the experimental
results in Entries 4–6 of Table 4, where the same (syn/anti) ratio
of homoallylic alcohol 23a was obtained from chloroallylic
sulfone 12a with different (Z/E) ratio.
Lower yields of homoallylic alcohol 22 (39–52%) compared
to the isomeric alcohol 23 (79–91%) reflects steric congestion
near the reaction center. Oxonia-Cope rearrangement of 22
proceeded with high stereoselectivity (Z/E at C-2 = 7–20:1)
under the condition using stoichiometric CSA and aldehyde 9a
at 80 °C as was the model case in Scheme 4. The optimized
condition of catalytic Sn(OTf)2 at 40 °C was utilized for the
rearrangement of homoallylic alcohols 23a-23f except for 23e to
give fare yields (65–88%) and Z/E ratios (3–4:1) of dienyl
sulfones 6a-6f. Because of decomposition of the methyl ether
under Sn(OTf)2 condition, oxonia-Cope rearrangement of 23e
was carried out under the CSA condition.
Scheme 5. Stereochemistry in the oxonia-Cope rearrangement of homoallylic
alcohol 23
Table 3. Optimization study for the oxonia-Cope rearrangement of homoallylic
alcohol 23
.
Entry
23 (X)[a]
9
(Y)
Acid (equiv.)[b]
6
(Y)
% Yield
at C-2)
(Z:E
1
ã
ã
ã
ã
a
a
a
a
: H
ã
-
: H
CAS (1.1)
ã
ã
ã
ã
a
a
a
a
: H
77 (3:2)
2[c]
3
: H
CAS (1.1)
: H
20 (3:1)
: H
ã: H
Sn(OTf)2 (0.1)
Sn(OTf)2 (0.1)
CAS (1.1)
: H
61 (2.6:1)
49 (3.5:1)
90 (2.5:1)
70 (3:1)
4[d]
5
: H
-
: H
: MeS
: MeS
: MeS
: MeS
a: MeS
: MeS
: MeS
: MeS
: MeS
6
-
CAS (1.1)
7
a
-
: MeS
Sn(OTf)2 (0.1)
Sn(OTf)2 (0.1)
97 (2.5:1)
88 (4:1)
8
[a] The (syn:anti) ratio of starting homoallylic alcohol 23 was 3.5–4:1. [b] The
reaction was performed either at 80 ºC for CSA or 40 ºC for Sn(OTf)2. [c] 24
was also obtained in 45% yield. [d] 24 was also obtained in 21% yield.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701229
European Journal of Organic Chemistry
FULL PAPER
O
O
H
R3
H
R2
OH
R2
9a
R2
SO2Ph
R2 = R3 = C6H4-p-X
S
9a
S
PhO2S
R3
Cl
CAS
or
SO2Ph
R3
SO2Ph
Z
Z
or Sn(OTf )2
In
S
S
S
11 R2 = C6H4-p-X, R3 = H
12
22 R2 = C6H4-p-X, R3 = H
R
2 = H, R3 = C6H4-p-X
23
5
6
p
R
2 = H, R3 = C6H4- -X
Scheme 6. Stereoselective preparation of dienyl sulfones
Cope rearrangement of homoallylic alcohols 22 and 23
5 and 6 by In-mediated addition of chloroallylic sulfones 11 or 12 to aldehyde 9a, followed by oxonia-
.
Table 4. The yields and stereo-isomeric ratios of homoallylic alcohols 22 and 23, and dienyl sulfones
5
and
6
in the reaction sequence of Scheme
Compound
[b] or 6[c]
at C-2
6.
Entry
Compound 11 or 12
Compound 22 or 23[a]
syn:anti
5
Z:
E
R2
R3
H
Yield (%)
52
Z:
E
Yield (%)
1
11a (8:1)
11b (6:1)
11c (8:1)
12a (3:1)
Ph
22a (11:1)
22b (syn)
5a (7:1)
5b (11:1)
5c (20:1)
6a (4:1)
70
56
55
88
2
p
-F-C6H4
-Cl-C6H4
H
51
3
p
H
22c (syn)
39
4
H
H
H
H
H
H
H
H
Ph
Ph
Ph
23a (3.5:1)
23a (3.5:1)
23a (3.3:1)
23b (2.7:1)
23c (2.1:1)
23d (2.7:1)
23e (2.7:1)
23f (2:1)
91
5
12a
(
E)
81
6
12a (Z)
79
7
12b (5:1)
12c (2:1)
12d (2:1)
12e (2.5:1)
12f (5:1)
p
p
p
p
p
-F-C6H4
86
6b (4:1)
6c (4:1)
6d (3:1)
6e[d] (3:1)
6f (3:1)
71
76
65
78
66
8
-Cl-C6H4
84
9
-Br-C6H4
-MeO-C6H4
-Me-C6H4
87
10
11
88
88
[a] In-mediated addition of chloroallylic sulfones 11 or 12 to aldehyde 9a was carried out at 70
Cope rearrangement of 22 with 9a at 80 C to produce dienyl sulfone . [c] Sn(OTf)2 was used for the oxonia-Cope rearrangement of 23 at 40
produce dienyl sulfone . [d] CSA condition was used for the oxonia-Cope rearrangement of 23e due to decomposition of methyl ether under Sn(OTf)2 condition.
°C in a 4:1 mixture of H2O/THF. [b] CSA was used for the oxonia-
°
5
°
C without 9a to
6
It was necessary at this stage to prove whether the above
two-step protocol for dienyl sulfone 6 must have been an ideal
stereoselective synthetic pathway. Dienyl sulfone 6 containing 3-
phenyl substituent was envisioned to be easily prepared by
allylic migratory sulfonation from tertiary vinyl alcohol 25, which
might be obtained by 1,2-addition of vinyl Grignard reagent to
(E)-chalcone derivatives 26 (Scheme 7). Mixed aldol
synthesis of dienyl sulfone 6 by this vinyl Grignard addition
method.
X
X
condensation
between
p-bromoacetophenone
and
p-
SO2Ph
OH
(methylthio)benzaldehyde 9a under aqueous basic condition
smoothly produced conjugated ketone 26d (X = Br) in 88% yield.
Seemingly easy 1,2-addition of vinylmagnesium bromide to
conjugated ketone 26 was really problematic. Only 11% yield of
the desired tertiary alcohol 25d was obtained by 1,2-addition.
Instead, -vinyl ketone 27d was the major product (54% yield)
through 1,4-addition presumably due to the combined steric and
electronic effects. There was not much effect by Ce(III) for the
promotion of 1,2-addition.[25] It was not practical to carry out the
S
S
6
25
27
O
O
MgBr
-78 oC
S
X
S
X
26
Scheme 7. Synthetic effort for dienyl sulfones
sulfonation with allylic migration.
6 by vinyl Grignard addition and
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701229
European Journal of Organic Chemistry
FULL PAPER
Synthesis of diphenyl-substituted carotenoids 2
and 3
groups of H, Br, MeO, and Me in order to investigate the
positional effect by comparing the conductance values of all-
trans-9,9′-diphenyl-carotenes 3 with those of all-trans-13,13′-
diphenyl-carotenes 1.[8] The 2:1 coupling between dienyl sulfone
6 and bis(chloroallylic) sulfone 8 was carried out under t-BuOK
base in DMF at -20 °C to give reasonable yields of the coupled
product 28 (69–84%). Ramberg-Bäcklund reaction under a
modified Meyers’ condition,[26] proceeded uneventfully, and the
base-promoted dehydro-desulfonation finally produced 9,9′-
diphenyl-, 9,9′-dibromophenyl-, 9,9′-dianisyl-, and 9,9′-ditoyl-
substituted all-trans-carotenes 3a (19%), 3d (13%), 3e (9%),
and 3f (19%), respectively after recrystallization. The crude
weight for 3 accounted for ~75% yield in 2 steps, which
contained significant amounts of cis-isomers (crude NMR
spectra were complicated). Fortunately, all-trans carotene 3a
was isolated by recrystallization from MeOH/THF due to the
solubility difference from cis-isomers.
Syntheses of diphenyl-substituted carotenes 2 and 3 were
carried out by the sulfone-mediated olefination utilizing dienyl
sulfones 5 and 6. Preliminary study on the synthesis of 3a
suggested that the route using C10 dihalide 8 was beneficial
compared to the one using C10 dialdehyde 7b in the isolation of
all-trans carotene 3. It was more difficult to form all-trans
polyene 3a presumably due to the presence of distal phenyl
substituents near the terminal benzene rings, compared to the
case of all-trans polyene 1a with internal phenyl substituents. It
is important to purify the coupling products and to minimize
possible isomerization routes in order to obtain all-trans
carotene 3. The method using C10 dihalide 8 allowed easy
isolation of the coupled product 28, and all-trans carotene 3 was
obtained upon a couple of dehydro-desulfonation reactions
(forming two C=C bonds). On the other hand, stereoisomers
from the coupling product with six chiral centers by reaction of 6
with C10 dialdehyde 7b did not allow purification of the coupled
products, and all-trans carotene 3 could not be easily isolated
after a couple of double elimination reactions (forming four C=C
bonds).
Table 5. The yields of products from each step in the reaction sequence of
Scheme 8.
Entry
X
Yield 28 (%)[a]
Yield
19
13
9
3
(%)[b]
1
2
3
4
a: H
84
67
69
79
d
: Br
: OMe
: Me
X
e
f
19
Cl
Cl
+
2
SO Ph
S
2
O
2
[a] Isolated yield of a diastereomeric mixture after column chromatographic
S
6
8
purification. [b] Isolated yield of all-trans-carotene
3
after recrystallization
t-BuOK
DMF
from MeOH/THF.
X
X
S
S
Cl
Cl
S
2
+
S
O
2
O
2
S
S
28
S = SO Ph
S
SO Ph
2
2
5a
8
t-BuOK
DMF
1. KOH
2. KOMe
benzene/MeOH
reflux
X
t
-BuOH
C Cl
Ph
Ph
2
6
S
S
PhO S
2
S
O
SO Ph
2
S
2
29
31%
S
S
3
1. KOH
t-BuOH
C Cl
2. KOMe/MeOH
benzene
reflux
2
6
X
Scheme 8. Synthesis of all-trans-9,9′-diphenyl-carotene
mediated olefination from (2 ,4 )-dienyl sulfone and bis(chloroallylic)
sulfone
3 by the sulfone-
Z
E
6
8.
2a 25%
Therefore, all-trans-carotenes
3 containing 9,9′-diphenyl
S
substitution were prepared by the sulfone-mediated olefination
method from (2Z,4E)-dienyl sulfone 6 and bis(chloroallylic)
sulfone 8 (Scheme 8 and Table 5). The phenyl substituent X
was selected according to the electronic nature among the
Scheme 9. Synthesis of 9,9′-cis-10,10′-diphenyl-carotene 2a by the sulfone-
mediated olefination from (2 ,4 )-dienyl sulfone 5a and bis(chloroallylic)
sulfone
Z
E
8.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701229
European Journal of Organic Chemistry
FULL PAPER
Even though all-trans-carotene 2 can’t be prepared from
(2Z,4E)-dienyl sulfone 5a, the synthesis of 9,9′-cis-10,10′-
diphenyl-carotene 2a was tried to check feasibility of the
synthetic method and possibility of isomerization to all-trans-
carotene.[6] The 2:1 coupling between (2Z,4E)-dienyl sulfone 5a
and bis(chloroallylic) sulfone 8 under t-BuOK base in DMF at -
20 °C produced tri-sulfone 29 in 31% yield (Scheme 9), which
reflected steric congestions near the reaction centers. Ramberg-
Conductance Measurement
Conductance of single molecular all-trans-9,9′-diphenyl-
carotenes 3 with a para substituent X (H, Br, OMe, and Me) was
measured in diluted mesitylene solution (0.5 M) by the STM
break junction method.[9] A gold-coated tip was repeatedly
pushed into and out of the carotene molecules, which were
anchored onto a gold electrode plate by a sulfur linkage (current
set point 300 pA; bias -0.3 V; ramp rate 8 Vs-1; pre-amplification
10 nAV-1). Electrical circuits were transiently constructed
between a gold tip and a gold plate through the carotene
molecules by forming gold-sulfur junctions. The decay curves of
current versus time show distinct steps, which correspond to
multiples of the current transported through a single carotene
molecule. The conductance (G0) values were treated statistically
by constructing a histogram from thousands of decay curves
(Figure 2) for each carotene 3 (X = H, Br, OMe, and Me).
Gaussian fitting for the peaks in the histogram gave the single
molecular conductance value at the maximum count.
Bäcklund reaction under
a
modified Meyers’ condition,[26]
followed by KOMe-promoted dehydro-desulfonation produced
9,9′-cis-10,10′-diphenyl-carotene 2a in 25% isolated yield after
recrystallization from MeOH and THF. 9,9′-cis-Carotene 2a was
fairly stable and no isomerization to all-trans-carotene was
observed under the thermal condition.
The stereochemistry of 9,9′-cis-carotene 2a and all-trans-
carotene 3 was deduced from the (2Z,4E) stereochemistry of
dienyl sulfone 5a and the (2Z,4E) stereochemistry of dienyl
1
sulfone 6, and more specifically from the H NMR chemical shift
of hydrogens near the phenyl substituents. The 10,10′- and 9,9′-
diphenyl substituents are expected to be located with large
dihedral angles to the plane of conjugated polyene presumably
due to steric interactions of the ortho-hydrogens of phenyl
groups and the near-by hydrogens of polyene.[27] The ring-
current effect of a phenyl group makes the near-by hydrogens,
which are located right above or below of the ring, up-field
shifted by magnetic anisotropy.[28] The chemical shift of H-8 (H-
8′) of 2a, which would have been up-field shifted by the benzene
ring current effect in all-trans-carotene 2, is most down-field
shifted at 6.63 ppm in 9,9′-cis-carotene 2a (Figure 1). The
corresponding near-by hydrogens of the phenyl groups in all-
trans-carotene 3a are up-field shifted at 6.22 ppm for H-7 (H-7′)
and at 6.13 ppm for H-11 (H′-11). There was a technical problem
in N.O.E. measurement because of overlapping peaks from H-8
and H-11 in 9,9′-cis-carotene 2a.
Figure 2. Histograms of single molecular conductance (G0) values measured
by the STM break junction method for all-trans-9,9′-di(p-X-C6H4)-carotenes 3
(X = H, Br, OMe, and Me) and their Gaussian fittings.
Table 6. The conductance (C) and UV absorption () values for all-trans-9,9′-
di(
p-X-C6H4)-carotenes
3
and all-trans-13,13′-di(
p-X-C6H4)-carotenes
1.
X
3
1[8]
C (nS)

(nm)
C (nS)
 (nm)
H
4.38±0.02
1.54±0.01
472, 500, 536
475, 499, 533
475, 499, 533
474, 499, 534
2.86±0.03
1.15±0.01
17.07±0.17
5.38±0.07
463, 490, 524
465, 491, 524
464, 492, 526
464, 491, 526
Br
OMe
Me
22.87±0.16
6.59±0.03
Figure 1. Comparison of 1H NMR spectra for 9,9′-cis-10,10′-diphenyl-carotene
2a and all-trans-9,9′-diphenyl-carotene 3a
.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701229
European Journal of Organic Chemistry
FULL PAPER
spectrometer in CDCl3 with tetramethylsilane as an internal reference
unless noted otherwise. Peaks with “*” mark in the NMR are from the
minor (anti or E) isomers. The column chromatography was performed by
the method of Still with silica gel 60, 70-230 mesh ASTM using a gradient
mixture of EtOAc/hexanes. Reactions were performed in a well-dried
flask under Argon atmosphere unless noted otherwise. Only general
experimental procedures and data for the parent phenyl substituent (X =
H for C6H4-p-X) are described in this section. The others are listed in the
Supporting Information-1.
The conductance values for all-trans-9,9′-diphenyl carotenes
3 were summarized in nano-Siemen unit according to the
substituent X, and compared with those of all-trans-13,13′-
diphenyl carotenes
1
(Table 6).[8] An electron-donating
substituent gives a higher conductance value by building up
more electron density in the HOMO of the polyene chain, which
is also reflected in the increased electron density in the phenyl
substituents (see Supporting Information-4 for DFT calculation).
This general trend following the electron donating ability of the
substituent (OMe > Me > H > Br) was observed in the series of
carotene 3 just like in the series of carotene 1.
Bromination of Acetophenones: 2-bromo-1-phenylethanone (13a).
To a stirred solution of acetophenone (15.00 g, 124.8 mmol) in MeCN
(130 mL) was added N-bromosuccinimide (23.23 g, 131.1 mmol) and
TMS·OTf (1.39 g, 6.24 mmol). The mixture was stirred at 25 °C for 3 d,
diluted with Et2O, washed with H2O, dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure. The crude product
was recrystallized from 1:4 hexane:EtOAc to give 13a (18.13 g, 91.10
mmol) in 73% yield as off-white solid. Data for 13a: 1H NMR  4.47 (s,
2H), 7.47–7.55 (m, 2H), 7.60–7.66 (m, 1H), 7.97–8.02 (m, 2H) ppm.
There was a slight but consistent positional effect of phenyl
substituents on the conductance of the carotenoid wires.[29] The
conductance values for 9,9′-diphenyl substitution (carotenes 3)
were a little higher than those for 13,13′-diphenyl substitution
(carotenes 1). The optimized geometries for the series of
carotenes 3 and carotenes 1 predicted by DFT calculations
{B3LYP/6-311G(d,p) level} show one significant difference (See
SI-4). The polyene chains of 13,13′-diphenyl carotenes 1 are
straight, but those of 9,9′-diphenyl carotenes 3 look slightly
curved, which may be the origin of the positional effect of the
phenyl substituents on the conductance. Of course, this is not a
big difference, but the energy gaps (~2.07 eV) between LUMO
and HOMO of carotenes 3 by DFT calculation are consistently
lower than those (~2.11 eV) of carotenes 1 (Table S4-7),
indicating more effective conjugation in the polyene chain of
carotenes 3 to give a slightly higher conductance value. In fact,
the  values of the UV absorption for carotenes 3 are red-shifted
by ~10 nm from those for carotenes 1, which confirms the above
theory (Table 6).
Vinyl Carbinol 14 from 13: 1-bromo-2-phenylbut-3-en-2-ol (14a). To a
stirred solution 13a (6.50 g, 32.65 mmol) in THF (50 mL) was added 1 M
THF solution of vinylmagnesium bromide (49 mL, 49 mmol) at -78 °C.
The mixture was stirred at -78 °C for 2 h, quenched with 10% NH4Cl
solution, extracted with EtOAc, washed with
1 M HCl, dried over
anhydrous Na2SO4, filtered, and concentrated under reduced pressure.
The crude product was purified by silica gel column chromatography to
give 14a (6.00 g, 26.42 mmol) in 81% yield as light yellow oil. Data for
14a: 1H NMR  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 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.
Homoallylic sulfide 17 from 14: 2-phenyl-1-(phenylthio)but-3-en-2-ol
(17a). To a stirred solution of 14a (4.60 g, 20.26 mmol) in THF (20 mL)
was added 8 M NaOH (1.62 g, 40.52 mmol) solution (5 mL) at 0 °C. The
mixture was stirred at 0 °C for 1 h, diluted with EtOAc, washed with H2O,
dried over anhydrous Na2SO4, filtered, and concentrated under reduced
pressure. To the solution of the above crude product in DMF (20 mL) was
added PhSNa (4.01 g, 30.37 mmol) at 0 °C. The mixture was stirred at
0 °C for 8 h, diluted with CH2Cl2, washed with 1 M NaOH and H2O, dried
over anhydrous Na2SO4, filtered, and concentrated under reduced
pressure. The crude product was purified by silica gel column
chromatography to give 17a (4.25 g, 16.58 mmol) in 82% yield as yellow
oil. Data for 17a: 1H NMR  3.08 (br s, 1H), 3.52 (A of ABq, J = 13.2 Hz,
1H), 3.54 (B of ABq, J = 13.2 Hz, 1H), 5.22 (dd, J = 10.6, 1.0 Hz, 1H),
5.37 (dd, J = 17.2, 1.0 Hz, 1H), 6.16 (dd, J = 17.2, 10.6 Hz, 1H), 7.15–
7.28 (m, 4H), 7.31–7.38 (m, 4H), 7.45–7.49 (m, 2H) ppm; 13C NMR 
48.5, 76.4, 114.7, 125.7, 126.8, 127.6, 128.6, 129.2, 130.5, 136.6, 142.4,
144.1 ppm; IR (KBr) 3490, 3058, 2926, 1480, 1447, 1439, 1336 cm-1;
HRMS (CI) calcd for C16H17OS 257.1000, found 257.1003.
Conclusions
A general synthetic pathway for diversely phenyl-substituted
carotenoids has been developed. Chloroallylic sulfones 11 and
12 with a regio-isomeric phenyl substitution were prepared from
acetophenones. Indium-mediated addition of chloroallylic
sulfones 11 or 12 to p-(methylthio)benzaldehyde 9a, followed by
the oxonia-Cope rearrangement produced dienyl sulfones 5 and
6 in a stereoselective manner as the key building blocks. The
sulfone-mediated olefination of dienyl sulfones 5 or 6 with
bis(chloroallylic)sulfone
8
produced 9,9′-cis-10,10′-diphenyl-
carotene 2 and all-trans-9,9′-diphenyl-carotene 3. Conductance
measurement of all-trans carotenoids 3 by the STM break
junction method and comparison with those of all-trans
carotenoids 1 revealed the positional effects of the phenyl
substituents as well as the polar effect of the phenyl substituent
X according to the electronic nature: an electron-donating
substituent gives a higher conductance and the distal phenyl
group gives a slightly higher conductance.
Oxidation of 17 to sulfone 18: 2-phenyl-1-(phenylsulfonyl)but-3-en-
2-ol (18a). To a stirred solution of 17a (1.12 g, 4.37 mmol) in MeOH (20
mL) was added Oxone (8.05 g, 13.10 mmol) at 0 °C. The mixture was
stirred at 0 °C for 6 h, diluted with CH2Cl2, washed with H2O, dried over
anhydrous Na2SO4, filtered, and concentrated under reduced pressure.
The crude product was purified by silica gel column chromatography to
give 18a (1.00 g, 3.46 mmol) in 80% yield as off-white solid. Data for 18a:
1H NMR  3.73 (A of ABq, J = 14.6 Hz, 1H), 3.79 (B of ABq, J = 14.6 Hz,
1H), 4.81 (s, 1H), 5.21 (dd, J = 10.4, 0.8 Hz, 1H), 5.46 (dd, J = 17.2, 0.8
Hz, 1H), 6.14 (dd, J = 17.2, 10.4 Hz, 1H), 7.15–7.24 (m, 3H), 7.28–7.33
Experimental Section
General Experimental. 1H and 13C NMR spectra were respectively
recorded on a 400 MHz and 100 MHz NMR (or a 300 MHz and 75 MHz)
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701229
European Journal of Organic Chemistry
FULL PAPER
(m, 2H), 7.39–7.45 (m, 2H), 7.54–7.59 (m, 1H), 7.65–7.69 (m, 2H) ppm;
13C NMR  65.7, 75.3, 115.1, 125.4, 127.7, 128.0, 128.6, 129.3, 133.8,
140.5, 141.2, 142.5 ppm; IR (KBr) 3483, 2925, 1448, 1305, 1145, 1083
cm-1; HRMS (CI) calcd for C16H15O3S 287.0742, found 287.0742.
The mixture was stirred at 0 °C for 4 h, diluted with EtOAc, washed with
H2O, dried over anhydrous Na2SO4, filtered, and concentrated under
reduced pressure. The crude product was purified by silica gel column
chromatography to give 12a (0.39 g, 1.50 mmol, a 3:1 Z:E mixture) in
91% yield as light yellow sticky oil. Data for 12a: 1H NMR  3.75 (d, J =
7.6 Hz, 2H),* 4.10 (d, J = 8.0 Hz, 2H), 4.18 (s, 2H), 4.20 (s, 2H),* 5.89 (t,
J = 8.4 Hz, 1H), 5.97 (t, J = 8.0 Hz, 1H),* 6.68–7.38 (m, 5H), 7.50–7.94
(m, 5H) ppm; 13C NMR 26.8, 28.7,* 39.4, 48.9,* 126.0, 127.0,* 127.9,
128.0,* 128.2,* 128.4, 128.5,* 128.5, 135.8,* 138.6, 140.4, 141.2* ppm;
IR (KBr) 3060, 2927, 1630, 1576, 1446, 1347, 1259, 1202, 769, 697 cm-
1; HRMS (CI) calcd for C16H16O2SCl 307.0559, found 307.0554.
Chlorination
of
18
to
11:
(4-chloro-2-phenylbut-2-
enylsulfonyl)benzene (11a). To a stirred solution of 18a (3.50 g, 12.13
mmol) in DMF (30 mL) was added (COCl)2 (6.35 mL, 72.82 mmol) at
0 °C. The mixture was stirred at 0 °C for 1 d, diluted with CH2Cl2, washed
with 1 M HCl, dried over anhydrous Na2SO4, filtered, and concentrated
under reduced pressure. The crude product was purified by silica gel
column chromatography to give 11a (3.01 g, 9.81 mmol, a 8:1 Z:E
mixture) in 81% yield as off-white solid. Data for 11a: 1H NMR  3.94 (d, J
= 7.8 Hz, 2H),* 4.16 (s, 2H),* 4.24 (d, J = 7.8 Hz, 2H), 4.38 (s, 2H), 5.83
(t, J = 8.0 Hz, 1H),* 6.22 (t, J = 8.0 Hz, 1H), 7.17–7.24 (m, 5H), 7.38–
7.44 (m, 2H), 7.50–7.56 (m, 1H), 7.74–7.78 (m, 2H) ppm; 13C NMR 
40.9, 57.8, 126.8, 128.4, 128.6, 128.7, 129.3, 132.0, 132.5, 134.1, 138.9,
140.0 ppm; IR (KBr) 3060, 1447, 1319, 1309, 1152, 1137, 1084, 913 743
cm-1; HRMS (CI) calcd for C16H16O2SCl 307.0559, found 307.0559.
Indium-mediated addition of 11/12 to 9a to give 22/23: 1-(4-
(methylthio)phenyl)-2-phenyl-2-(phenylsulfonylmethyl)but-3-en-1-ol
(22a). To a stirred solution of 11a (0.43 g, 1.40 mmol) in THF (10 mL)
were added Indium (0.19 g, 1.68 mmol), 4-(methylthio)benzaldehyde (9a)
(0.36 g, 1.54 mmol), and H2O (40 mL). The mixture was heated at 70 °C
for 6 h, diluted with CH2Cl2, washed with 1 M HCl, dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure. The crude
product was purified by silica gel column chromatography to give 22a
(0.31 g, 0.73 mmol) in 52% yield (a 11:1 syn:anti mixture) as off-white
solid. Data for syn-22a: 1H NMR  2.47 (s, 3H), 2.67 (br s, 1H), 3.55 (d, J
= 14.8 Hz, 1H), 3.84 (d, J = 14.8 Hz, 1H), 5.08 (d, J = 18.0 Hz, 1H), 5.43
(d, J = 11.2 Hz, 1H), 5.85 (br s, 1H), 6.30 (dd, J = 18.0, 11.2 Hz, 1H),
7.10–7.19 (m, 7H), 7.24–7.29 (m, 2H), 7.34–7.40 (m, 2H), 7.48–7.52 (m,
1H), 7.52–7.57 (m, 2H) ppm; 13C NMR  15.6, 53.5, 62.6, 75.9, 117.6,
125.4, 127.3, 128.0, 128.9, 128.9, 129.1, 133.0, 136.2, 138.2, 138.4,
138.4, 138.5, 141.3 ppm; IR (KBr) 3498, 3078, 2924, 1732, 1591, 1444,
1288, 1149, 1084, 845, 750, 582 cm-1; HRMS (CI) calcd for C24H25O3S2
425.1245, found 425.1247.
Chlorination of acetophenones: 2-chloro-1-phenylethanone (19a).
To a stirred solution of acetophenone (17.00 g, 126.8 mmol) in MeCN
(120 mL) were added N-chlorosuccinimide (16.93 g, 126.8 mmol) and p-
TsOH·H2O (36.20g, 190.2 mmol). The mixture was heated at 80 °C for 7
h, and cooled to room temperature. The mixture was diluted with Et2O,
washed with H2O, dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. The crude product was
recrystallized from a 1:4 mixture of hexane/EtOAc to give 2-chloro-1-
phenylethanone (19a) (16.66 g, 107.8 mmol) in 85% yield as off-white
solid. Data for 19a: 1H NMR  4.73 (s, 2H), 7.48–7.55 (m, 2H), 7.60–7.66
(m, 1H), 7.96–8.02 (m, 2H) ppm.
(1S,2R)-1-(4-(Methylthio)phenyl)-3-phenyl-2-
(phenylsulfonylmethyl)but-3-en-1-ol (23a). Following the procedure for
22a, 12a (2.76 g, 8.98 mmol) in THF (10 mL) and H2O (40 mL) was
reacted with Indium (1.03 g, 9.00 mmol) and 4-methylthiobenzaldehyde
(9a) (1.49 g, 9.82 mmol) at 70 °C for 8 h to give 23a (3.47 g, 8.18 mmol)
in 91% yield (a 3.5:1 syn:anti mixture) as off-white solid. Data for 23a: 1H
NMR  2.42 (s, 3H), 2.87 (br s, 1H), 3.28 (dd, J = 14.4, 8.0 Hz, 1H), 3.48
(dd, J = 14.4, 4.0 Hz, 1H), 3.51–3.58 (m, 1H), 4.79 (d, J = 3.2 Hz, 1H),
4.94 (s, 1H), 5.28 (s, 1H), 7.08 (br s, 4H), 7.16–7.26 (m, 5H), 7.40–7.47
(m, 2H), 7.54–7.60 (m, 1H), 7.68–7.73 (m, 2H) ppm; 13C NMR 16.7,
46.4, 56.6, 74.0, 117.2, 126.1, 126.8, 127.5, 127.6, 127.9, 128.2, 129.1,
133.6, 137.0, 138.0, 149.3, 141.3, 145.9 ppm; IR (KBr) 3495, 3055, 1597,
1265, 1138, 768 cm-1; HRMS (EI) calcd for C24H25O3S2 425.1245, found
425.1243.
Vinyl carbinol 20 from 19: 1-chloro-2-phenylbut-3-en-2-ol (20a). To a
stirred solution of 19a (2.10 g, 13.58 mmol) in THF (30 mL) was added 1
M THF solution of vinylmagnesium bromide (20 mL, 20 mmol) at -78 °C.
The mixture was stirred at that temperature for 1 h, quenched with 10%
NH4Cl solution, extracted with EtOAc, washed with H2O, dried over
anhydrous Na2SO4, filtered, and concentrated under reduced pressure.
The crude product was purified by silica gel column chromatography to
give 20a (2.06 g, 11.28 mmol) in 83% yield as light yellow oil. Data for
20a: 1H NMR  2.75 (s, 1H), 3.88 (s, 2H), 5.32 (dd, J = 10.6, 0.8 Hz, 1H),
5.42 (dd, J = 17.2, 0.8 Hz, 1H), 6.17 (dd, J = 17.2, 10.6 Hz, 1H), 7.27–
7.42 (3H , m), 7.44–7.51 (2H , m) ppm; 13C NMR 53.5, 76.2, 115.9,
125.6, 127.8, 128.5, 140.2, 142.0 ppm; IR (KBr) 3551, 3466, 3062, 2960,
1644, 1449, 1172, 1003 cm-1; HRMS (CI) calcd for C10H10Cl [C10H12OCl –
H2O] 165.0468, found 165.0471.
Oxonia-Cope rearrangement of 22 to 5: methyl(4-((1E,3Z)-4-phenyl-
5-(phenylsulfonyl)penta-1,3-dienyl)phenyl)sulfane (5a). To a stirred
solution of 22a (1.15 g, 2.71 mmol) in benzene (20 mL) were added
Bromination of 20 to 21: (4-bromo-1-chlorobut-2-en-2-yl)benzene
(21a). To a stirred solution of 20a (1.75 g, 9.59 mmol) in Et2O (15 mL)
was added PBr3 (0.45 mL, 4.8 mmol) at 0 °C. The mixture was stirred at
0 °C for 7 h, diluted with Et2O, washed with H2O, dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure. The crude
product was purified by silica gel column chromatography to give 21a
(2.11 g, 8.58 mmol, a 3:1 Z:E mixture) in 90% yield as yellow oil. Data for
21a: 1H NMR 3.88 (d, J = 8.4 Hz, 2H),* 4.23 (d, J = 8.8 Hz, 2H), 4.32
(br s, 2H),* 4.52 (s, 2H), 6.16 (t, J = 8.4 Hz, 1H),* 6.25 (t, J = 8.8 Hz, 1H),
7.27–7.50 (m, 5H) ppm; 13C NMR  26.8, 28.8,* 39.6, 49.0,* 126.2,
127.1,* 128.1, 128.2,* 128.4,* 128.5, 128.6,* 128.6, 136.0,* 138.8, 140.7,
141.5* ppm; IR (KBr) 3029, 2970, 1738, 1446, 1366, 1203, 769, 696 cm-
1; HRMS (CI) calcd for C10H9BrCl 246.9526, found 246.9524.
camphoresulfonic
acid
(0.70
g,
2.98
mmol)
and
4-
(methylthio)benzaldehyde (9a) (0.45 g, 2.98 mmol). The mixture was
heated at 80 °C for 6 h, cooled to room temperature, diluted with CH2Cl2,
washed with H2O, dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. The crude product was purified by
silica gel column chromatography to give 5a (0.77 g, 1.89 mmol) in 70%
yield (a 7:1 Z:E mixture at C-2) as off-white solid. Data for 5a: 1H NMR
2.52 (s, 3H), 4.58 (s, 2H), 6.72 (d, J = 14.4 Hz, 1H), 6.58 (d, J = 11.2 Hz,
1H), 6.78 (dd, J = 14.4, 11.2 Hz, 1H), 7.20–7.45 (m, 10H), 7.75–7.83 (m,
2H) ppm; IR (KBr) 3057, 2922, 1711, 1589, 1444, 1306, 1136, 741, 526
cm-1; 13C NMR  15.4, 58.0, 123.4, 126.1, 126.2, 127.1, 127.3, 127.4,
128.3, 128.5, 128.7, 133.4, 133.5, 134.8, 136.0, 138.5, 138.8, 140.2 ppm;
HRMS (CI) calcd for C24H23O2S2 407.1139, found 407.1136.
Sulfonation
of
21
to
12:
(4-chloro-3-phenylbut-2-
enylsulfonyl)benzene (12a). To a stirred solution of 21a (0.40 g, 1.64
mmol) in DMF (10 mL) was added NaSO2Ph (0.30 g, 1.80 mmol) at 0 °C.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701229
European Journal of Organic Chemistry
FULL PAPER
Oxonia-Cope rearrangement of 23 to 6: methyl(4-((1E,3Z)-3-phenyl-
5-(phenylsulfonyl)penta-1,3-dienyl)phenyl)sulfane (6a). To a stirred
solution of 23a (3.20 g, 7.54 mmol) in CH2Cl2 (50 mL) was added
Sn(OTf)2 (0.31 g, 0.75 mmol). The mixture was stirred at 40 °C for 8 h,
diluted with CH2Cl2, washed with 1 M HCl, dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure. The crude product
was purified by silica gel column chromatography to give 6a (2.70 g, 6.64
mmol) in 88% yield (a 4:1 Z:E mixture at C-3) as off-white solid. Data for
6a: 1H NMR  2.47 (s, 3H), 2.49 (s, 3H),* 3.77 (d, J = 8.0 Hz, 2H), 4.19 (d,
J = 8.4 Hz, 2H),* 5.51 (t, J = 8.4 Hz, 1H),* 5.85 (t, J = 8.0 Hz, 1H), 5.94 (d,
J = 16.0 Hz, 1H), 6.19 (d, J = 16.0 Hz, 1H),* 6.61–6.60 (m, 2H), 6.94 (d, J
= 16.0 Hz, 1H), 7.09–7.24 (m, 4H), 7.24–7.38 (m, 3H), 7.47–7.56 (m, 2H),
7.64–7.69 (m, 1H), 7.75–7.80 (m, 2H) ppm; 13C NMR  15.6, 57.4, 117.3,
126.3, 127.0, 127.7, 128.3, 128.6, 128.9, 129.1, 130.5, 133.0, 133.4,
133.7, 135.5, 138.5, 138.6, 148.8 ppm; IR (KBr) 3037, 2904, 1585, 1442,
1307, 1140, 962, 833, 735, 550 cm-1; HRMS (ESI) calcd for
C24H22NaO2S2 429.0953, found 429.0952.
(941,300), 536 (802,300) nm; HRMS (FAB) calcd for C46H44S2 660.2884,
found 660.2879.
Trisulfone 29. Following the procedure for 28a, 5a (2.1 g, 5.1 mmol) in
DMF (20 mL) was deprotonated by t-BuOK (0.62 g, 5.5 mmol) at -20 °C
for 30 min, which was then reacted with 8 (0.63 g, 2.3 mmol) at -20 °C for
2 h and then at room temperature for 10 h to give 29 (0.72 g, 0.71 mmol)
in 31% yield as yellow amorphous solid. Data for 29: Rf = 0.25 (3:2
hexane/EtOAc); 1H NMR  1.58 (s, 6H), 2.46 (s, 6H), 2.68–2.78 (m, 2H),
2.97–3.06 (m, 2H), 3.43–3.57 (m, 4H), 4.09–4.15 (m, 2H), 5.26 (t, J = 7.2
Hz, 2H), 6.55 (d, J = 10.8 Hz, 2H), 6.59 (d, J = 14.8 Hz, 2H), 6.65 (dd, J =
14.8, 10.8 Hz, 2H), 6.83–6.88 (m , 4H), 7.12 (d, J = 8.8 Hz, 4H), 7.16 (d,
J = 8.8 Hz, 4H), 7.16–7.21 (m, 6H), 7.42–7.48 (m, 4H), 7.56–7.62 (m,
4H), 7.76–7.81 (m, 4H) ppm; 13C NMR  17.5, 18.9, 39.1, 51.6, 70.1,
114.5, 124.4, 126.3, 127.1, 127.5, 128.2, 128.7, 129.0, 129.3, 132.5,
133.5, 133.7, 134.2, 135.5, 137.8, 138.7, 139.5, 141.2 ppm; IR (KBr)
3023, 2986, 1588, 1491, 1446, 1387, 1305, 1219, 1144, 1085, 973, 902,
723, 649 cm-1; HRMS (FAB) calcd for C46H47O2S3 (C58H59O6S5
2×C6H6O2S) 727.2738, found 727.2736.
–
Coupling of dienyl sulfone 6 with 8: preparation of 28a. To a stirred
solution of 6a (2.19 g, 5.39 mmol) in DMF (20 mL) at -20 °C under argon
atmosphere was added t-BuOK (0.66 g, 5.88 mmol). The reaction
9,9′-cis-10,10′-Diphenyl-carotene 2a. Following the procedure for 3a,
29 (0.69 g, 0.68 mmol) in CH2Cl2 (20 mL) was treated with t-BuOH (8mL)
and CCl4 (8 mL). The resulting solution was reacted with KOH (0.38 g
6.80 mmol) at 25 °C for 12 h to give the crude triene product (Rf = 0.55 in
2:3 EtOAc/hexane, 0.75 g), which was reacted with KOMe (1.67 g 23.9
mmol) in toluene (20 mL) and MeOH (20 mL) at 100 °C for 20 h to give
the crude product (240 mg), which was purified by SiO2 flash column
chromatography and then recrystallization from THF/MeOH to give 2a
(0.11 g, 0.17 mmol) in 25% overall yield in two steps as red solid. Data
for 2a: Rf = 0.53 (1:4 EtOAc/hexane); 1H NMR  1.92 (s, 6H), 2.44 (s, 6H),
5.98 (d, J = 15.2 Hz, 2H), 6.01–6.11 (m, 2H), 6.45–6.55 (m, 2H), 6.51 (d,
J = 10.8 Hz, 2H), 6.58 (d, J = 15.6 Hz, 4H), 6.63 (dd, J = 15.2, 10.8 Hz,
2H), 7.10 (d, J = 8.0 Hz, 4H), 7.15 (d, J = 8.0 Hz, 4H), 7.18–7.24 (m, 4H),
7.34–7.40 (m, 2H), 7.41–7.47 (m, 4H) ppm; 13C NMR  12.7, 15.7, 126.3,
126.5, 126.8, 127.3, 128.2, 130.0, 130.1, 132.0, 132.2, 132.4, 133.4,
134.5, 136.2, 136.3, 137.6, 137.7, 143.3 ppm; IR (KBr) 3027, 2922, 2855,
1592, 1491, 1439, 1394, 1319, 1256, 1182, 1148, 1092, 1014. 965, 805,
708, 615 cm-1; UV (c = 1.942×10-6 M in CH2Cl2) λ (ε) 462 (87,800), 489
(117,000), 524 (98,200) nm; HRMS (FAB) calcd for C46H44S2 660.2884,
found 660.2889.
mixture was stirred at -20 °C for 30 min, and the solution of the C10
-
dichloride 8 (0.66 g, 2.45 mmol) in DMF (5 mL) was added. The mixture
was stirred at -20 °C for 2 h, and warmed up to and stirred at 25 °C for 10
h. The reaction mixture was diluted with EtOAc, washed with 1 M HCl
and H2O, dried over anhydrous Na2SO4, filtered, and concentrated under
reduced pressure. The crude product was purified by SiO2 flash column
chromatography to give the coupled product 28a (2.09 g, 2.07 mmol) in
84% yield as yellow amorphous solid. Data for 28a: 1H NMR  1.42–1.72
(s, 6H), 2.45–2.50 (s, 6H), 2.44–2.59 (m, 2H), 2.78–3.14 (m, 2H), 3.40–
3.64 (m, 4H), 3.65–4.38 (m, 2H), 5.17–5.60 (m, 4H), 5.82–6.08 (d, J =
16.0 Hz, 2H), 6.38–6.90 (d, J = 16.0 Hz, 2H), 7.02–7.07 (m, 2H), 7.10–
7.21 (m, 12H), 7.23–7.33 (m, 4H), 7.40–7.48 (m, 2H), 7.50–7.70 (m, 4H),
7.72–7.90 (m, 4H) ppm; IR (KBr) 3023, 2922, 1588, 1510, 1495, 1446,
1405, 1305, 1223, 1144, 1085, 969, 839, 749, 705, 690 cm-1; HRMS
(ESI) calcd for C58H58NaO6S5 1033.2729, found 1033.2731.
Ramberg-Bäcklund reaction and sulfone elimination to give
carotenoids 3: all-trans-9,9′-diphenyl-carotene 3a. To stirred solution
of 28a (2.03 g, 2.01 mmol) in CH2Cl2 (20 mL) were added t-BuOH (20
mL), CCl4 (20 mL) and pulverized KOH (1.12 g, 20.07 mmol) under argon
atmosphere. The mixture was stirred at 25 °C for 3 h, diluted with CH2Cl2,
washed with 1 M HCl, dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure to give the crude triene product. To
a stirred solution of the above triene (2.00 g) in benzene (50 mL) and
cyclohexane (50 mL) was added KOMe (4.45 g, 63.47 mmol). The
mixture was heated at reflux for 9 h, and cooled to room temperature.
The mixture was diluted with EtO2, washed with H2O, dried over
anhydrous Na2SO4, and filtered. The aqueous layer was extracted with
CH2Cl2, dried over anhydrous Na2SO4, and filtered. The combined
organic layer was concentrated under reduced pressure to give a crude
product (1.00 g), which was purified by SiO2 flash column
chromatography and then recrystallization from THF/MeOH to give all-
trans 3a (0.25 g, 0.38 mmol) in 19% yield as red solid. Data for all-trans
3a: 1H NMR  1.74 (s, 6H), 2.48 (s, 6H), 6.13 (d, J = 16.0 Hz, 2H), 6.22
(dd, J = 14.8, 11.6 Hz, 2H), 6.20–6.29 (m, 2H), 6.42 (d, J = 14.8 Hz, 2H),
6.52 (d, J = 11.6 Hz, 2H), 6.54–6.62 (m, 2H), 7.03 (d, J = 16.0 Hz, 2H),
7.15 (d, J = 8.4 Hz, 4H), 7.23–7.32 (m, 4H), 7.26 (d, J = 8.4 Hz, 4H),
7.35–7.42 (m, 2H), 7.42–7.48 (m, 4H) ppm; 13C NMR12.7, 15.8, 126.6,
126.7, 126.9, 127.3, 128.2, 128.3, 129.0, 130.0, 130.4, 132.3, 133.2,
134.6, 136.7, 137.4, 137.7, 138.7, 142.2 ppm; IR (KBr) 3027, 2922, 2851,
1737, 1595, 1491, 1442, 1398, 1260, 1092, 1029, 965, 805, 779, 752,
708 cm-1; UV (c = 2.3 × 10-6 M in CH2Cl2) λ (ε) = 472 (717,700), 500
Acknowledgements
This research was supported by Basic Science Research
Program (NRF-2016R1A2B4007684) and by Priority Research
Centers Program (NRF-2009-0093816) both through the
National Research Foundation of Korea funded by the Ministry
of Science, ICT and Future Planning. We appreciate Professor
Nongjian Tao and Professor Stuart Lindsay at A.S.U. for
valuable suggestions for the conductance measurement of the
carotenoid wires.
Keywords: Carotenoids • Indium • Molecular electronics •
Olefination • Pericyclic reaction
[1]
[2]
a) N. I. Krinsky, Annu. Rev. Nutr. 1993
J. Agric. Food Chem. 2012 60, 2409-2417; c) R. Alvarez, B. Vaz, H.
Gronemeyer, A. R. de Lera, Chem. Rev. 2014 114, 1-125.
a) C. Enzeil, Pure Appl. Chem. 1985 57, 693-700; b) N. I. Krinsky, Free
Radic. Biol. Med. 1989 , 617-635.
, 13, 561-587; b) L. H. Skibsted,
,
,
,
,
7
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701229
European Journal of Organic Chemistry
FULL PAPER
[3]
a) M. Wrona, M. Rozanowska, T. Sarna, Free Radic. Biol. Med. 2004
,
[17] R. W. Hoffmann, Chem. Rev. 1989
[18] a) C.-J. Li, T.-H. Chan, Tetrahedron 1999
H. Ito, Y. Butsugan, J. Org. Chem. 1988
T.-H. Chan, Tetrahedron Lett. 1995 36, 8957-8960.
[19] J.-H. Min, S.-Y. Jung, B. Wu, J. T. Oh, M. Lah, S. Koo, Org. Lett. 2006
, 1459-1462.
[20] a) J. Nokami, K. Yoshizane, H. Matsuura, S.-i. Sumida, J. Am. Chem.
Soc. 1998 120, 6609-6610; b) J. Nokami, K. Nomiyama, S. Matsuda, N.
Imai, K Kataoka, Angew. Chem. Int. Ed. 2003 42, 1273-1276; c) S.-i.
Sumida, M. Ohga, J. Mitani, J. Nokami, J. Am. Chem. Soc. 2000
1310-1313; d) J. Nokami, L. Anthony, S.-i. Sumida, Chem. Eur. J. 2000
, 2909-2913.
[21] a) T.-P. Loh, Q.-Y. Hu, L.-T. Ma, J. Am. Chem. Soc. 2001, 123, 2450-
2451; b) T.-P. Loh, K.-T. Tan, Q.-Y. Hu, Angew. Chem. Int. Ed. 2001
40, 2921-2922; c) T.-P. Loh, H.-S. Cheng, J. Am. Chem. Soc. 2003,
,
89, 1841-1860.
55, 11149-11176; b) S. Araki,
53, 1833-1835; c) M. B. Isaac,
36, 1094-1101; b) M. Fuciman, P. Chabera, A. Zupcanova, P. Hribek, J.
B. Arellano, F. Vacha, J. Psencik, T. Polivka, Phys. Chem. Chem. Phys.
,
,
2010
,
12, 3112-3120.
,
[4]
[5]
J. Maeng, S. B. Kim, N. J. Lee, E. Choi, S.-Y. Jung, I. Hong, S.-H. Bae,
,
J. T. Oh, B. Lim, J. W. Kim, C. J. Kang, S. Koo, Chem. Eur. J. 2010
,
16
,
8
7395-7399.
a) S. Mackowski, S. Wormke, T. H. P. Brotosudarmo, C. Jung, R. G.
Hiller, H. Scheer, C. Brauchle, Biophys. J. 2007 93, 3249-3258; b) H. A.
Frank, G. W. Brudvig, Biochem. 2004 43, 8607-8615; c) A. Zaidi, H. Li,
,
,
.
,
,
,
122
,
H.-R. Sliwka, V. Partali, H. Ernst, T. B. Melo, Tetrahedron 2013, 69,
,
219-227.
6
[6]
[7]
The systematic name of stereochemistry for alkenes suggested by
IUPAC was not used for carotenes and . Instead, the cis trans
1,
2
3
/
,
convention for the conjugated polyenes ignoring substituents was used
together with the numbering system of carotenoids.
125, 4990-4991; d) T.-P. Loh, Q.-Y. Hu, L.-T. Ma, Org. Lett. 2002, 4,
S. B. Kim, H. Kim, B. Lim, J. Maeng, S.-H. Bae, E. Choi, J. T. Oh, I.
2389-2391.
Hong, S.-Y. Jung, J. E. Yeo, S. Koo, Pure Appl. Chem. 2011
,
83, 613-
[22] S.-Y. Jung, J.-H. Min, J. T. Oh, S. Koo, J. Org. Chem. 2006
,
71, 4823-
620.
4828.
[8]
[9]
Y. Zhao, S. Lindsay, S. Jeon, H.-J. Kim. L. Su, B. Lim, S. Koo, Chem.
Eur. J. 2013 19, 10832-10835.
a) B. Xu, N. J. Tao, Science 2003
Estroff, J. K. Kriebel, R. G. Nuzzo, G. M. Whitesides, Chem. Rev. 2005
[23] H. E. Zimmerman, M. D. Traxler, J. Am. Chem. Soc. 1957, 79, 1920-
,
1923.
,
301, 1221-1223; b) J. C. Love, L. A.
[24] The stereochemistry of homoallylic alcohols 11 or 12 (syn/anti) and
dienyl sulfones or
) was assigned by comparison of 1H NMR
,
5
6 (Z/E
105, 1103-1169; c) J. He, F. Chen, J. Li, O. F. Sankey, Y. Terazono, C.
Herrero, D. Gust, T. A. Moore, A. L. Moore, S. M. Lindsay, J. Am.
chemical shifts with those of authentic samples, which were
respectively confirmed by X-ray crystallographic analysis or N.O.E.
experiment (See the 1H NMR spectra in Supporting Information-3).
Chem. Soc. 2005, 127, 1384-1385.
[10] J. S. You, S. Jeon, Y. J. Byun, S. Koo, S. S. Choi, Food Chem. 2015
,
[25] a) J. Limanto, B. Dorner, P. N. Devine, Synthesis 2006, 4143-4150; b)
177, 39-345.
E. Ciganek, J. Org. Chem. 1992
Kopp, P. Knochel, Angew. Chem. Int. Ed. 2006
[26] a) C. Y. Meyers, A. M. Malte, W. S. Matthews, J. Am. Chem. Soc. 1969
91, 7510-7512; b) S. Choi, S. Koo, J. Org. Chem. 2005 70, 3328-3331.
[27] K. Golibrzuch, F. Ehlers, M. Scholz, R. Oswald, T. Lenzer, K. Oum, H.
Kim, S. Koo, Chem. Phys. Phys. Chem. 2011 13, 6340-6351.
[28] a) R. H. Mitchell, V. S. Iyer, N. Khalifa, R. Mahadevan, S. Venugopalan,
S. A. Weerawarna, P. Zhou, J. Am. Chem. Soc. 1995 117, 1514-1532;
b) R. G. Viglione, R. Zanasi, Org. Lett. 2004 , 2265-2267.
[29] A. C. Aragones, N. Darwish, J. Im, B. Lim, J. Choi, S. Koo, I. Diez-
Perez, Chem. Eur. J. 2015 21, 7716-7720.
,
57, 4521-4527; c) A. Krasovskiy, F.
[11] M. Ji, H. Choi, Y. C. Jeong, J. Jin, W. Baik, S. Lee, J. S. Kim, M. Park,
S. Koo, Helv. Chim. Acta 2003 86, 2620-2628.
[12] R. J. K. Taylor, Org. React. 2003 62, 357-475.
,
45, 497-500.
,
,
,
,
[13] S. K. Guha, B. Wu, B. S. Kim, W. Baik, S. Koo, Tetrahedron Lett. 2006
,
47, 291-293.
,
[14] M. Onaka, K. Sugita, H. Takeuchi, Y. Izumi, J. Chem. Soc., Chem.
Commum. 1988, 1173-1174.
,
[15] S. Choi, J.-D. Yang, M. Ji, H. Choi, M. Kee, K.-H. Ahn, S.-H. Byeon, W.
, 6
Baik, S. Koo, J. Org. Chem. 2001, 66, 8192-8198.
[16] J. C. Lee, Y. H. Bae, S.-K. Chang, Bull. Korean Chem. Soc. 2003
,
24,
,
407-408.
This article is protected by copyright. All rights reserved.