Sulfoximine version of double elimination protocol for synthesis of chiral acetylenic cyclophanes

Article abstract of DOI:10.1002/1521-3765(20020503)8:9<2005::AID-CHEM2005>3.0.CO;2-I

A new strategy for constructing enantiopure acetylenic cyclophanes is described on the basis of one-pot double elimination reaction starting from dialdehydes and bis(sulfoximine)s. In this case, the conventional sulfone protocol affords poorer yields of t

Full text of DOI:10.1002/1521-3765(20020503)8:9<2005::AID-CHEM2005>3.0.CO;2-I

FULL PAPER
Sulfoximine Version of Double Elimination Protocol for Synthesis of Chiral
Acetylenic Cyclophanes
Akihiro Orita, De Lie An, Takehiko Nakano, Jayamma Yaruva, Nianchun Ma, and
Junzo Otera*[a]
Abstract: A new strategy for constructing enantiopure acetylenic cyclophanes is
described on the basis of one-pot double elimination reaction starting from
dialdehydes and bis(sulfoximine)s. In this case, the conventional sulfone protocol
affords poorer yields of the desired cyclophanes. Thus, arylene ethynylene moieties
with terminal sulfoximine or formyl functions are linked to binaphthyl cores and
these building blocks are then subjected to double elimination reaction. The desired
macrocycles are obtained in up to 35% yield. The corresponding Sonogashira
coupling fails to afford cyclophanes indicative of effectiveness of the double
elimination methodology.
Keywords: alkynes ¥ arenes ¥ chiral
auxiliaries ¥ elimination ¥ synthetic
method
In the preceding paper, we disclosed that the double
elimination methodology is effective for constructing cyclic
Introduction
À
À
Cyclophanes with an arylene ethynylene motif have attracted
acetylenes because, in this protocol, the carbon carbon bond
extensive attention in view of both synthetic and physical
organic chemistries.[1] In addition, these macrocycles are of
particular promise in terms of applications to new materials in
electronics[2] and precursors for novel carbon materials.[3]
From the synthetic standpoint, incorporation of acetylene
units in the ring system is a key technology to this end. Since
the linear disposition is strongly directed with sp carbon, the
coupling between terminal acetylenes and aryl halides, which
is the most commonly employed technology for generating
is initially formed between sp3 carbons and the successive
eliminations follow giving rise to sp2 and finally sp carbons in a
stepwise manner.[7] As a result, involvement of bent sp3 or sp2
À
carbons should allow this protocol to build arylene
ethynylene cyclophane skeletons more easily than the termi-
nal acetylene coupling modes. We present here a double
elimination strategy for the rational design of this class of
compounds by use of binaphthyl group as a stereogenic
arylene moiety. Furthermore, it is demonstrated that sulfox-
imines serve as better substrates than sulfones for cyclization.
[4]
À
aryl acetylene bond, often suffers low yield in cyclization.
Another subject that remains unexplored is the synthesis of
chiral derivatives, for which useful optical properties are
expected. In addition, these compounds may serve as unique
chiral host molecules. Several chiral acetylenic cyclophanes
were reported, but, unfortunately, most of them were
obtained as racemates.[3b, 5] According to our literature survey,
the studies on non-racemic compounds are rather limited.[6]
All of these procedures made recourse to the terminal
acetylene coupling technology.
Results and Discussion
First, we attempted application of the conventional double
elimination reaction involving coupling between disulfone
and dialdehyde units as shown in Scheme 1. A binaphthyl
group with R conformer was employed as a stereogenic core,[8]
À
to which arylene ethynylene moieties with terminal sulfone
or formyl functions are linked.
These building blocks, 1 and 2, were readily prepared
according to the procedures shown in Schemes 2 and 3.[9]
Unfortunately, however, the double elimination reaction
between these partners led to poor yields of the desired
macrocycles 3 (Scheme 1).
[a] Prof. Dr. J. Otera, Dr. A. Orita, Dr. De L. An, T. Nakano,
Dr. J. Yaruva, Dr. N. Ma
Department of Applied Chemistry
Okayama University of Science
Then, we turned our attention to employ sulfoximines 13
instead of 1. The synthesis of 13 is shown in Scheme 4, where
the requisite sulfoximine was conveniently synthesized by
E-mail: otera@high.ous.ac.jp
Supporting information for this article is available on the WWW under
http://www.wiley-vch.de/home/chemistry/ or from the author.
Chem. Eur. J. 2002, 8, No. 9
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2005

J. Otera et al.
FULL PAPER
The same methodology was
applied to pyridine-containing
cyclophane 18 (Scheme 6). The
yield was better than the sul-
fone protocol.
CH2SO2Ph
CH2SO2Ph
OHC
OHC
+
n-2
1
2a: n = 2
2b: n = 3
2c: n = 4
Another type of sulfoximine
19 was also successfully em-
ployed
to
provide
3c
i)
(Scheme 7). It should be noted
that the Sonogashira-coupling
failed to afford the desired
macrocycle (Scheme 8). Only a
trace amount of 3a was detect-
ed on TLC upon treatment of
diacetylene 12 and diiodide 20,
n
3a: n = 2, 9%
3b: n = 3, 8%
3c: n = 4, 9%
Scheme 1. i) BuLi, THF; ClP(O)(OEt)2; tBuOK.
indicative of the effectiveness of the double elimination
protocol. As a consequence, the convergent double elimina-
tion methodology has been achieved to afford a variety of
non-racemic acetylenic cyclophanes. These results suggest the
i)
+
SO2Ph
Br
5
4
I
I
OH
i)
SPh
ii)
CH2SO2Ph
CH2SO2Ph
14
15
O
I
I
iii)
SPh
NTs
SPh
NTs
1 73%
16
Scheme 2. i) [Pd(Ph3P)4], CuI, iPr2NH, toluene, 758C, 12 h.
CH2SO(=NTs)Ph
CH2SO(=NTs)Ph
iv)
one-pot conversion of sulfide through successive action of
Chloramine-T[10] and RuO2/NaIO4.[11]
Treatment of 13 with 2 under double elimination conditions
led to a good deal of improvement for the yield of 3
(Scheme 5).
13 77%
Scheme 4. i) (PhS)2, Bu3P; ii) Chloramine-T; iii) RuO2, NaIO4; iv) 4,
[Pd(Ph3P)4], CuI, iPr2NH, toluene, 758C, 12 h.
CHO
CHO
i)
+
I
CHO
6
4
2a 99%
ii)
iv)
iii)
I
Et2N3
Et2N3
I
H2N
I
SiMe3
SiMe3
vi)
10 86%
7
8 95%
9 98%
SiMe3
SiMe3
v)
12 95%
4
11 93%
CHO
CHO
vii)
2b 98%
Scheme 3. i) [Pd(Ph3P)4], CuI, iPr2NH, toluene, 758C, 12 h; ii) NaNO2, HCl; then Et2NH, K2CO3; iii) trimethylsilylacetylene, [Pd(Ph3P)4], CuI, iPr2NH,
toluene, 508C, 3 h; iv) MeI, 1308C, 12 h; v) 10, [Pd(Ph3P)4], CuI, iPr2NH, toluene, 758C, 15 h; vi) K2CO3, THF, MeOH; vii) 6, [Pd(Ph3P)4], CuI, iPr2NH,
toluene, 758C, 12 h.
2006
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Chem. Eur. J. 2002, 8, No. 9

Synthesis of Chiral Cyclophanes
2005 2010
iterative Sonogashira reactions
and found to possess a twisted
double helical structure on the
CH2SO(=NTs)Ph
CH2SO(=NTs)Ph
OHC
OHC
+
basis of X-ray analysis.[12]
A
n-2
characteristic CD spectral pro-
file of this compound is appa-
rent by comparison with an
acyclic compound (R)-21.[13]
13
2a: n = 2
2b: n = 3
2d: n = 5
i)
n
3a: n = 2, 35%
3b: n = 3, 28%
3d: n = 5, 31%
Scheme 5. i) BuLi, THF; ClP(O)(OEt)2; tBuOK.
21
The rigid double helical struc-
ture of 3e is reflected on dis-
appearance of the strong Cot-
ton effect with zero-point at
320 nm observed for (R)-21
concurrent with loss of a neg-
ative peakat 340 nm. On the
other hand, the higher homo-
logues 3a d give rise to differ-
ent patterns. The revival of the
Cotton effect in these com-
pounds implies that the aryle-
CH2SO(=Y)Ph
CH2SO(=Y)Ph
OHC
OHC
N
N
+
13: Y = NTs
1: Y = O
17
i)
N
N
18 20 % (Y = NTs)
13 % (Y = O)
À
ne acetylene rings are so flex-
Scheme 6. i) BuLi, THF; ClP(O)(OEt)2; tBuOK.
ible that the double helical
structure could not be fixed.
Notably, the strength of the
negative peakat 340 nm in-
creases with increasing ring
size. Apparently, the relatively
smaller compounds such as
3a c are partially twisted while
virtually no double helicity re-
mains on the largest ring of 3d.
In other words, the CD spectros-
copy serves for diagnosis of the
helicity of acetylenic cyclo-
phanes.
CH2SO(=NTs)Ph
CH2SO(=NTs)Ph
OHC
OHC
+
19
2b
i)
3c 30 %
Scheme 7. i) BuLi, THF; ClP(O)(OEt)2; tBuOK.
H
H
I
I
+
12
20
i)
3a
a trace amount
Scheme 8. i) [Pd(Ph3P)4], CuI, iPr2NH, toluene.
synthetic potential of sulfoximine chemistry although rather
little attention has been paid on this field so far.
CD spectra of the acetylenic cyclophanes thus obtained are
shown in Figure 1 together with that of the smallest one (R,P)-
3e (n ˆ 1). This compound was prepared separately by
Figure 1. CD spectra of acetylenic cyclophanes.
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2007

J. Otera et al.
FULL PAPER
(15 mg, 0.08 mmol), diisopropylamine (5 mL) and toluene (25 mL). After
being stirred at 758C for 15 h, the reaction mixture was cooled to room
temperature and filtered. The filtrate was poured into aqueous NH4Cl, and
extracted with ethyl acetate. The extract was then washed with brine, dried
over MgSO4, and filtered. The solvent was evaporated in vacuo, and the
residue was prified by chromatography (hexane/CH2Cl2 1:3) to give 2a
(824 mg, 99%) as a yellow foam. 1H NMR (500 MHz, CDCl3): d ˆ 6.99 (d,
J ˆ 7.7 Hz, 2H), 7.12 (s, 2H), 7.26 (t, J ˆ 7.7 Hz, 2H), 7.35 7.42 (m, 4H), 7.53
(t, J ˆ 7.3 Hz, 2H), 7.64 (d, J ˆ 7.7 Hz, 2H), 7.79 (d, J ˆ 8.5 Hz, 2H), 8.00 (d,
J ˆ 8.3 Hz, 2H), 8.03 (d, J ˆ 8.5 Hz, 2H), 9.81 (s, 2H); 13C NMR (125 MHz,
In summary, the double elimination protocol has proved to
be effective for the synthesis of acetylenic cyclophanes. The
difficulty encountered in the cyclization involving sp carbon
can be overcome by bond formation between sp3 or sp2
carbons prior to generation of sp carbons. In case where
sulfones are not effective, sulfoximines may serve better. The
sulfoximine protocol thus achieved is not necessarily excellent
with respect to yield, yet acceptable if the difficulties in this
sort of cyclization technology is taken into account. The
conciseness of the process and successful synthesis of other-
wise difficult-to-obtain molecules will find a wide range of
applications.
ꢀ
ꢀ
CDCl3): d ˆ 90.86 (2C ), 92.14 (2C ), 121.06 (2C), 124.16 (2C), 126.56
(2CH), 126.83 (2CH), 126.95 (2CH), 127.93 (2CH), 128.08 (2CH), 128.17
(2CH), 128.20 (2CH), 128.64 (2CH), 132.53 (2C), 132.91 (2CH), 133.13
(2C), 136.11 (2C), 136.43 (2CH), 140.66 (2C), 191.28 (2CHO); ESI-MS:
‡
calcd for 510.16; found 510.21 [M] .
Preparation of 2b (Scheme 3): A 100 mL flaskwas charged with 12 (1.57 g,
3.12 mmol), 6 (1.67 g, 7.18 mmol), [Pd(Ph3P)4] (180 mg, 0.16 mmol), CuI
(30 mg, 0.16 mmol), diisopropylamine (10 mL) and toluene (50 mL). After
being stirred at 758C for 12 h, the reaction mixture was cooled to room
temperature and filtered. The filtrate was poured into aqueous NH4Cl, and
extracted with ethyl acetate. The extract was then washed with brine, dried
over MgSO4, and filtered. The solvent was evaporated in vacuo, and the
residue was purified by chromatography (hexane/CH2Cl2 1:3) to give 2b
(2.18 g, 98%) as a pale yellow foam. 1H NMR (500 MHz, CDCl3): d ˆ 6.71
(d, J ˆ 7.7 Hz, 2H), 6.94 (s, 2H), 7.10 (t, J ˆ 7.8 Hz, 2H), 7.30 (d, J ˆ 8.0 Hz,
2H), 7.34 7.40 (m, 4H), 7.51 7.55 (m, 4H), 7.75 (d, J ˆ 7.7 Hz, 2H), 7.79 (d,
J ˆ 8.6 Hz, 2H), 7.85 (d, J ˆ 7.7 Hz, 2H), 7.99 (d, J ˆ 8.0 Hz, 2H), 8.01 (s,
2H), 8.02 (d, J ˆ 8.0 Hz, 2H), 10.03 (s, 2H); 13C NMR (125 MHz, CDCl3):
Experimental Section
General: All reactions were carried out under an atmosphere of nitrogen
with freshly distilled solvents, unless otherwise noted. Tetrahydrofuran
(THF) was distilled from sodium/benzophenone. Other solvents such as
toluene and diisopropylamine were distilled from CaH2. A hexane solution
of BuLi was purchased from Aldrich and titrated before use by Gilman
method.[14] [Pd(PPh3)4] was prepared according to the reported method.[15]
Silica gel (Daiso gel IR-60) was used for column chromatography. NMR
spectra were recorded at 258C on Varian Gemini-300, JEOL Lambda300
and JEOL Lambda500 instruments and calibrated with tetramethylsilane
(TMS) as an internal reference. Mass spectra were recorded on JEOL
MStation JMS-700, Shimadzu/Kratos MALDI4 and PlatformII single
quadrupole (Micromass, Altrinchan, UK) mass spectrometers. Elemental
analyses were performed by the Perkin Elmer PE2400. Optical rotation
was measured on a JASCO DIP-1000 polarimeter. UV/Vis and circular
dichroism were measured on HITACHI U-3000 and JASCO J-820
spectrometers, respectively.
ꢀ
ꢀ
ꢀ
ꢀ
d ˆ 88.11 (2C ), 90.01 (2C ), 90.18 (2C ), 92.60 (2C ), 121.31 (2C),
122.51 (2C), 123.52 (2C), 124.20 (2C), 126.56 (2CH), 126.67 (2CH), 126.86
(2CH), 128.03 (2CH), 128.08 (2CH), 128.10 (2CH), 128.13 (2CH), 129.04
(2CH), 129.06 (2CH), 130.87 (2CH), 131.29 (2CH), 132.55 (2C), 132.73
(2CH), 133.05 (2C), 134.25 (2CH), 136.41 (2C), 136.95 (2CH), 140.44
‡
(2C), 191.39 (2CHO); ESI-MS: calcd for 710.2; found 710.0 [M] .
Preparation of 15 (Scheme 4): A 100 mL flaskwas charged with 14 (9.2 g,
39.3 mmol), diphenyl disulfide (9.4 g, 43.1 mmol) and THF (40 mL).
Tributylphosphine (8.7 g, 43.1 mmol) was added dropwise slowly at room
temperature with stirring, and then the resulting solution was stirred for
6 h. The reaction mixture was poured into water, and extracted with ethyl
acetate. The extract was washed with NaOH (aq. 10%) followed by brine,
dried over MgSO4, and filtered. The solvent was evaporated in vacuo, and
the residue was purified by chromatography (hexane/AcOEt 50:1) to give
15 (12.2 g, 95%) as a colorless oil. 1H NMR (500 MHz, CDCl3): d ˆ 4.01 (s,
2H), 6.99 (t, J ˆ 7.8 Hz, 1H), 7.21 (t, J ˆ 6.6 Hz, 2H), 7.24 7.29 (m, 4H),
7.55 (d, J ˆ 7.9 Hz, 1H), 7.61 (s, 1H); 13C NMR (125 MHz, CDCl3): d ˆ
38.53 (CH2), 94.23 (C), 126.70 (CH), 127.96 (CH), 128.87 (2CH), 130.06
(CH), 130.28 (2CH), 135.53 (C), 136.13 (CH), 137.67(CH), 139.91 (C).
Synthesis of 3 with disulfone 1 (representative) (Scheme 1): BuLi (1.39m in
hexane, 1.99 mL, 2.76 mmol) was added to a THF solution (25 mL) of
disulphone 1 (1.05 g, 1.38 mmol) at À788C, and the mixture was stirred for
1 h. Dialdehyde 2a (705 mg, 1.38 mmol) in THF (50 mL) was added
dropwise over 30 min at this temperature. After an additional 1 h,
ClP(O)(OEt)2 (0.44 mL, 3.04 mmol) was added at À788C and the mixture
was stirred at room temperature for 1 h. After addition of tBuOK (3.81 g,
27.6 mmol) at À788C, the mixture was stirred at this temperature for
10 min and, then, at room temperature for 3 h. After usual work-up with
aqueous NH4Cl solution and AcOEt, the organic layer was evaporated. The
crude mixture was subjected to column chromatography (hexane/CH2Cl2
2:1) to give 3a (114 mg, 9%) as a pale yellow foam. The similar treatment
of 1a (1.05 g, 1.38 mmol) with 2b (981 mg, 1.38 mmol) or 2c (1.26 g,
1.38 mmol) furnished 3b (127 mg, 8%) or 3c (168 mg, 9%), respectively.
Characterization data of these compounds are given later.
Preparation of 16 (Scheme 4): Solid Chloramine-T trihydrate (7.8 g,
27.7 mmol) was added slowly with stirring at room temperature to a
solution of sulfide 15 (7.02 g, 21.5 mmol) and tributyl hexadecylphospho-
nium bromide (639 mg, 1.26 mmol) in CH2Cl2 (70 mL). The mixture was
stirred at 358C for 3 h. After addition of CH2Cl2 (20 mL), RuO2(167 mg,
1.25 mmol) and NaIO4 (10.8 g, 50.5 mmol) in H2O (60 mL) were added.
After being stirred for overnight, the reaction mixture was extracted with
CH2Cl2. Isopropanol (12 mL) was added to organic layer and the mixture
was stirred for 10 min to reduce residual ruthenium tetroxide to the
insoluble ruthenium dioxide. The mixture was then dried over MgSO4 and
filtered. The solvent was evaporated in vacuo, and the residue was purified
by chromatography (CH2Cl2/AcOEt 30:1) to give 16 (10.7 g, 97%) as a
colorless oil. 1H NMR (500 MHz, CDCl3): d ˆ 2.39 (s, 3H), 4.71, 4.79 (AB,
JAB ˆ 13.8 Hz, 2H), 6.98 (t, J ˆ 7.7 Hz, 1H), 7.09 (d, J ˆ 7.7 Hz, 1H), 7.18 (s,
1H), 7.26 (d, J ˆ 7.9 Hz, 2H), 7.49 (t, J ˆ 7.9 Hz, 2H), 7.63 7.68 (m, 4H),
7.87 (d, J ˆ 8.3 Hz, 2H); 13C NMR (125 MHz, CDCl3): d ˆ 21.35 (Me), 63.56
(CH2), 93.62 (C), 126.37 (2CH), 128.54 (2CH), 128.65 (C), 129.04 (2CH),
129.09 (2CH), 130.03 (CH), 130.48 (CH), 134.26 (C), 134.44 (CH), 138.11
(CH), 139.80 (CH), 140.54 (C), 142.66 (C).
Preparation of 1 (Scheme 2): A 100 mL flaskwas charged with 4 (913 mg,
3.02 mmol), 5 (2.35 g, 7.55 mmol), [Pd(Ph3P)4] (174 mg, 0.15 mmol), CuI
(29 mg, 0.15 mmol), diisopropylamine (10 mL) and toluene (50 mL). After
being stirred at 758C for 12 h, the reaction mixture was cooled to room
temperature and filtered. The filtrate was poured into aqueous NH4Cl, and
extracted with ethyl acetate. The extract was then washed with brine, dried
over MgSO4, and filtered. The solvent was evaporated in vacuo, and the
residue was purified by chromatography (CH2Cl2/AcOEt 50:1) to give 1
(1.68 g, 73%) as a yellow foam. 1H NMR (500 MHz, CDCl3): d ˆ 4.10 (s,
4H), 6.49 (s, 2H), 6.64 (d, J ˆ 7.6 Hz, 2H), 6.82 (d, J ˆ 7.6 Hz, 2H), 6.96 (t,
J ˆ 7.8 Hz, 2H), 7.28 7.36 (m, 8H), 7.47 7.50 (m, 4H), 7.53 (d, J ˆ 8.3 Hz,
4H), 7.72 (d, J ˆ 8.6 Hz, 2H), 7.95 (d, J ˆ 7.0 Hz, 2H), 7.97 (d, J ˆ 8.3 Hz,
13
ꢀ
2H); C NMR (125 MHz, CDCl3): d ˆ 62.35 (2CH2), 90.03 (2C ), 92.65
ꢀ
(2C ), 121.28 (2C), 123.54 (2C), 126.54 (2CH), 126.56 (2CH), 126.77
(2CH), 127.97 (2CH), 127.98 (2CH), 128.04 (2CH), 128.07 (2C), 128.13
(2CH), 128.40 (4CH), 128.81 (4CH), 130.05 (2 CH), 131.35 (2CH), 132.49
(2C), 132.97(2C), 133.40 (2CH), 133.69 (2CH), 137.53 (2C), 140.31 (2C);
Preparation of 13 (Scheme 4): A 100 mL flaskwas charged with 4 (1.0 g,
3.3 mmol), 16 (3.8 g, 7.45 mmol), [Pd(Ph3P)4] (191 mg, 0.17 mmol), CuI
(32 mg, 0.17 mmol), diisopropylamine (10 mL) and toluene (50 mL). After
being stirred at 758C for 12 h, the reaction mixture was cooled to room
‡
ESI-MS: calcd for 762.19; found 762.01 [M] .
Preparation of 2a (Scheme 3): A 100 mL flaskwas charged with 4 (493 mg,
1.63 mmol), 6 (873 mg, 3.76 mmol), [Pd(Ph3P)4] (92 mg, 0.08 mmol), CuI
2008
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Chem. Eur. J. 2002, 8, No. 9

Synthesis of Chiral Cyclophanes
2005 2010
temperature and filtered. The filtrate was poured into aqueous NH4Cl, and
extracted with ethyl acetate. The extract was then washed with brine, dried
over MgSO4, and filtered. The solvent was evaporated in vacuo, and the
residue was purified by chromatography (CH2Cl2/AcOEt 25:1) to give 13
(2.73 g, 77%) as a yellow foam (a mixture of diastereomers). 1H NMR
(500 MHz, CDCl3): d ˆ 2.37 (s, 6H), 4.50 4.54 (m, 2H), 4.68 4.74 (m,
2H), 6.27 6.34 (m, 2H), 6.63 6.65 (m, 2H), 6.79 (d, J ˆ 6.7 Hz, 2H), 6.94
(t, J ˆ 7.6 Hz, 2H), 7.24 (d, J ˆ 7.4 Hz, 4H), 7.29 7.34 (m, 8H), 7.45 7.52
(m, 8H), 7.71 (dd, J ˆ 8.6, 2.5 Hz, 2H), 7.86 (d, J ˆ 7.0 Hz, 2H), 7.87 (d, J ˆ
7.4 Hz, 2H), 7.95 (d, J ˆ 8.9 Hz, 2H), 7.97 (d, J ˆ 8.9 Hz, 2H); 13C NMR
(CHCl3, 8.95  10À6 m): lmax (emax) ˆ 240 (1.3  105), 282 (3.4  105), 305
(2.5  105), 332 (8.3  104); CD (c ˆ 4.47  10À6 m in CHCl3, 1.0 cm cell):
q ˆÀ 13.7, De ˆ À93.3 (at 279 nm); q ˆ 39.6, De ˆ 268.3 (at 309 nm); q ˆ
À30.6, De ˆ À207.8 (at 336 nm).
Preparation of 18 (Scheme 6): BuLi (1.39m in hexane, 0.23 mL, 0.32 mmol)
was added at À788C to
a THF solution (30 mL) of 13 (141.2 mg,
0.15 mmol), and the mixture was stirred for 10 min. A THF solution
(8 mL) of 17 (118 mg, 0.17 mmol) was added dropwise over 30 min. After
15 min, ClP(O)(OEt)2 (0.06 mL, 0.40 mmol) was added at À788C, and the
reaction mixture was stirred at room temperature for 1.5 h. tBuOK
(337 mg, 3.0 mmol) was added at À788C, and the reaction mixture was
stirred at room temperature for 2.5 h. After usual work-up with aqueous
NH4Cl solution and AcOEt, the organic layer was evaporated. The crude
mixture was subjected to column chromatography (hexane/CH2Cl2 1:2) to
give 18 (34.7 mg, 20%) as a yellow foam. 1H NMR (300 MHz, CDCl3): d ˆ
6.70 (dd, J ˆ 1.1, 7.7 Hz, 4H), 7.04 (t, J ˆ 7.7 Hz, 4H), 7.27 7.38 (m, 18H),
7.46 (m, 4H), 7.54 (t, J ˆ 7.8 Hz, 4H), 7.88 (d, J ˆ 8.4 Hz, 4H) , 7.94 (d,
J ˆ 8.1 Hz, 4H), 8.03(d, J ˆ 8.4 Hz, 4H); 13C NMR (75 MHz, CDCl3): d ˆ
88.47, 88.61, 90.11, 92.36, 121.43, 122.03, 123.64, 126.21, 126.45, 126.61,
126.73, 128.03, 128.06, 128.18, 128.41, 131.18, 131.80, 132.52, 132.97, 134.70,
ꢀ
ꢀ
(125 MHz, CDCl3): d ˆ 21.21 (Me), 63.77 (CH2), 90.03 (C ), 90.04 (C ),
ꢀ
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ꢀ
ꢀ
ꢀ
90.06 (C ), 90.08 (C ), 92.22 (C ), 92.24 (C ), 92.25 (C ), 120.88 (C),
120.95 (C), 123.25 (C), 126.23 (CH), 126.27 (CH), 126.34 (C), 126.46 (CH),
126.54 (CH), 126.62 (CH), 126.67 (CH), 127.69 (CH), 127.75 (CH), 127.87
(CH), 127.94 (CH), 128.01 (CH), 128.26 (CH), 128.81 (CH), 128.97 (CH),
130.43 (CH), 131.59 (CH), 131.62 (CH), 132.21 (C), 132.75 (C), 132.78 (C),
133.70 (CH), 133.75 (CH), 134.12 (CH), 134.26 (C), 140.07 (C),140.10
(C),140.12 (C), 140.14 (C), 140.60 (C), 140.63 (C), 142.50 (C); ESI-MS:
‡
calcd for 940.32; found 940.66 [M] .
Synthesis of 3 with bis(sufoximine) (representative procedure) (Scheme 5):
BuLi (1.39m in hexane, 0.81 mL, 1.13 mmol) was added at À788C to a THF
solution (50 mL) of bis(sulfoximine) 13 (547 mg, 0.51 mmol), and the
mixture was stirred for 5 min. Dialdehyde 2a (286 mg, 0.56 mmol) in THF
(25 mL) was added dropwise over 20 min at this temperature. After an
additional 1 h, ClP(O)(OEt)2 (0.21 mL, 1.41 mmol) was added at À788C
and the mixture was stirred at room temperature for 1 h. After addition of
tBuOK (1.14 g, 10.2 mmol) at À788C, the mixture was stirred at this
temperature for 10 min and, then, at room temperature for 3 h. After usual
work-up with aqueous NH4Cl solution and ethyl acetate, the organic layer
was evaporated. The crude mixture was subjected to column chromatog-
raphy (hexane/CH2Cl2 2:1) to give 3a (170 mg, 35%) as a pale yellow foam.
1H NMR (500 MHz, CDCl3): d ˆ 6.73 (d, J ˆ 7.7 Hz, 4H), 7.05 (t, J ˆ 7.7 Hz,
4H), 7.25 (d, J ˆ 8.0 Hz, 4H), 7.27 (d, J ˆ 7.7 Hz, 4H), 7.31 (t, J ˆ 7.7 Hz,
4H), 7.47 (t, J ˆ 8.0 Hz, 4H), 7.49 (s, 4H), 7.83 (d, J ˆ 8.6 Hz, 4H), 7.92 (d,
J ˆ 8.0 Hz, 4H), 7.96 (d, J ˆ 8.6 Hz, 4H); 13C NMR (125 MHz, CDCl3): d ˆ
‡
136.31, 140.18, 143.35; ESI-MS: calcd for 1155.4; found 1155.4 [M‡H] ;
[a]2D9:3 ˆ À58.80 (c ˆ 1.000, CHCl3); [M]D ˆ À679.3; UV/Vis (CHCl3,
8.74  10À5 m): lmax (emax) ˆ 245 (1.1  105), 281 (2.4  105), 313 (1.5  105);
CD (c ˆ 8.74  10À5 m in CHCl3, 0.1 cm cell): q ˆ À29.0, De ˆ À100.4 (at
281 nm); q ˆ 59.2, De ˆ 205.4 (at 310 nm); q ˆ À34.5, De ˆ À119.5 (at
337 nm).
Preparation of 19: A 100 mL flaskwas charged with 12 (1.66 g, 3.30 mmol),
16 (3.53 g, 6.93 mmol), [Pd(Ph3P)4] (191 mg, 0.17 mmol), CuI (32 mg,
0.17 mmol), diisopropylamine (10 mL) and toluene (50 mL). After being
stirred at 708C for 2 h, the reaction mixture was cooled to room
temperature and filtered. The filtrate was poured into aqueous NH4Cl,
and extracted with ethyl acetate. The extract was then washed with brine,
dried over MgSO4, and filtered. The solvent was evaporated in vacuo, and
the residue was chromatographed (CH2Cl2/AcOEt 25:1) to give 19 (2.56 g,
68%) as a yellow foam (a mixture of inseparable diastereomers). 1H NMR
(500 MHz, CDCl3):[16] d ˆ 2.36 (s, 6H), 4.74, 4.88 (JAB ˆ 13.9 Hz, 4H),
6.65 8.05 (m, 46H); 13C NMR (75 MHz, CDCl3) d ˆ 21.35, 63.99, 88.39,
89.29, 90.05, 92.53, 121.18, 122.56, 123.33, 123.42, 126.45, 126.61, 126.79,
126.90, 128.00, 128.01, 128.06, 128.54, 128.60, 129.07, 129.14, 130.75, 131.05,
131.10, 132.22, 132.42, 132.95, 134.03, 134.19, 134.36, 134.50, 140.33, 140.66,
ꢀ
ꢀ
ꢀ
89.14 (4C ), 89.74 (4C ), 92.07 (4C ), 121.45 (4C), 122.96 (4C), 123.58
(4C), 126.42 (4CH), 126.49 (4CH), 126.74 (4CH), 128.04 (4CH), 128.07
(4CH), 128.13 (4CH), 128.39 (4CH), 130.56 (4CH), 130.89 (4CH), 132.49
(4C), 132.96 (4C), 134.86 (4CH), 139.95 (4C); MALDI-MS: calcd for
952.3; found 952.8 [M] ; [a]D29:2 ˆ ‡81.2 (c ˆ 0.995, CHCl3); [M]D ˆ ‡773.9;
‡
UV/Vis (CHCl3, 4.5  10À6 m): lmax (emax) ˆ 239 (1.0  105), 281 (1.7  105),
305 (1.1  104), 331 (5.0  104); CD (c ˆ 7.9  10À5 m in CHCl3, 0.1 cm cell):
q ˆ À57.3, De ˆ À218.7 (at 282 nm); q ˆ 69.8, De ˆ 266.3 (at 308 nm); q ˆ
À29.5, De ˆ À112.5 (at 337 nm).
142.70; ESI-MS: calcd for 713.2; found 713.9 [M‡H] .
‡
Preparation of 3c with sulfoximine 19 (Scheme 7): BuLi (1.39m in hexane,
0.43 mL, 0.60 mmol) was added at À788C to a THF solution (50 mL) of 19
(285 mg, 0.25 mmol), and the mixture was stirred for 15 min. Dialdehyde
2b (196 mg, 0.28 mmol) in THF (20 mL) was added dropwise over 40 min
at this temperature with stirring. After 15 min, ClP(O)(OEt)2 (0.10 mL,
0.69 mmol) was added at À788C and the mixture was stirred at room
temperature for 2.5 h. To this mixture was added tBuOK (337 mg,
3.0 mmol) at À788C and the mixture was stirred at room temperature
for overnight. After usual work-up with aqueous NH4Cl solution and
AcOEt, the organic layer was evaporated. The crude mixture was subjected
to column chromatography (hexane/CH2Cl2 2:1) to give 3c (103 mg, 30%).
1H NMR (500 MHz, CDCl3): d ˆ 6.68 (d, J ˆ 7.8 Hz, 4H), 7.00 (s, 4H), 7.07
(t, J ˆ 7.8 Hz, 4H), 7.28 (d, J ˆ 7.7 Hz, 4H), 7.30 7.36 (m, 12H), 7.46 (d, J ˆ
7.7 Hz, 4H), 7.49 7.52 (m, 8H), 7.71 (s, 4H), 7.78 (d, J ˆ 8.6 Hz, 4H), 7.98
(d, J ˆ 8.6 Hz, 4H), 8.00 (d, J ˆ 8.6 Hz, 4H); 13C NMR (125 MHz, CDCl3):
The similar treatment of 13 (547 mg, 0.51 mmol) with 2b (398 mg,
0.56 mmol) or 2d (622 mg, 0.56 mmol) furnished 3b (165 mg, 28%) or 3d
(246 mg, 31%), respectively. 3b: 1H NMR (500 MHz, CDCl3): d ˆ 6.65 (d,
J ˆ 7.6 Hz, 4H), 7.04 (t, J ˆ 7.8 Hz, 4H), 7.12 (s, 4H), 7.26 7.35 (m, 14H),
7.43 (d, J ˆ 8.3 Hz, 4H), 7.46 (t, J ˆ 7.5 Hz, 4H), 7.70 (s, 2H), 7.84 (d, J ˆ
8.3 Hz, 4H), 7.94 (d, J ˆ 8.0 Hz, 4H), 8.01 (d, J ˆ 8.6 Hz, 4H); 13C NMR
ꢀ
ꢀ
ꢀ
(125 MHz, CDCl3): d ˆ 88.78 (4C ), 89.19 (4C ), 90.12 (4C ), 92.68
ꢀ
(4C ), 121.45 (4C), 122.85 (4C), 123.38 (4C), 123.50 (4C), 126.47 (4CH),
126.62 (4CH), 126.84 (4CH), 128.05 (4CH), 128.09 (8CH), 128.13 (4CH),
128.46 (2CH), 130.80 (4CH), 131.08 (4CH), 131.25 (4CH), 132.58 (4C),
132.98 (4C), 134.42 (4CH), 134.68 (2CH), 140.41 (4C); MALDI-MS: calcd
for 1152.4; found 1151.2 [M] ; [a]2D8:1 ˆ ‡9.2 (c ˆ 1.000, CHCl3); [M]D
ˆ
‡
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
‡106.1; UV/Vis (CHCl3, 4.5  10À6 m): lmax (emax) ˆ 245 (1.1  105), 281
(2.6  105), 305 (1.6  105), 332 (8.7  104); CD (c ˆ 9.19  10À6 m in CHCl3,
1.0 cm cell): q ˆ À47.7, De ˆ À157.3 (at 280 nm); q ˆ 82.4, De ˆ 271.5 (at
310 nm); q ˆ À42.9, De ˆ À141.8 (at 336 nm); 3d: 1H NMR (500 MHz,
CDCl3): d ˆ 6.67 (d, J ˆ 7.8 Hz, 4H), 7.02 (s, 4H), 7.06 (t, J ˆ 7.8 Hz, 4H),
7.28 (d, J ˆ 8.0 Hz, 4H), 7.31 7.37 (m, 14H), 7.45 7.52 (m, 16H), 7.70 (s,
d ˆ 88.77 (4C ), 89.15 (4C ), 89.28 (4C ), 90.09 (4C ), 92.64 (4C ),
121.44 (4C), 122.87 (4C), 123.36 (4C), 123.49 (4C), 123.54 (4C), 126.60
(4CH), 126.63 (4CH), 126.85 (4CH), 128.05 (4CH), 128.09 (8CH), 128.15
(4CH), 128.53 (4CH), 130.79 (4CH), 131.05 (4CH), 131.37 (8CH), 132.58
(4C), 133.06 (4C), 134.47 (4CH), 134.71 (4CH), 140.40 (4C); MALDI-MS:
calcd for 1352.4; found 1351.0 [M] : [a]2D9:2 ˆ À70.47 (c ˆ 0.990, CHCl3);
‡
[M]D ˆ À953.9; UV/Vis (CHCl3, 7.83  10À5 m): lmax (emax) ˆ 246 (1.3  104),
282 (3.1  105), 305 (2.2  105), 332 (8.8  104); CD (c ˆ 7.8  10À5 m in
CHCl3, 0.1 cm cell): q ˆ À19.6, De ˆ À76.7 (at 281 nm); q ˆ 65.5, De ˆ
255.6 (at 310 nm); q ˆ À48.9, De ˆ À191.0 (at 338 nm).
4H), 7.74 (s, 2H), 7.80 (d, J ˆ 8.6 Hz, 4H), 7.98 (d, J ˆ 8.0 Hz, 4H), 8.01 (d,
13
ꢀ
J ˆ 8.6 Hz, 4H); C NMR (125 MHz, CDCl3): d ˆ 88.76 (4C ), 89.14
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
(4C ), 89.17 (4C ), 89.24 (4C ), 90.07 (4C ), 92.64 (4C ), 121.42 (4C),
122.85 (4C), 123.32 (4C), 123.36 (4C), 123.43 (4C), 123.50 (4C), 126.57
(4CH), 126.64 (4CH), 126.85 (4CH), 128.06 (4CH), 128.10 (8CH), 128.14
(4CH), 128.52 (4CH), 128.55 (2CH), 130.81 (4CH), 131.07 (4CH), 131.36
(8CH), 131.45 (4CH), 132.56 (4C), 133.03 (4C), 134.40 (4CH), 134.70
(4CH), 134.74 (2CH), 140.38 (4C); MS (MALDI): calcd for 1552.5; found
Reaction between 12 and 20 (Scheme 8): A two-necked flask was charged
with [Pd(Ph3P)4] (40 mg, 35 mmol), CuI (7 mg, 35 mmol), diisopropylamine
(2 mL), and toluene (10 mL). Then, to the above suspension was added a
solution of 12 (174 mg, 0.35 mmol) and 20 (245 mg, 0.35 mmol) in
diisopropylamine (10 mL) and toluene (50 mL) at 758C by a syringe pump
1553.0 [M] ; [a]2D9:8 ˆ À69.22 (c ˆ 0.795, CHCl3); [M]D ˆ À1075.56; UV/Vis
‡
Chem. Eur. J. 2002, 8, No. 9
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0809-2009 $ 20.00+.50/0
2009

J. Otera et al.
FULL PAPER
(2.5 mL hÀ1). The reaction mixture was cooled to room temperature and
filtered. The filtrate was poured into aqueous NH4Cl, and extracted with
ethyl acetate. The extract was then washed with brine, dried over MgSO4
and filtered. The solvents were evaporated in vacuo, and the crude mixture
was subjected to column chromatography (1:1.5 hexane/CH2Cl2) to give a
trace amount of 3a (<2.7%, not pure).
Youngs, J. Chem. Soc. Chem. Commun. 1994, 243; c) A. Rajca, A.
Safronov, S. Rajca, R. Shoemaker, Angew. Chem. 1997, 109, 504;
Angew. Chem. Int. Ed. Engl. 1997, 36, 488; d) S. K. Collins, G. P. A.
Yap, A. G. Fallis, Org. Lett. 2000, 2, 3189; e) M. J. Marsella, I. T. Kim,
F. Tham, J. Am. Chem. Soc. 2000, 122, 974; f) P. N. W. Baxter, J. Org.
Chem. 2001, 66, 4170.
[6] a) S. Anderson, U. Neidlein, V. Gramlich, F. Diederich, Angew. Chem.
1995, 107, 1722; Angew. Chem. Int. Ed. Engl. 1995, 34, 1596; b) A.
B‰hr, A. S. Droz, M. P¸ntener, U. Neidlein, S. Anderson, P. Seiler, F.
Diederich, Helv. Chim. Acta 1998, 81, 1931; c) J. M. Fox, D. Lin, Y.
Itagaki, T. Fujita, J. Org. Chem. 1998, 63, 2031; d) K. Nakamura, H.
Okubo, M. Yamaguchi, Org. Lett. 2001, 3, 1097.
The preparation of 2c, 2d, 4, 5, 6, 8 12, and 17 is described in the
Supporting Information.
Acknowledgement
[7] A. Orita, D. Hasegawa, T. Nakano, J. Otera, Chem. Eur. J. 2002, 8,
Financial support from New Energy and Industrial Technology Develop-
ment Organization (NEDO) of Japan for Industrial Technology Research
Grant Program (01B68006d) to A.O. is gratefully acknowledged.
2000, preceding paper in this issue.
À
[8] For open chain arylene ethynylenes with binaphthyl cores: a) L. Pu,
Acta Polym. 1997, 48, 116; b) L. Pu, Chem. Rev. 1998, 98, 2405; c) M. S.
Gin, T. Yokozawa, R. B. Prince, J. S. Moore, J. Am. Chem. Soc. 1999,
121, 2643.
[9] Only preparation of 2a and 2b is described. The analogous procedures
for 2c and 2d are given in the Supporting Information.
[10] A. L. Marzinzik, K. B. Sharpless, J. Org. Chem. 2001, 66, 594.
[11] H. S. Veale, J. Levin, D. Swern, Tetrahedron Lett. 1978, 19, 503.
[12] D. L. An, T. Nakano, A. Orita, J. Otera, Angew. Chem. 2002, 114, 179;
Angew. Chem. Int. Ed. 2002, 41, 171.
[13] B. Wael, S. Herbert, B. Jochanan, Tetrahedron 1996, 52, 8349.
[14] H. Gilman, F. K. Cartledge, J. Organomet. Chem. 1967, 2, 447.
[15] D. R. Coulson, Inorg. Synth. 1972, 13, 121.
[1] Recent review articles: a) J. M. Tour, Chem. Rev. 1996, 96, 537; b) J. S.
Moore, Acc. Chem. Res. 1997, 30, 402; c) M. M. Haley, Synlett 1998,
557; d) W. J. Youngs, C. A. Tessier, J. D. Bradshow, Chem. Rev. 1999,
99, 3153; e) M. M. Haley, J. J. Pak, S. C. Brand, Top. Curr. Chem. 1999,
201, 81.
[2] Conjugated Polymers and Related Materials: The Interconnection of
Chemical and Electronic Structure (Eds.: W. R. Salaneck, I. Ludstrˆm,
B. Ranby), Oxford University Press, Oxford (UK), 1993.
[3] a) F. Diederich, Y. Rubin, Angew. Chem. 1992, 104, 1123; Angew.
Chem. Int. Ed. Engl. 1992, 31, 1101; b) R. Boese, A. J. Matzger,
K. P. C. Vollhardt, J. Am. Chem. Soc. 1997, 119, 2052.
[16] Some of the aromatic carbon signals overlapped and could not be
calculated.
[4] P. S. Siemsen, R. C. Livingston, F. Diederich, Angew. Chem. 2000, 112,
2740; Angew. Chem. Int. Ed. 2000, 39, 2632.
[5] a) J. K. Judice, S. J. Keipert, D. J. Cram, J. Chem. Soc. Chem.
Commun. 1993, 1323; b) L. Guo, J. D. Bradshaw, C. A. Tessier, W. J.
Received: November 26, 2001 [F3706]
2010
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0809-2010 $ 20.00+.50/0
Chem. Eur. J. 2002, 8, No. 9