Double elimination protocol for access to pyridine-containing arylene-ethynylenes

Article abstract of DOI:10.1246/cl.2004.1298

The arylene-ethynylene arrays involving pyridine were constructed successfully by taking advantage of double elimination reaction of β-substituted sulfones (sulfoximines) which are easily accessible from arylmethyl sulfones (sulfoximines) and aromatic aldehydes. This protocol was utilized for synthesis of an enantiopure arylene-ethynylene framework bearing a binaphthyl stereogenic core.

Full text of DOI:10.1246/cl.2004.1298

1298
Chemistry Letters Vol.33, No.10 (2004)
Double Elimination Protocol for Access to Pyridine-Containing Arylene–Ethynylenes
Akihiro Orita, Takehiko Nakano, Taisaku Yokoyama, Govindarajulu Babu, and Junzo OteraÃ
Department of Applied Chemistry, Okayama University of Science, Ridai-cho, Okayama 700-0005
(Received July 23, 2004; CL-040868)
The arylene–ethynylene arrays involving pyridine were con-
When a model reaction for incorporation of a triple bond be-
tween pyridines was attempted by use of 1 and 5 (for route A
in Figure 1), only a trace amount of the desired dipyridylacety-
lene was produced together with a number of byproducts.
In sharp contrast to this disappointing result, acetylene for-
mation was effected by use of sulfone 11 and 2 though in a mod-
est yield (for route B in Figure 1, Scheme 3). However, when
benzyl sulfoximine 13 and a pyridinecarboxaldehyde derivative
14 were combined, the same product 12 was prepared in 83%
yield (Scheme 3). These results prompted us to employ route
B for construction of the target compound 10. Enantionpure di-
sulfoximine 15 was prepared according to the procedure previ-
structed successfully by taking advantage of double elimination
reaction of ꢀ-substituted sulfones (sulfoximines) which are easi-
ly accessible from arylmethyl sulfones (sulfoximines) and aro-
matic aldehydes. This protocol was utilized for synthesis of an
enantiopure arylene–ethynylene framework bearing a binaph-
thyl stereogenic core.
Pyridine derivatives have received great attention as build-
ing blocks for supramolecules1 and ligands for transition metal
catalysts2 and luminecent complexes.3 Especially great interest
has been focused on pyridylene–ethynylenes. Although such ar-
ray is usually formed by the Sonogashira coupling between bro-
mopyridines and terminal acetylenes, a more versatile methodol-
ogy is still in demand particularly for pyridylene–ethynylenes
having functional groups.1b In this context, we have developed
a new synthetic process for acetylenes by utilizing double elim-
ination of ꢀ-substituted sulfones which could be easily derived
from sulfones and aldehydes. In this process, a series of reactions
such as aldol-type C–C bond formation, protection of the result-
ing aldolate and double elimination of the ꢀ-substituted sulfones
are integrated in one-pot. Based on this protocol, various types of
acetylenes such as unsymmetrically substituted aromatic poly-
ynes4 and highly strained5 and chiral acetylenic cyclophanes6
were obtained. We expected that this protocol would be useful
for construction of pyridylene–ethynylene units having various
functional groups (Scheme 1).
PhCHO
2
ClP(O)(OEt)2
BuLi
THF
LiHMDS
SO2Ph
N
N
3
84%
1
BuLi, 2,
ClP(O)(OEt)2
LiHMDS -PhSO2H
OP(O)(OEt)2
LiHMDS
N
N
-HOP(O)(OEt)2
PhSO2
PhSO2
+
SO2Ph
OHC
OHC
N
N
4
5
3
76%
+
CHO
SO2Ph
N
N
7
75%
6
4 (2.0 equiv.)
SO2Ph
N
1 (2.0 equiv.)
+
+
N
N
SO2Ph
R
X
OHC
Y
R'
R
X
Y
R'
CHO
CHO
X, Y: N, CH
9 49 %
Scheme 1.
8
Herein, we describe the double elimination protocol for pyr-
Scheme 2.
idine-containing arylene–ethynylenes. First of all, we conducted
the reaction of 2-pyridylmethyl sulfone 1 with benzaldehyde (2)
(Scheme 2). This reaction proceeded smoothly giving rise to for-
mation of the desired pyridylacetylene 3. An alternative combi-
nation of benzyl sulfone 4 and 2-pyridinecarboxaldehyde (5)
produced 3 in 76% yield. Dialdehydes were employable as well.
Treatment of 4 with 2,6-pyridinedicarboxaldehyde (6) afforded
the desired diyne 7, and enantiopure dialdehyde 8 reacted with
1 to provide tetrayne 9.
route B
route A
C6H13
N
N
N
N
C6H13
10
M+: Ag+, Cu+
With these results in hand, we tackled to prepare enantio-
pure pyridine-containing arylene–ethynylene 10 which had been
revealed to form a unique double helicate A upon complexation
with copper(I) and silver(I).7 Previously, this compound was
synthesized by the Sonogashira coupling, yet repetition of the
Sonogashira coupling resulted in coloration of the product and
required repeating column chromatography for purification.
C6H13
N
N
N
N
C6H13
A
Figure 1.
Copyright Ó 2004 The Chemical Society of Japan

Chemistry Letters Vol.33, No.10 (2004)
1299
1) TMSCl
2) LiHMDS
3) LDA
employed instead of 15 yellowish product 10 was obtained only
in 30% yield.
+
OHC
SO2Ph
THF
N
N
In summary, the double elimination protocol has proved to
be effective for synthesis of pyridylacetylenes.
N
N
12 48%
11
2
1) BuLi
2) 14
3) ClP(O)(OEt)2
4) LiHMDS
Financial support from New Energy and Industrial
Technology Development Organization (NEDO) of Japan for
Industrial Technology Research Grant Program (01B68006d)
and the Sumitomo Foundation to A. O. is gratefully acknowl-
edged.
+
12 83%
SO(=NTs)Ph
OHC
THF
N
N
14
13
Scheme 3.
TMS
Pd(PPh3)4
CuI
1) BuLi
2) DMF
3) HCl
References and Notes
1
K2CO3
17 98%
a) C. A. Schalley, A. Lutzen, and M. Albrecht, Chem.—Eur.
¨
THF
Br
OHC
N
Br
N
OHC
N
78%
Br
J., 10, 1072 (2004). b) C. Tschierske, Angew. Chem., Int.
Ed., 39, 2454 (2000). c) J.-M. Lehn, Chem.—Eur. J., 6,
2097 (2000).
TMS
C6H13
95%
I
TMS
Pd(PPh3)4
CuI
2
3
a) T. Kawano, T. Shinomaru, and I. Ueda, Org. Lett., 4, 2545
(2002). b) T. Kawano, J. Kuwana, T. Shinomaru, C.-X. Du,
and I. Ueda, Chem. Lett., 2001, 1230.
Pd(PPh3)4
CuI
K2CO3
18 91%
Br
N
Br
N
Br
73%
a) X. Shen, T. Moriuchi, and T. Hirao, Tetrahedron Lett., 44,
7711 (2003). b) A. Khatyr and R. Ziessel, Tetrahedron Lett.,
43, 7431 (2002). c) H. S. Joshi, R. Jamshidi, and Y. Tor,
Angew. Chem., Int. Ed., 38, 2722 (1999). d) V. Balzani, A.
Juris, and M. Venturi, Chem. Rev., 96, 759 (1996).
a) F. Ye, A. Orita, A. Doumoto, and J. Otera, Tetrahedron,
59, 5635 (2003). b) A. Orita, F. Ye, A. Doumoto, and
J. Otera, Chem. Lett., 32, 104 (2003).
OHC
N
17
Pd(PPh3)4
CuI
N
OHC
N
+
4
C6H13
16 74%
Br
N
18
C6H13
5
6
A. Orita, D. Hasegawa, T. Nakano, and J. Otera, Chem.—
Eur. J., 8, 2000 (2002).
a) D.-L. An, T. Nakano, A. Orita, and J. Otera, Angew.
Chem., Int. Ed., 41, 171 (2002). b) A. Orita, D. Hasegawa,
D.-L. An, T. Nakano, J. Yaruva, N. Ma, and J. Otera,
Chem.—Eur. J., 8, 2005 (2002).
Scheme 4.
SO(=NTs)Ph
N
+
OHC
N
SO(=NTs)Ph
7
8
A. Orita, T. Nakano, D.-L. An, K. Tanikawa, K. Wakamatsu,
and J. Otera, J. Am. Chem. Soc., 126 10389 (2004).
To a THF solution (3 mL) of disulfoxime 15 (213.9 mg,
0.20 mmol) was added BuLi (0.33 mL, 1.35 M hexane solu-
tion, 0.46 mmol) at À78 ꢀC, and the mixture was stirred for
0.5 h. To this solution was added a THF solution (3 mL) of
16 (164.8 mg, 0.42 mmol), and the mixture was stirred for
1.5 h. After ClP(O)(OEt)2 (0.064 mL, 0.44 mmol) had been
added, the reaction mixture was stirred at RT for 2 h. After
lithium hexamethyldisilazide (3.0 mL, 1.0 M THF solution,
3.0 mmol) had been added at À78 ꢀC, the mixture was stirred
at À78 ꢀC for 1 h and at RT for 1 h. After usual workup with
sat. NH4Cl aq/CH2Cl2, the combined organic layer was
washed with brine and dried over anhydrous soudium sul-
fate. The organic layer was evaporated under vacuum, and
the residue was subjected to column chromatography to give
10 (130.1 mg, 53%).
C6H13
16
15
1) BuLi
2) 16
C6H13
3) ClP(O)(OEt)2
4) LiHMDS
N
N
N
N
THF
C6H13
10 53% white powder
Scheme 5.
ously reported.6b A pyridylcarboxaldehyde 16 was accessible by
repeating the Sonogashira coupling as shown in Scheme 4.
The aldol-type coupling between an enantiopure disulfox-
imine 15 and pyridylcarboxaldehyde 16 followed by double
elimination of the resulting ꢀ-substituted sulfoximine furnished
the desired acetylene 10 in 53% yield (Scheme 5).8 Notably, the
product thus formed suffered from no coloration and enjoyed
facile purification. When the corresponding disulfone was
Published on the web (Advance View) September 11, 2004; DOI 10.1246/cl.2004.1298