Novel synthesis of macrocycles with chalcone moieties through mixed aldol reaction

Article abstract of DOI:10.1016/S0040-4039(01)01793-2

24-Membered novel macrocycles with chalcone structural moieties and isobutenyl ether linkages in the core have been prepared through mixed aldol reaction.

Full text of DOI:10.1016/S0040-4039(01)01793-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8351–8355
Novel synthesis of macrocycles with chalcone moieties through
mixed aldol reaction
Maddali L. N. Rao, Hirohiko Houjou and Kazuhisa Hiratani*
Nanoarchitectonics Research Center, National Institute of Industrial Science and Technology, Tsukuba, Ibaraki 305-8562, Japan
Received 3 September 2001; accepted 21 September 2001
Abstract—24-Membered novel macrocycles with chalcone structural moieties and isobutenyl ether linkages in the core have been
prepared through mixed aldol reaction. © 2001 Elsevier Science Ltd. All rights reserved.
Macrocyles with novel functionalities as part of the
core are important for molecular recognition and pho-
tophysical properties.1 In this respect, chalcone struc-
tural moiety has an excellent potential to be a part of
macrocyclic structures, since the photophysical proper-
ties of chalcones have been well exploited for various
optical applications.2 So, we envisioned that the incor-
poration of chalcone moieties in macrocyclic core
would be useful for molecular recognition studies and
as photo-functional materials. The strategy to synthe-
size macrocycle with chalcone structural moiety was
depicted in Scheme 1, where the mixed aldol reaction of
bis-arylaldehyde 1 and bis-arylmethyl ketone 2 is
expected to give a macrocyle 3 with two chalcone
moieties incorporated into 24-membered ring along
with two isobutenyl ether linkages. We report herein,
our preliminary results on the synthesis of macrocylces
of the type 3 with chalcone moieties.
The selection of 1 and 2 was important from the fact
that either 1 or 2 easily undergo tandem Claisen rear-
rangement under thermal conditions, thus can generate
phenolic hydroxy functionalities either in acyclic or
cyclic structures.3 Hence, the presence of ether linkages
in the molecular core of 3 are useful for further modifi-
cation of the macrocycles via tandem Claisen rear-
R2
R1
R1
R2
H3C
CHO
CHO
O
O
O
O
O
O
O
O
(a)
O
O
O
O
+
H3C
R2
R1
R1
R2
3
2
1
1a. R1 = H
1b. R1 = Cl
2a. R2 = H
2b. R2 = OMe
2c. R2 = CH3
1a + 2a = 3a (41%)
1a + 2b = 3b (28%)
1a + 2c = 3c (33%)
1b + 2a = 3d (26%)
1c + 2a = 3e (39%)
1c. R1 = CH3
(a) t-BuOK (10mol%), r.t., 16h, THF
Scheme 1. Macrocycles with chalcone moieties.
Keywords: mixed aldol reaction; potassium tert-butoxide; chalcones; macrcocyles.
* Corresponding author. Tel.: +81-298-61-3020; fax: +81-298-61-3029; e-mail: k.hiratani@aist.go.jp
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01793-2

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M. L. N. Rao et al. / Tetrahedron Letters 42 (2001) 8351–8355
rangement. So, macrocycles thus formed will possess
two chalcone moieties in addition to either two or four
phenolic hydroxy groups (depending on tandem Claisen
rearrangement) along with two isobutenyl groups. In
fact, this strategy of generating phenolic hydroxy func-
tionalities in crownophanes molecular structures has
been earlier demonstrated at this laboratory.3,4
the reaction components over a long period of time in
our conditions.6
The structure of the compound 3a was fully character-
ized by NMR and other spectroscopic techniques.7 The
macrocycle 3a has four phenyl groups, two chalcone
moieties along with two isobutenyl ether linkages. The
double bond of chalcone is trans configured judging
from the coupling constants (J=16.1 Hz) obtained for
the enone vinylic protons from 1H NMR. With the
same protocol, a variety of macrocycles 3a–3e, with
different substituents on aryl groups of 1 or 2, have
been synthesized. Thus, macrocycles 3a–3e having
chloro, methoxy and methyl substituents have been
obtained in 26–41% yields after GPC isolation (Scheme
1). All the macrocycles were fully characterized by IR,
NMR and ESI–MS.7
The bis-aldehyde 1 or bis-ketone 2 were prepared using
the reported procedure from the coupling reaction of
corresponding hydroxy aryl aldehydes or ketones with
isobutenyl dichloride in the presence of NaH as given in
Scheme 2.3,5 The mixed aldol reaction of 1a (1 equiv.)
and 2a (1 equiv.) was carried out using t-BuOK (1
equiv.) in THF (30 mL) for 16 h. Under these condi-
tions, macrocycle 3a (Scheme 1) was formed in 12%
yield along with unwanted oligomer or polymer prod-
ucts. Whereas, the same reaction with t-BuOK in cata-
lytic amount (10 mol% with respect to one aldehyde or
ketone group) afforded the yield up to 41%.
Here, we felt that the changing of phenyl groups to
naphthyls in macrocycle 3 is useful for further modi-
fications of the macrocycles using tandem Clasien
rearrangement under thermal conditions at lower
temperatures.4c,8 Presence of the naphthyl rings will
also allow macrocycles to exhibit enhanced photophysi-
cal properties. Hence, compound 7 which is a naphthyl
derivative of 1 was synthesized (Scheme 3) starting
from commercially available 2-hydroxy-3-naphthoic
acid methyl ester 4. Methyl ester 4 was reduced to
alcohol 5 with lithium aluminum hydride. Coupling
reaction of alcohol 5 with isobutenyl chloride afforded
6 which was further oxidized using PCC and obtained
aldehyde 7 in good yield.
The use of base as catalyst helped the reaction to
undergo in controllable fashion to produce macrocycle
3a in acceptable yield in the syntheses of such macrocy-
cles. This is important from the point that we have not
employed high dilution conditions or slow addition of
R1 (or R2)
OH
R
R
NaH
O
O
Cl
Cl
The mixed aldol reaction of aldehyde 7 and ketone 2a
with t-BuOK (10 mol% with respect to one aldehyde or
ketone group) in dry THF gave macrocycle 8a with
naphthyl and phenyl groups in 31% yield (Fig. 1). And
the reaction of aldehyde 7 with ketone 2b afforded the
macrocycle 8b in 27% yield (Fig. 1)10.
+
DMF, 70oC, 12h
R
R1 (or R2)
1a. R = CHO, R1 = H, 70%
1b. R = CHO, R1 = Cl, 70%
1c. R = CHO, R1 = CH3, 70%
2a. R = COCH3, R2 = H, 50%
2b. R = COCH3, R2 = OMe, 67%
2c. R = COCH3, R2 = CH3, 50%
R1 (or R2)
1 or 2
The molecular structure of 8a obtained by single crystal
X-ray analysis was given in Fig. 2.11 From Fig. 2 it is
clear that 8a is a 24-membered macrocycle possessing
naphthyl and phenyl groups along with two chalcone
structural moieties and two isobutenyl ether linkages.
Scheme 2. Synthesis of 1 and 2.5
Cl
COOMe
OH
CH2OH
a
Cl
OH
b
4
5
c
O
O
O
O
CH2OH
CHO
CH2OH
CHO
6
7
Scheme 3. Synthesis of compound 7.9 Reagents and conditions: (a) LiAlH4, THF, rt, 70%; (b) NaH, DMF, 70°C, 83%; (c)
pyridinium chlorochromate (PCC), dichloromethane, rt, 70%.

M. L. N. Rao et al. / Tetrahedron Letters 42 (2001) 8351–8355
8353
R2
O
O
O
O
OH
OH
O
O
O
O
O
O
R2
9a
8
7a + 2a = 8a (31%)
7a + 2b = 8b (27%)
Figure 1. Macrocycles.
References
1. Lehn, J.-M. Supramolecular Chemistry: Concepts and
Perspectives; VHC: Weinheim, 1995.
2. (a) Matsushima, R.; Fujimoto, S.; Tokumura, K. Bull.
Chem. Soc. Jpn. 2001, 74, 827; (b) Rurack, K.; Dekhty-
har, M. L.; Bricks, J. L.; Genger, U. R.; Rettig, W. J.
Phys. Chem. A 1999, 103, 9626 and references cited
therein.
3. (a) Hiratani, K.; Takahashi, T.; Kasuga, K.; Sugihara,
H.; Fujiwara, K.; Ohashi, K. Tetrahedron Lett. 1995, 36,
5567; (b) Hiratani, K.; Kasuga, K.; Goto, M.; Uzawa, H.
J. Am. Chem. Soc. 1997, 119, 12677.
4. (a) Hiratani, K.; Goto, M.; Nagawa, Y.; Kasuga, K.;
Fujiwara, K. Chem. Lett. 2000, 1364; (b) Tokuhisa, H.;
Ogihara, T.; Nagawa, Y.; Hiratani, K. J. Incl. Phenom.
Macrocycl. Chem. 2001, 39, 347; (c) Nagawa, Y.;
Fukazawa, N.; Suga, J.; Horn, M.; Tokuhisa, H.;
Hiratani, K.; Watanabe, K. Tetrahedron Lett. 2000, 41,
9261; (d) Choi, W.; Hiratani, K. Tetrahedron Lett. 2000,
41, 5895; (e) Tokuhisa, H.; Nagawa, Y.; Uzawa, H.;
Hiratani, K. Tetrahedron Lett. 1999, 40, 8007; (f)
Hiratani, K.; Uzawa, H.; Kasuga, K.; Kambayashi, H.
Tetrahedron Lett. 1997, 38, 8993; (g) Uzawa, H.;
Hiratani, K.; Minoura, N.; Takahashi, T. Chem. Lett.
1998, 307.
Figure 2. Molecular structure of 8a determined by single
crystal X-ray analysis.11
The double bond of enone moiety is trans configured.
1
This is in agreement with H NMR analysis showing
high coupling constants (J=16.1 Hz) for enone vinylic
protons. The twisted orientation of macrocycle 8a was
evidently due to the trans configuration of the two
double bonds forcing the core to adopt such orienta-
tion. The tandem Claisen rearrangement of macrocycle
8a also underwent cleanly at 155°C with the formation
of a new 24-macrocycle 9a (Fig. 1) having two phenolic
hydroxy functionalities.12 It is noteworthy to mention
that the macrocycle 9a has two phenolic hydroxy
groups, two chalcone moieties along with two ether
linkages.
1
5. Characterization of 1a: H NMR (500 MHz, CDCl3): l
4.79 (s, 4H, -OCH2), 5.52 (s, 2H, ꢀCH2), 7.02 (d, 2H,
J=8.4, Ar), 7.06 (t, 2H, J=7.5, Ar), 7.54 (m, 2H, Ar),
7.83 (dd, 2H, J=1.8, 7.6, Ar), 10.48 (s, 2H, -CHO); 13C
NMR (125.75 MHz, CDCl3): l 68.94, 112.71, 116.99,
121.28, 125.07, 128.90, 135.99, 138.92, 160.54, 189.28;
ESI-MS: 319 (M+Na).
1
Characterization of 1b: H NMR (500 MHz, CDCl3): l
4.77 (s, 4H, -OCH2), 5.53 (s, 2H, ꢀCH2), 6.98 (d, 2H,
J=9.0, Ar), 7.48 (dd, 2H, J=2.7, 8.9, Ar), 7.77 (d, 2H,
J=2.7, Ar), 10.39 (s, 2H, -CHO); 13C NMR (125.75
MHz, CDCl3): l 69.23, 114.32, 117.70, 125.89, 127.02,
128.46, 135.41, 138.17, 158.83, 187.81; ESI-MS: 387 (M+
Na).
In conclusion, we have demonstrated a novel approach
to synthesize 24-membered macrocycles with two chal-
cone structural moieties and two isobutenyl ether link-
ages. The presence of two isobutenyl ether linkages are
useful for modifications of the macrocycle core under
thermal conditions as demonstrated in the conversion
of macrocycle 8a to 9a (Fig. 1). The photophysical and
molecular recognition properties of these macrocycles
will be the focus of our further study.
1
Characterization of 1c: H NMR (500 MHz, CDCl3): l
2.31 (s, 6H, CH3), 4.75 (s, 4H, -OCH2), 5.49 (s, 2H,
ꢀCH2), 6.91 (d, 2H, J=8.5, Ar), 7.34 (dd, 2H, J=2.3, 8.5,
Ar), 7.62 (d, 2H, J=2.3, Ar), 10.45 (s, 2H, -CHO); 13C
NMR (125.75 MHz, CDCl3): l 20.20, 69.00, 112.71,

8354
M. L. N. Rao et al. / Tetrahedron Letters 42 (2001) 8351–8355
116.59, 124.68, 128.75, 130.65, 136.55, 139.20, 158.65,
-OCH2), 5.19 (s, 2H, ꢀCH2), 5.30 (s, 2H, ꢀCH2), 6.55 (d,
2H, J=8.4, Ar), 6.75 (d, 2H, J=8.3, Ar), 6.88 (dd, 2H,
J=2.2, 8.4, Ar), 6.98 (t, 2H, J=7.4, Ar), 7.20–7.25 (m,
4H, Ar), 7.48 (dd, 2H, J=1.5, 7.6, Ar), 7.54 (d, 2H,
J=16.2, -CHꢀCH), 7.69 (d, 2H, J=16.2, -CHꢀCH); 13C
NMR (125.75 MHz, CDCl3): l 20.28, 68.78, 69.51,
112.21, 112.17, 115.29, 116.23, 121.25, 123.97, 128.94,
129.45, 130.24, 130.41, 131.30, 132.21, 132.93, 139.31,
139.36, 140.55, 154.22, 157.42, 194.94; IR (KBr, cm−1):
1655.5 (CꢀO), 1593 (CꢀC); ESI-MS: 635 (M+Na).
189.40; ESI-MS: 347 (M+Na).
Characterization of 2a: H NMR (500 MHz, CDCl3): l
1
2.60 (s, 6H, -COMe), 4.76 (s, 4H, -OCH2), 5.50 (s, 2H,
ꢀCH2), 6.98 (d, 2H, J=8.4, Ar), 7.02 (dt, 2H, J=0.8, 7.5,
Ar), 7.44 (m, 2H, Ar), 7.71 (dd, 2H, J=1.9, 7.6, Ar); 13C
NMR (125.75 MHz, CDCl3): l 31.72, 69.18, 112.67,
117.29, 121.15, 128.74, 130.47, 133.57, 139.27, 157.46,
199.61; ESI-MS: 347 (M+Na).
1
Characterization of 2b: H NMR (500 MHz, CDCl3): l
1
2.61 (s, 6H, -COMe), 3.79 (s, 6H, -OMe), 4.70 (s, 4H,
-OCH2), 5.46 (s, 2H, ꢀCH2), 6.91 (d, 2H, J=9.0, Ar),
7.00 (dd, 2H), J=3.4, 9.0, Ar), 7.26 (d, 2H, J=3.4, Ar);
13C NMR (125.75 MHz, CDCl3): l 31.79, 55.81, 69.92,
113.99, 114.47, 116.95, 120.08, 129.01, 139.81, 151.98,
153.77, 199.21; ESI-MS: 407 (M+Na).
Characterization of 3d: H NMR (500 MHz, CDCl3): l
4.56 (s, 8H, -OCH2), 5.24 (s, 2H, ꢀCH2), 5.27 (s, 2H,
ꢀCH2), 6.67 (m, 4H, Ar), 6.99 (t, 2H, J=7.4, Ar), 7.12
(dd, 2H, J=2.4, 8.7, Ar), 7.26 (m, 2H, Ar), 7.38 (d, 2H,
J=2.6, Ar), 7.47 (m, 2H, Ar), 7.49 (d, 2H, J=16.0,
-CHꢀCH), 7.54 (d, 2H, J=16.0, -CHꢀCH); 13C NMR
(125.75 MHz, CDCl3): l 69.16, 69.24, 112.15, 113.60,
116.38, 117.31, 121.16, 125.53, 126.44, 129.33, 130.00,
130.38, 130.71, 131.28, 132.79, 138.44, 138.76, 138.83,
155.71, 156.36, 193.81; IR (KBr, cm−1): 1648.8 (CꢀO),
1601 (CꢀC), ESI-MS: 675 (M+Na).
1
Characterization of 2c: H NMR (500 MHz, CDCl3): l
2.28 (s, 6H, -Me), 2.58 (s, 6H, -COMe), 4.72 (s, 4H,
-OCH2), 5.47 (s, 2H, ꢀCH2), 6.87 (dd, 2H, J=1.4, 8.8,
Ar), 7.23 (d, 2H, J=8.4, Ar), 7.50 (s, 2H, Ar); 13C NMR
(125.75 MHz, CDCl3): l 20.10, 31.60, 69.14, 112.61,
116.74, 128.17, 130.29, 130.50, 133.94, 139.46, 155.41,
199.60; ESI-MS: 375 (M+Na).
1
Characterization of 3e: H NMR (500 MHz, CDCl3): l
2.29 (s, 6H, Me), 4.53 (s, 4H, -OCH2), 4.56 (s, 4H,
-OCH2), 5.21 (s, 2H, ꢀCH2), 5.23 (s, 2H, ꢀCH2), 6.63 (m,
4H, Ar), 6.92 (t, 2H, J=7.4, Ar), 6.99 (d, 2H, J=7.3,
Ar), 7.10 (d, 2H, J=7.0, Ar), 7.26 (d, 2H, J=6.0, Ar),
7.45 (d, 2H, J=7.4, Ar), 7.49 (d, 2H, J=16.0, -CHꢀCH),
7.65 (d, 2H, J=16.0, CHꢀCH); 13C NMR (125.75 MHz,
CDCl3): l 20.32, 68.85, 69.20, 112.03, 112.15, 115.60,
115.98, 120.77, 123.48, 128.61, 129.68, 130.02, 130.39,
131.97, 132.20, 132.28, 138.92, 139.58, 140.75, 155.36,
156.11, 194.71; IR (KBr, cm−1); 1649.8 (CꢀO), 1600
(CꢀC), ESI-MS: 635 (M+Na).
6. Macrocycle Synthesis; Parker, D., Ed.; Oxford University
Press: New York, 1996.
7. Representative procedure for mixed aldol reaction for the
synthesis of 3b: Compound 1a, 0.88 gm (3 mmol) and 2b,
1.15 g (3 mmol) were taken in to a schlenk containing 30
ml of dry THF under nitrogen. Potassium tert-butoxide
0.067 gm (0.6 mmol) was added under nitrogen and the
reaction mixture was stirred at rt for 16 h. Reaction
mixture was quenched with dil. HCl and was extracted
with dichloromethane (2×50 ml). The combined organic
extract was washed with water, brine, dried over MgSO4
and concentrated. The crude product obtained was sub-
jected to GPC purification to obtain macrocycle 3b in
28% (0.55 g) yield. Macrocycle 3b was identified by IR,
8. Yoshida, H.; Saigo, K.; Hiratani, K. Chem. Lett. 2000,
116–117.
9. Synthesis of 5: Lithium aluminum hydride 8.54 g (225
mmol) in 100 ml is slowly added to the R.B. flask
containing 30 g (150 mmol) of 2-hydroxy-3-naphthoic
acid methyl ester 4 in 300 ml of tetrahydrofuran under
nitrogen. After addition is complete, the contents were
stirred for 12 h at room temperature. Reaction mixture
was poured carefully into a beaker containing crushed ice
cubes. After all the excess lithium aluminum hydride
destroyed, conc. hydrochloric acid is added with stirring
till the white turbidity is dissolved. The organic product
was extracted with excess chloroform repeatedly. Organic
layer was washed with water, brine, dried over MgSO4
and concentrated. White crystalline compound 5 was
obtained in 70% (18.3 g) yield. Characterization of 5:
1H NMR (500 MHz, DMSO): l 4.64 (s, 2H), 5.15 (s, 1H,
-OH), 7.11 (s, 1H, Ar), 7.25 (t, 1H, J=7.6, Ar); 7.33 (t,
1H, J=7.6, Ar), 7.64 (d, 1H, J=8.1, Ar), 7.76 (d, 1H,
J=8.1, Ar), 7.81 (s, 1H, Ar), 9.84 (s, 1H, Ar-OH); 13C
NMR (125.75 MHz, CDCl3): l 64.23, 113.55, 128.22,
130.99, 131.14, 132.95, 133.31, 137.47, 138.94, 158.70.
Synthesis of 6: NaH 1.056 g (44 mmol) in dry DMF 20
ml is added slowly under nitrogen to the R.B. flask
containing alcohol 5, 7.66 g (44 mmol) in 150 ml dry
DMF. The reaction mixture stirred further for 1 h at
room temperature and isobutenyl chloride 2.48 g (19.84
mmol) in dry DMF 30 ml was added. The contents were
stirred at 70°C overnight. After reaction mixture was
brought to rt and 5 ml of water was added. DMF was
1
NMR and ESI-MS; H NMR (500 MHz, CDCl3): l 3.75
(s, 6H, -OMe), 4.51 (s, 4H, -OCH2), 4.60 (s, 4H, -OCH2),
5.18 (s, 2H, ꢀCH2), 5.31 (s, 2H, ꢀCH2), 6.58 (d, 2H,
J=9.0, Ar), 6.67 (dd, 2H, J=3.2, 9.0, Ar), 6.76 (d, 2H,
J=8.1, Ar), 6.96 (t, 2H, J=7.8, Ar), 7.00 (d, 2H, J=3.2,
Ar), 7.23 (m, 2H, Ar), 7.46 (dd, 2H, J=1.5, 6.1, Ar),
7.54 (d, 2H, J=16.0, -CHꢀCH), 7.70 (d, 2H, J=16.0,
-CHꢀCH); 13C NMR (125.75 MHz, CDCl3): l 55.62,
68.67, 69.88, 112.10, 113.64, 114.13, 115.23, 116.36,
118.39, 121.23, 123.78, 128.60, 130.07, 131.36, 132.07,
139.21, 139.35, 140.70, 150.40, 153.52, 157.34, 194.17; IR
(KBr, cm−1): 1651.7 (CꢀO), 1594 (CꢀC); ESI-MS: 667
(M+Na).
1
Characterization of 3a: H NMR (500 MHz, CDCl3): l
4.56 (s, 8H, -OCH2), 5.21 (s, 2H, ꢀCH2), 5.27 (s, 2H,
ꢀCH2), 6.60 (d, 2H, J=8.4, Ar), 6.74 (d, 2H, J=8.4, Ar),
6.91 (t, 2H, J=7.3, Ar), 6.97 (t, 2H, J=7.4, Ar), 7.10 (m,
2H, Ar), 7.22 (m, 2H, Ar), 7.45 (m, 4H, Ar), 7.49 (d, 2H,
J=16.1, -CHꢀCH), 7.69 (d, 2H, J=16.1, -CHꢀCH); 13C
NMR (125.75 MHz, CDCl3): l 68.77, 69.26, 112.03,
112.18, 115.68, 116.31, 120.95, 121.39, 123.87, 128.81,
129.69, 130.03, 131.50, 131.78, 132.34, 138.92, 139.29,
140.70, 156.10, 157.33, 194.91; IR (KBr, cm−1): 1649.8
(CꢀO), 1598 (CꢀC); ESI-MS: 607 (M+Na).
1
Characterization of 3c: H NMR (500 MHz, CDCl3): l
2.25 (s, 6H, Me), 4.56 (s, 4H, -OCH2), 4.59 (s, 4H,

M. L. N. Rao et al. / Tetrahedron Letters 42 (2001) 8351–8355
8355
evaporated under reduced pressure and product was
extracted with chloroform (2×100 ml). The combined
extract was washed with water, brine, dried over MgSO4
and concentrated. Compound 6 (yield=6.64 g, 83%) was
obtained in pure form after recrystallization from
156.20, 194.45; IR (KBr, cm−1): 1655.8 (CꢀO), 1599
(CꢀC); ESI-MS: 707 (M+Na).
1
Characterization of 8b: H NMR (500 MHz, CDCl3): l
3.46 (s, 6H, -OMe), 4.44 (s, 4H, -OCH2), 4.68 (s, 4H,
-OCH2), 5.11 (s, 2H, ꢀCH2), 5.34 (s, 2H, ꢀCH2), 6.33 (dd,
2H, J=3.0, 9.0, Ar), 6.41 (d, 2H, J=9.0, Ar), 6.95 (m,
4H, Ar), 7.32 (t, 2H, J=7.1, Ar), 7.40 (t, 2H, J=7.0, Ar),
7.54 (d, 2H, J=8.2, Ar), 7.73 (d, 2H, J=8.0, Ar), 7.77 (d,
2H, J=16.0, -CHꢀCH), 7.83 (d, 2H, J=16.0, -CHꢀCH),
7.89 (bs, 2H, Ar); 13C NMR (125.75 MHz, CDCl3): l
55.80, 69.36, 70.30, 107.67, 113.83, 114.71, 115.44, 116.67,
118.61, 124.98, 125.71, 126.89, 128.26, 128.68, 129.03,
129.97, 130.33, 133.88, 135.41, 139.65, 139.76, 141.07,
151.01, 153.88, 155.34, 194.11; IR (KBr, cm−1): 1651.3
(CꢀO), 1582 (CꢀC); ESI-MS: 767 (M+Na).
1
CH2Cl2/hexane mixture. Characterization of 6: H NMR
(500 MHz, CDCl3): l 2.50 (s, 2H, -CH2OH), 4.82 (s, 4H,
-CH2OH), 4.84 (s, 4H, -OCH2), 5.52 (s, 2H, ꢀCH2), 7.15
(s, 2H, Ar), 7.34 (dt, 2H, J=1.2, 7.4, Ar), 7.42 (dt, 2H,
J=1.3, 7.4, Ar), 7.67 (d, 2H, J=8.1, Ar), 7.75 (s, 4H,
Ar); 13C NMR (125.75 MHz, CDCl3): l 62.04, 68.78,
106.42, 116.55, 124.15, 126.39, 126.50, 127.66, 127.78,
128.84, 130.53, 133.92, 139.75, 154.49; ESI-MS: 423 (M+
Na).
Synthesis of 7: To PCC 19.4
g (90 mmol) in
dichloromethane (200 ml), 6 g of alcohol 6 (15 mmol) in
100 ml of dichloromethane was added slowly and con-
tents were stirred at room temperature for 3 h. Diethyl
ether 100 ml is added to the flask and the reaction
mixture was filtered through a Celite bed. The filtrate
again passed through small silica gel column to get pure
pale yellow aldehyde 7 (yield=4.0 g, 80%). Characteriza-
tion of 7: 1H NMR (500 MHz, CDCl3): l 4.94 (s, 4H,
-OCH2), 5.61 (s, 2H, ꢀCH2), 7.25 (s, 2H, Ar), 7.40 (t, 2H,
J=8.2, Ar), 7.54 (t, 2H, J=8.2, Ar), 7.70 (d, 2H, J=8.2,
Ar), 7.88 (d, 2H, J=8.2, Ar) 8.37 (s, 2H, Ar), 10.62 (s,
2H, -CHO); 13C NMR (125.75 MHz, CDCl3): l 68.9,
107.59, 116.86, 124.94, 125.63, 126.71, 127.94, 129.38,
129.88, 131.47, 137.36, 139.01, 156.21, 189.75; ESI-MS:
419 (M+Na).
11. Crystal data for 8a: C53H36O6, Mw=768.86, crystal sys-
tem=triclinic, space group=P1 (c2), Z=4 in a cell of
,
dimensions: a=12.735(1), b=16.112(1), c=10.1921(6) A,
h=91.044(2), i=103.322(4), k=102.337(4)°, V=
1983.1(2) A , Dcalcd=1.288 g cm−1. The data were col-
3
,
lected at −80°C on a Rigaku RAXIS-RAPID Imaging
,
Plate diffractometer, u (Mo Ka)=0.7107 A, v=0.83
cm−1
,
18830 measured and 8717 unique reflections
(2qmax=55.00, Rint=0.042). R=0.127, Rw=0.193. Note:
The correct molecular formula for macrocycle 8a is
C46H36O6. The obtained molecular formula C53H36O6
was due to some solvent molecules in the crystal lattice,
which are not identified.
12. Tandem Claisen rearrangement of 8a: Compound 8a was
heated under neat conditions at 155°C for 1.5 h under
vacuum to give 9a (yield=85%, by NMR). 1H NMR (500
MHz, CDCl3): l 3.87 (s, 4H, CH2-Ar), 4.65 (s, 4H,
-OCH2), 5.03 (s, 2H, ꢀCH2), 5.29 (s, 2H, ꢀCH2), 5.91 (s,
2H, Ar-OH), 6.90 (d, 2H, J=8.2, Ar), 7.04 (t, 2H, J=7.3,
Ar), 7.28 (t, 2H, J=7.7, Ar), 7.40–7.46 (m, 4H, Ar),
7.60–7.64 (m, 4H, Ar), 7.72–7.78 (m, 4H, Ar); 13C NMR
(125.75 MHz, CDCl3): l 32.10, 69.30, 112.71, 114.44,
114.81, 117.02, 121.50, 122.53, 123.91, 124.50, 127.81,
128.78, 129.15, 129.69, 129.87, 130.47, 130.78, 132.86,
134.03, 138.61, 139.88, 146.14, 150.87, 156.61, 193.78;
ESI-MS: 707 (M+Na).
1
10. Characterization of 8a: H NMR (500 MHz, CDCl3): l
4.56 (s, 4H, -OCH2), 4.75 (s, 4H, -OCH2), 5.22 (s, 2H,
ꢀCH2), 5.37 (s, 2H, ꢀCH2), 6.48 (d, 2H, J=8.2, Ar), 6.67
(t, 2H, J=7.5, Ar), 6.79 (m, 2H, Ar), 6.99 (s, 2H, Ar),
7.40 (m, 4H, Ar), 7.47 (t, 2H, J=7.0, Ar), 7.58 (d, 2H,
J=8.0, Ar), 7.73 (d, 2H, J=16.0, -CHꢀCH), 7.80 (d, 2H,
J=8.0, Ar), 7.85 (d, 2H, J=16.0, -CHꢀCH), 7.99 (s, 2H,
Ar); 13C NMR (125.75 MHz, CDCl3): l 68.96, 69.33,
107.26, 111.78, 115.87, 116.47, 120.88, 124.60, 125.37,
126.54, 127.80, 128.25, 128.70, 129.52, 129.71, 130.00,
132.28, 133.00, 135.04, 138.88, 139.30, 140.41, 154.82,