Enantioselective Br?nsted base catalyzed [4+2] cycloaddition using novel amino-substituted tetraphenylene derivatives

Article abstract of DOI:10.1016/j.tet.2010.10.064

This paper is concerned with the syntheses of 1,8,9,16- tetrahydroxytetraphenylene derivatives and their applications as Br?nsted base organocatalysts for [4+2] cycloaddition between anthrone and maleimides. The structural modifications of the catalysts and their related catalytic properties are described and discussed in details.

Full text of DOI:10.1016/j.tet.2010.10.064

Tetrahedron 66 (2010) 9860e9874
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Enantioselective Brønsted base catalyzed [4þ2] cycloaddition using novel
amino-substituted tetraphenylene derivatives
,
b
,
,b,c,
*
Chun-Kit Hau a c, Hao He d, Albert W.M. Lee d, David T.W. Chik d, Zongwei Cai d, Henry N.C. Wong a
a Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China
b Centre of Novel Functional Molecules, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China
c Institute of Molecular Functional Materials, The Chinese University of Hong Kong,y Shatin, New Territories, Hong Kong SAR, China
d Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong SAR, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 August 2010
Received in revised form 1 October 2010
Accepted 22 October 2010
Available online 28 October 2010
This paper is concerned with the syntheses of 1,8,9,16-tetrahydroxytetraphenylene derivatives and their
applications as Brønsted base organocatalysts for [4þ2] cycloaddition between anthrone and mal-
eimides. The structural modifications of the catalysts and their related catalytic properties are described
and discussed in details.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Tetraphenylene
Brønsted base
Enantioselective cycloaddition
1. Introduction
Tetraphenylene (tetrabenzo[a,c,e,g]cyclooctatetraene) (1) is
a structurally exceptional molecule featuring a rigid conformation
Since its discovery in 1926, DielseAlder reaction is regarded as
one of the most important and fascinating transformations in or-
ganic synthesis.1 It has been extensively used as one of the most
versatile synthetic tools in the construction of a large number of
important building blocks. Many past efforts have shown that chiral
metal complexes are efficient catalysts in asymmetric DielseAlder
reaction. Years ago, Corey reviewed the art of enantioselective
metal-catalyzed DielseAlder reaction, which had been developed
by his group.1 In contrast, asymmetric DielseAlder reaction cata-
lyzed by organocatalysts has only a rather short history and has
been neglected for quite a long time.
(Scheme 1).8 It consists of four benzene rings, which are arranged
alternatively above and below the mean plane of the molecule. The
molecule then belongs to a D2d symmetry point group.9,10 Due to the
high inversion barrier of the central cyclooctatetraene,11 a chiral
version of tetraphenylenes can be obtained by introducing sub-
stituents appropriately. A program has then been initiated in our
laboratories in the syntheses of building blocks 2,12 3,13 4,14 5,15 and
OH HO
OH HO
OH
OH
After the first example was reported by Kagan in 1989,2 there
was limited examples for Brønsted base-catalyzed DielseAlder
reactions.3e5 More recently, Tan reported a highly enantioselective
and diastereoselective DielseAlder reaction between anthrones
and maleimides using modified guanidines.6 Deng also reported
a highly enantioselective and diastereoselective DielseAlder re-
action with pyrones using modified cinchona alkaloids as an acid-
base bifunctional catalyst.7
1
2
3
OH OH
OH OH
HO
HO
OH
OH
OH HO
OH HO
OH
OH
OH OH
5
OH OH
* Corresponding author. E-mail address: hncwong@cuhk.edu.hk (H.N.C. Wong).
An Area of Excellence Scheme established under the University Grants Com-
mittee (Hong Kong).
4
6
y
Scheme 1.
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.10.064

C.-K. Hau et al. / Tetrahedron 66 (2010) 9860e9874
9861
6.16 Noteworthy is that 2e4 are chiral, while 5 and 6 are achiral.
Geometrically, 3 is a linear unit containing reactive sites, pointing
toward opposite directions.
In this article, we would like to report the syntheses of thirteen
amino-alcohols derived from tetraphenylenol 3 and their catalytic
efficiencies by employing them as organocatalysts in [4þ2] cyclo-
addition reactions.
Three different amino-alcohols were accordingly prepared fol-
lowed by hydrogenolysis.
Alcohol (S,S)-10 was also converted to the corresponding cyano-
compound (S,S)-18 through esterification and palladium-catalyzed
cyanation. With (S,S)-18 in hand, the hydroxy group was then
protected and subsequent reduction by DIBAL-H to give the cor-
responding aldehyde. After preliminary purification, the resulting
aldehyde was allowed to undergo reductive amination with pyr-
rolidine to give amine (S,S)-20 in a moderate yield. Subsequent
hydrogenolysis provided amino-alcohol (S,S)-21, in which there is
only one carbon between the pyrrolidine and the core tetraphe-
nylene (Scheme 4).
2. Results and discussion
Scheme 2 shows that tetraphenylenol 3 can be resolved in its
optically pure forms after sulfonylation to the two corresponding
HO
HO
OH
OH
*RO
*RO
OR* *RO
+
OR*
OR*
i
R*:
O
OR* *RO
SO
3
(S,S)-7a (47%)
(R,R)-7b (45%)
*RO
*RO
OR*
OR*
HO
HO
OH
iii
O
O
OH
OH
ii
OH
(S,S)-7a
(S,S)-3
(S,S)-8
O
O
OC7H15
OC7H15
HO
HO
OC7H15
OC7H15
iv
vi
v
(S,S)-10
(S,S)-9
PMBO
HO
OC7H15
OC7H15
(S,S)-11
Scheme 2. Reagents and conditions: (i)R*CI, Et3N, THF, 0e23 ꢀC. (ii) KOH (aq), MeOH, reflux, 97%. (iii) Cs2CO3, DMSO, 38%. (iv) C7Hi5Br, Cs2CO3, DMF, 80 ꢀC, 88%. (v) H2, PdeC, THF,
EtOH, 95%. (vi) PMBBr, K2CO3, DMF, 79%.
diastereomeric tetrakis-(S)-camphorsulfonates. The diastereomer
7a was subjected to hydrolysis to give the (S,S)-tetraphenylenol 3.
Two of the hydroxy groups of (S,S)-3 was then protected. The
remaining hydroxy groups underwent Williamson ether synthesis
to introduce the long lipophilic alkyl chains on the core structure,
which significantly enhance the solubility in organic solvents. Diol
(S,S)-10 was obtained in good yields after hydrogenolysis. Con-
trolled mono-protection of the hydroxy groups that led to the for-
mation of the key intermediate (S,S)-11.
All the four synthesized amino-alcohols were able to catalyze the
cycloaddition reactions. As shown in Table 1, (S,S)-13 catalyzed the
reaction to furnish the desired DielseAlder adduct in 15.3% ee value
(entry 2). The enantioselectivity provided by (S,S)-15 was much
lower (entry 3). The long distance between the active site (pyrroli-
dine) and the hydroxy group seems to reduce the influence of the
hydroxy group in asymmetric reactions. Unfortunately, neither
(S,S)-17 nor (S,S)-21 demonstrated a better catalytic activity than
that of (S,S)-13. The product yields were low at 40% even though
complete reactions were resulted. When the pyrrolidine was
replaced by N,N-dimethylamine, only partial enantioselectivity was
As can be seen in Scheme 3, (S,S)-11 was allowed to react with
different chloro-substituted amines through substitution reaction.
R
Cl
N
R
PMBO
O
OC7H15
OC7H15
HO
O
OC7H15
OC7H15
i
ii
(S,S)-11
N
R
N
R
R
R
(S,S)-12, R = −(CH2CH2)2−, n = 1 (75%) (S,S)-13, R = −(CH CH ) −, n = 1
(67%)
(S,S)-14, R = −(CH2CH ) −, n = 2 (61%) (S,S)-15, R = −(CH22CH2)2−, n = 2 (80%)
2 2
2 2
(72%)
(S,S)-16, R = CH3, n = 1
(S,S)-17, R = CH3, n = 1
(75%)
Scheme 3. Reagents and conditions: (i) Kl, Cs2CO3, DMF, reflux, (ii) H2, PdeC, THF, EtOH.

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C.-K. Hau et al. / Tetrahedron 66 (2010) 9860e9874
According to the aforementioned results, the spatial environ-
ment between the hydroxy group and the pyrrolidine was estimated
to be less effective for providing a good enantioselectivity. To im-
prove the spatial environment of the cavity, we designed to link two
tetraphenylenes together. Scheme 5 describes the syntheses of two
different dimeric forms of amino-alcohol based on the structural
framework of the amino-alcohol (S,S)-13.
HO
NC
OC7H15
OC7H15
BnO
NC
OC7H15
OC7H15
i, ii
iii
(S,S)-10
(S,S)-18
(S,S)-19
Thus, alcohol (S,S)-10 was first mono-protected and was fol-
lowed by reaction with 1,3-bromopropane to form bromo-con-
taining compound (S,S)-23. Compound (S,S)-24 was obtained in the
same manner by changing 1,3-dibromopropane into 1,4-dibromo-
butane. Either (S,S)-23 or (S,S)-24 reacted with a slightly excess
(S,S)-10, giving dimeric alcohols (S,S,S,S)-25 and (S,S,S,S)-26, re-
spectively. Each of the dimeric alcohols was allowed to undergo
substitution reaction and hydrogenation to provide the dimeric
amino-alcohols (S,S,S,S)-27 and (S,S,S,S)-28.
Further modifications were carried out based on the structural
framework of (S,S,S,S)-27, as described in Scheme 6. Alcohol (S,S)-18
was coupled with bromo-containing compound (S,S)-23, affording
the dimeric cyano-compound (S,S,S,S)-29. Further reduction of the
cyano group and reductive amination with pyrrolidine gave the
corresponding amine. Subsequent hydrogenolysis gave the amino-
alcohol (S,S,S,S)-30 in an acceptable yield.
BnO
N
OC7H15
OC7H15
HO
OC7H15
OC7H15
iv, v
vi
N
(S,S)-20
(S,S)-21
Scheme 4. Reagents and conditions: (i) PhNTf2, collidine, DMAP, CH2CI2, 93%. (ii) Zn
(CN)2, Pd(PPh3)4, DMF, reflux, 48 h, 99%. (iii) BnBr, K2CO3, DMF, 93%. (iv) DIBAL-H, CH2CI2,
ꢁ78 ꢀC, 83%. (v) Pyrrolidine, NaBH3CN, THF, MeOH, 68%. (vi) H2, PdeC, THF, EtOH, 70%.
Table 1
Summary of results of the [4þ2] cycloaddition reaction in the catalysis of chiral
amino-alcohols (S,S)-13, (S,S)-15, (S,S)-17, and (S,S)-21
O
O
*
O
N
Me
10 mol% Cat.
(0.01M)
*
O
+
N
Me
HO
O
Furthermore, compound (S,S)-31 was prepared from diol (S,S)-
10 using a similar method as that for the preparation of compound
(S,S)-23 (Scheme 7). Cross-coupling of (S,S)-18 and (S,S)-31 gave the
cyano-compound (S,S,S,S)-32, in which a two-carbon linkage was
placed in-between the two tetraphenylenes. Similar to the prepa-
ration of (S,S,S,S)-30, amino-alcohol (S,S,S,S)-34 was obtained in an
acceptable yield after a three-step reaction. The catalytic properties
of each dimeric form of amino-alcohol in DielseAlder reaction are
summarized in Table 2.
(1.1 equiv.)
(1 equiv.)
22
Entry
Cat.
Solvent/Temp (ꢀC)
Time (min)
Yield (%)
ee% (S,S)a
1
2
3
4
5
Et3N
CHCl3/18
CHCl3/20
CHCl3/16
CHCl3/20
CHCl3/20
15
40
40
40
40
92
75
83
40
40
d
(S,S)-13
(S,S)-15
(S,S)-17
(S,S)-21
15.3
4.1
11.7
1.3
a
ee% was determined by HPLC with Chiralcel OD, absolute configuration of 22 was
determined by comparison of the optical rotation value with literature value.2e4
As expected, the dimeric form of the amino-alcohol (S,S,S,S)-27
provided a better enantioselectivity than the monomeric form
(S,S)-13, and up to 25.3% ee was obtained (entry 2). The product
yield of 22 was also slightly increased and a lower loading of cat-
alyst was needed. However, when the distance of the ether linkage
between the two tetraphenylenes increased from three-carbon to
four-carbon, the enantioselectivity dropped to only 10% (entry 3).
This has led to an observation that the cavity size of (S,S,S,S)-28 was
observed, which implied that the cyclic amine structure showed
some noticeable effects on the reactivity as well as the enantiose-
lectivity of the catalyst (entry 4). However, when the distance be-
tween the core and the pyrrolidine was shortened to one carbon
distance, the enantioselectivity dropped dramatically from 15.3 to
1.3% (entry 5).
BnO
OC7H15
OC7H15
HO
HO
OC7H15
OC7H15
i, ii
O
n
Br
(S,S)-10
(S,S)-23, n=1
(S,S)-24, n=2
n
C7H15
O
O
OC7H15
OC7H15
O
(S,S)-10
iii
+
C7H15O
OBn
HO
(S,S)-23 or (S,S)-24
(S,S,S,S)-25, n=1 (65%)
(S,S,S,S)-26, n=2 (87%)
n
C7H15
O
O
O
O
O
OC7H15
OC7H15
iv, v
C7H15
OH
N
(S,S,S,S)-27, n=1 (2-steps: 48%)
(S,S,S,S)-28, n=2 (2-steps: 33%)
Scheme 5. Reagents and conditions: compound (S,S)-23: (i) BnBr, K2CO3, DMF, 89%. (ii) 1,3-Dibromopropane, Cs2CO3, DMF, 80 ꢀC, 95%. Compound (S,S)-24: (i) BnBr, K2CO3, DMF,
89%. (ii) 1,4-Dibromobutane, Cs2CO3, DMF, 80 ꢀC, 95%. (iii) Cs2CO3, DMF, 80 ꢀC. (iv) 1-(2-Chloroethyl) pyrrolidine, KI, Cs2CO3, DMF, reflux, (v) H2, PdeC, THF, EtOH.

C.-K. Hau et al. / Tetrahedron 66 (2010) 9860e9874
9863
C7H15
O
O
O
OC7H15
OC7H15
O
i
(S,S)-18 + (S,S)-23
C7H15
OBn
NC
(S,S,S,S)-29
C7H15
O
O
O
O
OC7H15
OC7H15
ii, iii, iv
C7H15
OH
N
(S,S,S,S)-30
Scheme 6. Reagents and conditions: (i) Cs2CO3, DMF, 80 ꢀC, 81%. (ii) DIBAL-H, CH2CI2, ꢁ78 ꢀC, 99%. (iii) Pyrrolidine, NaBH3CN, MeOH, 54%. (iv) H2, PdeC, THF, 67%.
BnO
O
OC7H15
OC7H15
HO
HO
OC7H15
OC7H15
i, ii
Br
(S,S)-10
(S,S)-31
C7H15
O
O
O
O
OC7H15
OC7H15
iii
(S,S)-18 + (S,S)-31
C7H15
OBn NC
(S,S,S,S)-32
C7H15
O
O
O
O
OC7H15
OC7H15
iv, v
C7H15
OBn
N
(S,S,S,S)-33
C7H15
O
O
O
O
OC7H15
OC7H15
vi
C7H15
OH
N
(S,S,S,S)-34
Scheme 7. Reagents and conditions: (i) BnBr, K2CO3, DMF, 89%. (ii) 1,2-Dibromopropane, CS2CO3, acetone, reflux, 74%. (iii) CS2CO3, acetone, reflux, 70%. (iv) DIBAL-H, CH2CI2, ꢁ78 ꢀC,
98%. (v) Pyrrolidine, NaBH3CN, THF, 46%. (vi) H2, PdeC, THF, 68%.
Table 2
Summary of results of the [4þ2] cycloaddition reaction in the catalysis of chiral amino-
too large and the conformation of (S,S,S,S)-28 was much flexible,
alcohols (S,S)-13, (S,S,S,S)-27, (S,S,S,S)-28, (S,S,S,S)-30, (S,S,S,S)-33, and (S,S,S,S)-34
which gave a low enantioselectivity of product.
O
O
*
O
At room temperature, (S,S,S,S)-30 was found to have a similar
reactivity as that of (S,S,S,S)-27 based on TLC monitoring. Prolonged
reaction time was used to ensure the completeness of the reaction.
Gratifyingly, the enantioselectivity was found to be improved,
which was upgraded to 35.9% ee (entry 4). Amino-alcohol (S,S,S,S)-
34 provided a better enantioselectivity than (S,S,S,S)-30 at room
temperature (entry 5). Unfortunately, amino-alcohol (S,S,S,S)-34
did not show improvement in the ee value when the reaction was
carried out at a lower temperature (entry 6). The conformation of
the catalyst may change to a less favorable form, leading to a low ee
value. The only difference between the chiral amine (S,S,S,S)-33 and
chiral amino-alcohol (S,S,S,S)-34 is the protected hydroxy group.
The absence of the hydroxy group did not affect the reactivity of the
catalyst, but largely deteriorated the enantioselectivity of the cat-
alyst (entries 6 and 7). This further demonstrated the importance of
N
Me
Cat.
*
O
+
N
Me
(0.01M)
HO
O
(1.1 equiv.)
(1 equiv.)
22
Entry Cat. (mol %)
Solvent/Temp (ꢀC) Time (min) Yield (%) ee% (S,S)a
1
2
3
4
5
6
7
(S,S)-13 (10)
CHCl3/20
40
60
60
75
85
85
81
15.3
25.3
10.0
35.9
41.8
11.5
31.5
(S,S,S,S)-27 (5) CHCl3/20
(S,S,S,S)-28 (5) CHCl3/20
(S,S,S,S)-30 (5) CHCl3/20
(S,S,S,S)-34 (5) CHCl3/21
(S,S,S,S)-33 (5) CHCl3/0
(S,S,S,S)-34 (5) CHCl3/0
100
120
120
120
91.3
89
88
a
ee% was determined by HPLC with Chiralcel OD, absolute configuration of 22 was
determined by comparison of the optical rotation value with literature value.2e4

9864
C.-K. Hau et al. / Tetrahedron 66 (2010) 9860e9874
the hydroxy group in the chiral catalytic induction, which might
imply the involvement of hydrogen bonding between the catalyst
and the substrate in the transition state of the catalysis.
Based on the above line of thinking, four different amino-alco-
hols were synthesized.
Cyano-compound (S,S)-19 was reduced to the corresponding
primary amine (S,S)-35 (Scheme 8). Aldehyde (S,S)-36, which was
also generated from (S,S)-19, was allowed to undergo reductive
amination with the amine (S,S)-35 and the cross-coupled amine
(S,S,S,S)-37 was obtained in good yield. Subsequent reductive
amination with formaldehyde and hydrogenolysis gave the amino-
alcohol (S,S,S,S)-38 in an acceptable yield.
(S,S,S,S)-34, the bromo-compound (R,R)-31 was synthesized from
tetrakis-(S)-camphorsulfonate (R,R)-7b through six-step se-
a
quence. Cross-coupling between (S,S)-18 and (R,R)-31 gave the
cyano-compound (R,R,S,S)-32 in good yield. After reduction by
DIBAL-H and reductive amination with pyrrolidine, the corre-
sponding amine was obtained in good yield. Hydrogenolysis of the
amine provided amino-alcohol (R,R,S,S)-34, in which the hydroxy
group was orientated according to the R configuration of the tet-
raphenylene (Scheme 10).
In order to further increase the cavity size of the catalyst, we
turned our effort to synthesize a trimeric form of tetraphenylenes.
As revealed in Scheme 11, dimeric cyano-compound (S,S,S,S)-32
C7H15
O
O
CH2NH2
OBn
C7H15
O
O
CN
i
C7H15
C7H15
OBn
(S,S)-19
(S,S)-35
C7H15
O
O
CHO
OBn
ii
C7H15
(S,S)-36
H
N
C7H15
O
OC7H15
OC7H15
iii
(S,S)-35 + (S,S)-36
C7H15O
OBnBnO
(S,S,S,S)-37
N
C7H15
O
O
OC7H15
OC7H15
iv, v
C7H15
OH HO
(S,S,S,S)-38
Scheme 8. Reagents and conditions: (i) LAH, THF, reflux, 85%. (ii) DIBAL-H, CH2CI2, ꢁ78 ꢀC, 98%. (iii) NaBH3CN, THF, MeOH, 80%. (iv) HCHO, NaBH4, TFA, THF, 85%. (v) H2, PdeC, THF, 48%.
On the other hand, cyano-compound (S,S,S,S)-32 underwent
reduction and was then allowed to react with piperidine, giving
chiral amine (S,S,S,S)-39 (Scheme 9). Subsequent hydrogenation
afforded amino-alcohol (S,S,S,S)-40.
HO
HO
OC7H15
OC7H15
BnO
O
OC7H15
OC7H15
4 steps
31%
i, ii
(R,R)-7b
Br
(R,R)-10
(R,R)-31
C7H15
O
O
O
O
OC7H15
OC7H15
i, ii
(S,S,S,S)-32
C7H15
O
O
O
OC7H15
OC7H15
C7H15
OBn
iii
(S,S)-18 + (R,R)-31
N
C7H15O
OBn NC
(S,S,S,S)-39
(R,R,S,S)-32
C7H15
O
O
O
O
OC7H15
OC7H15
C7H15
O
O
O
O
OC7H15
OC7H15
iv, v, vi
iii
C7H15
OH
C7H15
OH
N
N
(S,S,S,S)-40
(R,R,S,S)-34
Scheme 10. Reagents and conditions: (i) BnBr, K2CO3, DMF, 89%. (ii) 1,2-Di-
bromopropane, Cs2CO3, acetone, reflux, 74%. (iii) Cs2CO3, acetone, reflux, 83%. (iv) DIBAL-
H, CH2CI2, ꢁ78 ꢀC, 98%. (v) Pyrrolidine, NaBH3CN, THF, 75%. (vi) H2, PdeC, THF, 50%.
Scheme 9. Reagents and conditions: (i) DIBAL-H, CH2CI2, ꢁ78 ꢀC, 98%. (ii) Piperidine,
NaBH3CN, THF, MeOH, 65%. (iii) H2, PdeC, THF, 86%.
To investigate any possibilities of chirality mismatch during the
catalysis, an amino-alcohol with mixed chiralities (R,R,S,S)-34 was
synthesized. Utilizing the same method for the preparation of
was deprotected by hydrogenolysis to generate alcohol (S,S,S,S)-41.
Compound (S,S,S,S)-41 was coupled with (S,S)-31 to furnish the
trimeric cyano-compound (S,S,S,S,S,S)-42 in a moderate yield.

C.-K. Hau et al. / Tetrahedron 66 (2010) 9860e9874
9865
C7H15
O
O
O
O
OC7H15
OC7H15
i
(S,S,S,S)-32
C7H15
OH NC
(S,S,S,S)-41
C7H15
O
O
CN
O
BnO
O
OC7H15
OC7H15
ii
(S,S,S,S)-41 + (S,S)-31
C7H15
O
O
(S,S,S,S,S,S)-42
C7H15
O
OC7H15
N
C7H15
O
O
HO
O
OC7H15
OC7H15
iii, iv, v
C7H15
O
O
O
O
(S,S,S,S,S,S)-43
C7H15
OC7H15
Scheme 11. Reagents and conditions: (i) H2, PdeC, THF, 70%. (ii) Cs2CO3, acetone, reflux, 43%. (iii) DIBAL-H, CH2CI2, ꢁ78 ꢀC. (iv) Pyrrolidine, NaBH3CN, THF, two-step: 58%. (v) H2,
PdeC, THF, 61%.
Compound (S,S,S,S,S,S)-42 underwent aldehyde generation and re-
ductive amination to give the corresponding amine. The trimeric
form of amino-alcohol (S,S,S,S,S,S)-43 was obtained in 61% after
hydrogenolysis.
The catalytic properties of the four different amino-alcohols in
DielseAlder reaction are summarized in Table 3.
Increasing the ring size of the amine decreased the product yield
of the DielseAlder adduct, as well as the ee value of the DielseAlder
adduct (entry 3). The result of entry 4 proved that the hydroxy
group orientation was crucial to the enantioselectivity of the cat-
alyst. If the hydroxy group was orientated in an opposite direction,
the enantioselectivity of (R,R,S,S)-34 (entry 4) was comparable with
that of protected amine (S,S,S,S)-33 (entry 6 in Table 2). The con-
formation of the trimeric form (S,S,S,S,S,S)-43 was found ineffective
to improve the enantioselectivity (entry 5).
Table 3
Summary of results of the [4þ2] cycloaddition reaction in the catalysis of chiral
amino-alcohols (S,S,S,S)-34, (S,S,S,S)-38, (S,S,S,S)-40, (R,R,S,S)-34, and (S,S,S,S,S,S)-43
Finally, to prove that the chiral induction was completely based
on the chirality of the tetraphenylene, the enantiomer of (S,S,S,S)-34
was also synthesized. Thus, compound (R,R,R,R)-34 was synthesized
from tetrakis-(S)-camphorsulfonate (R,R)-7b in a way similar to the
same synthetic route for amino-alcohol (S,S,S,S)-34 (Scheme 12).
Amino-alcohol 34 was chosen as the best catalyst for the Diel-
seAlder cycloaddition reaction among all the aforementioned
synthetic amino-alcohols. The corresponding enantiomers were
tested with different solvent systems and different substituent on
the maleimide.
Fig. 1 illustrates the plausible reaction mechanism of the cata-
lytic DielseAlder cycloaddition by (S,S,S,S)-34. As can be seen, the
pyrrolidine moiety will first interact with anthrone to generate the
corresponding enolate and the enolate will then position itself near
the catalyst due to electrostatic interaction. It is suggested that the
tetraphenylene, in its (S,S) configuration, will provide a chiral en-
vironment during the catalytic process. With the presence of the
hydroxy group, the N-methylmaleimide will be directed toward the
enolate from a more favorable direction by hydrogen bonding.
As revealed in Table 4, the result of entry 2 strongly sub-
stantiated that the enantioselectivity of the catalyst was chirality-
dependent, because (R,R,R,R)-34 provided the opposite enantiose-
lectivity to that of (S,S,S,S)-34.
O
O
*
O
N
Me
5 mol% Cat.
(0.01M)
*
O
+
N
Me
HO
O
(1.1 equiv.)
(1 equiv.)
22
Entry Cat. (mol %)
Solvent/Temp (ꢀC) Time (min) Yield (%) ee% (S,S)a
1
2
3
4
5
(S,S,S,S)-34
(S,S,S,S)-38
(S,S,S,S)-40
(R,R,S,S)-34
CHCl3/21
CHCl3/21
CHCl3/0
CHCl3/0
120
1260
120
120
120
91.3
58
68.8
84
41.8
2.5
15.5
10.9
9.1
(S,S,S,S,S,S)-43 CHCl3/0
88
a
ee% was determined by HPLC with Chiralcel OD, absolute configuration of 22
was determined by comparison of the optical rotation value with literature
value.2e4
The change of the amine group from pyrrolidine into a bulky
alkyl tertiary amine greatly retarded the reactivity of the catalyst,
not only on the rate of reaction, but also on the yield of the Diel-
seAlder adduct. The amine group positioned at the centre of the
linking chain was unfavorable for asymmetric DielseAlder re-
actions (entry 2). For this reason, (S,S,S,S)-38 provided almost no
enantioselectivity for the reaction.

9866
C.-K. Hau et al. / Tetrahedron 66 (2010) 9860e9874
The increase in size of the substituent on the maleimide led to
the decrease of the ee value of the DielseAlder adduct. Notably,
flexible alkyl chains like iso-butyl group caused severe effect to the
enantioselectivity of the catalyst, while cyclic or aromatic sub-
stituent caused relatively less effect on the ee value of the Diel-
seAlder adduct. Such variation should be counted on the strength
of the directing effect by the hydroxy group of the catalyst after the
formation of the transition state with anthrone.
*RO
*RO
OR*
OR*
C7H15
O
O
CN
OH
5 steps
28%
R*:
O
SO
C7H15
(R,R)-7b
(R,R)-18
C7H15
O
O
O
O
OC7H15
OC7H15
i
(R,R)-18 + (R,R)-31
C7H15
OBn NC
3. Conclusion
(R,R,R,R)-32
In summary, over 10 chiral amino-alcohols were synthesized
and tested for the enantioselectivity of the DielseAlder cycloaddi-
tion reaction between anthrone and maleimide. Amino-alcohol 34
was found to be the best performer among all, and up to 40% ee was
achieved. The chirality of the DielseAlder adduct was found to be
dependent on the chirality of the tetraphenylenes in the catalyst,
indicating that the chirality of tetraphenylene is the key chiral
factor to affect the enantioselectivity of the cycloaddition. More-
over, up to 80% recovery of all the synthetic amino-alcohol catalysts
were achieved after the DielseAlder reaction without lost of cata-
lytic properties. Further efforts will be put to introduce bulky alkyl
substituents on the ortho-positions of the phenyl rings on the tet-
raphenylenes, which may magnify the chiral effect by the tetra-
phenylenes. On the other hand, changing the hydroxy group into
a much stronger hydrogen bond donor will expectedly enhance the
directing effect during the catalytic procedure. Based on mecha-
nistic consideration, our catalysts may also be potential catalysts for
asymmetric Michael addition reaction or asymmetric Mor-
itaeBayliseHillman reaction.
C7H15
O
O
O
O
OC7H15
OC7H15
ii, iii, iv
C7H15
OH
N
(R,R,R,R)-34
Scheme 12. Reagents and conditions: (i) Cs2CO3, acetone, reflux, 70%. (ii) DIBAL-H,
CH2CI2, ꢁ78 ꢀC. (iii) Pyrrolidine, NaBH3CN, THF, two-steps: 46%. (iv) H2, PdeC, THF, 68%.
OC7H15
OC7H15
(S,S,S,S)-34
O
H
N
C7H15
C7H15
O
O
O
O
H
O
O
Me
N
O
4. Experimental
more favorable approach direction
for N-methylmaleimide
4.1. General information
Fig. 1. The plausible reaction mechanism of the catalytic DielseAlder cycloaddition by
(S,S,S,S)-34.
All reagents and solvents were reagent grade. Further purifica-
tion and drying following the guidelines of Perrin and Armarego
were used when necessary.17 Organic solvents were concentrated
under reduced pressure on a rotary evaporator. Chromatographic
purification of products was performed on Macherey Nagel Kie-
selgel 60 M (230e400 mesh). Thin-layer chromatography (TLC)
was performed on E. Merck silica gel 60 F254 (0.25 mm thickness)
coated on aluminum plates. Visualization of the developed chro-
Table 4
Summary of results of the [4þ2] cycloaddition reaction in the catalysis of chiral
amino-alcohols (S,S,S,S)-34 and (R,R,R,R)-34 at different conditions
O
O
*
O
N
R
5 mol% Cat.
(0.01M)
*
O
+
N
R
HO
O
matogram was performed by
a spray of 5% w/v dodeca-
(1.1 equiv.)
(1 equiv.)
molybdophosphoric acid in ethanol and subsequent heating.
Melting points were measured with a Reichert apparatus in Celsius
degrees and are uncorrected. Optical rotations were obtained with
a PerkineElmer model 341 polarimeter, operating at 589 nm. Nu-
clear magnetic resonance (NMR) spectra were recorded with
a Bruker DPX300 NMR spectrometer at 300 MHz (1H) or at 75 MHz
Entry Cat. (mol %) Solvent/Temp(ꢀC)
R
Yield (%) ee% (S,S)a
1
2
3
4
5
6
7
8
(S,S,S,S)-34 CHCl3/21
(R,R,R,R)-34 CHCl3/24
(R,R,R,R)-34 Toluene/23
(R,R,R,R)-34 TBME/23
(S,S,S,S)-34 CHCl3/21
(S,S,S,S)-34 CHCl3/21
(S,S,S,S)-34 CHCl3/21
(S,S,S,S)-34 CHCl3/21
Me (22)
Me (22)
Me (22)
Me (22)
Ph (44)
i-Bu (45)
91.3
92
82
93
89
41.8
ꢁ41.1 (R,R)
ꢁ43.3 (R,R)
ꢁ5.7 (R,R)
31.9
0.9
17.1
(
13C) or a Bruker ADVANCE-III NMR spectrometer at 400 MHz (1H)
or at 100 MHz (13C). All NMR measurements were carried out at
room temperature in deuterated solution and were internally ref-
erenced to residual proton solvent signals (note: CDCl3 referenced
76
Cyclohexyl (46) 52
m-NO2Ph (47) 67
26.3
a
at
etone-d6 referenced at
septet in 13C; DMSO-d6 referenced at
d d
7.26 in 1H and 77.16 for central line of the triplet in 13C; ac-
ee% was determined by HPLC with Chiralcel OD, absolute configuration of each
DielseAlder adduct was determined by comparison of the optical rotation value or
d
2.05 in 1H and
d
29.84 for central line of the
2.50 in 1H and
39.52 for
5.32 in 1
the retention time with literature value.2e4
d
d
central line of the quintet in 13C; CD2Cl2 referenced at
d
H
and
d
53.10 for central line of the quintet in 13C). Data for 1H NMR
ppm), multiplicity
Compound (R,R,R,R)-34 performed similarly in toluene as well
as in CHCl3, except a lower product yield was obtained in the for-
mer solvent. When the reaction was carried out in tert-butyl methyl
ether (TBME), a similar product yield was obtained but the ee value
decreased dramatically. This may be due to the hydrogen bonding
interaction between TBME and the hydroxy group of the catalyst. It
is likely that more phenolic tautomer 9-anthracenol was formed in
TBME that manifested an interference effect.
are reported as follows: chemical shift (
d
(s¼singlet, d¼doublet, t¼triplet, q¼quartet, p¼pentet, br s¼broad
singlet, dd¼doublet of doublets, dt¼doublet of triplets, td¼triplet
of doublets, m¼multiplet), integration, coupling constant (Hz) and
assignment. Data for 13C NMR are reported in terms of chemical
shift. Mass spectrometry (MS) and high resolution mass spec-
trometry (HRMS) were measured on a ThermoFinnigan MAT 95XL

C.-K. Hau et al. / Tetrahedron 66 (2010) 9860e9874
9867
and Bruker Autoflex MALDI-TOF MS. Elemental analyses were car-
ried out by Shanghai Institute of Organic Chemistry, the Chinese
Academy of Science, China. HPLC analysis was performed on
a Hewlett Packard Series 1050 HPLC, or Hewlett Packard Series 1100
HPLC, or Agilent 1100 HPLC with a diode array UV detector
4.2.4. 4-Hydroxy-2-cyclohexyl-3a,4,9,9a-tetrahydro-4,9[10,20]-ben-
zeno-1H-benz[f]isoindole-1,3(2H)-dione (46). Column chromatog-
raphy on silica gel (3 g, EtOAc/hexanes, 1:12) gave pure product
(15.9 mg, 52%) as colorless solids from maleimide18 (14.8 mg,
0.08 mmol): Rf¼0.28 (EtOAc/hexanes, 1:12); 1H NMR (400 MHz,
(
l
¼214e258 nm), using Chiralcel OD (0.46 cmꢂ25 cm), Chiracel OD
CDCl3): d 0.76e0.87 (m, 2H, CH2), 0.98e1.13 (m, 3H, CH2), 1.52e1.71
Guard (0.46ꢂ5 cm), and Chiralpak AD-H (0.46 cmꢂ25 cm) as noted
(m, 5H, CH2), 3.01 (d, J¼8.6 Hz, 1H, CH), 3.23 (dd, J¼3.6, 8.6 Hz, 1H,
CH), 3.46e3.54 (m, 1H, CH), 4.61 (br s, 1H, OH), 4.71 (d, J¼3.5 Hz, 1H,
CH), 7.13e7.28 (m, 5H, ArH), 7.36 (d, J¼7.2 Hz, 1H, ArH), 7.49 (d,
J¼7.4 Hz, 1H, ArH), 7.68 (d, J¼7.4 Hz, 1H, ArH); 13C NMR (100 MHz,
for each compound.
4.2. General procedure for the catalytic DielseAlder reaction
CDCl3): d 25.0, 25.7, 27.9, 28.1, 44.8, 47.1, 50.1, 51.6,120.8,121.2,123.8,
To a solution of amino-alcohol (S,S,S,S)-34 (5 mol %, 0.01 M) in
CHCl3, anthrone (1.1 equiv) was added. After stirring for 10 min,
maleimide (1 equiv) was added in one portion to the mixture. The
stirring was continued for another 2 h. The mixture was directly
purified by column chromatography on silica gel (EtOAc/n-hex-
anes) to yield the desired DA product.
124.7, 126.8, 126.9, 127.1, 127.2, 136.7, 139.2, 141.1, 142.7, 176.7, 178.4.
The ee values were determined by chiral HPLC; CHIRALPAK AD-
H; hexanes/2-propanol 60:40; flow rate 0.75 mL/min; temp 25 ꢀC;
detection UV 214 nm; retention time: 10.2 min (S) and 12.1 min (R).
4.2.5. 4-Hydroxy-2-(3-nitrophenyl)-3a,4,9,9a-tetrahydro-4,9[10,20]-
benzeno-1H-benz[f]isoindole-1,3(2H)-dione (47). Column chroma-
tography on silica gel (2 g, EtOAc/hexanes, 1:2) gave pure product
(17.2 mg, 67%) as colorless solids from maleimide19 (13.9 mg,
0.06 mmol): Rf¼0.15 (EtOAc/hexanes, 1:4); 1H NMR (400 MHz,
Column chromatography on silica gel (MeOH/CHCl3, 1:40) was
used to recover the catalyst.
4.2.1. 4-Hydroxy-2-methyl-3a,4,9,9a-tetrahydro-4,9[10,20]-benzeno-
1H-benz[f]isoindole-1,3(2H)-dione (22). Column chromatography
on silica gel (3 g, EtOAc/hexanes, 1:5) gave pure 22 (27 mg, 93%) as
colorless solids from N-methylmaleimide (11 mg, 0.09 mmol):
CD2Cl2):
d
3.34 (d, J¼8.6 Hz, 1H, CH), 3.56 (dd, J¼3.5, 8.6 Hz, 1H, CH),
4.68 (br s, 1H, OH), 4.85 (d, J¼3.5 Hz, 1H, CH), 6.91e6.94 (m, 1H,
ArH), 7.23e7.38 (m, 6H, ArH), 7.45e7.57 (m, 3H, ArH), 7.71 (d,
J¼7.2 Hz, 1H, ArH), 8.15e8.17 (m, 1H, ArH); 13C NMR (100 MHz,
Rf¼0.29 (EtOAc/hexanes, 1:4); 1H NMR (400 MHz, CDCl3):
d 2.50 (s,
3H, CH3), 3.11 (d, J¼8.6 Hz, 1H, CH), 3.32 (dd, J¼3.4, 8.5 Hz, 1H, CH),
4.50 (br s, 1H, OH), 4.73 (d, J¼3.4 Hz, 1H, CH), 7.13e7.28 (m, 5H,
ArH), 7.37 (d, J¼7.2 Hz, 1H, ArH), 7.48 (d, J¼7.4 Hz, 1H, ArH), 7.69 (d,
CD2Cl2): d 44.5, 47.5, 50.7, 77.0, 120.4, 120.6, 121.3, 123.3, 123.6,
124.4, 126.6, 127.1, 127.2, 129.7, 131.7, 132.0, 136.4, 138.4, 140.6, 141.8,
148.0, 174.5, 176.1.
The ee values were determined by chiral HPLC; CHIRALPAK AD-
H; hexanes/2-propanol 60:40; flow rate 0.75 mL/min; temp 25 ꢀC;
detection UV 214 nm; retention time: 38.4 min (S) and 48.5 min (R).
J¼7.4 Hz, 1H, ArH); 13C NMR (100 MHz, CDCl3):
d
24.4, 44.6, 47.7,
50.9, 120.9, 120.9, 123.8, 124.6, 126.9, 126.9, 127.2, 127.3, 136.5, 139.1,
140.8, 142.5, 176.6, 178.0.
The ee values were determined by chiral HPLC; CHIRALCEL OD
with guard column; hexanes/2-propanol 50:50; flow rate 0.75 mL/
min; temp 25 ꢀC; detection UV 214 nm; retention time: 11.1 min (R)
and 13.5 min (S).
4.3. Synthesis and characterization
4.3.1. Resolution of 1,8,9,16-tetrahydroxytetraphenylene (3)13
.
Compound3 (1 g, 2.7 mmol) was first dissolved in dry THF (30 mL)
under nitrogen atmosphere, followed by the subsequent addition
of Et3N (3.7 mL, 27 mmol) and (1S)-camphor-10-sulfonyl chloride
(3.2 g, 12.2 mmol) at 0 ꢀC. The mixture was warmed to room tem-
perature and stirred overnight. The mixture was diluted with water
(100 mL) and extracted with CH2Cl2 (20 mLꢂ3). The combined or-
ganic layer was washed with aqueous HCl solution (2 M, 30 mLꢂ2)
successively and was then dried over anhydrous Na2SO4. After
concentration, the residue was purified by column chromatography
on silica gel (150 g, EtOAc/toluene, 1:4) to give the two di-
astereomers. The less polar fraction isolated was diastereomer
(S,S)-7a (1.55 g, 47%) as colorless solids: mp 167e168 ꢀC (lit.:13
4.2.2. 4-Hydroxy-2-phenyl-3a,4,9,9a-tetrahydro-4,9[10,20]-benzeno-
1H-benz[f]isoindole-1,3(2H)-dione (44). Column chromatography
on silica gel (3 g, EtOAc/hexanes, 1:8) gave pure product (19.7 mg,
89%) as colorless solids from N-phenylmaleimide (10.5 mg,
0.06 mmol): Rf¼0.29 (EtOAc/hexanes, 1:6); 1H NMR (300 MHz,
CDCl3):
d
3.27 (d, J¼8.7 Hz, 1H, CH), 3.48 (dd, J¼3.3, 8.7 Hz, 1H, CH),
4.59 (br s, 1H, OH), 4.84 (d, J¼3.3 Hz, 1H, CH), 6.48e6.51 (m, 2H,
ArH), 7.24e7.34 (m, 8H, ArH), 7.42 (d, J¼7.2 Hz, 1H, ArH), 7.57 (d,
J¼7.5 Hz, 1H, ArH), 7.75 (d, J¼7.2 Hz, 1H, ArH); 13C NMR (75 MHz,
CDCl3): d 44.9, 47.8, 50.9, 121.0,121.2,123.9,124.8,126.4,127.0,127.1,
127.4, 129.1, 129.3, 131.0, 136.7, 139.0, 141.0, 142.4, 175.8, 177.3.
The ee values were determined by chiral HPLC; CHIRALPAK AD-
H; hexanes/2-propanol 80:20; flow rate 0.75 mL/min; temp 25 ꢀC;
detection UV 214 nm; retention time: 29.9 min (S) and 38.2 min (R).
168e169 ꢀC); 1H NMR (400 MHz, CDCl3):
d
0.80 (s, 12H, 4ꢂCH3),
1.04 (s, 12H, 4ꢂCH3), 1.35e1.42 (m, 4H, 2ꢂCH2), 1.48e1.55 (m, 4H,
2ꢂCH2), 1.88 (s, 2H, CH2), 1.93 (s, 2H, CH2), 1.95e2.04 (m, 4H,
2ꢂCH2), 2.06e2.08 (m, 4H, 2ꢂCH2), 2.29e2.38 (m, 8H, 4ꢂCH2), 2.99
(d, J¼15 Hz, 4H, 2ꢂSCH2), 3.15 (d, J¼15 Hz, 4H, 2ꢂSCH2), 7.30e7.37
(m, 8H, ArH), 7.38e7.40 (m, 4H, ArH); MS (ESI) m/z 1247 [MþNa]þ.
The more polar fraction isolated was diastereomer (R,R)-7b
(1.48 g, 45%) as colorless solids: mp 159e160 ꢀC (lit.:13 160e161 ꢀC);
4.2.3. 4-Hydroxy-2-isobutyl-3a,4,9,9a-tetrahydro-4,9[10,20]-benzeno-
1H-benz[f]isoindole-1,3(2H)-dione (45). Column chromatography
on silica gel (3 g, EtOAc/hexanes, 1:8) gave pure product (22.6 mg,
76%) as colorless solids from maleimide18 (13 mg, 0.08 mmol):
Rf¼0.49 (EtOAc/hexanes, 1:4); 1H NMR (400 MHz, CDCl3):
1H NMR (400 MHz, CD2Cl2):
d
0.77 (s, 12H, 4ꢂCH3), 0.94 (s, 12H,
d
0.43e0.47 (m, 6H, CH3), 1.37e1.47 (m, 1H, CH), 2.89e2.98 (m, 2H,
4ꢂCH3), 1.38e1.43 (m, 4H, 2ꢂCH2), 1.52e1.59 (m, 8H, 4ꢂCH2), 1.88
(s, 2H, CH2), 1.89 (s, 2H, CH2), 1.93e2.02 (m, 6H, 3ꢂCH2), 2.05e2.09
(m, 6H, 3ꢂCH2), 2.31e2.38 (m, 4H, 2ꢂCH2), 2.80 (d, J¼15 Hz, 4H,
2ꢂSCH2), 3.53 (d, J¼15 Hz, 4H, 2ꢂSCH2), 7.19e7.22 (m, 4H, ArH),
7.36e7.41 (m, 8H, ArH); MS (ESI) m/z 1247 [MþNa]þ.
CH2), 3.11 (d, J¼8.9 Hz, 1H, CH), 3.30 (dd, J¼3.4, 8.8 Hz, 1H, CH), 4.48
(br s,1H, OH), 4.73 (d, J¼3.2 Hz,1H, CH), 7.12e7.28 (m, 5H, ArH), 7.35
(d, J¼7.2 Hz, 1H, ArH), 7.51 (d, J¼7.4 Hz, 1H, ArH), 7.67 (d, J¼7.4 Hz,
1H, ArH); 13C NMR (100 MHz, CDCl3):
d 20.0, 20.1, 27.2, 44.5, 46.4,
47.5, 50.6, 120.8, 121.2, 123.8, 124.7, 126.8, 126.9, 127.4, 127.5, 136.9,
139.5, 141.2, 142.9, 176.8, 178.3.
The ee values were determined by chiral HPLC; CHIRALCEL OD;
hexanes/2-propanol 50:50; flow rate 0.75 mL/min; temp 25 ꢀC;
detection UV 214 nm; retention time: 10.4 min (S) and 15.7 min (R).
To a suspension of the diastereomer (S,S)-7a or (R,R)-7b (2 g,
1.6 mmol) in methanol (150 mL) was added aqueous KOH solution
(3 M, 30 mL). The mixture was heated to reflux overnight. After
solvent was evaporated, the mixture was diluted with water
(50 mL) and extracted with EtOAc (30 mLꢂ3) successively. The

9868
C.-K. Hau et al. / Tetrahedron 66 (2010) 9860e9874
combined organic layer was dried over anhydrous Na2SO4 and
concentrated. After column chromatography on silica gel (100 g,
EtOAc/CH2Cl2, 1:8), pure (S,S)-3 (590 mg, 97%) or (R,R)-3 (571 mg,
94%) was isolated: mp >300 ꢀC (lit.:13 >300 ꢀC); 1H NMR (300 MHz,
(174 mg, 95%) as colorless solids: mp 176e178 ꢀC; Rf¼0.25 (EtOAc/
hexanes, 1:4); 1H NMR (300 MHz, CDCl3):
d
0.87 (t, J¼7.2 Hz, 6H,
2ꢂCH3), 1.16e1.26 (m, 16H, 8ꢂCH2), 1.43e1.48 (m, 4H, 2ꢂCH2),
3.69e3.74 (m, 4H, 2ꢂOCH2), 4.93 (br s, 2H, OH), 6.74 (dd, J¼0.6,
8.1 Hz, 2H, ArH), 6.81 (dd, J¼0.9, 7.5 Hz, 2H, ArH), 6.85 (dd, J¼0.9,
8.1 Hz, 2H, ArH), 6.88 (dd, J¼1.2, 7.5 Hz, 2H, ArH), 7.16 (dd, J¼8.1,
8.1 Hz, 2H, ArH), 7.20 (dd, J¼7.8, 7.8 Hz, 2H, ArH); 13C NMR (75 MHz,
acetone-d6):
d
6.72 (dd, J¼0.9, 6.2 Hz, 4H, ArH), 6.75 (dd, J¼1.2,
6.8 Hz, 2H, ArH), 7.06 (dd, J¼7.8, 7.8 Hz, 2H, ArH); MS (EI) m/z 368
20
20
[M]þ. Compound (R,R)-3: [
a]
þ53.3 (c 0.83, MeOH) (lit.:13
[a]
D
D
20
þ55.3 (c 1.07, MeOH)); (S,S)-3: [
a
]
ꢁ54.8 (c 0.93, MeOH) (lit.:13
CDCl3): d 14.3, 22.7, 25.9, 29.1, 29.4, 32.0, 68.9, 111.7, 114.5, 120.2,
D
[
a]
20 ꢁ55.8 (c 1.05, MeOH)).
120.4, 121.5, 126.9, 128.1, 129.8, 142.4, 145.3, 152.3, 156.6; HRMS (EI)
D
m/z calcd for C38H44O4 [M]þ 564.3234, found 564.3251; (R,R)-10:
20
4.3.2. (S,S)- and (R,R)-5,22-Dihydrobenzo[h]tetraphenyleno[1,16-
bcd][1,6]dioxecine-13,14-diol (8). Compound (S,S)-3 (667 mg,
1.65 mmol) was first added to a suspension of Cs2CO3 (805 mg,
2.47 mmol) in DMSO (33 mL). The mixture was then heated to 80 ꢀC
for 30 min with stirring. After heating, the mixture was cooled to
[a
]
20 ꢁ2.8 (c 1.07, CHCl3); (S,S)-10: [
a]
þ5.7 (c 0.83, CHCl3).
D
D
4.3.5. (S,S)-8,9-Bis(heptyloxy)-16-(4-methoxybenzyloxy)tetrapheny-
len-1-ol (11). To solution of compound (S,S)-10 (112 mg,
a
0.20 mmol) in dried DMF (3 mL) under nitrogen atmosphere, K2CO3
(30 mg, 0.22 mmol) was added. The mixture was allowed to stir for
15 ꢀC.
A
solution of 1,2-bis(bromomethyl)benzene20 (480 mg,
1.82 mmol) in DMSO (33 mL) was added to the mixture dropwise
by a dropping funnel. After the addition, the mixture was stirred for
30 min at room temperature. The mixture was then diluted with
water (50 mL) and was extracted with CH2Cl2 (60 mLꢂ3). The
combined organic layer was washed with saturated brine solution
(200 mLꢂ2) successively. The organic layer was then dried over
anhydrous Na2SO4 and concentrated. After column chromatogra-
phy on silica gel (70 g, EtOAc/CH2Cl2, 1:90), pure 8 (295 mg, 38%)
was collected as colorless sticky solids: Rf¼0.15 (EtOAc/CH2Cl2,
20 min at room temperature. p-Methoxybenzyl bromide (28 mL,
0.20 mmol) was injected to the mixture slowly. After stirring for an-
other 1 h, the mixture was diluted with water and was extracted with
EtOAc (15 mLꢂ3). The combined organic layer was washed with
saturated brine solution (20 mLꢂ2) successively. The organic layer
was dried over anhydrous Na2SO4 and concentrated. The residue was
purified by column chromatography on silica gel (10 g, EtOAc/hex-
anes, 1:4) to yield pure (S,S)-11 (107 mg, 79%) as colorless solids: mp
150e151 ꢀC; Rf¼0.25 (EtOAc/hexanes, 1:4); 1H NMR (400 MHz,
1:90); 1H NMR (300 MHz, DMSO-d6):
d
5.08 (br s, 2H, OCH2), 5.30
CDCl3):
d
0.88 (t, J¼7.0 Hz, 3H, CH3), 0.88 (t, J¼7.3 Hz, 3H, CH3),
(d, J¼11.4 Hz, 2H, OCH2), 6.45 (d, J¼7.4 Hz, 2H, ArH), 6.66 (d,
J¼7.9 Hz, 2H, ArH), 6.73 (d, J¼5.3 Hz, 2H, ArH), 6.96 (dd, J¼7.7,
7.7 Hz, 2H, ArH), 7.07 (d, J¼7.7 Hz, 2H, ArH), 7.13 (d, J¼6.4 Hz, 2H,
ArH), 7.33 (dd, J¼3.4, 5.3 Hz, 2H, ArH), 7.49 (br s, 2H, ArH), 8.97 (br s,
1.13e1.28 (m, 16H, 8ꢂCH2), 1.46e1.51 (m, 4H, 2ꢂCH2), 3.71e3.76 (m,
4H, 2ꢂOCH2), 3.77 (s, 3H, OCH3), 4.81 (dd, J¼12.4,14.0 Hz, 2H, OCH2),
4.89 (br s, 1H, OH), 6.72e6.75 (m, 2H, ArH), 6.76e6.85 (m, 7H, ArH),
6.94 (dd, J¼1.1, 7.6 Hz, 1H, ArH), 7.00e7.04 (m, 2H, ArH), 7.12e7.16 (m,
3H, ArH), 7.18 (dd, J¼5.5, 5.5 Hz,1H, ArH); 13C NMR (100 MHz, CDCl3):
2H, OH); 13C NMR (75 MHz, DMSO-d6):
d 113.7, 119.3, 121.7, 124.2,
127.4, 127.8, 128.6, 131.5, 136.3, 143.0, 143.6, 154.4; HRMS (EI) m/z
d 14.2, 22.7, 25.9, 29.1, 29.4, 31.9, 55.1, 68.8, 68.8, 71.0,111.2,111.6,113.7,
calcd for C32H22O4 [M]þ 470.1513, found 470.1508. Compounds
113.7, 114.2, 120.4, 120.6, 122.6, 123.6, 124.7, 126.9, 127.0, 127.7, 127.9,
128.4, 128.6, 129.0, 129.1, 142.5, 143.3, 143.6, 145.6, 152.5, 155.0, 156.4,
156.4, 159.1; HRMS (MALDI-TOF) m/z calcd for C46H52O5 [MþNa]þ
20
(S,S)-8 and (R,R)-8: [
a
]
cannot be determined due to the poor
D
solubility in organic solvents or water.
707.3706, found 707.3712; [
a
]
20 ꢁ68.1 (c 1.29, CHCl3).
D
4.3.3. (S,S)- and (R,R)-13,14-Bis(heptyloxy)-5,22-dihydrobenzo[h]
tetraphenyleno[1,16-bcd][1,6]dioxecine (9). To a stirring suspension
of compound (S,S)-8 (176 mg, 0.37 mmol) and Cs2CO3 (365 mg,
1.12 mmol) inDMF (3 mL),1-bromoheptane (200 mg,1.12 mmol) was
added. The mixture was heated to 80 ꢀC for 30 min. After that, the
mixture was cooled and diluted with water (15 mL). The mixture was
extracted with EtOAc (15 mLꢂ3). The combined organic layer was
then washed with saturated brine solution (30 mLꢂ2). The organic
layerwasdriedoveranhydrousNa2SO4 andconcentrated. Theresidue
was purified by column chromatography on silica gel (15 g, EtOAc/
hexanes,1:6) to give pure (S,S)-9 (217 mg, 88%) as colorless solids: mp
233e234 ꢀC; Rf¼0.35 (EtOAc/hexanes, 1:4); 1H NMR (400 MHz,
4.3.6. (S,S)-1-(2-(8,9-Bis(heptyloxy)-16-(4-methoxybenzyloxy)tetra-
phenylen-1-yloxy)ethyl)-py rrolidine (12). To a solution of com-
pound (S,S)-11 (152 mg, 0.22 mmol) in DMF (2 mL) under nitrogen
atmosphere, Cs2CO3 (188 mg, 0.58 mmol) and KI (17 mg,
0.11 mmol) were added. After the injection of 1-(2-chloroethyl)
pyrrolidine21 (59 mg, 0.44 mmol), the mixture was heated to reflux
overnight. The mixture was then cooled and diluted with water.
The biphasic mixture was extracted with CH2Cl2 (20 mLꢂ3) suc-
cessively. The combined organic layer was dried over anhydrous
Na2SO4 and concentrated. After column chromatography on silica
gel (15 g, MeOH/CHCl3, 1:40), pure compound (S,S)-12 (128 mg,
75%) was isolated as colorless sticky solids: Rf¼0.15 (MeOH/CHCl3,
CDCl3):
d
0.87 (t, J¼7.2 Hz, 6H, 2ꢂCH3), 1.14e1.19 (m, 12H, 6ꢂCH2),
1.22e1.26 (m, 4H, 2ꢂCH2), 1.44e1.49 (m, 4H, 2ꢂCH2), 3.68e3.77 (m,
4H, 2ꢂOCH2), 5.08 (d, J¼1.2 Hz, 2H, OCH2), 5.28 (d, J¼1.2 Hz, 2H,
OCH2), 6.74 (dd, J¼8.6, 8.6 Hz, 4H, ArH), 6.84 (d, J¼7.5 Hz, 2H, ArH),
6.93 (d, J¼8.0 Hz, 2H, ArH), 7.09e7.15 (m, 4H, ArH), 7.29e7.33 (m, 2H,
1:20); 1H NMR (400 MHz, CDCl3):
d
0.89 (t, J¼7.2 Hz, 6H, 2ꢂCH3),
1.18e1.28 (m, 16H, 8ꢂCH2), 1.45e1.49 (m, 4H, 2ꢂCH2), 1.69 (m, 4H,
2ꢂCH2), 2.33e2.40 (m, 4H, 2ꢂNCH2), 2.53e2.59 (m, 1H, 0.5ꢂNCH2),
2.66e2.71 (m, 1H, 0.5ꢂNCH2), 3.68e3.77 (m, 4H, 2ꢂOCH2), 3.76 (s,
3H, OCH3), 3.90e3.93 (m, 2H, OCH2), 4.77 (s, 2H, OCH2), 6.72e6.80
(m, 7H, ArH), 6.84e6.89 (m, 4H, ArH), 6.96 (d, J¼8.6 Hz, 2H, ArH),
7.11 (dd, J¼7.9, 7.9 Hz, 1H, ArH), 7.12e7.17 (m, 2H, ArH), 7.19 (dd,
ArH), 7.34e7.37 (m, 2H, ArH); 13C NMR (100 MHz, CDCl3):
d 14.3, 22.7,
25.8, 29.1, 29.5, 32.0, 69.1, 111.7, 121.5, 122.4, 127.1, 127.7, 127.8, 128.4,
128.8, 131.5, 136.3, 143.1, 143.9, 156.4; HRMS (MALDI-TOF) m/z calcd
20
for C46H50O4 [MþNa]þ 689.3601, found 689.3585; (R,R)-9: [
a]
J¼7.9, 7.9 Hz,1H, ArH); 13C NMR (100 MHz, CDCl3):
d 14.2, 22.7, 23.5,
D
þ265.3 (c 0.95, CHCl3); (S,S)-9: [
a
]
20 ꢁ242.8 (c 0.75, CHCl3).
25.9, 29.1, 29.4, 31.9, 54.5, 54.6, 55.3, 67.9, 69.0, 70.8, 111.0, 111.5,
111.6, 112.9, 113.6, 120.6, 120.7, 121.1, 121.5, 126.8, 127.1, 127.2, 127.7,
127.8, 128.0, 128.2, 130.0, 143.2, 143.3, 143.8, 144.0, 155.9, 156.0,
D
4.3.4. (S,S)- and (R,R)-8,9-Bis(heptyloxy)tetraphenylene-1,16-diol
(10). A mixed solution of compound (S,S)-9 (217 mg, 0.33 mmol) in
THF and EtOH (1:1, v/v ratio) was prepared, followed by the addi-
tion of palladium black catalyst (10 mol %). The mixture was stirred
under H2 for 2 h. The mixture was then filtered through Celite. The
filtrate was concentrated and purified by column chromatography
on silica gel (20 g, EtOAc/hexanes, 1:4) to yield pure (S,S)-10
156.5, 158.9; HRMS (ESI) m/z calcd for C52H63O5N [MþH]þ
20
782.4779, found 782.4791; [
a
]
ꢁ35.5 (c 1.28, CHCl3).
D
4.3.7. (S,S)-8,9-Bis(heptyloxy)-16-(2-(pyrrolidin-1-yl)ethoxy)tetra-
phenylen-1-ol (13). A mixed solution of compound (S,S)-12
(128 mg, 0.16 mmol) in THF and EtOH (1:1, v/v, 2 mL) was prepared,

C.-K. Hau et al. / Tetrahedron 66 (2010) 9860e9874
9869
followed by the addition of palladium black (10 mol %). The mixture
was stirred under H2 for 7 h. The mixture was then filtered through
a Celite pad. The filtrate was diluted with CH2Cl2 (20 mL). The or-
ganic layer was then washed with aqueous HCl solution (2 M,
15 mL) and aqueous NaOH solution (3 M, 20 mL). The organic layer
was dried over anhydrous Na2SO4 and concentrated. After column
chromatography on silica gel (13 g, MeOH/CHCl3, 1:20), pure
compound (S,S)-13 (72 mg, 67%) was obtained as colorless sticky
solids: Rf¼0.23 (MeOH/CHCl3, 1:20); 1H NMR (400 MHz, CD2Cl2):
16 was prepared from (S,S)-11 (36 mg, 0.06 mmol) by using the same
preparative method as that for compound 12 from compound 11,
except 2-chloro-N,N-dimethylethanamine (16 mg, 0.11 mmol) was
used.
Column chromatography on silica gel (5 g, MeOH/CHCl3, 1:100)
gave pure (S,S)-16 (28 mg, 72%) as colorless waxy solids: Rf¼0.45
(MeOH/CHCl3, 1:40); 1H NMR (300 MHz, CDCl3):
d
0.89 (t, J¼7.2 Hz,
6H, 2ꢂCH3), 1.17e1.27 (m, 16H, 8ꢂCH2), 1.45e1.49 (m, 4H, 2ꢂCH2),
2.08 (s, 6H, 2ꢂNCH3), 2.41e2.45 (m, 2H, NCH2), 3.70e3.79 (m, 4H,
2ꢂOCH2), 3.84e3.87 (m, 2H, OCH2), 4.87 (s, 2H, OCH2), 6.75 (dd,
J¼8.4, 8.4 Hz, 4H, ArH), 6.80 (d, J¼7.0 Hz, 1H, ArH), 6.84e6.90 (m, 3H,
ArH), 7.05e7.09 (m, 2H, ArH), 7.11e7.17 (m, 3H, ArH), 7.19e7.24 (m,
d
0.89 (t, J¼7.1 Hz, 6H, 2ꢂCH3), 1.21e1.27 (m, 16H, 8ꢂCH2),
1.49e1.52 (m, 4H, 2ꢂCH2), 1.91 (br s, 4H, 2ꢂCH2), 2.65e2.67 (m, 2H,
NCH2), 2.78e2.87 (m, 3H, 1.5ꢂNCH2), 2.99e3.02 (m, 1H, 0.5ꢂNCH2),
3.76e3.80 (m, 4H, 2ꢂOCH2), 4.12e4.16 (m, 1H, 0.5ꢂOCH2),
4.22e4.26 (m, 1H, 0.5ꢂOCH2), 6.76e6.82 (m, 6H, ArH), 6.89 (dd,
J¼7.3, 7.3 Hz, 2H, ArH), 7.11 (dd, J¼7.8, 7.8 Hz, 1H, ArH), 7.16e7.25
3H, ArH); 13C NMR (75 MHz, CDCl3):
d 14.3, 22.7, 25.9, 29.1, 29.4, 32.0,
45.8, 58.0, 67.6, 69.1, 70.8, 111.3, 111.6, 112.4, 120.7, 120.8, 121.2, 121.5,
126.6, 127.0, 127.2, 127.4, 127.7, 127.8, 127.8, 128.0, 128.2, 138.0, 143.3,
(m, 3H, ArH); 13C NMR (75 MHz, CD2Cl2):
d
13.6, 22.2, 22.8, 25.4,
143.4, 143.9, 144.0, 155.9, 156.0, 156.5; [
a
]
20 ꢁ27.8 (c 0.96, CHCl3).
D
28.6, 28.9, 31.4, 53.8, 54.1, 65.2, 68.3, 110.4, 110.5, 110.7, 118.4, 120.2,
120.9, 121.3, 126.1, 126.2, 126.7, 127.3, 127.5, 127.9, 142.5, 143.1, 143.2,
143.7, 153.8, 154.5, 155.9, 156.0; HRMS (MADLI-TOF) m/z calcd for
C44H55O4N [MþH]þ 662.4204, found 662.4235. Anal. Calcd for
Compound (S,S)-17 was prepared from pure (S,S)-16 (28 mg,
0.04 mmol) by using the same preparative method as that for
compound 13 from compound 12.
Column chromatography on silica gel (5 g, MeOH/CHCl3, 1:20)
gave pure compound (S,S)-17 (19 mg, 75%) as colorless waxy solids:
C44H55O4N$1/2CH3COOCH2CH3: C, 78.26; H, 8.42; N, 1.98, found C,
20
77.94; H, 8.23; N, 1.84; [
a]
ꢁ120.2 (c 0.93, CH2Cl2).
Rf¼0.33 (MeOH/CHCl3, 1:20); 1H NMR (400 MHz, CDCl3):
d 0.88 (t,
D
J¼7.2 Hz, 6H, 2ꢂCH3), 1.17e1.29 (m, 16H, 8ꢂCH2), 1.42e1.49 (m, 4H,
2ꢂCH2), 2.29 (s, 6H, 2ꢂNCH3), 3.68e3.77 (m, 4H, 2ꢂOCH2),
4.01e4.10 (m, 2H, OCH2), 6.72 (d, J¼8.1 Hz, 3H, ArH), 6.79e6.86 (m,
4.3.8. (S,S)-1-(3-(8,9-Bis(heptyloxy)-16-(4-methoxybenzyloxy)tetra-
phenylen-1-yloxy)propyl) pyrrolidine (14). Compound (S,S)-14 was
prepared from compound (S,S)-11 (103 mg, 0.15 mmol) by using the
same preparative method as that for compound 12 from compound
11, except 1-(3-chloropropyl)pyrrolidine22 (44 mg, 0.30 mmol) was
used.
5H, ArH), 7.06e7.17 (m, 4H, ArH); 13C NMR (100 MHz, CDCl3):
d 14.3,
22.7, 25.9, 29.1, 29.5, 32.0, 45.1, 57.8, 65.2, 69.1, 110.7, 111.5, 111.7,
119.4, 120.9, 121.0, 121.8, 121.9, 126.7, 127.1, 127.3, 127.6, 127.7, 127.9,
128.8, 143.1, 143.6, 143.7, 143.4, 153.8, 155.1, 156.3, 156.4; HRMS (EI)
20
Column chromatography on silica gel (10 g, MeOH/CHCl3, 1:40)
gave pure (S,S)-14 (72 mg, 61%) as colorless sticky solids: Rf¼0.35
m/z calcd for C42H53O4N [M]þ 635.3969, found 635.3945; [
ꢁ76.3 (c 0.63, CHCl3).
a]
D
(MeOH/CHCl3, 1:20); 1H NMR (400 MHz, CDCl3):
d
0.88 (t, J¼7.2 Hz,
6H, 2ꢂCH3), 1.66e1.26 (m, 16H, 8ꢂCH2), 1.45e1.48 (m, 4H, 2ꢂCH2),
1.79 (br s, 6H, 3ꢂCH2), 2.26e2.33 (m, 1H, 0.5ꢂNCH2), 2.35e2,42 (m,
1H, 0.5ꢂNCH2), 2.51 (br s, 4H, 2ꢂNCH2), 3.66e3.81 (m, 6H, 3ꢂOCH2),
3.77(s,3H, OCH3), 4.72 (s, 2H, OCH2), 6.7e6.77(m, 6H, ArH),6.79e6.84
(m, 2H, ArH), 6.88 (dd, J¼6.7, 6.7 Hz, 2H, ArH), 6.94 (d, J¼8.6 Hz, 2H,
4.3.11. (S,S)-and (R,R)-8,9-Bis(heptyloxy)-16-hydroxytetraphenylene-
1-carbonitrile (18). To a solution of compound (S,S)-10 (21 mg,
0.04 mmol) in CH2Cl2 (0.5 mL) under nitrogen atmosphere, colli-
dine (15 mL, 0.11 mmol) and DMAP (4.6 mg, 0.04 mmol) were
added. The mixture was cooled to ꢁ78 ꢀC with stirring. 1,1,1-Tri-
fluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide
(15 mg, 0.04 mmol) was added to the mixture. After that, the
mixture was warmed to room temperature. The stirring was con-
tinued for 2 h. The mixture was then diluted with water (10 mL)
and extracted by CH2Cl2 (10 mLꢂ2). The combined organic layer
was dried over anhydrous Na2SO4 and concentrated. After column
chromatography on silica gel (5 g, EtOAc/CH2Cl2/hexanes, 1:1:10),
pure triflate compound (24 mg, 93%) was yielded as colorless sticky
solids: Rf¼0.35 (EtOAc/hexanes, 1:6).
ArH), 7.09e7.21 (m, 4H, ArH); 13C NMR (100 MHz, CDCl3):
d 14.2, 22.7,
23.5, 25.9, 28.0, 29.1, 29.4, 31.9, 53.0, 54.0, 55.3, 67.2, 69.0, 69.0, 70.0,
111.5, 111.6, 112.1, 113.2, 113.6, 120.6, 120.7, 121.4, 121.7, 127.1, 127.2,
127.7, 127.8, 127.9, 128.0, 128.4, 129.9, 143.2, 143.3, 143.8, 144.1, 156.0,
156.0, 156.5, 156.6, 159.0; HRMS (EI) m/z calcd for C53H65O5N [M]þ
795.4857, found 795.4872; [
a
]
20 ꢁ41.5 (c 1.03, CHCl3).
D
4.3.9. (S,S)-8,9-Bis(heptyloxy)-16-(3-(pyrrolidin-1-yl)propoxy)tetra-
phenylen-1-ol (15). Compound (S,S)-15 was prepared from com-
pound (S,S)-14 (58 mg, 0.07 mmol) by using the same preparative
method as that for compound 13 from compound 12.
A Schlenk bottle was charged with a mixture of compound (S,S)-
triflate compound (103.3 mg, 0.15 mmol), Pd(PPh3)4 (135 mg,
0.12 mmol), and Zn(CN)2 (91 mg, 0.78 mmol). The mixture was
degassed and refilled with nitrogen three times. Dried DMF (2 mL)
was injected to the mixture. The mixture was again degassed and
refilled with nitrogen three times. After that, the mixture was
heated to 150 ꢀC for 18 h. The mixture was cooled and filtered
through a Celite pad. The filtrate was diluted with EtOAc (30 mL)
and washed with saturated brine solution (30 mLꢂ2) successively.
The organic layer was dried over anhydrous Na2SO4 and concen-
trated. The residue was purified by column chromatography on
silica gel (10 g, EtOAc/CH2Cl2/hexanes, 1:1:10) to give compound
(S,S)-18 (85 mg, 99%) as colorless sticky solids: Rf¼0.21 (EtOAc/
Column chromatography on silica gel (6 g, MeOH/CHCl3, 1:20)
gave pure (S,S)-15 (38 mg, 80%) as colorless sticky solids: Rf¼0.23
(MeOH/CHCl3, 1:20); 1H NMR (400 MHz, CD2Cl2):
d 0.90 (t,
J¼7.2 Hz, 6H, 2ꢂCH3), 1.18e1.31 (m, 16H, 8ꢂCH2), 1.50e1.55 (m, 4H,
2ꢂCH2), 1.76e1.82 (m, 6H, 3ꢂCH2), 2.22e2.28 (m, 1H, 0.5ꢂNCH2),
2.45e2.56 (m, 5H, 2.5ꢂNCH2), 3.77e3.81 (m, 4H, 2ꢂOCH2),
3.89e3.96 (m, 1H, 0.5ꢂOCH2), 3.97e4.00 (m, 1H, 0.5ꢂOCH2),
6.72e6.82 (m, 6H, ArH), 6.88 (d, J¼7.6 Hz, 2H, ArH), 7.12 (dd, J¼7.8,
7.8 Hz, 1H, ArH), 7.16e7.22 (m, 2H, ArH), 7.24 (dd, J¼7.9, 7.9 Hz, 1H,
ArH); 13C NMR (100 MHz, CD2Cl2):
d 13.6, 22.2, 22.9, 25.4, 27.7, 28.6,
28.9, 31.5, 52.0, 66.9, 68.4, 110.4, 110.6, 111.6, 115.0, 120.0, 120.1,
121.3, 124.9, 125.1, 126.2, 126.3, 127.4, 127.5, 127.6, 128.1, 142.5, 143.1,
143.2, 144.3, 153.1, 155.2, 155.9; HRMS (EI) m/z calcd for C45H57O4N
hexanes, 1:10); 1H NMR (400 MHz, CDCl3):
d
0.88 (t, J¼7.2 Hz, 6H,
2ꢂCH3), 1.14e1.28 (m, 16H, 8ꢂCH2), 1.44e1.51 (m, 4H, 2ꢂCH2),
3.70e3.76 (m, 4H, 2ꢂOCH2), 5.28 (br s, 1H, OH), 6.66 (dd, J¼0.8,
8.0 Hz, 1H, ArH), 6.73 (dd, J¼0.6, 8.2 Hz, 1H, ArH), 6.76e6.84 (m, 3H,
ArH), 6.88 (dd, J¼0.9, 7.6 Hz, 1H, ArH), 7.11e7.20 (m, 3H, ArH), 7.30
(dd, J¼7.7, 7.7 Hz, 1H, ArH), 7.47 (dd, J¼1.3, 7.8 Hz, 1H, ArH), 7.54 (dd,
[M]þ 675.4282, found 675.4268; [
a
]
20 ꢁ113.7 (c 0.98, CH2Cl2).
D
4.3.10. (S,S)-2-(16-(Benzyloxy)-8,9-bis(heptyloxy)tetraphenylen-1-
yloxy)-N,N-dimethyl ethanamine (16) and (S,S)-16-(2-(dimethylamino)
ethoxy)-8,9-bis(heptyloxy) tetraphenylen-1-ol (17). Compound (S,S)-
J¼1.3, 7.7 Hz,1H, ArH); 13C NMR (100 MHz, CDCl3):
d 14.3, 22.7, 25.9,

9870
C.-K. Hau et al. / Tetrahedron 66 (2010) 9860e9874
25.9, 29.1, 29.4, 31.9, 68.7, 68.9, 111.2, 112.1, 113.4, 114.8, 118.6, 120.2,
120.9, 121.0, 123.9, 126.1, 127.1, 127.9, 128.3, 128.3, 129.7, 131.6, 133.0,
(MeOH/CHCl3, 1:20); 1H NMR (300 MHz, CDCl3):
d
0.87 (t, J¼6.9 Hz,
6H, 2ꢂCH3), 1.24e1.32 (m, 16H, 8ꢂCH2), 1.49e1.51 (m, 4H, 2ꢂCH2),
1.76e1.90 (m, 4H, 2ꢂCH2), 2.50e2.53 (m, 2H, NCH2), 2.65e2.68 (m,
2H, NCH2), 3.07 (d, J¼11.7 Hz, 1H, 0.5ꢂNCH2), 3.71e3.78 (m, 5H,
2ꢂOCH2, and 0.5ꢂNCH2), 6.67e6.72 (m, 4H, ArH), 6.84 (dd, J¼0.9,
7.5 Hz, 1H, ArH), 6.88 (dd, J¼1.2, 8.1 Hz, 1H, ArH), 7.03e7.15 (m, 6H,
140.1, 141.3, 142.3, 143.7, 144.5, 152.0, 156.4, 156.6; HRMS (EI) m/z
20
calcd for C39H43O3N [M]þ 573.3237, found 573.3234; (S,S)-18: [
a]
D
20
ꢁ65.3 (c 0.76, CHCl3); (R,R)-18: [
a]
þ59.3 (c 0.95, CHCl3).
D
4.3.12. (S,S)-16-(Benzyloxy)-8,9-bis(heptyloxy)tetraphenylene-1-car-
ArH); 13C NMR (75 MHz, CDCl3):
d 14.3, 22.7, 23.3, 25.9, 29.1, 29.5,
baldehyde (36) and (S,S)-1-((16-(benzyloxy)-8,9-bis(heptyloxy)tet-
32.0, 53.1, 59.3, 68.9, 111.2, 111.4, 119.7, 119.9, 120.5, 120.6, 126.6,
127.0, 127.2, 127.5, 127.8, 128.2, 128.8, 128.9, 130.2, 134.6, 137.7,
raphenylen-1-yl)methyl)pyrrolidine
(20). Compound
(S,S)-19
(34 mg, 0.05 mmol) was first dissolved in CH2Cl2 (2 mL) under ni-
143.5, 143.5, 143.7, 143.8, 155.1, 156.0, 156.2; HRMS (MADLI-TOF) m/
20
trogen atmosphere with stirring. After cooling to ꢁ78 ꢀC, DIBAL-H
z calcd for C43H53O3N [MþH]þ 632.4098, found 632.4117; [
ꢁ155.0 (c 0.56, CHCl3).
a]
D
solution (1 M in cyclohexane, 61 mL, 0.06 mmol) was injected to the
mixture slowly. The mixture was kept stirring at ꢁ78 ꢀC for 1 h.
After the addition of aqueous HCl solution (2 M, 1 mL), the mixture
was warmed to room temperature. The mixture was stirred for
15 min and was diluted with water. The mixture was partitioned
between water and CH2Cl2 (10 mLꢂ2). The combined organic layer
was dried over anhydrous Na2SO4 and concentrated. The residue
was diluted with CH2Cl2 (10 mL) and filtered through a silica gel
pad. The filtrate was concentrated to give crude (S,S)-36 (28 mg,
83%) as a pale yellow oil: Rf¼0.21 (EtOAc/hexanes, 1:10); 1H NMR
4.3.14. 1-(Benzyloxy)-16-(3-bromopropoxy)-8,9-bis(heptyloxy)tetra-
phenylene (23). To a stirring solution of compound 10 (86 mg,
0.15 mmol) in dried DMF (2 mL) under nitrogen atmosphere, K2CO3
(23 mg, 0.17 mmol) was added. After stirring for 20 min at room
temperature, benzyl bromide (19 mL, 0.15 mmol) was injected to the
mixture slowly. The stirring was continued for another 1 h. After
that, the mixture was diluted with water (30 mL) and extracted
with EtOAc (15 mLꢂ3). The combined organic layer was washed
with saturated brine solution (20 mLꢂ2). The organic layer was
dried over anhydrous Na2SO4 and concentrated. The residue was
purified by column chromatography on silica gel (10 g, EtOAc/
hexanes, 1:4) to yield pure protected alcohol (88 mg, 89%) as col-
orless solids: mp 131e132 ꢀC; Rf¼0.25 (EtOAc/hexanes, 1:4).
The isolated alcohol (87 mg, 0.13 mmol) was the dissolved in
DMF (2 mL), followed by the addition of Cs2CO3 (66 mg,
(400 MHz, CD2Cl2):
d
0.90 (t, J¼7.0 Hz, 6H, 2ꢂCH3), 1.22e1.31 (m,
16H, 8ꢂCH2), 1.53e1.56 (m, 4H, 2ꢂCH2), 3.81 (q, J¼6.6 Hz, 4H,
2ꢂOCH2), 4.88 (dd, J¼12.3, 23.6 Hz, 2H, OCH2), 6.77e6.87 (m, 5H,
ArH), 6.93 (dd, J¼0.8, 7.6 Hz, 1H, ArH), 7.02e7.04 (m, 2H, ArH),
7.17e7.29 (m, 6H, ArH), 7.41 (dd, J¼7.1, 7.1 Hz, 1H, ArH), 7.51 (dd,
J¼1.4, 7.5 Hz, 1H, ArH), 7.82 (dd, J¼1.4, 7.6 Hz, 1H, ArH), 9.64 (s, 1H,
CHO); 13C NMR (100 MHz, CD2Cl2):
d 13.6, 22.2, 25.5, 28.6, 28.9,
28.9, 31.5, 68.2, 68.3, 69.9, 110.6, 110.8, 111.0, 120.0, 120.1, 121.1,
124.8,124.9,125.8,126.4, 126.4,127.1,127.2,127.7,127.8,127.9,128.8,
133.5, 136.5, 139.4, 141.6, 142.1, 143.3, 143.8, 154.8, 156.0, 156.0,
192.1; HRMS (EI) m/z calcd for C46H50O4 [M]þ 666.3704, found
666.3732.
Without further purification, compound (S,S)-36 (28 mg,
0.04 mmol) was dissolved in a mixed solution of THFand MeOH (v/v,
1:1, 2 mL) under nitrogen atmosphere. After cooling to 0 ꢀC, pyrro-
0.20 mmol). After the injection of 1,3-dibromopropane (54 mL,
0.53 mmol), the mixture was heated to 80 ꢀC with stirring. After
1 h, the mixture was cooled and diluted with water (15 mL). The
mixture was extracted with EtOAc (10 mLꢂ3). The combined or-
ganic layer was washed with saturated brine solution (20 mLꢂ2)
successively and was dried over anhydrous Na2SO4. After filtration
and concentration, the residue was purified by column chroma-
tography on silica gel (10 g, EtOAc/CH2Cl2/hexanes, 1:1:25) to give
pure 23 (96 mg, 95%) as colorless waxy solids: Rf¼0.53 (EtOAc/
lidine (21
mL, 0.25 mmol) was added. Sodium cyanoborohydride
(1.0 M in THF, 51
mL, 0.05 mmol) was injected slowly to the mixture
hexanes, 1:20); 1H NMR (400 MHz, CDCl3):
d
0.89 (t, J¼7.2 Hz, 6H,
after 30 min. The mixture was stirred overnight at room tempera-
ture. Dilute HCl solution (2 M, 2 mL) was dropped to the mixture
slowly. The mixture was then diluted with water and extracted with
CH2Cl2 (10 mLꢂ3). The combined organic layer was washed with
aqueous HCl solution (2 M, 20 mL) and aqueous NaOH solution (3 M,
30 mL) successively and then was dried over anhydrous Na2SO4. The
organic layer was concentrated and purified by column chroma-
tography on silica gel (5 g, MeOH/CHCl3, 1:60) to give pure (S,S)-20
(20 mg, 68%) as colorless waxy solids: Rf¼0.45 (MeOH/CHCl3, 1:20);
2ꢂCH3), 1.18e1.27 (m, 16H, 8ꢂCH2), 1.47e1.50 (m, 4H, 2ꢂCH2),
1.96e2.01 (m, 2H, CH2), 3.13e3.22 (m, 2H, CH2Br), 3.68e3.88 (m,
6H, 3ꢂOCH2), 4.85 (dd, J¼12.6, 21.2 Hz, 2H, OCH2), 6.72e6.79 (m,
4H, ArH), 6.84e6.91 (m, 4H, ArH), 7.04 (dd, J¼1.3, 7.5 Hz, 2H, ArH),
7.11e7.25 (m, 7H, ArH); 13C NMR (100 MHz, CDCl3):
d 14.3, 22.7,
25.9, 29.1, 29.5, 30.4, 32.0, 32.8, 66.5, 69.0, 69.0, 70.9, 111.6, 111.9,
112.5, 120.7, 121.5, 121.6, 126.7, 127.2, 127.2, 127.3, 127.3, 127.7, 127.8,
127.9, 128.0, 128.2, 137.9, 143.2, 143.3, 143.9, 144.0, 155.8, 155.9,
156.6; HRMS (EI) m/z calcd for C48H55O4Br [MþH]þ 775.3356, found
775.3352.
1H NMR (300 MHz, CDCl3):
d
0.88 (t, J¼7.2 Hz, 6H, 2ꢂCH3),1.18e1.27
(m, 16H, 8ꢂCH2), 1.48 (br s, 4H, 2ꢂCH2), 1.72 (br s, 4H, 2ꢂCH2), 2.40
(br s, 4H, 2ꢂNCH2), 3.16 (d, J¼13.8 Hz,1H, 0.5ꢂNCH2), 3.67e3.76 (m,
4H, 2ꢂOCH2), 3.82 (d, J¼14.1 Hz, 1H, 0.5ꢂNCH2), 4.76 (dd, J¼12.3,
26.7 Hz, 2H, OCH2), 6.71e6.74 (m, 3H, ArH), 6.77e6.81 (m, 2H, ArH),
6.89(d, J¼6.9 Hz,1H, ArH), 6.94e6.96(m, 2H, ArH), 7.09e7.24(m, 8H,
4.3.15. (S,S)-1-(Benzyloxy)-16-(4-bromobutoxy)-8,9-bis(heptyloxy)
tetraphenylene (24). Compound (S,S)-24 was prepared from (S,S)-
10 (106 mg, 0.16 mmol) by using the same preparative method as
that for compound 23 from compound 10, except using 1,4-dibro-
mobutane (105 mg, 0.48 mmol).
ArH), 7.65 (d, J¼7.2 Hz, 1H, ArH); 13C NMR (75 MHz, CDCl3):
d 14.3,
22.7, 23.4, 25.9, 29.1, 29.4, 32.0, 54.0, 57.1, 68.9, 71.3,111.3,111.6,113.6,
120.0, 120.7, 122.1, 126.8, 127.1, 127.2, 127.6, 127.8, 128.4, 129.1, 135.7,
137.2,142.7,143.6,144.0,154.9,156.4,156.6; HRMS (MADLI-TOF) m/z
Column chromatography on silica gel (10 g, EtOAc/CH2Cl2/hex-
anes, 1:1:25) gave pure compound (S,S)-24 (120 mg, 95%) as color-
less waxy solids: Rf¼0.53 (EtOAc/hexanes, 1:20); 1H NMR (400 MHz,
calcd for C50H59O3N [MþH]þ 722.4568, found 722.4549; [
(c 0.99, CHCl3).
a
]
20 ꢁ39.2
CDCl3):
d
0.89 (t, J¼7.1 Hz, 6H, 2ꢂCH3), 1.18e1.30 (m, 16H, 8ꢂCH2),
D
1.45e1.51 (m, 4H, 2ꢂCH2), 1.55e1.64 (m, 2H, CH2), 1.66e1.77 (m, 2H,
CH2), 3.08e3.18 (m, 2H, CH2Br), 3.68e3.79 (m, 6H, 3ꢂOCH2), 4.86
(dd, J¼12.6, 15.5 Hz, 2H, OCH2), 6.73e6.77 (m, 4H, ArH), 6.86 (d,
J¼7.2 Hz, 2H, ArH), 6.88e6.91 (m, 2H, ArH), 7.04e7.07 (m, 2H, ArH),
4.3.13. (S,S)-8,9-Bis(heptyloxy)-16-(pyrrolidin-1-ylmethyl)tetraphe-
nylen-1-ol (21). Compound (S,S)-21 was prepared from (S,S)-20
(19 mg, 0.03 mmol) by using the same preparative method as that
for compound 13 from compound 12.
Column chromatography on silica gel (3 g, MeOH/CHCl3, 1:20)
gave pure (S,S)-21 (11.6 mg, 70%) as colorless waxy solids: Rf¼0.35
7.12e7.24 (m, 7H, ArH); 13C NMR (100 MHz, CDCl3):
d 14.3, 22.7, 25.9,
27.9, 29.1, 29.5, 29.8, 32.0, 33.9, 68.0, 69.1, 69.1, 70.8,111.5,111.6,112.6,
120.7, 120.8, 121.3, 121.6, 126.6, 127.1, 127.2, 127.3, 127.3, 127.4, 127.7,
127.8, 127.9, 128.0, 128.2, 138.0, 143.4, 143.9, 155.8, 156.1, 156.6, 156.6;

C.-K. Hau et al. / Tetrahedron 66 (2010) 9860e9874
9871
HRMS (ESI) m/z calcd for C49H57O4Br [MþNa]þ 811.3332, found
ArH), 6.68e6.82 (m, 12H, ArH), 6.86 (dd, J¼7.3, 7.3 Hz, 2H, ArH),
7.05e7.17 (m, 8H, ArH); 13C NMR (100 MHz, CDCl3):
14.3, 22.7,
811.3323; [
a
]
20 ꢁ40.9 (c 1.11, CHCl3).
d
D
23.4, 25.9, 29.1, 29.3, 29.4, 32.0, 54.3, 54.4, 64.7, 65.6, 67.2, 69.0, 69.1,
111.0, 111.1, 111.4, 111.6, 111.7, 112.2, 114.0, 120.2, 120.5, 120.6, 120.6,
120.7, 120.7, 121.3, 121.8, 124.3, 125.5, 126.8, 127.0, 127.1, 127.2, 127.2,
127.7, 127.7, 127.8, 128.0, 128.5, 143.0, 143.3, 143.5, 143.7, 143.9,
144.8, 153.4, 155.6, 155.7, 156.0, 156.4, 156.5, 156.5, 156.6; HRMS
4.3.16. 16-(3-(16-(Benzyloxy)-8,9-bis(heptyloxy)tetraphenylen-1-
yloxy)propoxy)-8,9-bis (heptyloxy)tetraphenylen-1-ol (25). To a so-
lution of compounds 10 (124 mg, 0.22 mmol) and 23 (108 mg,
0.14 mmol) in DMF (2 mL), Cs2CO3 (79 mg, 0.24 mmol) was added.
The mixture was heated to 80 ꢀC with stirring overnight. After
cooling, the mixture was diluted with water (15 mL). The mixture
was extracted with EtOAc (15 mLꢂ3) subsequently. The combined
organic layer was washed with saturated brine solution (30 mLꢂ2)
and was dried over anhydrous Na2SO4. After concentration and
column chromatography on silica gel (10 g, EtOAc/CH2Cl2/hexanes,
1:1:10), pure 25 (114 mg, 65%) was collected as colorless waxy
solids: Rf¼0.25 (EtOAc/hexanes, 1:10); 1H NMR (400 MHz, CDCl3):
(ESI) m/z calcd for C85H103O8N [MþH]þ 1266.7756, found
20
1266.7758; [
a
]
ꢁ84.9 (c 1.05, CHCl3).
D
4.3.19. (S,S,S,S)-16-(4-(8,9-Bis(heptyloxy)-16-(2-(pyrrolidin-1-yl)
ethoxy)tetraphenylen-1-yloxy)butoxy)-8,9-bis(heptyloxy)tetrapheny-
len-1-ol (28). Compound (S,S,S,S)-28 was prepared from (S,S,S,S)-26
(65 mg, 0.05 mmol) by using the same preparative method as that
for compound (S,S)-13 from compounds (S,S)-11.
Column chromatography on silica gel (8 g, MeOH/CH2Cl3, 1:40)
gave pure (S,S,S,S)-28 (21 mg, two-steps overall yield: 33%) as col-
orless waxy solids: Rf¼0.31 (MeOH/CH2Cl3, 1:20); 1H NMR
d
0.88 (t, J¼7.2 Hz, 6H, 2ꢂCH3), 0.88 (t, J¼7.2 Hz, 6H, 2ꢂCH3),
1.18e1.26 (m, 32H, 16ꢂCH2), 1.47e1.52 (m, 8H, 4ꢂCH2), 1.65e1.69
(m, 2H, CH2), 3.65e3.78 (m, 12H, 6ꢂOCH2), 4.70 (s, 2H, OCH2), 4.85
(br s, 1H, OH), 6.57 (d, J¼8.2 Hz, 1H, ArH), 6.64 (dd, J¼7.7, 7.7 Hz, 2H,
ArH), 6.70e6.75 (m, 8H, ArH), 6.79 (d, J¼7.4 Hz, 1H, ArH), 6.83e6.89
(m, 4H, ArH), 6.92e6.94 (m, 2H, ArH), 7.05e7.18 (m, 11H, ArH); 13C
(400 MHz, CDCl3):
d
0.89 (t, J¼7.2 Hz, 12H, 4ꢂCH3), 1.18e1.27 (m,
32H, 16ꢂCH2), 1.40e1.48 (m, 12H, 6ꢂCH2), 1.72 (br s, 4H, 2ꢂCH2),
2.45 (br s, 4H, 2ꢂNCH2), 2.59e2.62 (m, 1H, 0.5ꢂNCH2), 2.69e2.72
(m, 1H, 0.5ꢂNCH2), 3.57e3.61 (m, 2H, OCH2), 3.66e3.77 (m, 10H,
5ꢂOCH2), 3.84e3.94 (m, 2H, OCH2), 6.64e6.83 (m, 15H, ArH), 6.89
(d, J¼7.5 Hz,1H, ArH), 7.04e7.15 (m, 7H, ArH), 7.19 (dd, J¼8.0, 8.0 Hz,
NMR (100 MHz, CDCl3): d 14.3, 22.7, 25.9, 29.0, 29.1, 29.5, 32.0, 64.9,
65.5, 69.0, 69.1, 71.0, 111.3, 111.4, 111.5, 111.6, 111.7, 112.0, 113.4, 114.1,
120.5, 120.6, 120.7, 120.9, 121.7, 121.9, 123.7,124.1, 126.7,126.8, 127.0,
127.1, 127.2, 127.3, 127.7, 127.7, 127.8, 127.9, 128.0, 128.2, 128.9, 137.9,
142.7, 143.3, 143.4, 143.6, 143.6, 144.0, 145.4, 152.6, 155.1, 155.7,
155.9, 156.4, 156.4, 156.5; HRMS (ESI) m/z calcd for C86H98O8
[MþNa]þ 1281.7154, found 1281.7180.
1H, ArH); 13C NMR (100 MHz, CDCl3):
d 14.3, 22.7, 23.4, 25.5, 25.8,
25.9, 29.1, 29.5, 32.0, 54.4, 54.6, 68.6, 68.9, 69.0, 69.1, 69.1, 110.7,
111.4, 111.5, 111.6, 111.7, 111.8, 112.2, 113.9, 120.2, 120.6, 120.6, 120.7,
120.7, 121.0, 121.1, 121.9, 124.1, 125.0, 126.7, 127.1, 127.1, 127.2, 127.7,
127.7, 127.7, 127.9, 128.1, 128.7, 142.9, 143.3, 143.4, 143.5, 143.7, 143.8,
145.1, 153.1, 155.5, 155.7, 156.2, 156.4, 156.5, 156.5, 156.6; HRMS
Column chromatography on silica gel (EtOAc/CH2Cl2/hexanes,
1:1:2) was used to recover un-reacted compound 10.
(MADLI-TOF) m/z calcd for C86H105O8N [MþH]þ 1280.7913, found
20
4.3.17. (S,S,S,S)-16-(4-(16-(Benzyloxy)-8,9-bis(heptyloxy)tetrapheny-
len-1-yloxy)butoxy)-8,9-bis(heptyloxy)tetraphenylen-1-ol
(26). Compound (S,S,S,S)-26 was prepared from (S,S)-10 (134 mg,
0.24 mmol) and (S,S)-24 (112 mg, 0.14 mmol) by using the same pre-
parative method as that for compound 25 from compounds 10 and 23.
Column chromatography on silica gel (10 g, EtOAc/CH2Cl2/hex-
anes, 1:1:10) gave pure (S,S,S,S)-26 (155 mg, 87%) as colorless waxy
solids: Rf¼0.25 (EtOAc/hexanes, 1:10); 1H NMR (400 MHz, CDCl3):
1280.7945; [
a
]
ꢁ62.3 (c 1.35, CHCl3).
D
4.3.20. (S,S,S,S)-16-(3-(16-(Benzyloxy)-8,9-bis(heptyloxy)tetraphe-
nylen-1-yloxy)prop-oxy)-8,9-bis(heptyloxy)tetraphenylene-1-car-
bonitrile (29). To
a solution of compounds (S,S)-18 (23 mg,
0.04 mmol) and (S,S)-23 (26 mg, 0.03 mmol) in DMF (2 mL), Cs2CO3
(20 mg, 0.06 mmol) was added. The mixture was heated to 80 ꢀC
with stirring overnight. After cooling, the mixture was diluted with
water (15 mL). The mixture was extracted with EtOAc (15 mLꢂ3)
successively. The combined organic layer was washed with satu-
rated brine solution (20 mLꢂ2) and was dried over anhydrous
Na2SO4. After removal of solvent, the residue was purified by col-
umn chromatography on silica gel (5 g, EtOAc/CH2Cl2/hexanes,
1:1:10) to give pure (S,S,S,S)-29 (33 mg, 81%) as colorless waxy
solids: Rf¼0.28 (EtOAc/hexanes, 1:10); 1H NMR (400 MHz, CDCl3):
d
0.89 (t, J¼7.2 Hz, 12H, 4ꢂCH3), 1.18e1.30 (m, 32H, 16ꢂCH2),
1.37e1.38 (m, 4H, 2ꢂCH2), 1.46e1.49 (m, 8H, 4ꢂCH2), 3.52e3.56 (m,
1H, 0.5ꢂOCH2), 3.60e3.63 (m, 3H, 1.5ꢂOCH2), 3.67e3.75 (m, 8H,
4ꢂOCH2), 4.77 (s, 2H, OCH2), 4.87 (br s, 1H, OH), 6.63 (dd, J¼0.8,
8.4 Hz, 1H, ArH), 6.69e6.75 (m, 8H, ArH), 6.76e6.79 (m, 3H, ArH),
6.83e6.90 (m, 4H, ArH), 6.95e6.98 (m, 2H, ArH), 7.06e7.22 (m, 11H,
ArH); 13C NMR (100 MHz, CDCl3):
d 14.3, 22.7, 25.3, 25.4, 25.9, 29.1,
29.5, 29.5, 32.0, 68.1, 68.6, 69.0, 69.0, 69.1, 69.1, 70.6,111.4,111.5,111.6,
111.7, 111.8, 112.1, 112.4, 114.1, 120.5, 120.7, 120.8, 120.8, 121.0, 121.5,
122.1, 123.7, 123.8, 124.0, 126.6, 127.0, 127.0, 127.1, 127.3, 127.3, 127.5,
127.7, 127.7, 127.8, 127.8, 127.9, 128.2, 129.0, 138.0, 142.7, 143.4, 143.4,
143.5, 143.6, 143.8, 143.9, 145.5, 152.5, 152.5, 155.2, 155.8, 156.2, 156.4,
156.5, 156.5; HRMS (MADLI-TOF) m/z calcd for C87H100O8 [MþNa]þ
d
0.89 (t, J¼7.2 Hz, 6H, 2ꢂCH3), 0.90 (t, J¼7.2 Hz, 6H, 2ꢂCH3),
1.19e1.29 (m, 32H, 16ꢂCH2), 1.49e1.50 (m, 8H, 4ꢂCH2), 1.67e1.78
(m, 2H, CH2), 3.67e3.76 (m, 12H, 6ꢂOCH2), 4.85 (s, 2H, OCH2), 6.55
(d, J¼8.0 Hz, 1H, ArH), 6.62 (d, J¼7.6 Hz, 1H, ArH), 6.71e6.79 (m, 8H,
ArH), 6.82e6.87 (m, 5H, ArH), 7.04e7.23 (m, 12H, ArH), 7.40 (dd,
J¼1.2, 7.7 Hz, 1H, ArH), 7.45 (dd, J¼1.2, 7.6 Hz, 1H, ArH); 13C NMR
1295.7310, found 1295.7355; [
a
]
20 ꢁ75.8 (c 0.99, CHCl3).
(100 MHz, CDCl3): d 14.3, 22.7, 25.9, 29.1, 29.1, 29.4, 29.5, 32.0, 65.6,
D
65.8, 68.7, 69.0, 69.0, 69.1, 70.8, 111.2, 111.3, 111.6, 111.7, 111.9, 112.5,
113.8, 118.8, 120.4, 120.8, 120.8, 120.9, 120.9, 121.1, 121.5, 126.0,
126.2, 126.7, 127.1, 127.1, 127.2, 127.3, 127.4, 127.7, 127.7, 127.9, 127.9,
128.1, 128.2, 128.2, 129.5, 131.1, 132.5, 138.0, 140.9, 141.6, 142.4,
143.4, 143.4, 143.8, 143.9, 155.1, 155.8, 156.0, 156.3, 156.5, 156.6;
4.3.18. (S,S,S,S)-16-(3-(8,9-Bis(heptyloxy)-16-(2-(pyrrolidin-1-yl)
ethoxy)tetraphenylen-1-yloxy)propoxy)-8,9-bis(heptyloxy)tetraphe-
nylen-1-ol (27). Compound (S,S,S,S)-27 was prepared from (S,S,S,S)-
25 (78 mg, 0.06 mmol) by using the same preparative method as
that for compound (S,S)-13 from compounds (S,S)-11.
HRMS (MADLI-TOF) m/z calcd for C87H97O7N [MþNa]þ 1290.7157,
20
Column chromatography on silica gel (10 g, MeOH/CH2Cl3, 1:40)
gave pure (S,S,S,S)-27 (36 mg, two-step overall yield: 48%) as col-
orless waxy solids: Rf¼0.31 (MeOH/CH2Cl3, 1:20); 1H NMR
found 1290.7112; [
a
]
D
ꢁ75.1 (c 1.06, CHCl3).
Column chromatography on silica gel (EtOAc/CH2Cl2/hexanes,
1:1:2) was used to recover un-reacted compound (S,S)-18.
(400 MHz, CDCl3):
d
0.89 (t, J¼7.2 Hz, 12H, 4ꢂCH3), 1.18e1.27 (m,
32H, 16ꢂCH2), 1.46e1.48 (m, 8H, 4ꢂCH2), 1.65e1.72 (m, 6H, 3ꢂCH2),
2.43 (br s, 4H, 2ꢂNCH2), 2.61 (br s, 2H, NCH2), 3.62e3.74 (m, 12H,
6ꢂOCH2), 3.86e3.87 (m, 2H, OCH2), 6.63 (dd, J¼8.6, 8.6 Hz, 2H,
4.3.21. (S,S,S,S)-16-(3-(8,9-Bis(heptyloxy)-16-(pyrrolidin-1-ylmethyl)
tetraphenylen-1-yloxy)propoxy)-8,9-bis(heptyloxy)tetraphenylen-1-
ol (30). Compound (S,S,S,S)-30 was prepared from (S,S,S,S)-29

9872
C.-K. Hau et al. / Tetrahedron 66 (2010) 9860e9874
(17.5 mg, 0.01 mmol) by using the same preparative method as that
for compound (S,S)-21 from compound (S,S)-19.
6.82e6.88 (m, 6H, ArH), 6.94e6.96 (m, 2H, ArH), 7.00e7.05 (m, 2H,
ArH), 7.16e7.20 (m, 10H, ArH), 7.39e7.41 (m, 1H, ArH); 13C NMR
Column chromatography on silica gel (5 g, MeOH/CH2Cl3, 1:40)
gave pure (S,S,S,S)-30 (4.3 mg, three-step overall yield: 35%) as
colorless waxy solids: Rf¼0.31 (MeOH/CH2Cl3, 1:20); 1H NMR
(100 MHz, CDCl3): d 14.3, 27.7, 25.9, 29.1, 29.1, 29.4, 29.4, 29.5, 32.0,
68.3, 68.5, 68.7, 69.0, 69.1, 70.8, 111.2, 111.6, 111.9, 112.3, 112.5, 113.1,
118.7,120.5, 120.9, 120.9, 121.0,121.4,121.5,121.6,126.2, 126.3, 126.7,
127.2, 127.2, 127.3, 127.4, 127.7, 127.9, 128.0, 128.0, 128.2, 129.7, 131.1,
132.4, 137.9, 140.7, 141.7, 142.3, 143.3, 143.4, 143.7, 143.8, 143.8,
155.5, 155.6, 156.3, 156.5, 156.5, 156.5, 156.6; HRMS (ESI) m/z calcd
for C86H95O7N [MþNa]þ 1276.7001, found 1276.6997; (S,S,S,S)-32:
(400 MHz, CD2Cl2):
d
0.88 (t, J¼7.1 Hz, 12H, 4ꢂCH3), 1.20e1.30 (m,
32H, 16ꢂCH2), 1.50e1.51 (m, 8H, 4ꢂCH2), 1.67e1.73 (m, 6H, 3ꢂCH2),
2.45 (br s, 4H, 2ꢂNCH2), 3.61e3.72 (m, 5H, 0.5ꢂNCH2, and
2ꢂOCH2), 3.76e3,80 (m, 9H, 0.5ꢂNCH2, and 4ꢂOCH2), 6.70e6.79
(m, 12H, ArH), 6.85e6.90 (m, 2H, ArH), 7.09e7.21 (m, 6H, ArH),
[
a
]
20 ꢁ71.7 (c 0.86, CHCl3); (R,R,R,R)-32: [
a]
20 þ64.4 (c 0.98, CHCl3);
D
D
20
7.23e7.30 (m, 3H, ArH); 13C NMR (75 MHz, CD2Cl2):
d
13.5, 22.2,
(R,R,S,S)-32: [
a
]
ꢁ15.1 (c 1.00, CHCl3).
D
22.6, 25.4, 28.4, 28.6, 28.9, 31.5, 55.1, 64.0, 64.6, 68.3, 68.3, 110.4,
110.6,111.2,119.7, 119.9,120.0, 120.8, 121.2, 123.3, 124.5, 126.2, 126.6,
127.3,127.4,127.5, 127.8, 128.1, 128.4, 136.1, 142.3, 142.4,142.6, 143.0,
143.1, 143.2, 144.5, 152.9, 154.4, 155.0, 155.8, 155.9, 156.1; HRMS
(MADLI-TOF) m/z calcd for C84H101O7N [MþH]þ 1236.7650, found
4.3.24. (S,S,S,S)-, (R,R,R,R)-, and (R,R,S,S)-1-((16-(2-(16-(Benzyloxy)-
8,9-bis(heptyloxy)tetraphenylen-1-yloxy)ethoxy)-8,9-bis(heptyloxy)
tetraphenylen-1-yl)methyl)pyrrolidine (33). Compound (S,S,S,S)-33
was prepared from (S,S,S,S)-32 (68 mg, 0.05 mmol) by using the
same preparative method as that for compound (S,S)-20.
1236.7663; [
a]
20 ꢁ75.3 (c 0.57, CHCl3).
D
Column chromatography on silica gel (8 g, MeOH/CHCl3, 1:70)
gave pure (S,S,S,S)-33 (32 mg, two-step overall yield: 45%) as color-
less waxy solids: Rf¼0.34 (MeOH/CHCl3, 1:20); 1H NMR (400 MHz,
4.3.22. (S,S)- and (R,R)-1-(Benzyloxy)-16-(2-bromoethoxy)-8,9-bis
(heptyloxy)tetraphenylene (31). Compound (S,S)-31 was prepared
from (S,S)-10 (184 mg, 0.28 mmol) by using the same preparative
method as that for compound 23 from compound 10, except using
1,2-dibromoethane (263 mg, 1.4 mmol) and acetone as solvent.
Column chromatography on silica gel (15 g, EtOAc/CH2Cl2/hex-
anes, 1:1:25) gave pure (S,S)-31 (145 mg, two-step overall yield:
66%) as colorless waxy solids: Rf¼0.53 (EtOAc/hexanes, 1:20); 1H
CDCl3):
d
0.88 (t, J¼7.2 Hz, 12H, 4ꢂCH3), 1.17e1.25 (m, 16H, 8ꢂCH2),
1.46 (br s, 8H, 4ꢂCH2), 1.64 (m, 8H, 2ꢂCH2, and 2ꢂNCH2), 3.53e3.73
(m, 14H, NCH2, and 6ꢂOCH2), 4.80 (s, 2H, OCH2), 6.44e6.52 (m, 2H,
ArH), 6.61 (d, J¼7.4 Hz, 1H, ArH), 6.66e6.76 (m, 8H, ArH), 6.80e6.88
(m, 4H, ArH), 7.00e7.21 (m, 14H, ArH); 13C NMR (100 MHz, CDCl3):
d
14.3, 22.7, 23.3, 25.9, 25.9, 29.1, 29.4, 29.4, 31.9, 67.6, 67.9, 68.8, 68.9,
NMR (400 MHz, CDCl3):
d
0.91 (t, J¼7.1 Hz, 6H, 2ꢂCH3), 1.20e1.30
69.0, 71.0, 111.1, 111.4, 111.5, 112.8, 113.0, 120.1, 120.6, 120.7, 120.8,
121.7, 126.7, 126.8, 127.1, 127.1, 127.2, 127.4, 127.5, 127.7, 127.9, 128.0,
128.3,128.6,135.7,137.9,142.6,142.9,143.2,143.3,143.6,143.8,144.0,
154.7, 155.7, 155.8, 156.3, 156.5, 156.5.
(m, 16H, 8ꢂCH2), 1.45e1.50 (m, 4H, 2ꢂCH2), 3.14e3.23 (m, 2H,
CH2Br), 3.70e3.80 (m, 4H, OCH2), 3.91e4.00 (m, 2H, OCH2), 4.88
(dd, J¼12.6, 20.9 Hz, 2H, OCH2), 6.74e6.77 (m, 3H, ArH), 6.81e6.90
(m, 4H, ArH), 6.97 (dd, J¼0.7, 7.6 Hz, 1H, ArH), 7.07e7.09 (m, 2H,
For (R,R,S,S)-33, 1H NMR (400 MHz, CDCl3):
d 0.85e0.90 (m, 12H,
ArH), 7.13e7.25 (m, 7H, ArH); 13C NMR (100 MHz, CDCl3):
d
14.3,
4ꢂCH3), 1.17e1.26 (m, 16H, 8ꢂCH2), 1.45e1.48 (m, 8H, 4ꢂCH2), 1.64
(m, 8H, 2ꢂCH2, and 2ꢂNCH2), 3.60e3.80 (m, 14H, NCH2, and
6ꢂOCH2), 4.73 (s, 2H, OCH2), 6.38 (d, J¼8.1 Hz, 1H, ArH), 6.60e6.73
(m, 9H, ArH), 6.80e6.83 (m, 2H, ArH), 6.86e6.90 (m, 2H, ArH),
22.7, 25.9, 29.1, 29.3, 29.4, 32.0, 69.0, 69.7, 70.9, 111.6, 111.6, 112.6,
113.8, 120.6, 120.7, 121.5, 122.5, 126.7, 127.0, 127.1, 127.2, 127.3, 127.8,
127.8,128.0,128.1,128.1,128.3,137.9,143.1,143.2,143.9,144.3,155.5,
155.7, 156.5, 156.6; HRMS (MADLI-TOF) m/z calcd for C47H53O4Br
6.96e7.16 (m, 15H, ArH); 13C NMR (100 MHz, CDCl3):
d 14.3, 22.7,
[MþNa]þ 785.3010, found 785.3021. Anal. Calcd for C47H53O4Br: C,
23.3, 25.9, 29.1, 29.5, 32.0, 67.7, 68.3, 68.9, 69.0, 69.0, 69.1, 71.0,111.4,
111.6, 112.6, 112.8, 120.2, 120.6, 120.7, 120.9, 121.6, 121.8, 121.8, 126.7,
127.1, 127.2, 127.2, 127.3, 127.5, 127.8, 127.8, 127.9, 128.2, 128.3, 128.5,
135.7, 137.8, 142.6, 142.9, 143.2, 143.4, 143.7, 143.7, 143.9, 155.3,
20
74.10; H, 7.01, found C, 74.18; H, 7.08; (S,S)-31: [
a
]
ꢁ31.4 (c 1.10,
D
CHCl3); (R,R)-31: [
a
]
20 þ30.1 (c 1.00, CHCl3).
D
4.3.23. (S,S,S,S)-, (R,R,R,R)-, and (R,R,S,S)-16-(2-(16-(Benzyloxy)-8,9-
bis(heptyloxy)tetraphenylen-1-yloxy)ethoxy)-8,9-bis(heptyloxy)tet-
raphenylene-1-carbonitrile (32). Compound (S,S,S,S)-32 was pre-
pared from (S,S)-18 (65 mg, 0.11 mmol) and (S,S)-31 (97 mg,
0.13 mmol) by using the same preparative method as that for
compound (S,S,S,S)-29, but using acetone as solvent.
Column chromatography on silica gel (5 g, EtOAc/CH2Cl2/hex-
anes, 1:1:10) gave pure (S,S,S,S)-32 (96 mg, 70%) as colorless waxy
solids: Rf¼0.26 (EtOAc/hexanes, 1:10); 1H NMR (400 MHz, CDCl3):
155.7, 156.1, 156.3, 156.5, 156.6; HRMS (ESI) m/z calcd for
20
C90H105O7N [MþH]þ 1312.7964, found 1312.7947; (S,S,S,S)-33: [
a]
D
20
ꢁ46.2 (c 0.67, CHCl3); (R,R,S,S)-33: [
a
]
ꢁ6.6 (c 0.90, CHCl3);
D
20
(R,R,R,R)-33: [
a
]
þ41.1 (c 0.80, CHCl3).
D
4.3.25. (S,S,S,S)-, (R,R,R,R)-, and (R,R,S,S)-16-(2-(8,9-Bis(heptyloxy)-
16-(pyrrolidin-1-ylmethyl)tetraphenylen-1-yloxy)ethoxy)-8,9-bis(hep-
tyloxy)tetraphenylen-1-ol (34). Compound (S,S,S,S)-34 was prepared
from (S,S,S,S)-33 (20 mg, 0.02 mmol) by using the same preparative
method as that for compound (S,S)-21 from compound (S,S)-20.
Column chromatography on silica gel (3 g, MeOH/CH2Cl3, 1:40)
gave pure (S,S,S,S)-34 (13 mg, 68%) as colorless waxy solids: Rf¼0.32
d
0.88e0.93 (m, 12H, 4ꢂCH3), 1.22e1.29 (m, 32H, 16ꢂCH2),
1.48e1.53 (m, 8H, 4ꢂCH2), 3.49 (br s, 2H, OCH2), 3.72e3.81 (m, 10H,
5ꢂOCH2), 4.87 (dd, J¼13.0, 18.3 Hz, 2H, OCH2), 5.73 (br s, 1H, ArH),
5.87 (br s, 1H, ArH), 6.38e6.39 (m, 2H, ArH), 6.62 (m, 2H, ArH),
6.69e6.77 (m, 7H, ArH), 6.82e6.84 (m, 3H, ArH), 6.95e7.01 (m, 2H,
ArH), 7.06e7.17 (m, 5H, ArH), 7.22e7.29 (m, 4H, ArH), 7.41 (d,
J¼7.1 Hz, 1H, ArH), 7.49 (d, J¼7.5 Hz, 1H, ArH); 13C NMR (100 MHz,
(MeOH/CH2Cl3, 1:20); 1H NMR (400 MHz, CDCl3):
d 0.88 (t, 12H,
J¼7.1 Hz, 4ꢂCH3),1.18e1.25 (m, 32H,16ꢂCH2),1.45 (br s, 8H, 4ꢂCH2),
1.73 (br s, 4H, 2ꢂCH2), 3.52e3.75 (m, 14H, NCH2, and 6ꢂOCH2), 6.42
(d, J¼8.1 Hz,1H, ArH), 6.48 (d, J¼8.1 Hz,1H, ArH), 6.62e6.84 (m,12H,
ArH), 6.90 (d, J¼7.4 Hz, 1H, ArH), 7.02e7.18 (m, 8H, ArH), 7.26e7.31
CDCl3): d 14.3, 22.7, 25.9, 25.9, 29.1, 29.1, 29.4, 29.5, 31.9, 32.0, 66.9,
67.0, 68.7, 68.7, 69.0, 70.5, 111.0, 111.3, 111.5, 112.0, 113.6, 118.7, 120.4,
120.7, 120.8, 120.9, 121.1, 121.2, 121.5, 125.4, 126.2, 126.6, 126.8,
126.9, 127.1, 127.2, 127.3, 127.4, 127.7, 127.9, 128.0, 128.1, 128.3, 128.4,
130.0, 131.1,132.7,138.0,140.7,140.9,141.8, 142.4, 142.9, 143.4, 143.4,
143.5, 143.8, 154.6, 155.4, 155.6, 156.3, 156.5, 156.5.
(m,1H, ArH); 13C NMR (100 MHz, CDCl3):
d 14.3, 22.7, 23.2, 25.9, 29.1,
29.4, 32.0, 67.9, 68.8, 68.9, 68.9, 69.0, 111.2, 111.3, 111.5, 111.7, 112.7,
114.3, 120.1, 120.5, 120.6, 122.1, 123.1, 123.7, 126.9, 127.0, 127.1, 127.2,
127.6,127.8,127.9,128.2,128.4,129.0,142.6,143.4,143.6,143.7,145.3,
153.0, 154.8, 155.5, 156.3, 156.4, 156.6, 156.7.
For (R,R,S,S)-32, 1H NMR (400 MHz, CDCl3):
d
0.88e0.91 (m, 12H,
For (R,R,S,S)-34, 1H NMR (300 MHz, CDCl3):
d 0.85e0.90 (m, 12H,
4ꢂCH3), 1.19e1.27 (m, 32H, 16ꢂCH2), 1.48e1.50 (m, 8H, 4ꢂCH2),
3.67e3.85 (m, 10H, 5ꢂOCH2), 3.88e3.97 (m, 2H, OCH2), 4.71 (s, 2H,
OCH2), 6.56 (d, J¼8.1 Hz, 3H, ArH), 6.71e6.76 (m, 5H, ArH),
4ꢂCH3), 1.17e1.27 (m, 16H, 8ꢂCH2), 1.46e1.48 (m, 10H, 5ꢂCH2), 1.71
(m, 6H, CH2, and 2ꢂNCH2), 3.68e3.90 (m, 14H, NCH2, and 6ꢂOCH2),
6.55e6.93 (m, 15H, ArH), 7.05e7.16 (m, 9H, ArH); 13C NMR (75 MHz,

C.-K. Hau et al. / Tetrahedron 66 (2010) 9860e9874
9873
CDCl3):
d
14.3, 22.7, 23.3, 25.9, 29.1, 29.4, 32.0, 67.9, 68.9, 69.0, 111.3,
After the addition of TFA (5
m
L, 0.06ꢂ10ꢁ3 mmol), the mixture was
111.5, 111.8, 113.8, 114.2, 119.9, 120.4, 120.7, 121.7, 122.9, 123.5, 127.0,
127.2,127.5,127.7,127.9,128.4,128.7,129.0,135.6,142.6,142.7,143.5,
143.8, 145.4, 152.8, 154.9, 155.8, 156.3, 156.4, 156.6; HRMS (ESI) m/z
calcd for C83H99O7N [MþH]þ 1222.7494, found 1222.7486; (S,S,S,S)-
stirred for 2 h at room temperature. The mixture was then cooled to
0 ꢀC. Sodium borohydride (6 mg, 0.15 mmol) was added slowly to
the mixture and warmed to room temperature. After stirring for
30 min, the mixture was diluted with water (5 mL) and extracted
with CH2Cl2 (5 mLꢂ3) successively. The combined organic layer
was dried over anhydrous Na2SO4 and concentrated. The residue
was purified by column chromatography on silica gel (3 g, EtOAc/
CH2Cl2/hexanes, 1:1:8) to give pure protected amine (17 mg, 85%)
as colorless waxy solids: Rf¼0.75 (EtOAc/hexanes, 1:4).
20
20
34: [a
]
ꢁ89.7 (c 0.63, CHCl3); (R,R,R,R)-34: [
a]
þ80.0 (c 0.66,
D
D
CHCl3); (R,R,S,S)-34: [
a]
20 ꢁ7.2 (c 0.69, CHCl3).
D
4.3.26. (S,S)-(16-(Benzyloxy)-8,9-bis(heptyloxy)tetraphenylen-1-yl)
methanamine (35). To a stirring solution of compound (S,S)-19
(25 mg, 0.037 mmol) in dried THF (1 mL) under nitrogen atmo-
sphere, lithium aluminum hydride (14 mg, 0.38 mmol) was added
slowly at 0 ꢀC. The mixture was then heated to reflux for 30 min.
After cooling to 0 ꢀC, the mixture was diluted with THF and water
(1 mL) was dropped slowly to it. After the formation of white pre-
cipitates, the mixture was filtered under vacuum and the residue
was washed with EtOAc (5 mLꢂ2). The filtrate was dried over an-
hydrous Na2SO4 and concentrated. The residue was purified by
column chromatography on silica gel (EtOAc/CH2Cl2/hexanes,1:1:3)
to give pure (S,S)-35 (21 mg, 85%) as colorless waxy solids: Rf¼0.31
Amixed solution of protected amine (17 mg, 0.01 mmol) inTHFand
EtOH (1:1, v/v, 2 mL) was prepared, followed by the addition of pal-
ladium black (10 mol %). The mixture was stirred under H2 for 7 h. The
mixture was then filtered through a Celite pad. The filtrate was diluted
with CH2Cl2 (20 mL). The organic layer was thenwashed with aqueous
HCl solution (2 M, 15 mL) and aqueous NaOH solution (3 M, 20 mL).
The organic layer was dried over anhydrous Na2SO4 and concentrated.
After column chromatography on silica gel (3 g, EtOAc/CH2Cl2/hex-
anes, 1:1:4), pure (S,S,S,S)-38 (7 mg, 48%) was obtained as colorless
waxy solids: Rf¼0.35 (EtOAc/hexanes,1:4); 1H NMR (400 MHz, CDCl3):
(EtOAc/hexanes,1:2); 1H NMR (400 MHz, CDCl3):
d
0.88 (t, J¼7.2 Hz,
d
0.87 (t, J¼7.1 Hz, 12H, 4ꢂCH3),1.14e1.26 (m, 32H,16ꢂCH2),1.46e1.48
3H, CH3), 0.88 (t, J¼7.2 Hz, 3H, CH3), 1.17e1.26 (m, 16H, 8ꢂCH2),
1.45e1.49 (m, 4H, 2ꢂCH2), 3.49 (dd, J¼14.2, 38.3 Hz, 2H, CH2),
3.67e3.77 (m, 4H, 2ꢂOCH2), 4.81 (dd, J¼12.4, 26.2 Hz, 2H, OCH2),
6.72 (d, J¼8.2 Hz, 2H, ArH), 6.77e6.81 (m, 2H, ArH), 6.84 (d, J¼6.9 Hz,
1H, ArH), 6.89 (d, J¼0.7, 7.5 Hz, 1H, ArH), 6.96e6.98 (m, 2H, ArH),
7.12e7.19 (m, 4H, ArH), 7.21e7.24 (m, 5H, ArH); 13C NMR (100 MHz,
(m, 8H, 4ꢂCH2), 1.69 (s, 3H, NCH3), 2.81 (d, J¼12.6 Hz, 2H, NCH2), 3.66
(d, J¼12.6 Hz, 2H, NCH2), 3.69e3.75 (m, 8H, 4ꢂOCH2), 6.66e6.75 (m,
8H, ArH), 6.79e6.81(m,4H, ArH), 7.03e7.12 (m, 6H, ArH), 7.14e7.23 (m,
6H, ArH); 13C NMR (100 MHz, CDCl3):
d 14.3, 22.7, 25.9, 29.1, 29.4, 32.0,
42.2, 58.9, 68.9,111.3,111.5,116.5,120.1,120.5,120.9,127.0,127.0,127.4,
127.6, 127.7, 127.9, 128.6, 129.3, 134.9, 135.7, 143.1, 143.2, 143.4, 144.2,
153.2, 156.2, 156.4; HRMS (ESI) m/z calcd for C79H93O6N [MþH]þ
CDCl3): d 14.3, 22.7, 25.9, 29.1, 29.4, 32.0, 45.3, 68.9, 71.1, 111.4, 111.7,
113.8, 119.9, 120.6, 122.0, 126.5, 126.8, 127.0, 127.1, 127.3, 127.5, 127.8,
128.0,128.4,129.2,135.1,137.4,142.9,143.0,143.7,144.1,154.8,156.5,
156.6; HRMS (ESI) m/z calcd for C46H53O3N [MþH]þ 668.4098, found
668.4094. Anal. Calcd for C46H53O3N: C, 82.72; H, 8.00; N, 2.10, found
1152.7076, found 1152.7055; [
a
]
D
20 ꢁ307.8 (c 0.20, CHCl3).
4.3.29. (S,S,S,S)-1-((16-(2-(16-(Benzyloxy)-8,9-bis(heptyloxy)tetra-
phenylen-1-yloxy)ethoxy)-8,9-bis(heptyloxy)tetraphenylen-1-yl)
methyl)piperidine (39). Compound (S,S,S,S)-39 was prepared from
(S,S,S,S)-32 (40 mg, 0.03 mmol) by using the same preparative
method as that for compound (S,S,S,S)-33, but using piperidine
C, 82.27; H, 7.92; N, 1.81; [
a
]
D
20 ꢁ28.1 (c 0.70, CHCl3).
4.3.27. (S,S,S,S)-Bis((16-(benzyloxy)-8,9-bis(heptyloxy)tetrapheny-
len-1-yl)methyl)amine (37). Compounds (S,S)-36 (20 mg,
0.03 mmol) and (S,S)-35 (21 mg, 0.03 mmol) were dissolved in
a mixed solution of THF and MeOH (v/v, 1:1, 0.6 mL) under nitrogen
atmosphere. The mixture was cooled to 0 ꢀC with stirring. After
(19
Column chromatography on silica gel (5 g, MeOH/CHCl3, 1:70)
gave pure (S,S,S,S)-39 (26 mg, 64%) as colorless waxy solids: Rf¼0.34
(MeOH/CHCl3, 1:20); 1H NMR (400 MHz, CDCl3):
0.88 (t, J¼7.3 Hz,
mL, 0.19 mmol) instead.
d
stirring for 2 h, NaBH3CN solution (1.0 M in THF, 45
mL, 0.045 mmol)
6H, 2ꢂCH3), 0.89 (t, J¼7.2 Hz, 6H, 2ꢂCH3), 1.18e1.26 (m, 32H,
16ꢂCH2), 1.47 (br s, 12H, 6ꢂCH2), 1.61 (br s, 2H, CH2), 1.99 (br s, 4H,
2ꢂNCH2), 3.50e3.54 (m, 2H, OCH2), 3.59e3.63 (m, 2H, OCH2),
3.67e3.79 (m, 8H, 4ꢂOCH2), 4.81 (s, 2H, OCH2), 6.31 (m, 1H, ArH),
6.36 (d, J¼8.0 Hz, 1H, ArH), 6.56 (d, J¼7.5 Hz, 1H, ArH), 6.64 (d,
J¼7.5 Hz,1H, ArH), 6.63e6.87 (m,10H, ArH), 6.91e7.16 (m,11H, ArH),
was injected slowly to the mixture. The stirring was continued
overnight at room temperature. The mixture was then treated with
aqueous HCl solution (2 M, 2 mL). After dilution with water, the
mixture was extracted with CH2Cl2 (10 mLꢂ3). The combined or-
ganic layer was washed with aqueous HCl solution (2 M, 20 mL)
and aqueous NaOH solution (3 M, 30 mL) successively. The organic
layer was dried over anhydrous Na2SO4 and concentrated. The
residue was purified by column chromatography on silica gel (3 g,
EtOAc/CH2Cl2/hexanes, 1:1:4) to give pure (S,S,S,S)-37 (31 mg, 80%)
as colorless waxy solids: Rf¼0.35 (EtOAc/hexanes, 1:4); 1H NMR
7.19e7.24 (m, 4H, ArH); 13C NMR (100 MHz, CDCl3):
d 14.3, 22.5, 22.7,
25.1, 25.9, 29.1, 29.5, 29.8, 32.0, 52.4, 67.7, 68.9, 69.0, 70.9,111.2,111.6,
120.4, 120.6, 120.7, 120.8, 121.6, 121.9, 126.7, 127.1, 127.2, 127.3, 127.3,
127.4,127.7,127.9,128.0,128.2,128.3,137.9,143.2,143.7,144.0,155.7,
156.1, 156.3, 156.5; HRMS (MADLI-TOF) m/z calcd for C91H107O7N
(400 MHz, CDCl3):
d
0.87 (t, J¼7.0 Hz, 12H, 4ꢂCH3), 1.14e1.25 (m,
[MþH]þ 1327.8154, found 1327.8208; [
a
]
20 ꢁ43.8 (c 0.88, CHCl3).
D
32H, 16ꢂCH2), 1.44e1.53 (m, 8H, 4ꢂCH2), 3.14 (d, J¼13.8 Hz, 2H,
NCH2), 3.29 (d, J¼13.8 Hz, 2H, NCH2), 3.65e3.75 (m, 8H, 4ꢂOCH2),
4.68 (dd, J¼16.3,19.6 Hz, 4H, 2ꢂOCH2), 6.67e6.72 (m, 7H, ArH), 6.81
(d, J¼7.1 Hz, 4H, ArH), 6.85e6.89 (m, 4H, ArH), 6.99e7.13 (m, 12H,
4.3.30. (S,S,S,S)-16-(2-(8,9-Bis(heptyloxy)-16-(piperidin-1-ylmethyl)
tetraphenylen-1-yloxy)ethoxy)-8,9-bis(heptyloxy)tetraphenylen-1-ol
(40). Compound (S,S,S,S)-40 was prepared from (S,S,S,S)-39 (26 mg,
0.02 mmol) by using the same preparative method as that for
compound (S,S)-21 from compound (S,S)-20.
ArH), 7.15e7.18 (m, 7H, ArH); 13C NMR (100 MHz, CDCl3):
d 14.3,
22.7, 25.9, 29.1, 29.4, 32.0, 51.5, 69.0, 69.1, 70.8, 111.4, 111.8, 113.3,
120.1, 120.7, 121.8, 126.5, 126.6, 127.1, 127.3, 127.3, 127.7, 127.9, 128.0,
128.3, 129.3, 135.4, 137.5, 138.9, 142.3, 143.1, 143.9, 144.0, 154.9,
Column chromatography on silica gel (5 g, MeOH/CHCl3, 1:40)
gave pure (S,S,S,S)-40 (21 mg, 86%) as colorless waxy solids: Rf¼0.32
156.4, 156.5; HRMS (FAB) m/z calcd for C92H103O6N [MþH]þ
(MeOH/CHCl3, 1:20); 1H NMR (400 MHz, CDCl3):
d
0.87 (t, J¼7.2 Hz,
20
1318.7858, found 1318.7848; [
a]
ꢁ46.2 (c 0.67, CHCl3).
12H, 4ꢂCH3), 1.17e1.25 (m, 32H, 16ꢂCH2), 1.46 (br s, 12H, 6ꢂCH2),
3.60e3.72 (m, 14H, NCH2, and 6ꢂOCH2), 6.47 (d, J¼8.1 Hz, 1H, ArH),
6.52e6.54 (m, 1H, ArH), 6.64e6.76 (m, 8H, ArH), 6.78e6.84 (m, 4H,
ArH), 6.91 (d, J¼7.4 Hz, 1H, ArH), 7.04e7.15 (m, 8H, ArH); 13C NMR
D
4.3.28. (S,S,S,S)-16,160-(Methylazanediyl)bis(methylene)bis(8,9-bis
(heptyloxy)tetrapheny len-1-ol) (38). Compound (S,S,S,S)-37
(20 mg, 0.015 mmol) was dissolved in a mixed solution of THF
(100 MHz, CDCl3): d 14.3, 22.7, 25.9, 25.9, 29.1, 29.4, 32.0, 67.8, 68.9,
(2 mL) and 37% HCHO solution (37
mL, 0.45 mmol) with stirring.
68.9, 68.9, 69.0, 111.2, 111.3, 111.5, 111.8, 112.6, 114.3, 120.4, 120.6,

9874
C.-K. Hau et al. / Tetrahedron 66 (2010) 9860e9874
120.7, 120.8, 122.0, 123.0, 123.7, 127.1, 127.1, 127.2, 127.4, 127.8, 127.9,
128.4, 128.9, 142.7, 143.5, 143.6, 143.6, 154.8, 156.3, 156.4, 156.5;
HRMS (ESI) m/z calcd for C84H101O7N [MþH]þ 1236.7651, found
124.2,125.7,127.0,127.1,127.2,127.5,127.9,128.2,128.9,140.4, 142.8,
143.1, 143.4, 143.8, 143.9, 144.9, 153.0, 155.0, 156.0, 156.3, 156.4,
156.5; HRMS (ESI) m/z calcd for C123H145O11N [MþH]þ 1814.0924,
20
1236.7612; [
a
]
20 ꢁ70.9 (c 0.80, CHCl3).
found 1814.0942; [
a
]
ꢁ48.6 (c 0.4, CHCl3).
D
D
4.3.31. (S,S,S,S)-16-(2-(8,9-Bis(heptyloxy)-16-hydroxytetraphenylen-
1-yloxy)ethoxy)-8,9-bis(heptyloxy)tetraphenylene-1-carbonitrile
(41). To a solution of compound (S,S,S,S)-32 (47 mg, 0.037 mmol) in
THF (2 mL), palladium black (10 mol %) was added. The mixture was
stirred under H2 for 3 h. The mixture was then filtered through
a Celite pad. The filtrate was dried over anhydrous Na2SO4 and
concentrated. The residue was purified by column chromatography
on silica gel (5 g, EtOAc/CH2Cl2/hexanes,1:1:6) to give pure (S,S,S,S)-
41 (31 mg, 70%) as colorless waxy solids: Rf¼0.3 (EtOAc/hexanes,
Acknowledgements
The work described in this project is supported by a grant from
the Research Grants Council of the Hong Kong Special Adminis-
trative Region, China (RGC Ref. No. CUHK 403909), as well as par-
tially by the Area of Excellence Scheme established under the
University Grants Committee of Hong Kong Special Administrative
Region, China (AoE/P-03/08).
1:4); 1H NMR (400 MHz, CDCl3):
d
0.87e0.92 (m, 12H, 4ꢂCH3),
Supplementary data
1.20e1.30 (m, 32H, 16ꢂCH2), 1.49e1.54 (m, 8H, 4ꢂCH2), 3.52 (br s,
2H, OCH2), 3.68e3.80 (m, 10H, 5ꢂOCH2), 4.86 (s, 1H, OH), 5.81e5.82
(m, 2H, ArH), 6.35e6.41 (m, 2H, ArH), 6.56e6.64 (m, 2H, ArH),
6.69e6.81 (m, 10H, ArH), 7.06e7.17 (m, 5H, ArH), 7.24e7.28 (m, 1H,
ArH), 7.42 (d, J¼7.3 Hz,1H, ArH), 7.51 (d, J¼7.6 Hz,1H, ArH); 13C NMR
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.10.064.
References and notes
(100 MHz, CDCl3):
d 14.3, 14.3, 22.7, 22.7, 25.9, 25.9, 29.1, 29.1, 29.1,
1. (a) Diels, O.; Alder, K. Justus Liebigs Ann. Chem. 1926, 450, 237e254; (b) Diels, O.;
Alder, K. Justus Liebigs Ann. Chem. 1927, 460, 98e122.
2. Corey, E. J. Angew. Chem., Int. Ed. 2002, 41, 1650e1667.
3. Riant, O.; Kagan, H. B. Tetrahedron Lett. 1989, 30, 7403e7406.
4. Riant, O.; Kagan, H. B.; Ricard, L. Tetrahedron 1994, 50, 4543e4554.
5. Okawura, H.; Nakamura, Y.; Iwagawa, T.; Nakatani, M. Chem. Lett. 1996, 193e194.
6. Shen, J.; Nguyen, T. T.; Goh, Y.-P.; Ye, W.; Fu, X.; Xu, J.; Tan, C.-H. J. Am. Chem. Soc.
2006, 128, 13692e13693.
29.1, 29.4, 29.4, 29.4, 31.9, 32.0, 66.7, 67.2, 68.7, 68.9, 110.9, 111.0,
111.2, 111.5, 111.6, 112.0, 113.5, 114.0, 118.8, 120.4, 120.6, 120.7, 120.7,
120.9,121.3,122.3,123.5,123.6,125.3,126.2,126.7,126.8,127.1,127.4,
127.9,127.9,128.2,128.4,128.5,129.3,130.0,131.2,132.8,140.9,141.8,
142.3,143.1,143.5,143.6,143.9,145.1,152.4,152.5,154.4,154.5,156.3,
156.4, 156.5, 156.6; HRMS (MADLI-TOF) m/z calcd for C79H89O7N
[MþNa]þ 1186.6531, found 1186.6581; [
a]
20 ꢁ84.9 (c 0.93, CHCl3).
7. Wang, Y.; Li, H.; Wang, Y.-Q.; Liu, Y.; Foxman, B. M.; Deng, L. J. Am. Chem. Soc.
2007, 129, 6364e6365.
D
8. For reviews, (a) Mak, T. C. W.; Wong, H. N. C. In Comprehensive Supramolecular
Chemistry; MacNicol, D. D., Toda, F., Bishop, P., Eds.; Pergamon: Oxford,1996; Vol.
6, pp 351e369; (b) Mak, T. C. W.; Wong, H. N. C. Top. Curr. Chem. 1987, 140,
141e164; (c) Hou, X.-L.; Huang, H.; Wong, H. N. C. Synlett 2005, 1073e1089; (d)
Rajca, A.; Rajca, S.; Pink, M.; Miyasaka, M. Synlett 2007, 1799e1822; (e) Marsella,
M. J.; Rahbarnia, S.; Wilmot, N. Org. Biomol. Chem. 2007, 5, 391e400; (f) Wang, C.;
Xi, Z. Chem. Commun. 2007, 5119e5133; (g) Hisaki, I.; Sonoda, M.; Tobe, Y. Eur. J.
Org. Chem. 2006, 833e847; (h) Huang, H.; Hau, C.-K.; Law, C. C. M.; Wong, H. N. C.
Org. Biomol. Chem. 2009, 7, 1249e1257.
9. Karle, I. L.; Brockway, L. O. J. Am. Chem. Soc. 1944, 66, 1974e1979.
10. Irngartinger, H.; Reibel, W. R. K. Acta Crystallogr. 1981, B37, 1724e1728.
11. Huang, H.; Stewart, S.; Gutmann, M.; Ohhara, T.; Niimura, N.; Li, Y.-X.; Wen, J.-F.;
Bau, R.; Wong, H. N. C. J. Org. Chem. 2009, 74, 359e369.
12. Wen, J.-F.; Hong, W.; Yuan, K.; Mak, T. C. W.; Wong, H. N. C. J. Org. Chem. 2003,
68, 8918e8931.
13. Peng, H.-Y.; Lam, C.-K.; Mak, T. C. W.; Cai, Z.; Ma, W.-T.; Li, Y.-X.; Wong, H. N. C.
J. Am. Chem. Soc. 2005, 127, 9603e9611.
14. Wu, A.-H.; Hau, C.-K.; Wong, H. N. C. Adv. Synth. Catal. 2007, 349, 601e608.
15. Hui, C. W.; Mak, T. C. W.; Wong, H. N. C. Tetrahedron 2004, 60, 3523e3532.
16. Lai, C. W.; Lam, C. K.; Lee, H. K.; Mak, T. C. W.; Wong, H. N. C. Org. Lett. 2003, 6,
823e826.
17. Perrin, D. D.; Armarego, W. L. F.; Perrin, D. R. Purification of Laboratory Chem-
icals; Butterworth-Heinemann: Oxford, 1997.
4.3.32. (S,S,S,S,S,S)-16-(2-(16-(2-(16-(Benzyloxy)-8,9-bis(heptyloxy)
tetraphenylen-1-yloxy)ethoxy)-8,9-bis(heptyloxy)tetraphenylen-1-
yloxy)ethoxy)-8,9-bis(heptyloxy)tetraphenylene-1-carbonitrile
(42). Compound (S,S,S,S,S,S)-42 was prepared from (S,S,S,S)-41
(37 mg, 0.03 mmol) and (S,S)-31 (79 mg, 0.10 mmol) by using the
same preparative method as that for compound (S,S,S,S)-32.
Column chromatography on silica gel (5 g, EtOAc/CH2Cl2/hexanes,
1:1:10)gavepure(S,S,S,S,S,S)-42(24 mg,43%)ascolorlesswaxysolids:
Rf¼0.51 (EtOAc/hexanes, 1:4); 1H NMR (400 MHz, CD2Cl2):
d 0.88 (t,
J¼7.1 Hz, 18H, 6ꢂCH3), 1.20e1.29 (m, 48H, 24ꢂCH2), 1.50 (br s, 12H,
6ꢂCH2), 3.74e3.83 (m, 20H, 10ꢂOCH2), 4.82 (s, 2H, OCH2), 6.51e6.60
(m, 4H, ArH), 6.61e6.71 (m, 4H, ArH), 6.74e6.88 (m, 14H, ArH),
6.99e7.01 (m, 2H, ArH), 7.07e7.22(m,14H, ArH), 7.31(dd,J¼7.7, 7.7 Hz,
1H, ArH), 7.44 (dd, J¼1.2, 7.7 Hz, 1H, ArH), 7.50 (dd, J¼1.2, 7.6 Hz, 1H,
ArH); 13C NMR (100 MHz, CD2Cl2):
d 13.6, 22.2, 25.4, 28.6, 28.9, 28.9,
31.5, 68.0, 68.2, 68.4, 70.1, 110.5, 111.0, 111.5, 112.0, 112.3, 112.7, 113.1,
118.0, 119.8, 120.1, 120.2, 120.9, 121.1, 121.2, 125.5, 126.0, 126.2, 126.4,
126.6, 126.7, 127.0, 127.0, 127.4, 127.5, 127.6, 127.7, 127.9, 129.3, 130.8,
132.1, 137.3, 140.1, 141.1, 141.7, 142.7, 142.8, 143.0, 143.2, 143.4, 143.5,
18. Prepared following the step (Wang, Z.Y. Synth. Commun.1990, 20, 1607e1610).1-
Isobutyl-1H-pyrrole-2,5-dione: 1H NMR (300 MHz, CDCl3):
d
0.82e0.93 (m, 8H,
CH3, and CH2),1.93e2.00 (m,1H, CH), 2.27e3.3 (m, 2H, NCH2), 6.66 (s, 2H, CH); 13
NMR (75 MHz, CDCl3): 20.0, 27.8, 45.2, 134.0, 171.1. 1-Cyclohexyl-1H-pyrrole-
2,5-dione: 1H NMR (400 MHz, CDCl3):
1.14e1.35 (m, 3H, CH2),1.63e1.66 (m, 3H,
CH2), 1.80e1.83 (m, 2H, CH2), 1.98e2.09 (m, 2H, CH2), 3.85e3.93 (m, 1H, NCH), 6.
61 (s, 2H, CH); 13C NMR (100 MHz, CDCl3):
25.2, 26.1, 30.1, 50.9, 134.0, 171.1.
C
154.9,155.2,155.5,155.8,155.9;HRMS(ESI)m/zcalcdforC126H141O11
N
d
[MþNa]þ 1868.0430, found 1868.0408; [
a]
D
20 ꢁ53.1 (c 0.79, CHCl3).
d
d
4.3.33. (S,S,S,S,S,S)-16-(2-(16-(2-(8,9-Bis(heptyloxy)-16-(pyrrolidin-
1-ylmethyl)tetraphenylen-1-yloxy)ethoxy)-8,9-bis(heptyloxy)tetra-
phenylen-1-yloxy)ethoxy)-8,9-bis(heptyloxy)tetraphenylen-1-ol
(43). Compound (S,S,S,S,S,S)-43 was prepared from (S,S,S,S,S,S)-42
(28 mg, 0.015 mmol) by using the same preparative method as that
for compound (S,S,S,S)-34 from compounds (S,S,S,S)-32.
19. Prepared following the step (Fielding, M.R.; Grigg, R.; Sridharan, V.; Thornton-
Pett, M.; Urch, C.J. Tetrahedron 2001, 57, 7737e7748). 1-(3-Nitrophenyl)-1H-
pyrrole-2,5-dione: 1H NMR (300 MHz, CDCl3):
d
6.93 (s, 2H, CH), 7.66 (dd, J¼8.1, 8.
1 Hz,1H, ArH), 7.77e7.80(m,1H, ArH), 8.21e8.25 (m,1H, ArH), 8.34(br s,1H, ArH);
13C NMR (75 MHz, CDCl3):
120.8, 122.5, 130.1, 131.4, 132.6, 134.6, 148.6, 168.7.
d
20. Prepared following the step (Kumar, D.N.; Sudhakar, N.; Rao, B.V.; Kishore, K.H.;
Murty, U.S. Tetrahedron Lett. 2006, 47, 771e774). 1,2-Bis(bromomethyl)benzene:
1H NMR (300 MHz, CDCl3): 4.67 (s, 4H, CH2), 7.28e7.39 (m, 4H, ArH); 13C NMR
d
Column chromatography on silica gel (2 g, MeOH/CHCl3, 1:40)
gave pure (S,S,S,S,S,S)-43 (9.5 mg, three-step: 35%) as colorless
waxy solids: Rf¼0.33 (MeOH/CHCl3, 1:20); 1H NMR (400 MHz,
(75 MHz, CDCl3):
d 30.1, 129.6, 131.2, 136.7.
21. Prepared following the step (Apelt, J.; Ligneau, X.; Pertz, H.H.; Arrang, J.-M.;
Ganellin, R.; Schwartz, J.-C.; Schunack, W.; Stark, H. J. Med. Chem. 2002, 45,
1128e1141). 1-(2-Chloroethyl)pyrrolidine: 1H NMR (300 MHz, CDCl3):
d
1.78e1.
81 (m, 4H, CH2), 2.56e2.65 (m, 4H, NCH2), 2.78e2.83 (m, 2H, NCH2), 3.56e3.61
(m, 2H, CH2Cl); 13C NMR (75 MHz, CDCl3):
23.6, 42.7, 54.3, 58.0.
CDCl3):
d
0.88 (t, J¼7.2 Hz, 18H, 6ꢂCH3), 1.17e1.25 (m, 48H,
24ꢂCH2), 1.46 (br s, 14H, 7ꢂCH2), 1.62 (br s, 6H, 3ꢂCH2), 3.53e3.74
(m, 22H, 10ꢂOCH2, and NCH2), 6.46e6.48 (m, 3H, ArH), 6.56e6.78
(m, 16H, ArH), 6.83e6.88 (m, 4H, ArH), 7.00e7.15 (m, 13H, ArH); 13C
d
22. Prepared following the steps (Page, P.C.B.; Buckley, B.R.; Blacker, A.J. Org. Lett.
2004, 6, 1543e1546 and Chattopadhyay, S.K.; Biswas, T.; Maity, S. Synlett 2006,
2211e2214). 1-(3-Chloropropyl)pyrrolidine: 1H NMR (300 MHz, CDCl3):
d 1.
NMR (100 MHz, CDCl3):
d 14.3, 22.7, 25.9, 29.1, 29.4, 32.0, 69.0, 70.7,
74e1.78 (m, 4H, CH2), 1.92e2.01 (m, 2H, CH2), 2.48e2.59 (m, 6H, NC H2), 3.59 (t,
111.3, 111.4, 111.6, 111.8, 113.9, 114.6, 116.8, 120.7, 120.8, 122.1, 122.6,
J¼6.6 Hz, 2H, CH2Cl); 13C NMR (75 MHz, CDCl3):
d 23.6, 32.1, 43.5, 53.7, 54.4.