Enantioselective synthesis of planar-chiral metacyclophanes through cationic Rh(I)/modified-BINAP-catalyzed inter- and intramolecular alkyne cyclotrimerizations

Article abstract of DOI:10.1016/j.tet.2007.10.085

We have achieved the first catalytic enantioselective synthesis of planar-chiral metacyclophanes by means of cationic Rh(I)/(S)-xyl-H₈-BINAP or (R)-H₈-BINAP complex-catalyzed inter- and intramolecular alkyne cyclotrimerizations. This highly enantioselective catalysis represents a versatile new method for the preparation of planar-chiral metacyclophanes.

Full text of DOI:10.1016/j.tet.2007.10.085

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 831e846
www.elsevier.com/locate/tet
Enantioselective synthesis of planar-chiral metacyclophanes through
cationic Rh(I)/modified-BINAP-catalyzed inter- and intramolecular
alkyne cyclotrimerizations
*
Ken Tanaka , Hiromi Sagae, Kazuki Toyoda, Masao Hirano
Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
Received 28 June 2007; accepted 1 October 2007
Available online 25 October 2007
Abstract
We have achieved the first catalytic enantioselective synthesis of planar-chiral metacyclophanes by means of cationic Rh(I)/(S )-xyl-H8-BI-
NAP or (R)-H8-BINAP complex-catalyzed inter- and intramolecular alkyne cyclotrimerizations. This highly enantioselective catalysis represents
a versatile new method for the preparation of planar-chiral metacyclophanes.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Alkyne; BINAP; Cyclotrimerization; Metacyclophanes; Rhodium
1. Introduction
might strictly limit the further development of the enantioselec-
tive [2þ2þ2] cycloadditions.3e5 We anticipated that Rh(I)/chi-
ral bisphosphine complexes, having a rigid chiral environment
and multiple free coordination sites, were potentially more suit-
able for enantioselective [2þ2þ2] cycloadditions than Ni(0)
complexes.
In 2001, a highly active transition-metal/bisphosphine com-
plex was discovered by Takeuchi and co-workers.6a They
found that a neutral Ir(I)/dppe [1,2-bis(diphenylphosphino)-
ethane] complex catalyzes [2þ2þ2] cycloadditions of
tethered diynes with monoalkynes in high yields.6 Furthermore
Transition-metal-catalyzed enantioselective cycloadditions
are powerful synthetic methods for the rapid construction of
chiral cyclic frameworks.1 Although a number of efficient
enantioselective cycloadditions have been developed, enantio-
selective [2þ2þ2] cycloadditions have been accomplished in
only a few examples at the time we started our project toward
cationic Rh(I)/bisphosphine complex-catalyzed [2þ2þ2] cy-
cloadditions in 2002.2e5 In 1994, Sato, Mori, and co-workers
reported an enantioselective desymmetrization of triynes lead-
ing to isoindoline and isoquinoline derivatives bearing a tertiary
in 2003, they reported that
(C6F5)2PCH2CH2P(C6F5)2 complex can also catalyze intermo-
a neutral Ir(I)/dppe or
stereocenter through a Ni(0)-catalyzed [2þ2þ2] cycloaddi-
3
tion. In 1999, Stara and co-workers reported a Ni(0)-catalyzed
lecular cross [2þ2þ2] cycloadditions.6b On the other hand,
´
enantioselective [2þ2þ2] cycloaddition of triynes leading to
a [6]helicene-like molecule.4 These pioneering works clearly
demonstrated the potential utility of enantioselective [2þ2þ2]
cycloadditions for the asymmetric synthesis of chiral aromatic
compounds. However, a lack of highly active transition-metal/
chiral bisphosphine complexes, other than Ni(0) complexes,
pioneering works by Muller7 and Grigg8 demonstrated that
¨
a neutral Rh(I) complex, such as RhCl(PPh3)3, can catalyze
an intramolecular [2þ2þ2] cycloaddition of tethered diynes
at elevated temperature,9 but such Rh(I) complexes generally
react with untethered terminal alkynes to give linear dimers.10
Independently, our research group discovered in 2003 that
cationic Rh(I)/BINAP [2,20-bis(diphenylphosphino)-1,10-bi-
naphthyl]-type bisphosphine complexes can catalyze both
inter- and intramolecular cross [2þ2þ2] cycloadditions of teth-
ered and untethered alkynes.11 The combination of a cationic
* Corresponding author.
E-mail address: tanaka-k@cc.tuat.ac.jp (K. Tanaka).
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.10.085

832
K. Tanaka et al. / Tetrahedron 64 (2008) 831e846
Rh(I) species and a BINAP-type bisphosphine ligand is essen-
tial for this reaction. A neutral Rh(I)/BINAP-type bisphosphine
complex, and both cationic and neutral iridium(I)/BINAP-type
bisphosphine complexes exhibit significantly decreased cata-
lytic activity.
chain of 3aa resides at one side of the aromatic ring, 3aa
can exhibit the planar-chirality.26 However, broad signals of
1
the benzylic protons of 3aa were observed by H NMR anal-
ysis at rt, which suggests rapid ring flipping.
Thus, the reaction of ether-linked terminal 1,9-diyne 1b and
dimethyl acetylenedicarboxylate (2b) was investigated to in-
crease the steric strain of the ansa chain. The reaction gave
the desired [6]ether metacyclophane 3bb with 23% ee, but
complete racemization of 3bb proceeded at rt over 48 h
(Scheme 2).
Fortunately, the cationic Rh(I)/BINAP-type bisphosphine
complexes can be applied to a wide variety of [2þ2þ2] cyclo-
additions of various unsaturated compounds including not only
alkynes11,12 but also isocyanates,13 isothiocyanates,14 carbon
disulfide,14 nitriles,15 aldehydes,16 ketones,16 and alkenes.17 We
have also developed a number of asymmetric variants of these
reactions to construct axial12a,cee,g,j,15b,16 and central12h,14,15a,17
chirality.18 The most striking feature of our cationic Rh(I)/BI-
NAP-type bisphosphine complex-catalyzed [2þ2þ2] cycload-
ditions is its applicability to cyclophane synthesis.11,12b,f
Maryanoff and co-workers have developed highly efficient syn-
theses of pyridinophanes by Co(I)-catalyzed [2þ2þ2] cycload-
ditions,19aed but synthesis of cyclophanes through alkyne
cyclotrimerization has some room for improvement.19a,e By
employing a cationic Rh(I)/H8-BINAP [2,20-bis(diphenylphos-
phino)-5,50,6,60,7,70,8,80-octahydro-1,10-binaphthyl]20 complex
as a catalyst, [6]e[21]carba-11,12b and polyethercyclophanes12f
can be synthesized in high yields through [2þ2þ2] cycloaddi-
tions of a,u-diynes with dialkyl acetylenedicarboxylates. In
this paper, we describe the first catalytic enantioselective
synthesis of planar-chiral metacyclophanes by means of cat-
ionic Rh(I)/(S )-xyl-H8-BINAP [2,20-bis{di(3,5-dimethylphe-
nyl)phosphino}-5,50,6,60,7,70,8,80-octahydro-1,10-binaphthyl]20
or (R)-H8-BINAP complex-catalyzed inter- and intramolecular
alkyne cyclotrimerizations.21
5 mol%
E
O
[Rh(cod)2]BF4/
E
O
O
(R)-H8-BINAP
+
E
CH2Cl2, rt,16h
(0.01M)
O
E
1b
3bb (meta) 17%, 23% ee
(rt, 24 h, 5% ee; 48 h, 0% ee)
4bb (ortho) 14%
1.0 equiv
2b E = CO2Me
Scheme 2. Synthesis of [6]metacyclophane 3bb through Rh(I)þ/(R)-H8-
BINAP-catalyzed intermolecular alkyne cyclotrimerization.
Consequently, we have gone onto employ internal diynes as
the substrates to avoid racemization of the products. The ex-
pected metacyclophanes would possess stable planar-chirality
since ring flipping would not be possible.27 We first examined
the reaction of methyl-substituted internal 1,9-diynes 1c with
2b in the presence of 5 mol % Rh(I)þ/(R)-H8-BINAP, which
led to a messy reaction (Table 1, entry 1). Although the reac-
tion of 1c with di-t-butyl acetylenedicarboxylate (2c) fur-
nished [6]orthocyclophane 4cc in 21% yield, the desired
planar-chiral [6]metacyclophane 3cc was obtained in <5%
yield with only 8% ee (entry 2). On the other hand, the use
of methoxymethyl-substituted internal 1,9-diyne 1d furnished
[6]metacyclophane 3dc with good ee (68% ee, entry 3).
After screening of various modified-BINAP ligands, we
were pleased to find that further improved ee (81% ee) could
be obtained by using (S )-xyl-H8-BINAP as a ligand (Table 2,
entry 2). The use of 10 mol % Rh catalyst and a slight excess
of 2c (1.5 equiv) increased the yield of cyclophanes (entry 3).
Interestingly, the enantioselectivity of this process is highly
dependent on the reaction concentration (0.01e0.2 M, entries
3e5). Although the yield of [6]metacyclophane 3dc
2. Results and discussion
2.1. Enantioselective synthesis of planar-chiral
metacyclophanes through cationic Rh(I)/modified-
BINAP-catalyzed intermolecular alkyne
cyclotrimerization
It is well established that certain cyclophanes having short
ansa chains exhibit planar-chirality due to the restricted rota-
tion of the aromatic ring.22 In spite of the potential utility of
the planar-chiral cyclophanes in areas of asymmetric synthe-
sis, hosteguest chemistry, and material science, the existing
methods for their synthesis are based exclusively on the opti-
cal resolution of racemic compounds and methods for straight-
forward enantioselective synthesis have not been reported to
date.23e25 We have reported the one-step synthesis of [6]car-
bametacyclophane 3aa from 1,9-decadiyne (1a) and diethyl
acetylenedicarboxylate (2a) (Scheme 1).11 At rt, if the ansa
Table 1
Effect of substituents on yield and enantioselectivity of [6]metacyclophanes 3
5 mol%
R
E
[Rh(cod)2]BF4/
O
E
O
O
(R)-H8-BINAP
+
E
R
CH2Cl2,rt
(0.01M)
O
R
E
R
4 (ortho-isomer)
3 (meta-isomer)
5 (para-isomer)
E
5 mol% [Rh(cod) ]BF /
4
2
(R)-H8-BINAP
E
E
Entry
1 (R)
2 (E )
Yielda (%)
ee (%)
+
CH2Cl2,rt,1h
(0.005 M)
4
3
5
3
E
1a
3aa 50%
achiral
1.0 equiv
1
2
3
a
1c (H)
1c (H)
1d (OMe)
2b (CO2Me)
2c (CO2t-Bu)
2c (CO2t-Bu)
d
21
7
d
<5
7
d
0
d
8
2a E = CO2Et
0
68
Scheme 1. Synthesis of [6]metacyclophane 3aa through Rh(I)þ/(R)-H8-
BINAP-catalyzed intermolecular alkyne cyclotrimerization.
Isolated yield.

K. Tanaka et al. / Tetrahedron 64 (2008) 831e846
833
Table 2
Effect of ligands and concentration on yield and enantioselectivity of [6]meta-
cyclophane 3dc
Figure 1 depicts possible intermediates AeC for the forma-
tion of metacyclophanes 3. At high concentration, the forma-
tion of rhodacyclopentadienes A or B, through intermolecular
coupling of the electron-deficient monoalkyne 2c and the elec-
tron-rich diynes 1, may be predominant, which provides pla-
nar-chiral metacyclophanes 3 with high enantioselectivity,
due to the steric interaction between the chiral ligand and
the tethering chains within 1. On the other hand, the formation
of rhodacyclopentadienes C, through intramolecular coupling
of the electron-rich diynes 1, may be increased at low concen-
tration,12f which decreases the ee values of 3, due to the small
steric interaction between the chiral ligand and the tethering
chains within 1.
5 mol%
[Rh(cod)2]BF4/
Ligand
OMe
+
E
O
E
O
O
E
OMe
CH2Cl2,rt
O
MeO
E
OMe
4 (ortho-isomer)
3 (meta-isomer)
5 (para-isomer)
1d
2c E = CO2t-Bu
Entry
Ligand
Concn (M)
Yielda (%)
ee (%)
4
3
5
3
1
(R)-H8-BINAP
0.01
0.01
0.01
0.05
0.2
7
7
7
9
0
0
0
0
0
68
81
82
89
95
2
(S )-Xyl-H8-BINAP
(S )-Xyl-H8-BINAP
(S )-Xyl-H8-BINAP
(S )-Xyl-H8-BINAP
3b
4b
5b
a
14
8
11
10
9
2.2. Enantioselective synthesis of planar-chiral
metacyclophanes through cationic Rh(I)/modified-
BINAP-catalyzed intramolecular alkyne
cyclotrimerization
<5
Isolated yield.
Catalyst: 10 mol %.
b
decreased, the highest ee of 3dc was obtained at the 0.2 M
concentration (95% ee, entry 5).
Although planar-chiral metacyclophanes can be synthe-
sized with high enantioselectivity through intermolecular al-
kyne cyclotrimerization, their yields are not satisfactory.
Therefore, we designed the intramolecular cyclotrimerization
A series of internal diynes 1dem was subjected to the
above optimal reaction conditions as shown in Table 3. Al-
though the formation of [8]metacyclophane 3fc was inefficient
(entry 3), the desired planar-chiral [6], [7], and [9]metacyclo-
phanes were obtained as major isomers with high ee values
(entries 1, 2, 4, and 8). On the other hand, although the rea-
ctions of diynes 1hej and 1l with 2c proceeded to give the
desired planar-chiral [10]e[12]metacyclophanes, their ee values
were lower than those of [6], [7], and [9]metacyclophanes (en-
tries 5e7 and 9). Planar-chiral [15]metacyclophane 3mc could
not be obtained by the reaction of diyne 1m with 2c at all (en-
try 10).28 In these reactions, the diynes 1 were consumed and
a complex mixture not containing 3e5 was generated.
E
E
OMe
+
Rh
OMe
MeO
MeO
+
MeO
+
Rh
E
Rh
E
MeO
A
B
C
E
E
Figure 1. Possible intermediates AeC for the formation of metacyclophanes.
Table 3
Enantioselective synthesis of planar-chiral metacyclophanes 3 through Rh(I)þ/(S )-xyl-H8-BINAP-catalyzed intermolecular alkyne cyclotrimerization
OMe
10 mol%
O
O
O
E
[Rh(cod)2]BF4/
(S)-xyl-H8-BINAP
E
Z
+
Z
E
OMe
CH2Cl2,rt
O
E
MeO
OMe
4 (ortho-isomer)
3 (meta-isomer)
5 (para-isomer)
2c E = CO2t-Bu
1
Entry
1 (Z )
Concn (M)
Yielda (%)
ee (%)
4
3
5
3
1
1d (d)
1e (CH2)
0.2
0.2
<5
12
0
9
0
0
95
98
d
92
52
56
62
92
80
d
2
12
<5
15
3
1f (CH2CH2)
1g (CH2CH2CH2)
1h (CH2CH2CH2CH2)
0.2
<5
5
4
0.01
0.01
0.01
0.01
0.2
0
5b
6b
7b
8
0
27
0
5c
1i (CH2CH2CH2CH2CH2)
11c
7c
8
9c
1j (CH2CH2CH2CH2CH2CH2)
1k (CH2OCH2)
1l (CH2OCH2CH2OCH2)
7c
11
<5
0
9b
10b
a
0.01
0.01
18
0
6
0
<5
<5
1m (CH2OCH2CH2OCH2CH2OCH2)
Isolated yield.
Ligand: (R)-H8-BINAP.
Isolated as a mixture of isomers.
b
c

834
K. Tanaka et al. / Tetrahedron 64 (2008) 831e846
of triynes bearing substituents at two alkyne termini, which
could furnish either achiral orthocyclophanes or chiral metacy-
clophanes, but the formation of achiral paracyclophanes could
be eliminated (Scheme 3). Oshima and co-workers realized
this type of macrocyclization using reactive triynes bearing
hydrogens at two alkyne termini in an aqueouseorganic bi-
phasic system, which diminished the formation of undesired
intermolecular reaction products.19e However, only [9] and
[10]metacyclophanes were obtained as minor products along
with the major orthocyclophanes, whilst [7] and [8]metacyclo-
phanes possessing short ansa chains were not obtained.19e,29
Furthermore, the intramolecular cyclotrimerization of less re-
active triynes bearing substituents at two alkyne termini has
not been realized to date.
Table 5. [7]e[10]Metacyclophanes 8a, 8cee, and 8h were ob-
tained in 10e29% yields with high ee values (91 to >98% ees,
entries 2e5 and 8). However, [12]metacyclophanes 8g and 8i
were obtained with low to moderate ee values (32 and 68%
ees, entries 7 and 9), and [6], [11], and [15]metacyclophanes
were not obtained at all (entries 1, 6, and 10). The absolute
configuration of [9]metacyclophane (ꢀ)-8d was determined
to be R by X-ray crystallographic analysis (Fig. 2).
Next, we examined the reactions of a series of triynes 9aej,
bearing an ether-linked 1,6-diyne moiety, with 5% Rh(I)þ/(R)-
H8-BINAP at rt as shown in Table 6. [7]e[10]Metacyclo-
phanes 11bee and 11h were obtained in improved yields
with high ee values (21e33% yields, 88 to >94% ees, entries
2e5 and 8). [11] and [12]Metacyclophanes 11f and 11g were
also obtained although lower ee values were observed (74 and
58% ees, entries 6 and 7). However, [6], [12], and [15]metapo-
lyethercyclophanes 11a, 11i, and 11j were not obtained at all
(entries 1, 9, and 10). Increasing the catalyst loading to
10 mol % did not improve the yields of cyclophanes signifi-
cantly (entry 4). In general, triynes bearing an ether-linked
1,6-diyne moiety furnished metacyclophanes in higher yields
than those bearing an ester-linked 1,6-diyne moiety, but enan-
tioselectivities of the former were lower than those of the lat-
ter. In the reactions shown in both Tables 5 and 6, the triynes 6
and 9 were consumed and a complex mixture not containing 7,
8, 10, and 11 was generated.
R2
R2
R1
M
R1
R2
–M
–M
achiral
M
R1
R2
R1
R2
R1
M
chiral (R2 ° H)
Scheme 3. Enantioselective synthesis of planar-chiral metacyclophanes
through intramolecular alkyne cyclotrimerization.
A possible mechanism for the highly enantioselective for-
mation of (R)-8d is shown in Scheme 4. Enantioselectivity
would be determined by preferential formation of intermediate
D, due to the high reactivity of the 1,6-diyne moiety to the
We first examined the reaction of methyl and methoxy-
methyl-substituted triyne 6a, bearing an ester-linked 1,6-diyne
moiety, with 5% Rh(I)þ/(R)-H8-BINAP at rt, which furnished
the desired [7]metacyclophane 8a with excellent enantioselec-
tivity (>98% ee), although 8a was obtained as a minor isomer
(Table 4, entry 1). The use of (R)-Segphos [(4,40-bi-1,3-benzo-
dioxole)-5,50-diylbis(diphenylphosphine)],30 (R)-BINAP, or (R)-
xyl-BINAP as a ligand slightly or considerably decreased the ee
values of the desired [7]metacyclophane 8a (entries 2e4).
Thus, the reactions of a series of triynes 6aej with 5%
Rh(I)þ/(R)-H8-BINAP at rt were investigated as shown in
Table 5
Enantioselective synthesis of planar-chiral metacyclophanes through Rh(I)þ/
(R)-H8-BINAP-catalyzed intramolecular alkyne cyclotrimerization of 6
O
Me
5 mol%
[Rh(cod)2]BF4/
(R)-H8-BINAP
O
O
Me
O
Z
O
CH2Cl2,rt
16 h
(0.01M)
Z
O
O
MeO
O
7 (ortho)
8 (meta)
OMe
6
Table 4
Effect of ligands on yield and enantioselectivity of [7]metacyclophane
Entry
6 (Z )
Yielda (%)
ee (%)
O
7
8
8
Me
1
2
3
4
5
6
7
8
9
10
a
6b (d)
6a (CH2)
53
31
0
d
O
O
5% [Rh(cod)2]BF4/
Ligand
Me
10
13
10
13
0
>98
>98
98
O
O
6c (CH2CH2)
6d (CH2CH2CH2)
6e (CH2CH2CH2CH2)
15
40
CH2Cl2, rt, 16 h
(0.01 M)
O
O
MeO
23
24
91
O
7a (ortho)
8a (meta)
OMe
6f (CH2CH2CH2CH2CH2)
6g (CH2CH2CH2CH2CH2CH2)
6h (CH2OCH2)
d
6a
29
18
32
29b
55
29b,c
24
>98
68
Entry
Ligand
Yielda (%)
ee (%)
6i (CH2OCH2CH2OCH2)
6j (CH2OCH2CH2OCH2CH2OCH2)
7a
8a
8a
(ca. 40)d
0
d
1
2
3
4
a
(R)-H8-BINAP
(R)-Segphos
31
37
25
13
10
7
>98
26
Isolated yield of a pure regioisomer.
Isolated as a mixture of 7h and 8h.
The corresponding chiral diol was isolated in pure form by treating 8h with
b
c
(R)-BINAP
9
15
91
83
(R)-Xyl-BINAP
LiAlH4.
d
Isolated yield.
Product 7j could not be isolated in a pure form (ca. 90% purity).

K. Tanaka et al. / Tetrahedron 64 (2008) 831e846
835
3. Conclusions
In conclusion, we have demonstrated that cationic rho-
dium(I)/(S )-xyl-H8-BINAP or (R)-H8-BINAP complex-cata-
lyzed inter- and intramolecular alkyne cyclotrimerizations
represent versatile new methods for the enantioselective
synthesis of planar-chiral metacyclophanes. Applications of cat-
ionic rhodium(I)/modified-BINAP complex-catalyzed [2þ2þ2]
cycloadditions to the synthesis of a variety of planar-chiral
cyclophanes including paracyclophanes will be reported in
due course.
Figure 2. ORTEP diagram of (R)-(ꢀ)-8d.
4. Experimental
Table 6
Enantioselective synthesis of planar-chiral metacyclophanes through Rh(I)þ/
4.1. General
(R)-H8-BINAP-catalyzed intramolecular alkyne cyclotrimerization of 9
Me
5 mol%
O
1H NMR spectra were recorded on 300 MHz (JEOL AL
300). 13C NMR spectra were obtained with complete proton
decoupling on 75 MHz (JEOL AL 300). HRMS data were ob-
tained on a JEOL JMS-T100LC. Infrared spectra were ob-
tained on a JASCO A-302. All reactions were carried out
under an atmosphere of argon or nitrogen in oven-dried glass-
ware with magnetic stirring.
O
[Rh(cod)2]BF4/
(R)-H8-BINAP
Me
O
O
Z
CH2Cl2, rt
16 h
(0.01 M)
Z
O
O
MeO
10 (ortho)
11 (meta)
OMe
9
Entry 9 (Z )
Yielda (%)
ee (%)
10
11
11
4.2. Materials
1
2
3
4
5b
6
7
8b
9
10
a
9a (d)
9b (CH2)
9c (CH2CH2)
87
37
35
0
25
33
d
90
93
Anhydrous CH2Cl2 (No. 27,099-7) was obtained from Al-
drich and used as received. Solvents for the synthesis of sub-
9d (CH2CH2CH2)
9e (CH2CH2CH2CH2)
15 (17c) 21 (24c) 94 (94c)
23
25
27
55d
0
30
22
19
30d
0
93
74
58
88
d
d
˚
strates were dried over molecular sieves 4 A prior to use.
9f (CH2CH2CH2CH2CH2)
9g (CH2CH2CH2CH2CH2CH2)
9h (CH2OCH2)
Diyne 1b was prepared according to a literature procedure.31
All other reagents were obtained from commercial sources
and used as received.
9i (CH2OCH2CH2OCH2)
9j (CH2OCH2CH2OCH2CH2OCH2) 90
0
4.3. Synthesis of a,u-diynes 1
Isolated yield of a pure regioisomer.
Reaction time: 40 h.
Catalyst: 10 mol %.
b
c
4.3.1. 1-(2-(But-2-ynyloxy)ethoxy)but-2-yne 1c
d
Isolated as a mixture of 10h and 11h.
A mixture of KOH (1.99 g, 35.4 mmol), ethylene glycol
(1.00 g, 16.1 mmol), and DMSO (80 mL) was stirred at rt for
2 h. To this mixture was added 1-bromo-2-butyne (4.7 g,
35.4 mmol) at 0 ꢁC, and the resulting mixture was stirred at rt
for 16 h. The reaction was quenched by the addition of water
and extracted with ether. The organic layer was washed with
brine, dried over Na2SO4, and concentrated. The residue was
purified by silica gel column chromatography (hexane/
EtOAc¼10:1) to afford 1c (1.36 g, 8.17 mmol, 51% yield) as
a pale yellow oil. IR (neat) 2850, 2200, 1350, 1140, 1090,
Rh(I)þ/H8-BINAP complex, the coordination of the terminal
methoxy group to the cationic rhodium, and the steric interac-
tion between the ansa chain of 6d and the PPh2 groups of
(R)-H8-BINAP.
O
O
Ph
Me
MeO
Ph
1
O
1040 cmꢀ1; H NMR (CDCl3, 300 MHz) d 4.16 (q, J¼2.4 Hz,
+
P
P
Rh(I)
+
Rh
Ph
4H), 3.69 (s, 4H), 1.85 (t, J¼2.4 Hz, 6H); 13C NMR (CDCl3,
75 MHz) d 82.5, 74.9, 68.6, 58.8, 3.5; HRMS (ESI) calcd for
C10H14O2Na [MþNa]þ 189.0892, found 189.0881.
Me
Z
Ph
D
O
O
OMe
O
6d Z = CH2CH2CH2
+
–Rh(I)
4.3.2. Representative procedure for synthesis of internal
a,u-diynes 1dem: synthesis of diyne 1d
n-BuLi (1.6 M in hexane, 18.1 mL, 29.0 mmol) was added
over 15 min to a cooled (ꢀ40 ꢁC) solution of 1b31 (2.00 g,
14.5 mmol) in ether (25 mL). To this mixture was added a so-
lution of bromomethyl methyl ether (2.90 g, 36.3 mmol) in
O
Me
O
O
Z
O
MeO
(R)-8d
Scheme 4. Possible mechanism for the formation of (R)-8d.

836
K. Tanaka et al. / Tetrahedron 64 (2008) 831e846
Et2O (10 mL), and the resulting mixture was stirred at rt for
1 h. The reaction was quenched by the addition of ice water
and extracted with Et2O. The organic layer was washed with
brine, dried over Na2SO4, and concentrated. The residue was
purified by silica gel column chromatography (hexane/
EtOAc¼10:1) to afford 1d (2.05 g, 62% yield) as a pale yellow
1H NMR (CDCl3, 300 MHz) d 4.27 (t, J¼1.8 Hz, 4H), 4.14
(t, J¼1.8 Hz, 4H), 3.72 (s, 4H), 3.39 (s, 6H); 13C NMR
(CDCl3, 75 MHz) d 82.3, 82.2, 68.7, 59.8, 58.6, 57.5;
HRMS (ESI) calcd for C12H18O4Na [MþNa]þ 249.1102,
found 249.1120.
4.3.8. Diyne 1j
Pale yellow oil; IR (neat) 2850, 1440, 1340, 1180, 1090,
1
900 cmꢀ1; H NMR (CDCl3, 300 MHz) d 4.18 (t, J¼1.8 Hz,
4H), 4.14 (t, J¼1.8 Hz, 4H), 3.50 (t, J¼6.6 Hz, 4H), 3.39
(s, 6H), 1.65e1.50 (m, 4H), 1.40e1.25 (m, 8H); 13C NMR
(CDCl3, 75 MHz) d 82.7, 81.8, 70.2, 59.9, 58.2, 57.6, 29.4,
29.2, 26.0; HRMS (ESI) calcd for C18H30O4Na [MþNa]þ
333.2042, found 333.2043.
oil. IR (neat) 2850, 1440, 1340, 1250, 1180, 1090, 900 cmꢀ1
;
4.3.9. Diyne 1k
Colorless oil; IR (neat) 2900, 1440, 1340, 1180, 1080,
1
900 cmꢀ1; H NMR (CDCl3, 300 MHz) d 4.26 (t, J¼1.8 Hz,
4H), 4.14 (t, J¼1.8 Hz, 4H), 3.74e3.64 (m, 8H), 3.38 (s,
6H); 13C NMR (CDCl3, 75 MHz) d 82.3, 82.2, 70.4, 69.0,
59.8, 58.6, 57.5; HRMS (ESI) calcd for C14H22O5Na
[MþNa]þ 293.1365, found 293.1366.
4.3.3. Diyne 1e
Pale yellow oil; IR (neat) 3250, 2900, 1440, 1340, 1080,
1
900 cmꢀ1; H NMR (CDCl3, 300 MHz) d 4.19 (t, J¼1.5 Hz,
4H), 4.15 (t, J¼1.5 Hz, 4H), 3.60 (t, J¼6.3 Hz, 4H), 3.39 (s,
6H), 1.90 (quint, J¼6.3 Hz, 2 H); 13C NMR (CDCl3, 75 MHz)
d 82.6, 81.9, 66.9, 59.8, 58.3, 57.6, 29.7; HRMS (ESI) calcd
for C13H20O4Na [MþNa]þ 263.1259, found 263.1241.
4.3.10. Diyne 1l
Pale yellow oil; IR (neat) 2850, 1440, 1340, 1100,
1
900 cmꢀ1; H NMR (CDCl3, 300 MHz) d 4.26 (t, J¼1.8 Hz,
4H), 4.14 (t, J¼1.8 Hz, 4H), 3.70e3.66 (m, 8H), 3.67 (s,
4H), 3.38 (s, 6H); 13C NMR (CDCl3, 75 MHz) d 82.3, 82.2,
70.5, 70.4, 69.0, 59.8, 58.6, 57.6; HRMS (ESI) calcd for
C16H26O6Na [MþNa]þ 337.1627, found 337.1624.
4.3.4. Diyne 1f
Colorless oil; IR (neat) 3250, 2850, 1440, 1340, 1180, 1080,
1
900 cmꢀ1; H NMR (CDCl3, 300 MHz) d 4.19 (t, J¼1.5 Hz,
4H), 4.14 (t, J¼1.5 Hz, 4H), 3.57e3.50 (m, 4H), 3.39 (s, 6H),
1.68 (quint, J¼2.7 Hz, 4H); 13C NMR (CDCl3, 75 MHz)
d 82.7, 81.8, 69.7, 59.8, 58.2, 57.6, 26.1; HRMS (ESI) calcd
for C14H22O4Na [MþNa]þ 277.1416, found 277.1429.
4.3.11. Diyne 1m
Pale yellow oil; IR (neat) 2850, 1440, 1340, 1100,
1
900 cmꢀ1; H NMR (CDCl3, 300 MHz) d 4.26 (t, J¼1.8 Hz,
4H), 4.14 (t, J¼1.8 Hz, 4H), 3.71e3.64 (m, 8H), 3.67 (s,
8H), 3.38 (s, 6H); 13C NMR (CDCl3, 75 MHz) d 82.4, 82.2,
70.6, 70.5, 70.4, 69.1, 59.9, 58.6, 57.6; HRMS (ESI) calcd
for C18H30O7Na [MþNa]þ 381.1889, found 381.1893.
4.3.5. Diyne 1g
Colorless oil; IR (neat) 2900, 1440, 1340, 1180, 1080,
1
900 cmꢀ1; H NMR (CDCl3, 300 MHz) d 4.18 (t, J¼1.8 Hz,
4.4. Representative procedure for rhodium-catalyzed
intermolecular alkyne cyclotrimerization (Table 3, entry 2)
4H), 4.14 (t, J¼1.8 Hz, 4H), 3.51 (t, J¼6.6 Hz, 4H), 3.39 (s,
6H), 1.63 (quint, J¼6.6 Hz, 4H), 1.50e1.36 (m, 2H); 13C
NMR (CDCl3, 75 MHz) d 82.7, 81.8, 70.0, 59.9, 58.2, 57.6,
29.2, 22.7; HRMS (ESI) calcd for C15H24O4Na [MþNa]þ
291.1572, found 291.1577.
(S )-Xyl-H8-BINAP (22.3 mg, 0.03 mmol) and [Rh(cod)2]-
BF4 (12.2 mg, 0.03 mmol) were dissolved in CH2Cl2
(3.0 mL) and the mixture was stirred at rt for 5 min. H2 was
introduced to the resulting solution in a Schlenk tube. After
stirring at rt for 0.5 h, the resulting mixture was concentrated
to dryness. To this was added a solution of di-tert-butyl acetyl-
enedicarboxylate (2c, 101.8 mg, 0.45 mmol) in CH2Cl2
(0.5 mL) at rt. To this solution was added a solution of diyne
1e (72.1 mg, 0.30 mmol) in CH2Cl2 (1.0 mL) at rt. The mix-
ture was stirred at rt for 48 h. The resulting solution was con-
centrated and purified by preparative TLC (pure 4ec and crude
3ec were obtained by hexane/triethylamine¼5:1, and 3ec was
then obtained pure by hexane/ethyl acetate¼2:1), to furnish
[7]metacyclophane (ꢀ)-3ec (16.8 mg, 0.036 mmol, 12% yield,
98% ee) as a colorless oil and [7]orthocyclophane 4ec
(17.0 mg, 0.0364 mmol, 12% yield) as a colorless solid.
4.3.6. Diyne 1h
Pale yellow oil; IR (neat) 2850, 1440, 1340, 1180, 1080,
1
900 cmꢀ1; H NMR (CDCl3, 300 MHz) d 4.18 (t, J¼1.8 Hz,
4H), 4.14 (t, J¼1.8 Hz, 4H), 3.50 (t, J¼6.6 Hz, 4H), 3.39 (s,
6H), 1.66e1.51 (m, 4H), 1.42e1.33 (m, 4H); 13C NMR
(CDCl3, 75 MHz) d 82.7, 81.8, 70.1, 59.9, 58.2, 57.6, 29.4,
25.9; HRMS (ESI) calcd for C16H26O4Na [MþNa]þ
305.1729, found 305.1714.
4.3.7. Diyne 1i
Pale yellow oil; IR (neat) 2850, 1440, 1340, 1180, 1090,
1
900 cmꢀ1; H NMR (CDCl3, 300 MHz) d 4.18 (t, J¼1.8 Hz,
4H), 4.14 (t, J¼1.8 Hz, 4H), 3.50 (t, J¼6.6 Hz, 4H), 3.39 (s,
6H), 1.65e1.50 (m, 4H), 1.40e1.30 (m, 6H); 13C NMR
(CDCl3, 75 MHz) d 82.7, 81.8, 70.2, 59.9, 58.2, 57.6, 29.4,
29.2, 26.0; HRMS (ESI) calcd for C17H28O4Na [MþNa]þ
319.1885, found 319.1910.
4.4.1. (ꢀ)-[7]Metacyclophane (ꢀ)-3ec
[a]2D5 ꢀ39.3 (c 0.440, CHCl3, 98% ee); IR (neat) 2900,
1710, 1440, 1370, 1300, 1150, 1110, 1070, 850 cmꢀ1 1H
;
NMR (CDCl3, 300 MHz) d 5.19 (d, J¼13.8 Hz, 1H), 5.07

K. Tanaka et al. / Tetrahedron 64 (2008) 831e846
837
(d, J¼13.8 Hz, 1H), 5.03 (d, J¼9.6 Hz, 1H), 5.00 (d, J¼
9.6 Hz, 1H), 4.61 (d, J¼12.6 Hz, 1H), 4.56 (d, J¼12.6 Hz,
1H), 4.52 (d, J¼13.8 Hz, 1H), 4.37 (d, J¼13.8 Hz, 1H),
3.70e3.55 (m, 2H), 3.36 (s, 3H), 3.31 (s, 3H), 2.35e2.15
(m, 2H), 1.63e1.50 (m, 1H), 1.59 (s, 9H), 1.58 (s, 9H),
1.08e0.92 (m, 1H); 13C NMR (CDCl3, 100 MHz) d 167.0,
166.1, 146.8, 143.4, 139.9, 134.3, 132.5, 131.0, 82.6, 82.4,
73.2, 69.0, 68.8, 68.7, 68.6, 67.3, 58.7, 57.8, 32.9, 28.2,
28.0; HRMS (ESI) calcd for C25H38O8Na [MþNa]þ
489.2464, found 489.2478. CHIRALPAK AD, hexane/2-
PrOH¼95:5, 1.0 mL/min, retention times: 9.8 min (minor iso-
mer) and 12.6 min (major isomer).
4.4.6. [6]Orthocyclophane 4cc (Table 1, entry 2)
Colorless solid; mp 81.2e82.0 ꢁC; IR (KBr) 2900, 1710,
1360, 1300, 1220, 1150, 840 cmꢀ1 1H NMR (CDCl3,
300 MHz) d 4.95 (s, 4H), 3.76 (s, 4H), 2.35 (s, 6H), 1.60 (s,
18H); 13C NMR (CDCl3, 100 MHz) d 168.0, 136.8, 133.8,
131.9, 82.6, 69.7, 65.6, 28.2, 16.2; HRMS (ESI) calcd for
C22H32O6Na [MþNa]þ 415.2097, found 415.2091.
;
4.4.7. [6]Orthocyclophane 4dc (Table 1, entry 3)
Colorless solid; mp 97.8e98.7 ꢁC; IR (KBr) 2900, 1710,
1
1360, 1300, 1220, 1160, 1100, 840 cmꢀ1; H NMR (CDCl3,
300 MHz) d 5.05 (s, 4H), 4.57 (s, 4H), 3.77 (s, 4H), 3.34 (s,
6H), 1.60 (s, 18H); 13C NMR (CDCl3, 75 MHz) d 167.2,
138.8, 134.8, 134.2, 83.0, 69.8, 68.4, 64.6, 58.2, 28.2; HRMS
(ESI) calcd for C24H36O8Na [MþNa]þ 475.2308, found
475.2330.
4.4.2. [7]Orthocyclophane 4ec
Mp 76.4e77.1 ꢁC; IR (KBr) 2900, 1710, 1360, 1300, 1160,
1
1100 cmꢀ1; H NMR (CDCl3, 400 MHz) d 4.96 (s, 4H), 4.57
(s, 4H), 3.66 (t, J¼5.6 Hz, 4H), 3.31 (s, 6H), 1.76 (quint,
J¼5.6 Hz, 2H), 1.59 (s, 18H); 13C NMR (CDCl3, 75 MHz)
d 183.3, 139.5, 134.5, 82.8, 77.2, 68.5, 67.8, 67.4, 57.9,
28.1; HRMS (ESI) calcd for C25H38O8Na [MþNa]þ
489.2464, found 489.2482.
4.4.8. (ꢀ)-[6]Metacyclophane (ꢀ)-3dc (Table 3, entry 1)
Colorless solid; mp 76.8e77.4 ꢁC; [a]D25 ꢀ41.8 (c 0.190,
CHCl3, 95% ee); IR (KBr) 2900, 1700, 1360, 1290, 1150,
1
1100, 1040, 840 cmꢀ1; H NMR (CDCl3, 300 MHz) d 5.08
(d, J¼13.2 Hz, 1H), 5.00 (d, J¼7.2 Hz, 1H), 4.97 (d, J¼
7.2 Hz, 1H), 4.94 (d, J¼13.2 Hz, 1H), 4.68 (d, J¼13.2 Hz,
1H), 4.67 (d, J¼12.9 Hz, 1H), 4.60 (d, J¼12.9 Hz, 1H), 4.47
(d, J¼13.2 Hz, 1H), 3.52e3.35 (m, 2H), 3.34 (s, 3H), 3.33
(s, 3H), 2.88e2.70 (m, 1H), 2.22e2.03 (m, 1H), 1.58 (s,
9H), 1.56 (s, 9H); 13C NMR (CDCl3, 75 MHz) d 166.9,
165.5, 148.9, 143.8, 141.6, 134.2, 132.6, 131.5, 82.5, 82.3,
72.8, 70.6, 69.9, 69.3, 68.6, 68.4, 58.8, 58.1, 28.2, 28.0;
HRMS (ESI) calcd for C24H36O8Na [MþNa]þ 475.2308,
found 475.2333. CHIRALPAK AD, hexane/2-PrOH¼95:5,
1.0 mL/min, retention times: 16.1 min (minor isomer) and
24.2 min (major isomer).
4.4.3. [6]Metacyclophane 3bb (Scheme 2)
Colorless solid; mp 85.6e86.0 ꢁC; IR (KBr) 2900, 1720,
1430, 1280, 1200, 1140, 1080, 1030, 840, 780 cmꢀ1 1H
;
NMR (CDCl3, 400 MHz) d 8.05 (s, 1H), 7.72 (s, 1H), 4.60e
5.00 (m, 2H), 4.15e4.60 (m, 2H), 3.903 (s, 3H), 3.901 (s,
3H), 3.50e3.72 (m, 4H); 13C NMR (CDCl3, 75 MHz)
d 167.4, 166.6, 140.7, 131.4, 72.4 (br), 52.8, 52.7; HRMS
(ESI) calcd for C14H16O6 [MþNa]þ 303.0845, found
303.0863; CHIRALPAK AD, hexane/2-PrOH¼80:20,
0.8 mL/min, retention times: 11.0 min (minor isomer) and
15.3 min (major isomer).
4.4.9. (þ)-[9]Metacyclophane (þ)-3gc (Table 3, entry 4)
Colorless solid; mp 110.2e110.8 ꢁC, [a]D25 þ12.0 (c 0.470,
CHCl3, 92% ee); IR (KBr) 2900, 1710, 1440, 1360, 1300,
4.4.4. [6]Orthocyclophane 4bb (Scheme 2)
Colorless solid; mp 33.7e35.6 ꢁC; IR (KBr) 2900, 1720,
1
1260, 1100, 1020, 890 cmꢀ1; H NMR (CDCl3, 300 MHz)
1
1250, 1150, 1080, 840 cmꢀ1; H NMR (CDCl3, 400 MHz)
d 7.54 (s, 2H), 4.99 (s, 4H), 3.90 (s, 6H), 3.81 (s, 4H); 13C
NMR (CDCl3, 75 MHz) d 167.6, 140.5, 131.3, 130.4, 72.4,
71.0, 52.7; HRMS (ESI) calcd for C14H16O6 [MþNa]þ
303.0845, found 303.0860.
d 5.19 (d, J¼11.7 Hz, 1H), 5.18 (d, J¼13.5 Hz, 1H), 5.16 (d,
J¼11.7 Hz, 1H), 5.13 (d, J¼13.5 Hz, 1H), 4.62 (d, J¼
13.5 Hz, 1H), 4.58 (d, J¼12.0 Hz, 1H), 4.54 (d, J¼12.0 Hz,
1H), 4.43 (d, J¼13.5 Hz, 1H), 3.54e3.45 (m, 2H), 3.36 (s,
3H), 3.32 (s, 3H), 3.28e3.21 (m, 1H), 3.12e3.05 (m, 1H),
1.71e1.50 (m, 1H), 1.60 (s, 9H), 1.59 (s, 9H), 1.20e0.95
(m, 3H), 0.60e0.45 (m, 2H); 13C NMR (CDCl3, 100 MHz)
d 167.3, 167.2, 143.0, 142.9, 138.1, 133.9, 133.5, 132.4,
83.2, 82.9, 69.3, 68.7, 67.8, 67.3, 67.1, 66.5, 58.8, 57.9,
28.24, 28.16, 28.0, 20.3; HRMS (ESI) calcd for C27H42O8Na
[MþNa]þ 517.2777, found 517.2756. CHIRALPAK AD, hex-
ane/2-PrOH¼95:5, 1.0 mL/min, retention times: 6.6 min (mi-
nor isomer) and 7.9 min (major isomer).
4.4.5. (þ)-[6]Metacyclophane (þ)-3cc (Table 1, entry 2)
Colorless solid; mp 122.0e122.8 ꢁC; [a]D25 þ6.3 (c 0.155,
CHCl3, 8% ee); IR (KBr) 2900, 1720, 1690, 1360, 1300,
1240, 1170, 1110, 1070, 840, 760 cmꢀ1; H NMR (CDCl3,
1
300 MHz) d 5.70 (d, J¼5.8 Hz, 1H), 5.56 (d, J¼5.8 Hz, 1H),
4.38 (d, J¼12.7 Hz, 1H), 4.27 (d, J¼12.7 Hz, 1H), 3.50e
3.80 (m, 2H), 3.08e3.35 (m, 2H), 2.35 (s, 3H), 1.93 (s, 3H),
1.49 (s, 9H), 1.40 (s, 9H); 13C NMR (CDCl3, 75 MHz)
d 170.0, 163.4, 157.7, 149.2, 143.4, 138.3, 134.5, 110.2,
80.5, 79.7, 72.7, 68.7, 67.4, 63.3, 28.4, 28.0, 13.2, 12.2;
HRMS (ESI) calcd for C22H32O6Na [MþNa]þ 415.2097,
found 415.2109. CHIRALPAK AD, hexane/2-PrOH¼98:2,
1.0 mL/min, retention times: 7.4 min (major isomer) and
10.2 min (minor isomer).
4.4.10. [9]Paracyclophane 5gc (Table 3, entry 4)
Colorless oil; IR (neat) 2900, 1710, 1360, 1300, 1150,
;
1100, 840 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 4.87 (d,
J¼12.6 Hz, 2H), 4.82 (d, J¼12.6 Hz, 2H), 4.75 (d,
J¼11.4 Hz, 2H), 4.58 (d, J¼11.4 Hz, 2H), 3.45 (s, 6H),

838
K. Tanaka et al. / Tetrahedron 64 (2008) 831e846
3.34e3.27 (m, 4H), 1.58 (s, 18H), 0.92e0.60 (m, 5H), 0.60e
0.40 (m, 1H); 13C NMR (CDCl3, 100 MHz) d 166.7, 140.0,
137.3, 135.0, 82.8, 67.9, 66.9, 66.3, 58.8, 28.7, 28.1, 21.0;
HRMS (ESI) calcd for C27H42O8Na [MþNa]þ 517.2777,
found 517.2783.
J¼11.7 Hz, 1H, 3jc), 4.74 (d, J¼13.5 Hz, 1H, 3jc), 4.69
(d, J¼11.4 Hz, 1H, 3jc), 4.61 (d, J¼11.4 Hz, 1H, 3jc), 4.60
(s, 4H, 4jc), 4.59 (s, 4H, 4jc), 4.55 (d, J¼13.8 Hz, 1H, 3jc),
3.59 (t, J¼5.4 Hz, 4H, 4jc), 3.45e3.21 (m, 4H, 3jc), 3.38 (s,
3H, 3jc), 3.30 (s, 3H, 3jc), 3.28 (s, 6H, 4jc), 1.80e0.85 (m,
12H, 3jc; 12H, 4jc), 1.60 (s, 9H, 3jc), 1.59 (s, 9H, 3jc),
1.58 (s, 18H, 4jc); 13C NMR (CDCl3, 75 MHz) d 167.6,
167.44, 167.41, 140.4, 139.74, 139.72, 138.2, 135.8, 135.4,
135.0, 134.8, 133.9, 82.9, 82.6, 82.4, 69.8, 68.8, 68.7, 68.1,
67.6, 67.0, 66.0, 65.63, 65.61, 58.5, 57.92, 57.86, 29.0, 28.8,
28.2, 28.13, 28.05, 27.4, 27.2, 26.14, 26.13, 24.7, 24.4, 22.9;
HRMS (ESI) calcd for C30H48O8Na [MþNa]þ 559.3247,
found 559.3240; CHIRALPAK AD-H, hexane/2-PrOH¼97:3,
1.0 mL/min, retention times: 6.1 min (major isomer) and
8.0 min (minor isomer).
4.4.11. (ꢀ)-[10]Metacyclophane (ꢀ)-3hc (Table 3, entry 5)
Colorless oil; [a]2D5 ꢀ5.8 (c 0.625, CHCl3, 52% ee); IR
(neat) 2900, 1710, 1420, 1360, 1300, 1150, 1090, 840 cmꢀ1
;
1H NMR (CDCl3, 300 MHz) d 5.12 (d, J¼13.8 Hz, 1H),
5.03 (d, J¼5.4 Hz, 1H), 5.02 (d, J¼13.8 Hz, 1H), 5.01 (d,
J¼5.4 Hz, 1H), 4.64 (d, J¼13.8 Hz, 1H), 4.61 (d, J¼11.7 Hz,
1H), 4.55 (d, J¼11.7 Hz, 1H), 4.40 (d, J¼13.5 Hz, 1H), 3.57e
3.47 (m, 2H), 3.35 (s, 3H), 3.32 (s, 3H), 3.09e2.90 (m, 2H),
1.600 (s, 9H), 1.595 (s, 9H), 1.45e1.30 (m, 2H), 1.30e1.12
(m, 2H), 1.12e0.96 (m, 2H), 0.75e0.63 (m, 2H); 13C NMR
(CDCl3, 75 MHz) d 167.6, 167.4, 141.9, 141.5, 136.8, 134.3,
134.1, 132.5, 83.1, 82.8, 69.0, 68.8, 68.2, 68.0, 67.0,
65.5, 58.6, 57.9, 29.11, 29.07, 28.2, 28.1, 25.50, 25.46;
HRMS (ESI) calcd for C28H44O8Na [MþNa]þ 531.2934,
found 531.2923; CHIRALPAK AD-H, hexane/2-PrOH¼97:3,
1.0 mL/min, retention times: 7.6 min (major isomer) and
10.7 min (minor isomer).
4.4.14. (þ)-[9]Metacyclophane (þ)-3kc (Table 3, entry 8)
Colorless solid; mp 98.0e99.6 ꢁC; [a]D25 þ28.4 (c 0.350,
CHCl3, 92% ee); IR (KBr) 2900, 1710, 1440, 1360, 1300,
1
1140, 1090, 840 cmꢀ1; H NMR (CDCl3, 300 MHz) d 5.20
(d, J¼13.5 Hz, 1H), 5.13 (d, J¼14.1 Hz, 1H), 5.00 (d,
J¼12.9 Hz, 1H), 4.96 (d, J¼12.9 Hz, 1H), 4.70 (d, J¼
14.1 Hz, 1H), 4.55 (d, J¼11.7 Hz, 1H), 4.51 (d, J¼11.7 Hz,
1H), 4.50 (d, J¼13.5 Hz, 1H), 3.74e3.64 (m, 2H), 3.40e
3.30 (m, 1H), 3.334 (s, 3H), 3.332 (s, 3H), 3.22e3.06 (m,
3H), 2.98e2.88 (m, 2H), 1.60 (s, 18H); 13C NMR (CDCl3,
100 MHz) d 167.61, 167.59, 144.4, 140.3, 135.5, 133.8,
133.1, 131.4, 83.0, 82.7, 70.4, 70.2, 68.8, 68.3, 67.9, 67.5,
67.1, 58.6, 58.5, 57.9, 28.2; HRMS (ESI) calcd for
C26H40O9Na [MþNa]þ 519.2570, found 519.2597. CHIRAL-
PAK AD, hexane/2-PrOH¼95:5, 1.0 mL/min, retention times:
9.5 min (minor isomer) and 11.1 min (major isomer).
4.4.12. [11]Orthocyclophane, (ꢀ)-[11]metacyclophane,
and [11]paracyclophane [4ic/(ꢀ)-3ic/5ic¼44:36:20,
Table 3, entry 6]
Colorless oil; IR (neat) 2900, 1710, 1430, 1360, 1300,
1150, 1090, 840 cmꢀ1; 1H NMR (CDCl3, 300 MHz) d 5.18 (d,
J¼13.2 Hz, 1H, 3ic), 5.09 (d, J¼13.5 Hz, 1H, 3ic), 5.07 (d, J¼
13.2 Hz, 2H, 5ic), 5.04 (d, J¼12.6 Hz, 1H, 3ic), 4.997 (d, J¼
11.7 Hz, 2H, 5ic), 4.995 (d, J¼12.6 Hz, 1H, 3ic), 4.69
(d, J¼13.5 Hz, 1H, 3ic), 4.597 (s, 4H, 4ic), 4.596 (d,
J¼13.2 Hz, 2H, 5ic), 4.58 (s, 4H, 4ic), 4.57 (d, J¼11.4 Hz,
1H, 3ic), 4.51 (d, J¼11.4 Hz, 1H, 3ic), 4.44 (d, J¼13.2 Hz, 1H,
3ic), 4.43 (d, J¼13.2 Hz, 2H, 5ic), 3.60 (t, J¼5.1 Hz, 4H, 4ic),
3.50e3.20 (m, 2H, 5ic; 4H, 3ic), 3.42 (s, 6H, 5ic), 3.37 (s, 3H,
3ic), 3.34 (s, 3H, 3ic), 3.30 (s, 6H, 4ic), 3.15e2.90 (m, 2H,
5ic), 1.60 (s, 18H, 3ic), 1.58 (s, 18H, 5ic; 18H, 4ic), 2.00e
0.16 (m, 10H, 5ic; 10H, 4ic; 10H, 3ic); 13C NMR (CDCl3,
75 MHz) d 167.4, 167.3, 141.4, 140.6, 140.55, 140.53, 138.9,
135.7, 135.6, 135.0, 134.7, 134.3, 134.1, 132.7, 119.5, 83.2,
83.1, 83.0, 82.5, 70.6, 68.8, 68.6, 67.8, 67.4, 66.6, 65.8, 64.7,
64.6, 64.0, 58.7, 58.5, 58.0, 57.9, 29.5, 28.14, 28.11, 28.1,
28.05, 27.3, 25.7, 25.5, 25.4, 24.9, 24.8, 22.8; HRMS (ESI)
calcd for C29H46O8Na [MþNa]þ 545.3090, found 545.3077;
CHIRALPAK AD-H, hexane/2-PrOH¼97:3, 1.0 mL/min, re-
tention times: 9.4 min (major isomer) and 18.4 min (minor
isomer).
4.4.15. [9]Orthocyclophane 4kc (Table 3, entry 8)
Colorless solid; mp 104.0e104.6 ꢁC; IR (KBr) 2850, 1710,
1
1440, 1360, 1300, 1150, 1100, 840 cmꢀ1; H NMR (CDCl3,
400 MHz) d 4.83 (s, 4H), 4.63 (s, 4H), 3.80e3.75 (m, 4H),
3.68e3.64 (m, 4H), 3.30 (s, 6H), 1.58 (s, 18H); 13C NMR
(CDCl3, 75 MHz) d 167.4, 138.9, 134.9, 134.7, 82.6, 72.7,
69.7, 68.6, 66.6, 57.9, 28.1; HRMS (ESI) calcd for
C26H40O9Na [MþNa]þ 519.2570, found 519.2588.
4.4.16. (þ)-[12]Metacyclophane (þ)-3lc (Table 3, entry 9)
Colorless oil; [a]2D5 þ5.3 (c 0.350, CHCl3, 80% ee); IR
1
(neat) 2800, 1700, 1360, 1300, 1140, 1090 cmꢀ1; H NMR
(CDCl3, 300 MHz) d 5.085 (d, J¼12.5 Hz, 1H), 5.082 (d,
J¼13.6 Hz, 1H), 5.01 (d, J¼12.5 Hz, 1H), 5.00 (d, J¼
13.2 Hz, 1H), 4.73 (d, J¼13.2 Hz, 1H), 4.61 (d, J¼11.7 Hz,
1H), 4.54 (d, J¼11.7 Hz, 1H), 4.49 (d, J¼13.6 Hz, 1H),
3.74e3.37 (m, 12H), 3.35 (s, 3H), 3.31 (s, 3H), 1.60 (s, 9H),
1.56 (s, 9H); 13C NMR (CDCl3, 75 MHz) d 167.60, 167.58,
141.6, 139.9, 135.3, 134.8, 134.0, 133.01, 82.9, 82.8, 70.7,
70.5, 70.4, 70.1, 69.2, 68.9, 68.5, 68.2, 67.1, 65.5, 58.4,
57.9, 28.13, 28.12; HRMS (ESI) calcd for C28H44O10Na
[MþNa]þ 563.2832, found 563.2808; CHIRALPAK AD-H,
hexane/2-PrOH¼95:5, 1.0 mL/min, retention times: 16.0 min
(minor isomer) and 19.8 min (major isomer).
4.4.13. (þ)-[12]Metacyclophane and [12]orthocyclophane
[(þ)-3jc/4jc¼50:50, Table 3, entry 7]
Colorless solid; mp 115.0e117.0 ꢁC; [a]D25 þ5.0 [c 0.640,
CHCl3 (calculated content of (þ)-3jc), 62% ee]; IR (KBr)
1
2850, 1720, 1430, 1360, 1300, 1150, 1090 cmꢀ1; H NMR
(CDCl3, 300 MHz) d 4.96 (d, J¼13.8 Hz, 1H, 3jc), 4.94 (d, J¼
11.7 Hz, 1H, 3jc), 4.87 (d, J¼13.5 Hz, 1H, 3jc), 4.86 (d,

K. Tanaka et al. / Tetrahedron 64 (2008) 831e846
839
4.4.17. [12]Orthocyclophane 4lc (Table 3, entry 9)
Colorless oil; IR (neat) 2900, 1710, 1360, 1300, 1150,
;
1090, 840 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 4.86 (s,
68.7, 68.5, 59.6, 58.4, 58.3, 57.3, 53.0, 3.6; HRMS (ESI) calcd
for C15H18O5Na [MþNa]þ 301.1208, found 301.1199.
4H), 4.63 (s, 4H), 3.80e3.70 (m, 8H), 3.69 (s, 4H), 3.26 (s,
6H), 1.57 (s, 18H); 13C NMR (CDCl3, 75 MHz) d 167.4,
138.6, 135.2, 134.8, 82.3, 71.7, 69.9, 69.7, 68.5, 66.5, 57.7,
28.0; HRMS (ESI) calcd for C28H44O10Na [MþNa]þ
563.2832, found 563.2807.
4.5.2. Triyne 6a
Colorless oil; IR (neat) 2850, 2240, 1710, 1350, 1240,
1070, 740 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 4.79 (t,
;
J¼1.8 Hz, 2H), 4.20 (t, J¼1.8 Hz, 2H), 4.18 (t, J¼1.8 Hz,
2H), 4.15 (t, J¼1.8 Hz, 2H), 3.60 (t, J¼6.3 Hz, 2H), 3.59 (t,
J¼6.3 Hz, 2H), 3.39 (s, 3H), 2.01 (s, 3H), 1.89 (quint,
J¼6.3 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 152.8, 86.9,
83.7, 82.6, 81.9, 79.2, 71.7, 67.1, 66.9, 59.9, 58.4, 58.3,
57.6, 53.3, 29.7, 3.8; HRMS (ESI) calcd for C16H20O5Na
[MþNa]þ 315.1208, found 315.1199.
4.5. Synthesis of triynes 6
4.5.1. Representative procedure for the synthesis of triynes
6: synthesis of triyne 6b
n-BuLi (1.6 M in hexane, 10.0 mL, 16.0 mmol) was added
over 15 min to a cooled (ꢀ40 ꢁC) solution of 1b31 (2.00 g,
14.5 mmol) in Et2O (25 mL). To this solution was added a so-
lution of chloromethyl methyl ether (1.28 g, 16.0 mmol) in
Et2O (5 mL), and the resulting solution was stirred at rt for
1 h. The reaction was quenched by the addition of ice water
and extracted with Et2O. The organic layer was washed with
brine, dried over Na2SO4, and concentrated. The residue was
purified by silica gel column chromatography (hexane/
EtOAc¼3:1) to give 1-methoxy-4-(2-(prop-2-ynyloxy)ethoxy)-
but-2-yne (0.873 g, 4.79 mmol, 33% yield) as a pale yellow
oil.
n-BuLi (1.6 M in hexane, 1.53 mL, 2.45 mmol) was added
dropwise to a THF (2.0 mL) solution of 1-methoxy-4-
(2-(prop-2-ynyloxy)ethoxy)but-2-yne (0.430 g, 2.36 mmol) at
ꢀ78 ꢁC and the resulting solution was stirred at ꢀ78 ꢁC for
15 min. A THF (10 mL) suspension of paraformaldehyde
(0.144 mg, 4.72 mmol) was added at ꢀ78 ꢁC, and the resulting
mixture was stirred at rt for 16 h. The reaction was quenched
by the addition of water and extracted with ethyl acetate. The
organic layer was dried over Na2SO4, concentrated, and puri-
fied by silica gel column chromatography (hexane/EtOAc¼
1:1), which furnished 4-[2-(4-methoxybut-2-ynyloxy)ethoxy]-
but-2-yn-1-ol (0.258 g, 1.07 mmol, 51% yield) as a pale yellow
oil.
4.5.3. Triyne 6c
Colorless oil; IR (neat) 2890, 2230, 1710, 1440, 1350,
1
1250, 1070, 750 cmꢀ1; H NMR (CDCl3, 300 MHz) d 4.79
(t, J¼1.8 Hz, 2H), 4.19 (t, J¼1.8 Hz, 2H), 4.17 (t, J¼1.8 Hz,
2H), 4.15 (t, J¼1.8 Hz, 2H), 3.53 (t, J¼6.3 Hz, 2H), 3.51 (t,
J¼6.3 Hz, 2H), 3.39 (s, 3H), 2.01 (s, 3H), 1.67 (quint,
J¼6.3 Hz, 4H); 13C NMR (CDCl3, 75 MHz) d 152.8, 86.9,
83.8, 82.7, 81.9, 79.2, 71.7, 69.9, 69.8, 59.9, 58.3, 58.2,
57.7, 53.4, 26.2, 26.0, 3.9; HRMS (ESI) calcd for
C17H22O5Na [MþNa]þ 329.1365, found 329.1336.
4.5.4. Triyne 6d
Colorless oil; IR (neat) 2900, 2280, 1710, 1440, 1360,
1
1250, 1070, 750 cmꢀ1; H NMR (CDCl3, 300 MHz) d 4.79
(t, J¼1.8 Hz, 2H), 4.18 (t, J¼1.8 Hz, 2H), 4.16 (t, J¼1.8 Hz,
2H), 4.15 (t, J¼1.8 Hz, 2H), 3.51 (t, J¼6.3 Hz, 2H), 3.49
(t, J¼6.3 Hz, 2H), 3.39 (s, 3H), 2.01 (s, 3H), 1.71e1.49 (m,
4H), 1.58e1.40 (m, 2H); 13C NMR (CDCl3, 75 MHz)
d 152.8, 86.9, 83.8, 81.9, 79.1, 77.2, 71.7, 70.2, 70.0, 59.9,
58.3, 58.2, 57.6, 53.3, 29.3, 22.7, 3.8; HRMS (ESI) calcd for
C18H24O5Na [MþNa]þ 343.1521, found 343.1507.
4.5.5. Triyne 6e
Pale yellow oil; IR (neat) 2900, 2250, 1700, 1430, 1350,
1
1240, 1080, 1020, 800 cmꢀ1; H NMR (CDCl3, 300 MHz)
To a CH2Cl2 (2.0 mL) solution of 4-N,N-dimethylamimo-
pyridine (7.0 mg, 0.057 mmol) and 4-[3-(4-methoxybut-2-
ynyloxy)ethoxy]but-2-yn-1-ol (0.258 g, 1.07 mmol) was
added dropwise a CH2Cl2 (3.0 mL) solution of 2-butynoic
acid (0.108 g, 1.28 mmol). The resulting solution was cooled
to 0 ꢁC. N,N0-Dicyclohexylcarbodiimide (0.265 g, 1.28 mmol)
was added at 0 ꢁC, and the resulting mixture was stirred at
0 ꢁC for 2 h and then at rt for 24 h. The reaction was quenched
by the addition of water and extracted with ethyl acetate. The
organic layer was dried over Na2SO4, concentrated, and puri-
fied by silica gel column chromatography (hexane/ethyl
acetate¼2:1), which furnished 6b (0.247 g, 0.888 mmol,
83% yield) as a colorless solid. Mp 147.2e148.0 ꢁC; IR
d 4.79 (t, J¼1.8 Hz, 2H), 4.25e4.09 (m, 6H), 3.50 (t,
J¼6.3 Hz, 2H), 3.48 (t, J¼6.3 Hz, 2H), 3.39 (s, 3H), 2.00 (s,
3H), 1.73e1.49 (m, 4H), 1.49e1.27 (m, 4H); 13C NMR
(CDCl3, 75 MHz) d 152.7, 86.8, 83.8, 82.7, 81.8, 79.1, 71.7,
70.2, 70.0, 59.8, 58.2, 58.1, 57.5, 53.2, 29.4, 29.3, 25.9,
25.8, 3.72; HRMS (ESI) calcd for C19H26O5Na [MþNa]þ
357.1678, found 357.1664.
4.5.6. Triyne 6f
Orange oil; IR (neat) 2935, 2857, 2240, 1716, 1437, 1354,
;
1305, 1098 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 4.80 (t,
J¼1.8 Hz, 2H), 4.18 (t, J¼1.8 Hz, 2H), 4.16 (t, J¼1.8 Hz,
2H), 4.15 (t, J¼1.8 Hz, 2H), 3.50 (t, J¼6.6 Hz, 2H), 3.48 (t,
J¼6.6 Hz, 2H), 3.39 (s, 3H), 2.00 (s, 3H), 1.63e1.51 (m,
3H), 1.40e1.30 (m, 7H); 13C NMR (CDCl3, 75 MHz)
d 152.8, 86.8, 83.9, 82.8, 81.8, 79.1, 71.7, 70.3, 70.2, 59.9,
58.2, 58.1, 57.6, 53.3, 29.41, 29.39, 29.2, 25.99, 25.97, 3.80;
1
(KBr) 2900, 2250, 1710, 1240, 1060, 740 cmꢀ1; H NMR
(CDCl3, 300 MHz) d 4.79 (t, J¼1.8 Hz, 2H), 4.26 (t,
J¼1.8 Hz, 2H), 4.25 (t, J¼1.8 Hz, 2H), 4.14 (t, J¼1.8 Hz,
2H), 3.71 (s, 4H), 3.39 (s, 3H), 2.01 (s, 3H); 13C NMR
(CDCl3, 75 MHz) d 152.5, 86.8, 83.1, 82.2, 82.0, 79.5, 71.5,

840
K. Tanaka et al. / Tetrahedron 64 (2008) 831e846
HRMS (ESI) calcd for C20H28O5Na [MþNa]þ 371.1834,
The reaction was quenched with water and extracted with
EtOAc. The organic layer was dried over Na2SO4, concen-
trated, and purified by silica gel column chromatography (hex-
ane/EtOAc¼5:1), which furnished 9b (0.415 g, 1.49 mmol,
75% yield) as a colorless oil. IR (neat) 2850, 1430, 1340,
found 371.1799.
4.5.7. Triyne 6g
Orange oil; IR (neat) 2934, 2858, 2242, 1717, 1249,
1066 cmꢀ1
;
1H NMR (CDCl3, 300 MHz)
d
4.80 (t,
1080, 890 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 4.28 (t,
;
J¼1.8 Hz, 2H), 4.18 (t, J¼1.8 Hz, 2H), 4.16 (t, J¼1.8 Hz,
2H), 4.14 (t, J¼1.8 Hz, 2H), 3.50 (t, J¼6.6 Hz, 2H), 3.48 (t,
J¼6.6 Hz, 2H), 3.39 (s, 3H), 2.00 (s, 3H), 1.65e1.51 (m,
3H), 1.42e1.23 (m, 9H); 13C NMR (CDCl3, 75 MHz)
d 152.8, 86.8, 83.9, 82.8, 81.8, 79.1, 71.7, 70.4, 70.3, 59.9,
58.2, 58.1, 57.6, 53.3, 29.5, 29.4, 29.3, 26.00, 25.98, 3.80;
HRMS (ESI) calcd for C21H30O5Na [MþNa]þ 385.1991,
found 385.2027.
J¼1.8 Hz, 2H), 4.20 (q, J¼2.4 Hz, 2H), 4.19 (t, J¼1.8 Hz,
2H), 4.18 (t, J¼1.8 Hz, 2H), 4.15 (t, J¼1.8 Hz, 2H), 3.600
(t, J¼6.3 Hz, 2H), 3.594 (t, J¼6.3 Hz, 2H), 3.39 (s, 3H),
1.88 (quint, J¼6.3 Hz, 2H), 1.86 (t, J¼2.4 Hz, 3H); 13C
NMR (CDCl3, 75 MHz) d 83.1, 82.8, 82.6, 81.9, 81.6, 74.3,
69.99, 66.97, 59.9, 58.4, 57.6, 57.2, 56.6, 29.8, 3.6; HRMS
(ESI) calcd for C16H22O4Na [MþNa]þ 301.1416, found
301.1396.
4.5.8. Triyne 6h
Pale orange oil; IR (neat) 2900, 2350, 1710, 1440, 1350,
4.6.2. Triyne 9a
Colorless oil; IR (neat) 2898, 2855, 1444, 1348,
;
1074 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 4.31e4.24 (m,
1
1240, 1070, 750 cmꢀ1; H NMR (CDCl3, 300 MHz) d 4.79
(t, J¼1.8 Hz, 2H), 4.26 (t, J¼1.8 Hz, 2H), 4.24 (t, J¼1.8 Hz,
2H), 4.14 (t, J¼1.8 Hz, 2H), 3.76e3.63 (m, 8H), 3.39 (s,
3H), 2.01 (s, 3H); 13C NMR (CDCl3, 75 MHz) d 152.1,
86.4, 83.0, 81.9, 81.8, 79.1, 71.2, 69.88, 69.87, 68.6, 68.5,
59.3, 58.1, 58.0, 57.0, 52.7, 3.2; HRMS (ESI) calcd for
C17H22O6Na [MþNa]þ 345.1314, found 345.1314.
6H), 4.20 (q, J¼2.4 Hz, 2H), 4.14 (t, J¼1.8 Hz, 2H), 3.72 (s,
4H), 3.39 (s, 3H), 1.86 (t, J¼2.4 Hz, 3H); 13C NMR
(CDCl3, 75 MHz) d 83.2, 82.41, 82.38, 82.21, 81.99, 74.2,
68.83, 68.80, 59.9, 58.6, 57.6, 57.2, 57.1, 56.5, 3.57; HRMS
(ESI) calcd for C15H20O4Na [MþNa]þ 287.1259, found
287.1233.
4.5.9. Triyne 6i
Orange oil; IR (neat) 2874, 2239, 1715, 1438, 1350, 1249,
4.6.3. Triyne 9c
Colorless oil; IR (neat) 2850, 1430, 1340, 1080, 900 cmꢀ1
;
1099 cmꢀ1; H NMR (CDCl3, 300 MHz) d 4.78 (t, J¼1.8 Hz,
1H NMR (CDCl3, 300 MHz) d 4.28 (t, J¼1.8 Hz, 2H), 4.20 (q,
J¼2.4 Hz, 2H), 4.18 (t, J¼1.8 Hz, 2H), 4.17 (t, J¼1.8 Hz, 2H),
4.14 (t, J¼1.8 Hz, 2H), 3.56e3.48 (m, 4H), 3.37 (s, 3H), 1.86
(t, J¼2.4 Hz, 3H), 1.71e1.62 (m, 4H); 13C NMR (CDCl3,
75 MHz) d 83.1, 82.9, 82.7, 81.9, 81.5, 74.3, 69.8, 69.7,
59.9, 58.2, 57.7, 57.6, 57.1, 56.6, 26.2, 3.57; HRMS (ESI)
calcd for C17H24O4Na [MþNa]þ 315.1572, found 315.1564.
1
2H), 4.25 (t, J¼1.8 Hz, 2H), 4.24 (t, J¼1.8 Hz, 2H), 4.14 (t,
J¼1.8 Hz, 2H), 3.81e3.54 (m, 12H), 3.38 (s, 3H), 2.00 (s, 3H);
13C NMR (CDCl3, 75 MHz) d 152.3, 86.5, 83.1, 82.0, 81.9,
79.2, 71.3, 70.2, 70.1, 69.99, 69.98, 68.8, 68.7, 59.42, 58.2,
58.1, 57.09, 52.8, 3.36; HRMS (ESI) calcd for C19H26O7Na
[MþNa]þ 389.1576, found 389.1567.
4.5.10. Triyne 6j
Orange oil; IR (neat) 2872, 2238, 1715, 1350, 1248,
4.6.4. Triyne 9d
Colorless oil; IR (neat) 2850, 1430, 1340, 1080, 900 cmꢀ1
;
1099 cmꢀ1
;
1H NMR (CDCl3, 300 MHz)
d
4.78 (t,
1H NMR (CDCl3, 300 MHz) d 4.28 (t, J¼1.8 Hz, 2H), 4.20 (q,
J¼2.4 Hz, 2H), 4.18 (t, J¼1.8 Hz, 2H), 4.17 (t, J¼1.8 Hz, 2H),
4.14 (t, J¼1.8 Hz, 2H), 3.51 (t, J¼6.3 Hz, 2H), 3.50 (t,
J¼6.3 Hz, 2H), 3.39 (s, 3H), 1.86 (t, J¼2.4 Hz, 3H), 1.68e
1.56 (m, 4H), 1.50e1.38 (m, 2H); 13C NMR (CDCl3,
75 MHz) d 83.1, 82.9, 82.7, 81.8, 81.5, 74.3, 70.02, 69.99,
59.9, 58.2, 57.6, 57.1, 56.6, 29.3, 22.7, 3.57; HRMS (ESI)
calcd for C18H26O4Na [MþNa]þ 329.1729, found 329.1717.
J¼1.8 Hz, 2H), 4.25 (t, J¼1.8 Hz, 2H), 4.24 (t, J¼1.8 Hz,
2H), 4.13 (t, J¼1.8 Hz, 2H), 3.72e3.59 (m, 16H), 3.37 (s,
3H), 2.01 (s, 3H); 13C NMR (CDCl3, 75 MHz) d 152.3,
86.6, 83.2, 82.1, 81.9, 79.2, 71.4, 70.24, 70.21, 70.03, 70.01,
68.8, 68.7, 59.5, 58.2, 58.1, 57.2, 52.9, 3.41; HRMS (ESI)
calcd for C21H30O8Na [MþNa]þ 433.1838, found 433.1822.
4.6. Synthesis of triynes 9
4.6.5. Triyne 9e
Pale orange oil; IR (neat) 2850, 1420, 1340, 1260, 1080,
;
1020, 800 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 4.27 (t,
4.6.1. Representative procedure for the synthesis of triynes
9: synthesis of triyne 9b
To a THF (10 mL) solution of 4-[3-(4-methoxybut-2-ynyl-
oxy)propoxy]but-2-yn-1-ol (0.450 g, 1.98 mmol), prepared
from 3-(3-(prop-2-ynyloxy)propoxy)propyne31 as following
the synthesis of 4-[3-(4-methoxybut-2-ynyloxy)ethoxy]but-2-
yn-1-ol described in the synthesis of 6b, was added NaH
(57.1 mg, 2.38 mmol). The resulting mixture was stirred at rt
for 30 min. 1-Bromo-2-butyne (0.342 g, 2.57 mmol) was
added and the resulting mixture was stirred at rt for 16 h.
J¼1.8 Hz, 2H), 4.20 (q, J¼2.4 Hz, 2H), 4.18 (t, J¼1.8 Hz,
2H), 4.17 (t, J¼1.8 Hz, 2H), 4.14 (t, J¼1.8 Hz, 2H), 3.50 (t,
J¼6.6 Hz, 2H), 3.49 (t, J¼6.6 Hz, 2H), 3.39 (s, 3H), 1.85 (t,
J¼2.4 Hz, 3H), 1.64e1.53 (m, 4H), 1.43e1.32 (m, 4H); 13C
NMR (CDCl3, 75 MHz) d 83.1, 82.9, 82.7, 81.8, 81.4, 74.3,
70.13, 70.11, 60.3, 59.9, 58.2, 57.6, 57.1, 56.6, 31.6, 29.4,
25.9, 26.6, 3.57; HRMS (ESI) calcd for C19H28O4Na
[MþNa]þ 343.1885, found 343.1864.

K. Tanaka et al. / Tetrahedron 64 (2008) 831e846
841
4.6.6. Triyne 9f
Colorless oil; IR (neat) 2934, 2855, 1445, 1349,
4.7. Representative procedure for the rhodium-catalyzed
intramolecular alkyne cyclotrimerization (Table 6,
entry 2)
1098 cmꢀ1
;
1H NMR (CDCl3, 300 MHz) d 4.28 (t, J¼
1.8 Hz, 2H), 4.20 (q, J¼2.4 Hz, 2H), 4.18 (t, J¼1.8 Hz, 2H),
4.17 (t, J¼1.8 Hz, 2H), 4.14 (t, J¼1.8 Hz, 2H), 3.496 (t,
J¼6.6 Hz, 2H), 3.488 (t, J¼6.6 Hz, 2H), 3.39 (s, 3H), 1.86
(t, J¼2.4 Hz, 3H), 1.69e1.51 (m, 4H), 1.42e1.27 (m, 6H);
13C NMR (CDCl3, 75 MHz) d 83.1, 83.0, 82.8, 81.8, 81.4,
74.3, 70.20, 70.17, 59.9, 58.2, 57.6, 57.1, 56.6, 29.4, 29.2.
26.0, 3.57; HRMS (ESI) calcd for C20H30O4Na [MþNa]þ
357.2042, found 357.2012.
A CH2Cl2 (1.0 mL) solution of (R)-H8-BINAP (7.9 mg,
0.012 mmol) was added to a CH2Cl2 (1.0 mL) solution of
[Rh(cod)2]BF4 (5.1 mg, 0.012 mmol) at rt. The mixture was
stirred at rt for 5 min. H2 was introduced to the resulting solu-
tion in a Schlenk tube. After stirring at rt for 0.5 h, the result-
ing solution was concentrated to dryness and the residue was
dissolved in CH2Cl2 (20 mL). To this solution was added drop-
wise over 10 min a CH2Cl2 (5.0 mL) solution of 9b (69.6 mg,
0.25 mmol). The solution was stirred at rt for 16 h. The result-
ing solution was concentrated and purified by preparative TLC
(hexane/EtOAc¼1:2), which furnished (ꢀ)-[7]metacyclo-
phane 11b (17.5 mg, 0.0629 mmol, 25% yield, 90% ee) as
a colorless solid and [7]orthocyclophane 10b (25.8 mg,
0.0927 mmol, 37% yield) as a colorless solid.
4.6.7. Triyne 9g
Colorless oil; IR (neat) 2926, 2855, 1446, 13489, 1260,
;
1097, 802 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 4.28 (t,
J¼1.8 Hz, 2H), 4.20 (q, J¼2.4 Hz, 2H), 4.181 (t, J¼1.8 Hz,
2H), 4.175 (t, J¼1.8 Hz, 2H), 4.14 (t, J¼1.8 Hz, 2H), 3.50
(t, J¼6.6 Hz, 2H), 3.49 (t, J¼6.6 Hz, 2H), 3.39 (s, 3H), 1.86
(t, J¼2.4 Hz, 3H), 1.67e1.49 (m, 4H), 1.43e1.20 (m, 8H);
13C NMR (CDCl3, 75 MHz) d 83.1, 83.0, 82.8, 81.8, 81.4,
74.3, 70.3, 70.2, 59.9, 58.2, 57.6, 57.1, 56.6, 29.5, 29.3,
26.0, 24.3, 3.57; HRMS (ESI) calcd for C21H32O4Na
[MþNa]þ 371.2198, found 371.2209.
4.7.1. (ꢀ)-[7]Metacyclophane (ꢀ)-11b
Mp 90.1e90.9 ꢁC; [a]D25 ꢀ16.4 (c 0.250, acetone, 90% ee);
IR (KBr) 3250, 2860, 2320, 1680, 1440, 1350, 1050,
900 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 5.24e5.17 (m,
;
4H), 5.11 (d, J¼12.6 Hz, 1H), 5.04 (d, J¼12.6 Hz, 1H), 5.02
(d, J¼12.0 Hz, 1H), 4.95 (d, J¼12.0 Hz, 1H), 4.57 (d,
J¼12.6 Hz, 1H), 4.11 (d, J¼12.6 Hz, 1H), 3.52e3.35 (m,
2H), 3.38 (s, 3H), 2.68e2.48 (m, 2H), 2.22 (s, 3H), 1.39e
1.22 (m, 2H); 13C NMR (CDCl3, 75 MHz) d 143.1, 138.9,
138.6, 137.3, 131.4, 130.5, 73.4, 72.9, 72.3, 68.7, 67.2, 67.1,
66.6, 58.7, 32.9, 15.4; HRMS (ESI) calcd for C16H22O4Na
[MþNa]þ 301.1416, found 301.1390; CHIRALPAK AD-H,
hexane/2-PrOH¼95:5, 1.0 mL/min, retention times: 16.1 min
(major isomer) and 22.6 min (minor isomer).
4.6.8. Triyne 9h
Pale yellow oil; IR (neat) 2900, 1260, 1070, 1020,
1
790 cmꢀ1; H NMR (CDCl3, 300 MHz) d 4.27 (t, J¼1.8 Hz,
2H), 4.26 (t, J¼1.8 Hz, 2H), 4.25 (t, J¼1.8 Hz, 2H), 4.20 (q,
J¼2.4 Hz, 2H), 4.14 (t, J¼1.8 Hz, 2H), 3.74e3.65 (m, 8H),
3.38 (s, 3H), 1.86 (t, J¼2.4 Hz, 3H); 13C NMR (CDCl3,
75 MHz) d 83.1, 82.6, 82.4, 82.2, 81.9, 74.3, 70.4, 69.09,
69.08, 59.9, 58.6, 57.6, 57.1, 56.5, 3.57; HRMS (ESI) calcd
for C17H24O5Na [MþNa]þ 331.1521, found 331.1510.
4.7.2. [7]Orthocyclophane 10b
4.6.9. Triyne 9i
Colorless oil; IR (neat) 2874, 1716, 1349, 1251,
Mp 98.8e99.0 ꢁC; IR (KBr) 3280, 2820, 2300, 1640, 1440,
1
1030, 890 cmꢀ1; H NMR (CDCl3, 300 MHz) d 5.19e5.13
1097 cmꢀ1
;
1H NMR (CDCl3, 300 MHz) d 4.31e4.22 (m,
(m, 2H), 5.13e5.05 (m, 2H), 4.96 (s, 2H), 4.71 (s, 2H), 4.54
(s, 2H), 3.73 (t, J¼5.4 Hz, 2H), 3.64 (t, J¼5.4 Hz, 2H), 3.44
(s, 3H), 2.26 (s, 3H), 1.77 (quint, J¼5.4 Hz, 2H); 13C NMR
(CDCl3, 75 MHz) d 138.38, 138.36, 136.4, 135.4, 131.1,
128.9, 73.8, 73.5, 69.4, 68.2, 67.8, 67.5, 67.2, 58.4, 30.9,
15.9; HRMS (ESI) calcd for C16H22O4Na [MþNa]þ
301.1416, found 301.1411.
6H), 4.20 (q, J¼2.4 Hz, 2H), 4.14 (t, J¼1.8 Hz, 2H), 3.77e
3.60 (m, 12H), 3.38 (s, 3H), 1.86 (t, J¼2.4 Hz, 3H); 13C
NMR (CDCl3, 75 MHz) d 83.1, 82.6, 82.4, 82.2, 81.8, 77.2,
74.2, 70.6, 70.4, 69.1, 59.9, 58.6, 57.6, 57.1, 56.5, 3.55;
HRMS (ESI) calcd for C19H28O6Na [MþNa]þ 375.1784,
found 375.1770.
4.6.10. Triyne 9j
4.7.3. [6]Orthocyclophane 7b (Table 5, entry 1)
Yellow oil; IR (neat) 2866, 1447, 1348, 1138, 1100 cmꢀ1
;
Colorless solid; mp 147.2e148.0 ꢁC; IR (KBr) 2900, 1760,
1100, 1020 cmꢀ1; 1H NMR (CDCl3, 300 MHz) d 5.27 (s, 2H),
5.14 (s, 2H), 4.90 (s, 2H), 4.55 (s, 2H), 3.81 (t, J¼6.0 Hz, 2H),
3.80 (t, J¼6.0 Hz, 2H), 3.46 (s, 3H), 2.78 (s, 3H); 13C NMR
(CDCl3, 75 MHz) d 171.1, 147.3, 143.3, 139.9, 136.5, 128.8,
122.8, 71.1, 69.1, 67.5, 67.3, 66.7, 66.1, 58.7, 12.9; HRMS
(ESI) calcd for C15H18O5Na [MþNa]þ 301.1052, found
301.1081.
1H NMR (CDCl3, 300 MHz) d 4.32e4.22 (m, 6H), 4.19 (q,
J¼2.4 Hz, 2H), 4.14 (t, J¼1.8 Hz, 2H), 3.76e3.58 (m, 16H),
3.38 (s, 3H), 1.86 (t, J¼2.4 Hz, 3H); 13C NMR (CDCl3,
75 MHz) d 83.1, 82.6, 82.4, 82.2, 81.8, 77.2, 74.2, 70.6,
70.5, 70.4, 69.1, 59.9, 58.6, 57.6, 57.1, 56.6, 3.56; HRMS
(ESI) calcd for C21H32O7Na [MþNa]þ 419.2046, found
419.2013.

842
K. Tanaka et al. / Tetrahedron 64 (2008) 831e846
4.7.4. (ꢀ)-[7]Metacyclophane (ꢀ)-8a (Table 5, entry 2)
Colorless oil; [a]2D5 ꢀ17.0 (c 0.360, acetone, >98% ee); IR
(d, J¼13.2 Hz, 1H), 4.70 (d, J¼13.2 Hz, 1H), 4.10 (d,
J¼13.2 Hz, 1H), 3.67e3.50 (m, 2H), 3.44 (s, 3H), 3.07e
2.97 (m, 1H), 2.93e2.86 (m, 1H), 2.77 (s, 3H), 1.58e1.40
(m, 1H), 1.33e0.98 (m, 3H), 0.62e0.24 (m, 2H); 13C NMR
(CDCl3, 75 MHz) d 171.1, 146.7, 146.1, 141.4, 138.6, 132.6,
121.5, 69.2, 68.1, 67.5, 66.9, 65.9, 65.3, 59.2, 28.1, 28.0,
20.0, 13.2; HRMS (ESI) calcd for C18H24O5Na [MþNa]þ
343.1521, found 343.1521; CHIRALPAK AD-H, hexane/2-
PrOH¼95:5, 1.0 mL/min, retention times: 23.6 min (major
isomer) and 25.8 min (minor isomer).
The absolute configuration of (ꢀ)-8d was determined to be
R by X-ray crystallographic analysis. X-ray intensity data
were collected using Cu Ka radiation up to 2q¼136.4ꢁ. The
crystal structure model was refined based on 2994 reflections
(1253 Friedel pairs) and gave final R factor of 0.0358. The
Flack parameter for the assigned absolute configuration shown
in Figure 1 is ꢀ0.03(18). The details of the refinement are
shown in Crystallographic Information File (CIF) attached as
Supplementary data.
(neat) 2900, 1750, 1060, 1020 cmꢀ1 1H NMR (CDCl3,
;
300 MHz) d 5.29 (d, J¼15.3 Hz, 1H), 5.22 (d, J¼15.3 Hz,
1H), 5.14 (d, J¼12.9 Hz, 1H), 5.13 (d, J¼12.9 Hz, 1H), 5.10
(d, J¼12.9 Hz, 1H), 4.97 (d, J¼12.9 Hz, 1H), 4.58 (d,
J¼12.9 Hz, 1H), 4.25 (d, J¼12.9 Hz, 1H), 3.59e3.48 (m,
2H), 3.40 (s, 3H), 2.68 (s, 3H), 2.60e2.46 (m, 1H), 2.36e
2.24 (m, 1H), 1.51e1.34 (m, 1H), 0.47e0.25 (m, 1H); 13C
NMR (CDCl3, 75 MHz) d 171.2, 150.3, 146.5, 141.9, 137.6,
132.1, 77.2, 72.8, 67.6, 67.3, 67.1, 66.9, 59.0, 33.0, 12.8;
HRMS (ESI) calcd for C16H20O5Na [MþNa]þ 315.1208,
found
315.1220;
CHIRALCEL
OD-H,
hexane/2-
PrOH¼90:10, 1.0 mL/min, retention times: 26.8 min (major
isomer) and 31.0 min (minor isomer).
4.7.5. [7]Orthocyclophane 7a (Table 5, entry 2)
Colorless solid; mp 126.5e127.4 ꢁC; IR (KBr) 2900, 1750,
1100, 1020 cmꢀ1; 1H NMR (CDCl3, 300 MHz) d 5.23 (s, 2H),
5.01 (s, 2H), 4.81 (s, 2H), 4.58 (s, 2H), 3.78 (t, J¼5.7 Hz, 2H),
3.74 (t, J¼5.7 Hz, 2H), 3.44 (s, 3H), 2.78 (s, 3H), 1.84 (quint,
J¼5.7 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 171.2, 146.4,
143.7, 139.6, 137.2, 129.7, 122.5, 68.9, 68.7, 67.94, 67.86,
67.6, 67.0, 58.5, 30.0, 13.0; HRMS (ESI) calcd for
C16H20O5Na [MþNa]þ 315.1208, found 315.1227.
4.7.9. [9]Orthocyclophane 7d (Table 5, entry 4)
Colorless solid; mp 118.2e119.3 ꢁC; IR (KBr) 2900, 1750,
1110, 1020 cmꢀ1; 1H NMR (CDCl3, 300 MHz) d 5.28 (s, 2H),
4.658 (s, 2H), 4.655 (s, 2H), 4.51 (s, 2H), 3.66 (t, J¼5.4 Hz,
2H), 3.60 (t, J¼5.4 Hz, 2H), 3.47 (s, 3H), 2.78 (s, 3H),
1.74e1.52 (m, 6H); 13C NMR (CDCl3, 75 MHz) d 183.3,
146.9, 143.4, 140.4, 138.1, 129.8, 122.9, 69.6, 69.1, 67.8,
67.2, 65.8, 65.0, 58.7, 26.4, 25.6, 21.0, 13.1; HRMS (ESI)
calcd for C18H24O5Na [MþNa]þ 343.1521, found 343.1511.
4.7.6. (ꢀ)-[8]Metacyclophane (ꢀ)-8c (Table 5, entry 3)
Colorless solid; [a]2D5 ꢀ24.1 (c 0.505, acetone, >98% ee);
IR (neat) 2900, 1750, 1150 cmꢀ1
;
1H NMR (CDCl3,
300 MHz) d 5.26 (s, 2H), 5.18 (d, J¼13.2 Hz, 1H), 5.109 (d,
J¼13.2 Hz, 1H), 5.108 (d, J¼13.2 Hz, 1H), 5.107 (d, J¼
13.2 Hz, 1H), 4.74 (d, J¼13.2 Hz, 1H), 4.26 (d, J¼13.2 Hz,
1H), 3.57e3.44 (m, 2H), 3.40 (s, 3H), 2.74 (s, 3H), 2.69e
2.56 (m, 2H), 1.37e1.12 (m, 2H), 0.62e0.32 (m, 2H); 13C
NMR (CDCl3, 75 MHz) d 171.1, 147.6, 146.6, 141.4, 138.5,
132.1, 122.0, 70.7, 67.5, 67.3, 67.1, 67.0, 66.6, 66.1, 59.0,
26.7, 13.0; HRMS (ESI) calcd for C17H22O5Na [MþNa]þ
329.1365, found 329.1342; CHIRALPAK AD-H, hexane/2-
PrOH¼90:10, 1.0 mL/min, retention times: 25.0 min (major
isomer) and 32.6 min (minor isomer).
4.7.10. (ꢀ)-[10]Metacyclophane (ꢀ)-8e (Table 5, entry 5)
Colorless oil; [a]2D5 ꢀ18.6 (c 0.385, acetone, 91% ee); IR
1
(neat) 2850, 2350, 1740, 1450, 1080, 1020 cmꢀ1; H NMR
(CDCl3, 300 MHz) d 5.30 (d, J¼15.3 Hz, 1H), 5.24 (d, J¼
15.3 Hz, 1H), 5.09 (d, J¼13.2 Hz, 1H), 5.05 (d, J¼13.2 Hz,
1H), 5.01 (d, J¼13.2 Hz, 1H), 4.99 (d, J¼13.2 Hz, 1H), 4.69
(d, J¼13.2 Hz, 1H), 4.17 (d, J¼13.2 Hz, 1H), 3.59e3.37 (m,
2H), 3.43 (s, 3H), 3.00 (dt, J¼9.6, 2.7 Hz, 1H), 2.90 (dt,
J¼9.6, 2.7 Hz, 1H), 2.78 (s, 3H), 1.50e1.24 (m, 2H), 1.18e
0.89 (m, 4H), 0.65e0.52 (m, 2H); 13C NMR (CDCl3,
75 MHz) d 171.3, 146.7, 145.0, 140.1, 138.8, 131.4, 121.6,
68.8, 68.2, 67.7, 67.5, 66.0, 64.7, 59.0, 29.3, 29.1, 25.0,
24.8, 13.2; HRMS (ESI) calcd for C19H26O5Na [MþNa]þ
357.1678, found 357.1693; CHIRALPAK AD-H, hexane/2-
PrOH¼95:5, 1.0 mL/min, retention times: 17.4 min (minor
isomer) and 18.9 min (major isomer).
4.7.7. [8]Orthocyclophane 7c (Table 5, entry 3)
Colorless solid; mp 102.4e103.0 ꢁC; IR (KBr) 2900, 1750,
1110, 1030 cmꢀ1; 1H NMR (CDCl3, 300 MHz) d 5.23 (s, 2H),
4.86 (s, 2H), 4.66 (s, 2H), 4.59 (s, 2H), 3.74 (t, J¼5.7 Hz, 2H),
3.67 (t, J¼5.7 Hz, 2H), 3.45 (s, 3H), 2.77 (s, 3H), 1.76 (quint,
J¼5.7 Hz, 4H); 13C NMR (CDCl3, 75 MHz) d 174.0, 148.0,
146.2, 143.9, 139.7, 137.2, 129.8, 70.9, 69.8, 67.5, 67.0,
66.43, 66.39, 58.5, 27.0, 26.6, 13.0; HRMS (ESI) calcd for
C17H22O5Na [MþNa]þ 329.1365, found 329.1382.
4.7.11. [10]Orthocyclophane 7e (Table 5, entry 5)
Colorless solid; mp 107.2e107.6 ꢁC; IR (KBr) 2850, 2350,
1
1740, 1440, 1080, 1020 cmꢀ1; H NMR (CDCl3, 300 MHz)
d 5.28 (s, 2H), 4.66 (s, 2H), 4.63 (s, 2H), 4.55 (s, 2H), 3.68
(t, J¼5.4 Hz, 2H), 3.57 (t, J¼5.4 Hz, 2H), 3.46 (s, 3H), 2.78
(s, 3H), 1.75e1.34 (m, 8H); 13C NMR (CDCl3, 75 MHz)
d 171.2, 147.1, 142.8, 140.5, 138.1, 129.6, 123.1, 69.5, 69.4,
67.8, 67.3, 66.5, 66.1, 58.7, 30.9, 27.6, 27.5, 22.7, 13.0;
HRMS (ESI) calcd for C19H26O5Na [MþNa]þ 357.1678,
found 357.1667.
4.7.8. (R)-(ꢀ)-[9]Metacyclophane (R)-(ꢀ)-8d (Table 5,
entry 4)
Colorless solid; mp 149.8e150.2 ꢁC; [a]D25 ꢀ16.6 (c 0.400,
acetone, 98% ee); IR (KBr) 2900, 1750, 1090, 1030 cmꢀ1; 1H
NMR (CDCl3, 300 MHz) d 5.27 (s, 2H), 5.200 (d, J¼13.2 Hz,
1H), 5.199 (d, J¼13.2 Hz, 1H), 5.16 (d, J¼13.2 Hz, 1H), 5.11

K. Tanaka et al. / Tetrahedron 64 (2008) 831e846
843
4.7.12. [11]Orthocyclophane 7f (Table 5, entry 6)
67.21, 67.0, 66.8, 65.8, 58.9, 58.6, 13.2, 13.0; HRMS (ESI)
calcd for C17H22O6Na [MþNa]þ 345.1314, found 345.1314;
CHIRALCEL OD-H, hexane/2-PrOH¼95:5, 1.0 mL/min, re-
tention times: 46.8 min (major isomer) and 67.7 min (minor
isomer). The corresponding chiral diol was isolated in a pure
form by treating (ꢀ)-8h with LiAlH4. Mp 149.8e150.2 ꢁC;
[a]2D5 þ3.50 (c 0.535, acetone, >99% ee); IR (KBr) 3300,
Colorless solid; mp 79.2e80.0 ꢁC; IR (KBr) 2926, 2855,
1
2360, 1758, 1100, 1024 cmꢀ1; H NMR (CDCl3, 300 MHz)
d 5.28 (s, 2H), 4.61 (s, 2H), 4.58 (s, 2H), 4.53 (s, 2H), 3.66
(t, J¼5.1 Hz, 2H), 3.57 (t, J¼5.1 Hz, 2H), 3.46 (s, 3H), 2.77
(s, 3H), 1.73e1.60 (m, 4H), 1.54e1.42 (m, 4H), 1.42e1.22
(m, 2H); 13C NMR (CDCl3, 75 MHz) d 171.2, 147.2, 142.4,
140.3, 138.1, 130.0, 123.3, 71.2, 70.6, 68.0, 67.4, 66.4, 66.0,
58.7, 27.6, 27.0, 25.53, 25.47, 25.45, 13.0; HRMS (ESI) calcd
for C20H28O5Na [MþNa]þ 371.1834, found 371.1833.
1
2900, 1080, 1000 cmꢀ1; H NMR (CDCl3, 300 MHz) d 5.07
(d, J¼13.8 Hz, 1H), 5.03 (d, J¼13.8 Hz, 1H), 5.01 (d, J¼
13.8 Hz, 1H), 4.98 (d, J¼13.8 Hz, 1H), 4.92 (d, J¼13.8 Hz,
1H), 4.77 (d, J¼13.8 Hz, 1H), 4.96e4.76 (m, 4H),
3.77e3.60 (m, 2H), 3.57e3.41 (m, 1H), 3.36 (s, 3H), 3.29e
3.09 (m, 3H), 2.90e2.80 (m, 1H), 2.80e2.70 (m, 2H),
2.59e2.49 (m, 1H), 2.46 (s, 3H); 13C NMR (CDCl3,
75 MHz) d 141.6, 138.7, 137.3, 136.38, 136.35, 135.5, 71.1,
70.70, 70.66, 69.6, 68.5, 67.40, 67.38, 59.6, 59.1, 58.5, 15.7;
HRMS (ESI) calcd for C17H26O6 [MþNa]þ 349.1627, found
349.1605.
4.7.13. (ꢀ)-[12]Metacyclophane (ꢀ)-8g (Table 5, entry 7)
Colorless oil; [a]2D5 ꢀ3.7 (c 0.210, acetone, 32% ee); IR
(neat) 2928, 2856, 2359, 2320, 1759, 1093, 1023 cmꢀ1; H
1
NMR (CDCl3, 300 MHz) d 5.38 (d, J¼15.3 Hz, 1H), 5.23
(d, J¼15.3 Hz, 1H), 4.96 (d, J¼10.8 Hz, 1H), 4.94 (d, J¼
13.5 Hz, 1H), 4.90 (d, J¼13.5 Hz, 1H), 4.84 (d, J¼10.8 Hz,
1H), 4.75 (d, J¼13.5 Hz, 1H), 4.34 (d, J¼13.5 Hz, 1H),
3.52e3.30 (m, 3H), 3.46 (s, 3H), 3.23 (dt, J¼9.6, 4.2 Hz,
1H), 2.81 (s, 3H), 1.65e1.38 (m, 1H), 1.38e1.02 (m, 6H),
1.02e0.72 (m, 5H); 13C NMR (CDCl3, 75 MHz) d 171.4,
147.2, 143.2, 139.3, 138.9, 131.3, 122.6, 69.5, 68.1, 67.6,
67.3, 66.7, 64.7, 59.0, 29.0, 28.6, 27.3, 26.8, 24.7, 24.3,
13.4; HRMS (ESI) calcd for C21H30O5Na [MþNa]þ
385.1991, found 385.1968; CHIRALPAK AD-H, hexane/2-
PrOH¼97:3, 1.0 mL/min, retention times: 19.6 min (major
isomer) and 21.9 min (minor isomer).
4.7.16. (ꢀ)-[12]Metacyclophane (ꢀ)-8i (Table 5, entry 9)
Colorless oil; [a]2D5 ꢀ3.48 (c 0.815, acetone, 68% ee); IR
1
(neat) 2868, 2359, 2320, 1751, 1095, 1022 cmꢀ1; H NMR
(CDCl3, 300 MHz) d 5.31 (d, J¼15.3 Hz, 1H), 5.23 (d, J¼
15.3 Hz, 1H), 5.08 (d, J¼13.2 Hz, 1H), 5.04 (d, J¼12.0 Hz,
1H), 4.99 (d, J¼12.0 Hz, 1H), 4.96 (d, J¼12.9 Hz, 1H), 4.77
(d, J¼12.9 Hz, 1H), 4.31 (d, J¼13.2 Hz, 1H), 3.81e3.47 (m,
8H), 3.42 (s, 3H), 3.47e3.28 (m, 4H), 2.78 (s, 3H); 13C
NMR (CDCl3, 75 MHz) d 171.3, 146.8, 145.1, 138.7, 138.3,
130.6, 121.9, 70.7, 70.5, 70.4, 70.1, 69.2, 68.19, 68.18, 67.9,
66.7, 64.5, 58.8, 13.2; HRMS (ESI) calcd for C19H26O7Na
[MþNa]þ 389.1576, found 389.1545; CHIRALPAK AD-H,
hexane/2-PrOH¼95:5, 1.0 mL/min, retention times: 65.9 min
(major isomer) and 74.8 min (minor isomer).
4.7.14. [12]Orthocyclophane 7g (Table 5, entry 7)
Colorless solid; mp 109.6e110.0 ꢁC; IR (KBr) 2926, 2859,
2360, 2325, 1759, 1103, 1021 cmꢀ1 1H NMR (CDCl3,
;
300 MHz) d 5.32 (s, 2H), 4.63 (s, 2H), 4.59 (s, 2H), 4.56 (s,
2H), 3.65 (t, J¼5.7 Hz, 2H), 3.62 (t, J¼5.7 Hz, 2H), 3.46 (s,
3H), 2.77 (s, 3H), 1.36e1.26 (m, 4H), 1.26e1.17 (m, 8H);
13C NMR (CDCl3, 75 MHz) d 171.4, 147.2, 140.7, 139.6,
137.5, 130.4, 123.6, 69.9, 69.7, 68.7, 67.4, 66.0, 65.7, 58.7,
28.5, 26.7, 26.4, 25.1, 23.0, 22.0, 13.0; HRMS (ESI) calcd
for C21H30O5Na [MþNa]þ 385.1991, found 385.1980.
4.7.17. [12]Orthocyclophane 7i (Table 5, entry 9)
Colorless solid; mp 103.3e103.8 ꢁC; IR (KBr) 2872, 2360,
2325, 1752, 1128, 1103, 1021 cmꢀ1 1H NMR (CDCl3,
;
300 MHz) d 5.33 (s, 2H), 4.99 (s, 2H), 4.78 (s, 2H), 4.59 (s,
2H), 3.84e3.71 (m, 8H), 3.68 (s, 4H), 3.43 (s, 3H), 2.77 (s,
3H); 13C NMR (CDCl3, 75 MHz) d 171.4, 146.6, 140.9,
139.2, 137.1, 131.1, 123.3, 72.3, 71.0, 70.0, 69.83, 69.76,
69.3, 68.6, 68.5, 67.2, 66.4, 58.4, 12.9; HRMS (ESI) calcd
for C19H26O7Na [MþNa]þ 389.1576, found 389.1542.
4.7.15. (ꢀ)-[9]Metacyclophane (ꢀ)-8h and
[9]orthocyclophane (ꢀ)-7h [(ꢀ)-8h/7h¼50:50, Table 5,
entry 8]
Colorless solid; mp 112.5e114.1 and 159.8e161.0 ꢁC;
[a]2D5 ꢀ13.1 [c 2.105, acetone (calculated content of (ꢀ)-8h),
>98% ee]; IR (KBr) 2880, 1750, 1440, 1350, 1100,
4.7.18. [15]Orthocyclophane 7j (Table 5, entry 10)
1
1
Yellow oil; H NMR (CDCl3, 300 MHz) d 5.34 (s, 2H),
1030 cmꢀ1; H NMR (CDCl3, 300 MHz) d 5.29 (s, 2H, 8h),
5.26 (d, J¼13.8 Hz, 2H, 8h), 5.21 (d, J¼13.8 Hz, 1H, 8h),
5.08 (d, J¼13.8 Hz, 1H, 8h), 4.94 (s, 2H, 7h), 4.87 (s, 2H,
7h), 4.81 (d, J¼13.8 Hz, 1H, 8h), 4.77 (s, 2H, 7h), 4.65 (s,
2H, 7h), 4.20 (d, J¼13.8 Hz, 1H, 8h), 3.81e3.68 (m, 4H,
8h; 4H, 7h), 3.68e3.61 (m, 1H, 8h; 1H, 7h), 3.46 (s, 3H,
8h), 3.45 (s, 3H, 7h), 3.36e3.13 (m, 1H, 8h; 1H, 7h), 3.18e
2.98 (m, 1H, 8h; 1H, 7h), 2.98e2.87 (m, 1H, 8h; 1H, 7h),
2.78 (s, 3H, 8h), 2.75 (s, 3H, 7h); 13C NMR (CDCl3,
75 MHz) d 171.4, 171.2, 148.6, 147.3, 146.2, 142.7, 140.2,
138.4, 138.1, 137.7, 129.9, 129.8, 123.1, 120.6, 72.9, 72.4,
70.8, 70.7, 70.4, 70.2, 69.1, 68.6, 67.9, 67.6, 67.5, 67.23,
4.92 (s, 2H), 4.75 (s, 2H), 4.58 (s, 2H), 3.82e3.51 (m, 16H),
3.38 (s, 3H), 2.77 (s, 3H); HRMS (ESI) calcd for
C21H30O8Na [MþNa]þ 433.1838, found 433.1801.
4.7.19. [6]Orthocyclophane 10a (Table 6, entry 1)
Colorless solid; mp 104.8e105.2 ꢁC; IR (KBr) 2897, 2360,
2325, 1100, 1044 cmꢀ1; 1H NMR (CDCl3, 300 MHz) d 5.22e
5.16 (m, 2H), 5.16e5.08 (m, 2H), 5.04 (s, 2H), 4.76 (s, 2H),
4.52 (s, 2H), 3.85e3.69 (m, 4H), 3.45 (s, 3H), 2.27 (s, 3H);
13C NMR (CDCl3, 75 MHz) d 138.7, 138.4, 135.7, 134.8,
131.5, 128.6, 73.8, 73.4, 70.0, 69.6, 67.7, 67.4, 65.0, 58.5,

844
K. Tanaka et al. / Tetrahedron 64 (2008) 831e846
15.9; HRMS (ESI) calcd for C15H20O4Na [MþNa]þ
58.5, 26.9, 25.5, 21.1, 15.9; HRMS (ESI) calcd for
C18H26O4Na [MþNa]þ 329.1729, found 329.1710.
287.1259, found 287.1235.
4.7.20. (ꢀ)-[8]Metacyclophane (ꢀ)-11c (Table 6, entry 3)
Colorless solid; [a]2D5 ꢀ10.0 (c 1.100, acetone, 93% ee); mp
58.2e58.7 ꢁC; IR (KBr) 3250, 2860, 2330, 1640, 1440, 1350,
4.7.24. (ꢀ)-[10]Metacyclophane (ꢀ)-11e (Table 6, entry 5)
Colorless solid; [a]2D5 ꢀ3.9 (c 0.365, acetone, 93% ee); mp
84.8e85.4 ꢁC; IR (KBr) 3250, 2890, 2350, 1440, 1350,
;
1080 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 5.24e5.18 (m,
1
1040, 900 cmꢀ1; H NMR (CDCl3, 300 MHz) d 5.22e5.17
(m, 2H), 5.179 (d, J¼12.9 Hz, 1H), 5.176 (d, J¼12.6 Hz,
1H), 5.09 (d, J¼12.6 Hz, 1H), 5.08 (d, J¼12.6 Hz, 1H), 5.04
(d, J¼11.4 Hz, 1H), 4.99 (d, J¼11.4 Hz, 1H), 4.66 (d,
J¼12.9 Hz, 1H), 4.13 (d, J¼12.6 Hz, 1H), 3.52e3.31 (m,
2H), 3.39 (s, 3H), 2.64 (t, J¼6.0 Hz, 1H), 2.60 (dt,
J¼6.0 Hz, 1H), 2.24 (s, 3H), 1.31e1.11 (m, 2H), 0.73e0.55
(m, 1H), 0.55e0.32 (m, 1H); 13C NMR (CDCl3, 75 MHz)
d 140.6, 139.0, 138.4, 137.7, 131.1, 130.9, 73.7, 73.4, 70.4,
68.2, 66.4, 66.1, 58.7, 26.63, 26.55, 16.0; HRMS (ESI)
calcd for C17H24O4Na [MþNa]þ 315.1572, found 315.1602;
CHIRALPAK AD-H, hexane/2-PrOH¼97:3, 1.0 mL/min, re-
tention times: 25.0 min (major isomer) and 27.2 min (minor
isomer).
2H), 5.19 (d, J¼12.0 Hz, 1H), 5.07 (d, J¼12.0 Hz, 1H), 5.06
(d, J¼13.2 Hz, 1H), 4.98 (d, J¼11.1 Hz, 1H), 4.95 (d,
J¼13.2 Hz, 1H), 4.93 (d, J¼11.1 Hz, 1H), 4.60 (d,
J¼13.2 Hz, 1H), 4.03 (d, J¼13.2 Hz, 1H), 3.59e3.46 (m,
2H), 3.41 (s, 3H), 3.05 (dt, J¼6.9, 2.7 Hz, 1H), 3.01 (dt,
J¼6.9, 2.7 Hz, 1H), 2.26 (s, 3H), 1.44e1.20 (m, 2H), 1.18e
0.89 (m, 4H), 0.76e0.49 (m, 2H); 13C NMR (CDCl3,
75 MHz) d 138.7, 138.1, 137.5, 137.3, 130.8, 130.3, 74.0,
73.8, 68.7, 67.71, 67.67, 67.3, 65.2, 58.7, 29.5, 29.3, 24.9,
24.8, 16.3; HRMS (ESI) calcd for C19H28O4Na [MþNa]þ
343.1885, found 343.1877; CHIRALPAK AD-H, hexane/2-
PrOH¼95:5, 1.0 mL/min, retention times: 11.6 min (minor
isomer) and 13.1 min (major isomer).
4.7.21. [8]Orthocyclophane 10c (Table 6, entry 3)
4.7.25. [10]Orthocyclophane 10e (Table 6, entry 5)
Colorless solid; mp 110.1e110.8 ꢁC; IR (KBr) 3250, 2890,
Colorless solid; mp 106.3e106.8 ꢁC; IR (KBr) 3250, 2850,
2330, 1640, 1440, 1060, 910 cmꢀ1
;
1H NMR (CDCl3,
2330, 1510, 1350, 1040 cmꢀ1; H NMR (CDCl3, 300 MHz)
1
300 MHz) d 5.18e5.12 (m, 2H), 5.12e5.05 (m, 2H), 4.79 (s,
2H), 4.58 (s, 2H), 4.55 (s, 2H), 3.76 (t, J¼5.4 Hz, 2H), 3.63
(t, J¼5.4 Hz, 2H), 3.44 (s, 3H), 2.25 (s, 3H), 1.79e1.64 (m,
4H); 13C NMR (CDCl3, 75 MHz) d 138.17, 138.15, 137.0,
134.9, 130.8, 129.0, 73.8, 73.5, 70.7, 69.1, 68.4, 67.5, 66.1,
58.3, 27.5, 26.6, 16.0; HRMS (ESI) calcd for C17H24O4Na
[MþNa]þ 315.1572, found 315.1541.
d 5.24e5.17 (m, 2H), 5.12e5.06 (m, 2H), 4.59 (s, 2H), 4.58
(s, 2H), 4.56 (s, 2H), 3.66 (t, J¼5.4 Hz, 2H), 3.51 (t,
J¼5.4 Hz, 2H), 3.44 (s, 3H), 2.25 (s, 3H), 1.76e1.41 (m,
8H); 13C NMR (CDCl3, 75 MHz) d 139.1, 138.6, 136.7,
135.8, 131.7, 128.5, 73.9, 73.8, 68.9, 68.8, 68.2, 67.9, 66.3,
58.5, 27.8, 27.5, 22.5, 22.4, 15.9; HRMS (ESI) calcd for
C19H28O4Na [MþNa]þ 343.1885, found 343.1870.
4.7.22. (ꢀ)-[9]Metacyclophane (ꢀ)-11d (Table 6, entry 4)
Colorless solid; [a]2D5 ꢀ2.8 (c 0.560, acetone, 94% ee); mp
51.0e51.6 ꢁC; IR (KBr) 3280, 2880, 2340, 1620, 1440, 1350,
4.7.26. (ꢀ)-[11]Metacyclophane (ꢀ)-11f (Table 6, entry 6)
Colorless oil; [a]2D5 ꢀ1.8 (c 0.220, acetone, 74% ee); IR
1
(neat) 2929, 2855, 2359, 2324, 1098, 1040 cmꢀ1; H NMR
1060 cmꢀ1
;
1H NMR (CDCl3, 300 MHz) d 5.24e5.18 (m,
(CDCl3, 300 MHz) d 5.22e5.18 (m, 2H), 5.15 (d, J¼
12.9 Hz, 1H), 5.14 (d, J¼13.8 Hz, 1H), 5.09 (d, J¼13.8 Hz,
1H), 5.04 (d, J¼12.9 Hz, 1H), 4.96 (d, J¼10.8 Hz, 1H), 4.90
(d, J¼10.8 Hz, 1H), 4.61 (d, J¼12.6 Hz, 1H), 4.00 (d,
J¼12.6 Hz, 1H), 3.44 (s, 3H), 3.37e3.22 (m, 2H), 3.06e
2.88 (m, 2H), 2.25 (s, 3H), 1.93e1.75 (m, 2H), 1.44e1.28
(m, 2H), 1.28e1.09 (m, 4H), 0.65e0.43 (m, 1H), 0.43e0.20
(m, 1H); 13C NMR (CDCl3, 75 MHz) d 139.4, 138.4, 137.0,
136.3, 131.2, 129.4, 74.1, 73.9, 67.3, 67.0, 64.2, 63.0, 62.5,
58.9, 28.34, 28.31, 24.89, 24.87, 22.9, 16.5; HRMS (ESI)
calcd for C20H30O4Na [MþNa]þ 357.2042, found 357.2036;
CHIRALPAK AD-H, hexane/2-PrOH¼97:3, 1.0 mL/min, re-
tention times: 14.7 min (minor isomer) and 16.2 min (major
isomer).
2H), 5.19 (d, J¼12.9 Hz, 1H), 5.17 (d, J¼12.9 Hz, 1H), 5.12
(d, J¼10.8 Hz, 1H), 5.10 (d, J¼12.9 Hz, 1H), 5.08 (d, J¼
12.9 Hz, 1H), 5.06 (d, J¼10.8 Hz, 1H), 4.58 (d, J¼12.9 Hz,
1H), 4.00 (d, J¼12.9 Hz, 1H), 3.59e3.44 (m, 2H), 3.42 (s,
3H), 3.11e2.94 (m, 2H), 2.25 (s, 3H), 1.59e1.39 (m, 1H),
1.39e1.22 (m, 1H), 1.22e0.81 (m, 2H), 0.53e0.29 (m, 2H);
13C NMR (CDCl3, 75 MHz) d 139.8, 138.6, 138.4, 137.2,
131.6, 130.4, 74.0, 73.7, 69.1, 68.5, 67.3, 65.8, 65.7, 58.9,
28.3, 28.2, 20.2, 16.3; HRMS (ESI) calcd for C18H26O4Na
[MþNa]þ 329.1729, found 329.1703; CHIRALPAK AD-H,
hexane/2-PrOH¼97:3, 1.0 mL/min, retention times: 21.3 min
(minor isomer) and 23.1 min (major isomer).
4.7.23. [9]Orthocyclophane 10d (Table 6, entry 4)
Colorless solid; mp 122.8e123.1 ꢁC; IR (KBr) 3280, 2880,
4.7.27. [11]Orthocyclophane 10f (Table 6, entry 6)
1
2340, 1620, 1510, 1060 cmꢀ1; H NMR (CDCl3, 300 MHz)
Colorless solid; mp 94.1e94.5 ꢁC; IR (KBr) 2909, 2849,
1
d 5.24e5.17 (m, 2H), 5.13e5.07 (m, 2H), 4.61 (s, 2H), 4.60
(s, 2H), 4.43 (s, 2H), 3.63 (t, J¼5.4 Hz, 2H), 3.55 (t,
J¼5.4 Hz, 2H), 3.44 (s, 3H), 2.25 (s, 3H), 1.74e1.53 (m,
6H); 13C NMR (CDCl3, 75 MHz) d 138.8, 138.5, 136.9,
135.8, 131.6, 128.7, 73.9, 73.7, 69.1, 68.9, 67.9, 67.8, 64.8,
2360, 2326, 1100, 1049 cmꢀ1; H NMR (CDCl3, 300 MHz)
d 5.24e5.17 (m, 2H), 5.13e5.06 (m, 2H), 4.55 (s, 2H), 4.53
(s, 2H), 4.41 (s, 2H), 3.64 (t, J¼5.1 Hz, 2H), 3.52 (t,
J¼5.1 Hz, 2H), 3.44 (s, 3H), 2.24 (s, 3H), 1.64e1.44 (m,
4H), 1.44e1.26 (m, 6H); 13C NMR (CDCl3, 75 MHz)

K. Tanaka et al. / Tetrahedron 64 (2008) 831e846
845
d 139.1, 138.7, 136.3, 135.8, 131.6, 128.8, 73.9, 73.8, 70.6,
70.4, 68.0, 68.0, 66.1, 58.5, 27.5, 27.3, 25.7, 25.5, 25.4,
15.9; HRMS (ESI) calcd for C20H30O4Na [MþNa]þ
357.2042, found 357.2033.
(m, 2H), 4.554 (s, 2H), 4.538 (s, 2H), 4.48 (s, 2H), 3.62 (t,
J¼5.4 Hz, 2H), 3.55 (t, J¼5.4 Hz, 2H), 3.43 (s, 3H), 2.25 (s,
3H), 1.73e1.54 (m, 4H), 1.54e1.32 (m, 8H); 13C NMR
(CDCl3, 75 MHz) d 139.1, 138.9, 135.4, 135.1, 131.1, 129.6,
74.1, 73.4, 71.14, 71.08, 71.03, 70.94, 70.61, 70.55, 69.9,
69.6, 68.5, 68.0, 66.4, 58.2, 15.9; HRMS (ESI) calcd for
C21H32O7Na [MþNa]þ 419.2046, found 419.2083.
4.7.28. (ꢀ)-[12]Metacyclophane (ꢀ)-11g (Table 6, entry 7)
Colorless oil; [a]2D5 ꢀ3.0 (c 0.275, acetone, 58% ee); IR
1
(neat) 2926, 2854, 2360, 2325, 1097, 1050 cmꢀ1; H NMR
(CDCl3, 300 MHz) d 5.27 (dd, J¼11.1, 2.4 Hz, 1H), 5.22 (d,
J¼11.1 Hz, 1H), 5.18 (d, J¼11.1 Hz, 1H), 5.08 (dd, J¼11.1,
2.4 Hz, 1H), 4.96 (d, J¼13.2 Hz, 1H), 4.88e4.79 (m, 2H),
4.86 (d, J¼13.2 Hz, 1H), 4.65 (d, J¼13.2 Hz, 1H), 4.13 (d,
J¼13.2 Hz, 1H), 3.52e3.23 (m, 4H), 3.44 (s, 3H), 2.29 (s,
3H), 1.66e1.40 (m, 2H), 1.40e1.01 (m, 6H), 1.01e0.79 (m,
4H); 13C NMR (CDCl3, 75 MHz) d 139.0, 138.2, 136.9,
136.7, 131.4, 129.5, 74.0, 73.9, 67.8, 67.71, 67.69, 67.59,
65.4, 58.7, 29.0, 28.9, 27.2, 27.1, 24.53, 24.49, 16.5; HRMS
(ESI) calcd for C21H32O4Na [MþNa]þ 371.2198, found
371.2195; CHIRALPAK AD-H, hexane/2-PrOH¼97:3,
1.0 mL/min, retention times: 11.5 min (minor isomer) and
13.2 min (major isomer).
Acknowledgements
This work was partly supported by a Grant-in-Aid for Sci-
entific Research (Nos. 16750072 and 19655011) from the
Ministry of Education, Culture, Sports, Science, and Techn-
ology, Japan. We thank Prof. Keiichi Noguchi for the X-ray
crystallographic analysis and Takasago International Corpora-
tion for the gift of modified-BINAP ligands.
Supplementary data
Crystallographic Information File (CIF) of (R)-(ꢀ)-8d is
provided. Supplementary data associated with this article
can be found in the online version, at doi:10.1016/j.tet.2007.
10.085.
4.7.29. [12]Orthocyclophane 10g (Table 6, entry 7)
Colorless solid; mp 104.2e104.5 ꢁC; IR (KBr) 2895, 2861,
1
2360, 2325, 1103, 1052 cmꢀ1; H NMR (CDCl3, 300 MHz)
d 5.28e5.16 (m, 2H), 5.13e5.04 (m, 2H), 4.73 (s, 2H), 4.71
(s, 2H), 4.55 (s, 2H), 3.77e3.53 (m, 16H), 3.41 (s, 3H), 2.25
(s, 3H); 13C NMR (CDCl3, 75 MHz) d 139.2, 139.1, 135.4,
135.1, 131.3, 129.0, 74.1, 73.5, 69.5, 68.0, 67.2, 65.7, 58.4,
28.4, 27.3, 26.4, 25.6, 23.0, 22.5, 15.9; HRMS (ESI) calcd
for C21H32O4Na [MþNa]þ 371.2198, found 371.2172.
References and notes
1. For recent reviews of transition-metal-catalyzed cycloadditions, see: (a)
Wender, P. A.; Croatt, M. P.; Deschamps, N. M. Comprehensive Organo-
metallic Chemistry; Mingos, D. M. P., Crabtree, R. H., Ojima, I., Eds.;
Elsevier: Oxford, 2007; Vol. 10, p 603; (b) Yet, L. Chem. Rev. 2000,
100, 2963; (c) Mehta, G.; Singh, V. Chem. Rev. 1999, 99, 881; (d) Ojima,
I.; Tzamarioudaki, M.; Li, Z.; Donovan, R. J. Chem. Rev. 1996, 96, 635;
(e) Lautens, M.; Klute, W.; Tam, W. Chem. Rev. 1996, 96, 49; (f) Schore,
N. E. Chem. Rev. 1988, 88, 1081.
2. For recent reviews of [2þ2þ2] cycloadditions of alkynes, see: (a)
Chopade, P. R.; Louie, J. Adv. Synth. Catal. 2006, 348, 2307; (b) Gandon,
V.; Aubert, C.; Malacria, M. Chem. Commun. 2006, 2209; (c) Kotha, S.;
Brahmachary, E.; Lahiri, K. Eur. J. Org. Chem. 2005, 4741; (d)
Yamamoto, Y. Curr. Org. Chem. 2005, 9, 503; (e) Malacria, M.; Aubert,
C.; Renaud, J. L. Science of Synthesis: HoubeneWeyl Methods for Molec-
ular Transformations; Lautens, M., Trost, B. M., Eds.; Georg Thieme:
New York, NY, 2001; Vol. 1, p 439; (f) Saito, S.; Yamamoto, Y. Chem.
Rev. 2000, 100, 2901; (g) Grotjahn, D. B. Comprehensive Organometallic
Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Hegedus, L.,
Eds.; Pergamon: Oxford, 1995; Vol. 12, p 741; (h) Boese, R.; Sickle,
A. P. V.; Vollhardt, K. P. C. Synthesis 1994, 1374; (i) Schore, N. E. Com-
prehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon:
Oxford, 1991; Vol. 5, p 1129; (j) Vollhardt, K. P. C. Angew. Chem., Int. Ed.
Engl. 1984, 23, 539.
4.7.30. (ꢀ)-[9]Metacyclophane (ꢀ)-11h and
[9]orthocyclophane (ꢀ)-10h [(ꢀ)-11h/10h¼35:65,
Table 6, entry 8]
Colorless solid; [a]2D5 ꢀ4.0 (c 2.575, acetone, 88% ee); mp
102.8e104.7 ꢁC; IR (KBr) 2850, 1430, 1350, 1100, 900 cmꢀ1
;
1H NMR (CDCl3, 300 MHz) d 5.21 (d, J¼12.3 Hz, 2H, 11h),
5.23e5.17 (m, 2H, 11h), 5.21e5.17 (m, 2H, 10h), 5.06e5.12
(m, 2H, 10h), 5.08 (d, J¼12.3 Hz, 2H, 11h), 4.94 (d,
J¼12.9 Hz, 1H, 11h), 4.89 (d, J¼12.9 Hz, 1H, 11h), 4.82 (s,
2H, 10h), 4.67 (d, J¼12.9 Hz, 1H, 11h), 4.63 (s, 2H, 10h),
4.60 (s, 2H, 10h), 4.09 (d, J¼12.9 Hz, 1H, 11h), 3.88e3.56
(m, 6H, 11h; 6H, 10h), 3.43 (s, 3H, 10h), 3.40 (s, 3H, 11h),
3.25e2.91 (m, 2H, 11h; 2H, 10h), 2.26 (s, 3H, 10h), 2.22
(s, 3H, 11h); 13C NMR (CDCl3, 75 MHz) d 141.4, 138.9,
138.6, 138.1, 136.3, 135.93, 135.90, 135.5, 131.5, 129.7,
129.1, 128.5, 74.0, 73.7, 73.63, 73.62, 72.5, 72.3, 70.7, 70.6,
69.8, 69.7, 69.3, 69.1, 68.6, 67.7, 66.9, 66.5, 66.2, 58.5,
58.3, 16.3, 15.8; HRMS (ESI) calcd for C17H24O5Na
[MþNa]þ 331.1521, found 331.1507; CHIRALPAK AD-H,
hexane/2-PrOH¼95:5, 1.0 mL/min, retention times: 19.8 min
(minor isomer) and 21.6 min (major isomer).
3. (a) Sato, Y.; Nishimata, T.; Mori, M. J. Org. Chem. 1994, 59, 6133; (b)
Sato, Y.; Nishimata, T.; Mori, M. Heterocycles 1997, 44, 443.
ˇ
4. (a) Stara, I. G.; Stary, I.; Kollarovic, A.; Teply, F.; Vyskocil, S.; Saman, D.
´
´
Tetrahedron Lett. 1999, 40, 1993; (b) Teply, F.; Stara, I. G.; Stary, I.;
ꢀ
´
ꢀ
´
´
´
ˇ
ˇ
´
ꢀ
ꢀ
Kollarovic, A.; Saman, D.; Vyskocil, S.; Fiedler, P. J. Org. Chem. 2003,
68, 5193.
5. For a Ni(0)-catalyzed enantioselective [2þ2þ2] cycloaddition of alkenes
with two alkynes to produce enantioenriched cyclohexadienes, see: Ikeda,
S.-I.; Kondo, H.; Arii, T.; Odashima, K. Chem. Commun. 2002, 2422.
6. (a) Takeuchi, R.; Tanaka, S.; Nakaya, Y. Tetrahedron Lett. 2001, 42, 2991;
(b) Takeuchi, R.; Nakaya, Y. Org. Lett. 2003, 5, 3659; (c) Kezuka, S.;
Tanaka, S.; Ohe, T.; Nakaya, Y.; Takeuchi, R. J. Org. Chem. 2006, 71,
4.7.31. [15]Orthocyclophane 10j (Table 6, entry 10)
1
Colorless oil; IR (neat) 2871, 2360, 2326, 1102 cmꢀ1; H
NMR (CDCl3, 300 MHz) d 5.24e5.16 (m, 2H), 5.13e5.02

846
K. Tanaka et al. / Tetrahedron 64 (2008) 831e846
(e) Kinoshita, H.; Shinokubo, H.; Oshima, K. J. Am. Chem. Soc. 2003,
543; (d) For a neutral Ir(I)/dppe complex-catalyzed [2þ2þ2] cycloaddi-
tion of enynes with alkynes, see: Kezuka, S.; Okado, T.; Niou, E.;
Takeuchi, R. Org. Lett. 2005, 7, 1711.
125, 7784.
20. Zhang, X.; Mashima, K.; Koyano, K.; Sayo, N.; Kumobayashi, H.;
Akutagawa, S.; Takaya, H. Tetrahedron Lett. 1991, 32, 7283.
21. The preliminary communication of this work has been reported; see:
Tanaka, K.; Sagae, H.; Toyoda, K.; Noguchi, K.; Hirano, M. J. Am.
Chem. Soc. 2007, 129, 1522.
7. Muller, E. Synthesis 1974, 761.
¨
8. (a) Grigg, R.; Scott, R.; Stevenson, P. Tetrahedron Lett. 1982, 23, 2691;
(b) Grigg, R.; Scott, R.; Stevenson, P. J. Chem. Soc., Perkin Trans. 1
1988, 1357.
9. For a review of Rh-catalyzed [2þ2þ2] cycloadditions, see: Fujiwara, M.;
Ojima, I. Modern Rhodium-Catalyzed Organic Reactions; Evans, P. A.,
Ed.; Wiley-VCH: Weinheim, 2005; p 129.
22. For reviews of cyclophanes, see: (a) Modern Cyclophane Chemistry;
Gleiter, R., Hopf, H., Eds.; Wiley: Chichester, 2004; (b) Cyclophane
Chemistry; Vogtle, F., Ed.; Wiley: Chichester, UK, 1993.
¨
10. (a) Ohshita, J.; Furumori, K.; Matsuguchi, A.; Ishikawa, M. J. Org. Chem.
1990, 55, 3277; (b) Field, L. D.; Ward, A. J.; Turner, P. Aust. J. Chem.
1999, 52, 1085.
23. For a review of cyclophane synthesis, see: Kane, V. V.; De Wolff, W. H.;
Bickelhaupt, F. Tetrahedron 1994, 50, 4574.
24. For a recent example of the synthesis and resolution of planar-chiral
[n]paracyclophanes, see: Ueda, T.; Kanomata, N.; Machida, H. Org.
Lett. 2005, 7, 2365.
11. (a) Tanaka, K.; Shirasaka, K. Org. Lett. 2003, 5, 4697; (b) For an account,
see: Tanaka, K. Synlett 2007, 1977.
12. (a) Tanaka, K.; Nishida, G.; Wada, A.; Noguchi, K. Angew. Chem., Int. Ed.
2004, 43, 6510; (b) Tanaka, K.; Toyoda, K.; Wada, A.; Shirasaka, K.;
Hirano, M. Chem.dEur. J. 2005, 11, 1145; (c) Tanaka, K.; Nishida, G.;
Ogino, M.; Hirano, M.; Noguchi, K. Org. Lett. 2005, 7, 3119; (d) Tanaka,
K.; Takeishi, K.; Noguchi, K. J. Am. Chem. Soc. 2006, 128, 4586; (e)
Nishida, G.; Suzuki, N.; Noguchi, K.; Tanaka, K. Org. Lett. 2006, 8,
3489; (f) Tanaka, K.; Sagae, H.; Toyoda, K.; Noguchi, K. Eur. J. Org.
Chem. 2006, 3575; (g) Tanaka, K.; Suda, T.; Noguchi, K.; Hirano, M.
J. Org. Chem. 2007, 72, 2243; (h) Tanaka, K.; Osaka, T.; Noguchi, K.;
Hirano, M. Org. Lett. 2007, 9, 1307; (i) Tanaka, K.; Hara, H.; Nishida,
G.; Hirano, M. Org. Lett. 2007, 9, 1907; (j) Nishida, G.; Noguchi, K.;
Hirano, M.; Tanaka, K. Angew. Chem., Int. Ed. 2007, 46, 3951.
13. Tanaka, K.; Wada, A.; Noguchi, K. Org. Lett. 2005, 7, 4737.
14. Tanaka, K.; Wada, A.; Noguchi, K. Org. Lett. 2006, 8, 907.
15. (a) Tanaka, K.; Suzuki, N.; Nishida, G. Eur. J. Org. Chem. 2006, 3917;
(b) Wada, A.; Noguchi, K.; Hirano, M.; Tanaka, K. Org. Lett. 2007, 9,
1295.
25. For the synthesis of cyclophanes via transition-metal-catalyzed or -medi-
ated macrocyclization, see: palladium-catalyzed coupling of enynes: (a)
Weibel, D.; Gevorgyan, V.; Yamamoto, Y. J. Org. Chem. 1998, 63,
1217; (b) Saito, S.; Tsuboya, N.; Yamamoto, Y. J. Org. Chem. 1997,
62, 5042 cycloaddition of Fischer chromium carbenes with alkynes: (c)
Wang, H.; Wulff, D. W.; Rheingold, L. A. J. Am. Chem. Soc. 2003,
125, 8980; (d) Wang, H.; Wulff, D. W.; Rheingold, L. A. J. Am. Chem.
Soc. 2000, 122, 9862; (e) Dotz, H. K.; Gerhardt, A. J. Organomet.
¨
Chem. 1999, 578, 223 intramolecular addition of rhodium carbenes: (f)
Doyle, M. P.; Hu, W. Synlett 2001, 1364; (g) Doyle, M. P.; Hu, W.;
Chapman, B.; Marnett, A. B.; Peterson, C. S.; Viatale, P. J.; Stanley,
S. A. J. Am. Chem. Soc. 2000, 122, 5718; Heck reaction: (h) Dyker, G.;
Kadzimirsz, D.; Henkel, G. Tetrahedron Lett. 2003, 44, 7905; (i) Geng,
X.; Miller, M. L.; Lin, S.; Ojima, I. Org. Lett. 2003, 5, 3733.
26. Wijsman, G. W.; de Kanter, F. J. J.; de Wolf, W. H.; Bickelhaupt, F.
Eur. J. Org. Chem. 2001, 2743.
27. For the synthesis of planar-chiral [n]metacyclophanes, see: (a) Piatek, P.;
Kalisiak, J.; Jurczak, J. Tetrahedron Lett. 2004, 45, 3309; (b) Kubik, S.;
Goddard, R. J. Org. Chem. 1999, 64, 9475; (c) Grimme, S.; Harren, J.;
16. Tanaka, K.; Otake, Y.; Wada, A.; Hirano, M. Org. Lett. 2007, 9, 2203.
17. Tanaka, K.; Nishida, G.; Sagae, H.; Hirano, M. Synlett 2007, 1426.
18. (a) For a chiral Co(I) complex-catalyzed enantioselective [2þ2þ2] cyclo-
addition of alkynes with nitriles for the synthesis of axially chiral aryl-
pyridines, see: Gutnov, A.; Heller, B.; Fischer, C.; Drexler, H.-J.;
Spannenberg, A.; Sundermann, B.; Sundermann, C. Angew. Chem., Int.
Ed. 2004, 43, 3795; (b) For a neutral Ir(I)/Me-Duphos complex-catalyzed
enantioselective [2þ2þ2] cycloaddition of alkynes for the synthesis of
axially chiral 1,4-teraryls, see: Shibata, T.; Fujimoto, T.; Yokota, K.;
Takagi, K. J. Am. Chem. Soc. 2004, 126, 8382.
Sobanski, A.; Vogtle, F. Eur. J. Org. Chem. 1998, 1491; (d) Grimme,
¨
S.; Pischel, I.; Vogtle, F.; Nieger, M. J. Am. Chem. Soc. 1995, 117, 157;
¨
Kang, G. J.; Chan, T. H. J. Org. Chem. 1985, 50, 452; (g) Vogtle, F.;
¨
(e) Meurer, K.; Luppertz, F.; Vogtle, F. Chem. Ber. 1985, 118, 4433; (f)
¨
Meurer, K.; Mannschreck, A.; Stuhler, G.; Puff, H.; Roloff, A.; Sievers,
¨
R. Chem. Ber. 1983, 116, 2630.
28. As the concentration of the reactions of 1gej and 1lem appeared to have
only small impact on enantioselection, they were conducted at 0.01 M
concentration.
19. For synthesis of cyclophanes via transition-metal-catalyzed [2þ2þ2]
~
cycloaddition, see: Co: (a) Bonaga, L. V. R.; Zhang, H.-C.; Moretto,
A. F.; Ye, H.; Gautheir, D. A.; Li, J.; Leo, G. C.; Maryanoff, B. E.
29. For preparation of bridged-type [4þ2]-cycloadducts utilizing alkyne-
Co2(CO)6 complex formation, see: Iwasawa, N.; Inada, K.; Nakayama,
S.; Aoki, M. Angew. Chem., Int. Ed. 2005, 44, 7447.
30. Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo, N.; Miura, T.;
Kumobayashi, H. Adv. Synth. Catal. 2001, 343, 264.
31. Ito, Y.; Inouye, M.; Yokota, H.; Murakami, M. J. Org. Chem. 1990, 55,
2567.
~
J. Am. Chem. Soc. 2005, 127, 3473; (b) Bonaga, L. V. R.; Zhang,
~
H.-C.; Maryanoff, B. E. Chem. Commun. 2004, 2394; (c) Bonaga,
L. V. R.; Zhang, H.-C.; Gautheir, D. A.; Reddy, I.; Maryanoff, B. E.
Org. Lett. 2003, 5, 4537; (d) Moretto, A. F.; Zhang, H.-C.; Maryanoff,
B. E. J. Am. Chem. Soc. 2001, 123, 3157; For use of RhCl(PPh3)3, see: