Molecular recognition of pyranosides by a family of trimeric, 1,1'- binaphthalene-derived cyclophane receptors

Article abstract of DOI:10.1002/(SICI)1522-2675(19981111)81:11<1931::AID-HLCA1931>3.0.CO;2-5

The synthesis and carbohydrate-recognition properties of a new family of optically active cyclophane receptors, 1-3, in which three 1,1'- binaphthalene-2,2'-diol spacers are interconnected by three buta-1,3- diynediyl linkers, are described. The macrocycles all contain highly preorganized cavities lined with six convergent OH groups for H-bonding and complementary in size and shape to monosaccharides. Compounds 1-3 differ by the functionality attached to the major groove of the 1,1'-binaphthalene- 2,2'-diol spacers. The major grooves of the spacers in 2 are unsubstituted, whereas those in 1 bear benzyloxy (BnO) groups in the 7,7'-positions and those in 3 2-phenylethyl groups in the 6,6'-positions. The preparation of the more planar, D₃-symmetrical receptors (R,R,R)-1 (Schemes 1 and 2), (S,S,S)- 1 (Scheme 4), (S,S,S)-2 (Scheme 5), and (S,S,S)-3 (Scheme 8) involved as key step the Glaser-Hay cyclotrimerization of the corresponding OH-protected 3,3'-diethynyl-1-1'-binaphthalene-2,2'-diol precursors, which yielded tetrameric and pentameric macrocycles in addition to the desired trimeric compounds. The synthesis of the less planar, C₂-symmetrical receptors (R,R,S)-2 (Scheme 6) and (S,S,R)-3 (Scheme 9) proceeded via two Glaser-Hay coupling steps. First, two monomeric precursors of identical configuration were oxidatively coupled to give a dimeric intermediate which was then subjected to macrocyclization with a third monomeric 1,1'-binaphthalene precursor of opposite configuration. The 3,3'-dialkynylation of the OH- protected 1,1'-binaphthalene-2,2'-diol precursors for the macrocyclizations was either performed by Stille (Scheme 1) or by Sonogashira (Schemes 4, 5, and 8) cross-coupling reactions. The flat D₃-symmetrical receptors (R,R,R)- 1 and (S,S,S)-1 formed 1:1 cavity inclusion complexes with octyl 1-O- pyranosides in CDCl₃ (300 K) with moderate stability (ΔG⁰ ca. -3 kcal mol^-1) as well as moderate diastereo(Δ(ΔG⁰) up to 0.7 kcal mol^-1) and enantioselectivity (Δ(ΔG⁰) =0.4 kcal mol^-1) (Table 1). Stoichiometric 1:1 complexation by (S,S,S)-2 and (S,S,S)-3 could not be investigated by ¹H- NMR binding titrations, due to very strong signal broadening. This broadening of the ¹H-NMR resonances is presumably indicative of higher-order associations, in which the planar macrocycles sandwich the carbohydrate guests. The less planar C₂-symmetrical receptor (S,S,R)-3 formed stable 1:1 complexes with binding free enthalpies of up to ΔG⁰ = - 5.0 kcal mol^-1 (Table 2). With diastereoselectivities up to Δ(ΔG⁰) = 1.3 kcal mol^-1 and enantioselectivities of Δ(ΔG⁰)= 0.9 kcal mol^-1, (S,S,R)-3 is among the most selective artificial carbohydrate receptors known.

Full text of DOI:10.1002/(SICI)1522-2675(19981111)81:11<1931::AID-HLCA1931>3.0.CO;2-5

Helvetica Chimica Acta ± Vol. 81 (1998)
1931
Molecular Recognition of Pyranosides by a Family of Trimeric,
1,1'-Binaphthalene-Derived Cyclophane Receptors
by Anja Bähr, Anne Sophie Droz, Martin Püntener, Ulf Neidlein, Sally Anderson, Paul Seiler, and
François Diederich*
Laboratorium für Organische Chemie, Eidgenössische Technische Hochschule, ETH-Zentrum,
Universitätstrasse 16, CH-8092 Zürich
Dedicated to Prof. Dr. Hans Bock on the occasion of his 70th birthday
The synthesis and carbohydrate-recognition properties of a new family of optically active cyclophane
receptors, 1 ± 3, in which three 1,1'-binaphthalene-2,2'-diol spacers are interconnected by three buta-1,3-
diynediyl linkers, are described. The macrocycles all contain highly preorganized cavities lined with six
convergent OH groups for H-bonding and complementary in size and shape to monosaccharides. Compounds
1 ± 3 differ by the functionality attached to the major groove of the 1,1'-binaphthalene-2,2'-diol spacers. The
major grooves of the spacers in 2 are unsubstituted, whereas those in 1 bear benzyloxy (BnO) groups in the 7,7'-
positions and those in 3 2-phenylethyl groups in the 6,6'-positions. The preparation of the more planar, D3-
symmetrical receptors (R,R,R)-1 (Schemes 1 and 2), (S,S,S)-1 (Scheme 4), (S,S,S)-2 (Scheme 5), and (S,S,S)-3
(Scheme 8) involved as key step the Glaser-Hay cyclotrimerization of the corresponding OH-protected 3,3'-
diethynyl-1,1'-binaphthalene-2,2'-diol precursors, which yielded tetrameric and pentameric macrocycles in
addition to the desired trimeric compounds. The synthesis of the less planar, C2-symmetrical receptors (R,R,S)-2
(Scheme 6) and (S,S,R)-3 (Scheme 9) proceeded via two Glaser-Hay coupling steps. First, two monomeric
precursors of identical configuration were oxidatively coupled to give a dimeric intermediate which was then
subjected to macrocyclization with a third monomeric 1,1'-binaphthalene precursor of opposite configuration.
The 3,3'-dialkynylation of the OH-protected 1,1'-binaphthalene-2,2'-diol precursors for the macrocyclizations
was either performed by Stille (Scheme 1) or by Sonogashira (Schemes 4, 5, and 8) cross-coupling reactions. The
flat D3-symmetrical receptors (R,R,R)-1 and (S,S,S)-1 formed 1:1 cavity inclusion complexes with octyl 1-O-
pyranosides in CDCl3 (300 K) with moderate stability (DG0 ca. 3 kcal mol 1) as well as moderate diastereo-
(D(DG0) up to 0.7 kcal mol 1) and enantioselectivity (D(DG0) ˆ 0.4 kcal mol 1) (Table 1). Stoichiometric 1 : 1
1
complexation by (S,S,S)-2 and (S,S,S)-3 could not be investigated by H-NMR binding titrations, due to very
strong signal broadening. This broadening of the 1H-NMR resonances is presumably indicative of higher-order
associations, in which the planar macrocycles sandwich the carbohydrate guests. The less planar C2-symmetrical
1
receptor (S,S,R)-3 formed stable 1 : 1 complexes with binding free enthalpies of up to DG0 ˆ 5.0 kcal mol
(Table 2). With diastereoselectivities up to D(DG0) ˆ 1.3 kcal mol and enantioselectivities of D(DG0) ˆ
1
0.9 kcal mol 1, (S,S,R)-3 is among the most selective artificial carbohydrate receptors known.
1. Introduction. ± Carbohydrate-protein recognition processes are ubiquitous in
nature [1 ± 3], and an increasing number of X-ray crystal structures has revealed the
highly complex nature of these phenomena [4][5]. It also has become apparent that
many of the underlying principles governing protein-carbohydrate interactions cannot
be identified or quantified on an atomic scale in biological studies only. Rather, there is
increasing consensus that investigations with well-defined synthetic receptors, whose
binding properties can be systematically varied and analyzed, could make important
contributions to the understanding of carbohydrate-recognition processes in biology.
Complexation of carbohydrates by proteins is based on a subtle balance between
hydrophobic and hydrophilic interactions [1 ± 4] (for some other recent examples of X-
ray crystal structures of protein-carbohydrate complexes, see [5]). Highly directional

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Helvetica Chimica Acta ± Vol. 81 (1998)
H-bonds, many of which are bidentate ionic ones (to the side-chain functionality of
aspartic acid (Asp), glutamic acid (Glu), arginine (Arg), asparagine (Asn), and
glutamine (Gln) residues) control the binding selectivity, whereas apolar interactions
and hydrophobic desolvation provide a large part of the thermodynamic driving force
for complexation. Contacts between protein and carbohydrate are frequently mediated
by H2O bridges [1b]. The overall binding picture has been elucidated by X-ray
crystallography of biological systems, but there remain many questions, which could be
addressed by systematic biomimetic studies [6] with synthetic receptors for example.
How many intermolecular host-guest H-bonds are needed to form a stable carbohy-
drate complex? What is the strength of individual neutral and ionic H-bonds involving
sugar OH groups, and which ionic H-bonding residues of proteins (anionic Asp, Glu,
phosphate vs. cationic Arg, histidine (His)) provide the strongest association [7]? X-
Ray structures of protein-carbohydrate complexes display a very large number of H-
bonds, yet the binding free enthalpy of such complexes often only amounts to values of
DG0 ˆ 7 to 8 kcal mol 1 [1b][8]. What is the contribution of cooperativity (i.e., the
sugar OH group acts both as a H-bond donor and acceptor) to H-bonding strength [9]?
How important are apolar interactions such as van der Waals dispersion interactions,
hydrophobic desolvation [10], and, in particular, sugar-CH ´´´ aromatic p-electron
interactions [11]? Biological X-ray crystal structures consistently show stacking
between aromatic amino-acid side chains, predominantly Tyr and Trp, with the apolar
faces of the bound sugars. It is clear that a great variety of medicinal-chemistry
programs would benefit from sound answers to these questions [12].
Despite recent significant interest in the development of efficient synthetic carbohy-
drate receptors, only modest advances have been achieved in this area. This is, at least in part,
due to the complex three-dimensional structure of sugars which contain both hydrophilic
and hydrophobic domains. Complexation by H-bonding in noncompetitive organic
solvent environments is hampered by the fact that some of the strong intramolecular H-
bonds within the sugar substrates themselves need to be disrupted [13] (for evaluations
of intramolecular H-bonding strengths in sugars, see [14]). Recognition in H2O
requires tight encapsulation of the limited hydrophobic surfaces of the sugars, yet an
unfavorable desolvation of their H-bonding sites must be avoided. Furthermore, H2O
competes strongly for the H-bonding sites on the receptor and the sugar OH groups.
Nevertheless, a variety of synthetic carbohydrate receptors have been developed.
The majority of the synthetic carbohydrate receptors form complexes in apolar solvents,
for example in CCl4 or CHCl3, taking advantage of H-bonding interactions as the major
driving force for association [13][15 ± 26]. In a few cases, optically active receptors were
shown to bind octyl glucosides enantioselectively, with differences in stability between
1
diastereoisomeric complexes D(DG0) ranging between 0.4 [22a,b] and 0.8 kcal mol
[18b][20]. X-Ray crystal structures of complexes between artificial receptors and
carbohydrates have, to the best of our knowledge, not yet been obtained. Carbohydrate
complexation by synthetic receptors in more polar solvents, which compete efficiently
for the H-bonding sites of the binding partners, is even less developed [11a,b] [22b]
[27 ± 31]. A popular and highly efficient strategy to recognize and transport
carbohydrates relies on the formation of cyclic boronate esters between boronic acids
and sugars in aqueous solutions [32 ± 39]; since this mode of recognition does not
primarily involve non-covalent interactions, its biomimetic relevance is rather limited.

Helvetica Chimica Acta ± Vol. 81 (1998)
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We describe here the synthesis and carbohydrate-recognition properties of the new
series of optically active cyclophane receptors 1 ± 3 in which three 1,1'-binaphthalene-
2,2'-diol spacers are interconnected by buta-1,3-diynediyl linkers to form highly pre-
organized cavities lined with six convergent OH groups [40]. These cavities mimic the
natural carbohydrate-recognition sites by providing a circular array of H-bonding
groups for interactions with the substrate. We show that both D3-symmetrical ((S,S,S)-
or (R,R,R)-configured) and C2-symmetrical ((S,S,R)- or (R,R,S)-configured) artificial
binders form complexes with octyl glycosides in CDCl3, with the less symmetrical
receptors displaying a much higher overall binding affinity as well as a remarkably
enhanced degree of diastereo- and enantioselectivity.
2. Results and Discussion. ± 2.1. Synthesis of the Receptors. The three receptors 1 ± 3
differ in their substituents in the 6,6'- and 7,7'-positions in the major groove of the 1,1'-
binaphthalene spacers. The first compounds prepared were D3-symmetrical (R,R,R)-1
[22b] and (S,S,S)-1 with benzyloxy (BnO) groups diverging from the 7,7'-positions to
provide solubility in organic solvents. The presence of these substituents, however,
caused several synthetic problems resulting in long synthetic routes (Sect. 2.1.1).
Therefore, we prepared optically pure D3- and C2-symmetrical 2 lacking functionality in
the major groove of the 1,1'-binaphthalene spacers by a significantly shorter route
(Sect. 2.1.2). However, C2-symmetrical 2 was found to be insoluble in CDCl3 and the
D3-symmetrical diastereoisomer presumably formed higher-order complexes with
carbohydrate substrates, thereby preventing the analysis of any 1:1 host-guest
association. Since the comparison between 1 and 2 clearly demonstrated that major-
groove functionality was required to prevent higher-order complexation, we ultimately
prepared, by an efficient synthetic route, optically pure D3- and C2-symmetrical 3 with
2-phenylethyl substituents in the 6,6'-positions (Sect. 2.1.3). In the case of (S,S,R)-3,
these residues efficiently prevented carbohydrate-induced aggregation of the receptor

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Helvetica Chimica Acta ± Vol. 81 (1998)
and higher-order complexation, and, therefore, first 1:1 host-guest binding studies
could be carried out on a C2-symmetrical trimer.
2.1.1. Synthesis of the C3-Symmetrical Receptors (R,R,R)-1 and (S,S,S)-1. The
preparation of (R,R,R)-1 in an eleven-step sequence (Schemes 1 and 2) started from 3-
bromonaphthalene-2,7-diol (4) [41]. Protection of the HO C(2) group as methoxy-
methyl (MOM) ether to give 5 (50%), followed by benzylation [42] of the remaining
OH group to afford 6 (94%), and removal of the MOM group [43] led to naphthol 7
(98%). Large-scale (up to 20 g) oxidative homo-coupling of 7 to 1,1'-binaphthalene-
2,2'-diol (Æ)-8 was best achieved (84%) with stoichiometric amounts of CuCl2 in
MeOH in the presence of t-BuNH2 [44], whereas coupling with catalytic amounts
(1 mol-%) of [CuCl(OH) ´ TMEDA] (prepared from CuCl2 and N,N,N',N'-tetrame-
thylethylenediamine (TMEDA)) [45] only afforded (Æ)-8 in 64% yield. The structure
of (Æ)-8 was confirmed by single-crystal X-ray diffraction [22b].
The optical resolution of (Æ)-8 was performed via formation of the two
diastereoisomeric cyclic menthyl phosphites [46] (using in situ-prepared (1R,2S,5R)-
menthyl phosphorodichloridite). The 31P-NMR spectrum of the crude product mixture
Scheme 1. Synthesis of the Macrocyclization Precursor (R)-13
a) MeOCH2Cl, K2CO3, MeCN, 188, 4 h, 50%. b) BnCl, K2CO3, DMF, 808, 1 h, 94%. c) Cat. conc. aq. HCl
soln., THF/MeOH 2 : 1, 708, 3 h, 98%. d) t-BuNH2, CuCl2, MeOH, 808, 1 h, 84%. e) (1R,2S,5R)-Menthyl
phosphorodichloridite, Et3N, THF, 188, 15 min, then recrystallization (2Â) from Et2O, 37%. f) K2CO3,
CHCl3/MeOH 1 : 1, 208, 30 min, 97%. g) Pd/C (10%), HCOONH4, MeOH, 608, 30 min, then BnCl, K2CO3,
DMF, 808, 2 h, 15%. h) PhCOCl (BzCl), 4-(dimethylamino)pyridine (DMAP), pyridine, CH2Cl2, 208, 2 h,
95%. i) Me3SiCꢀCSnMe3, [Pd(PPh3)4], 2,6-di(tert-butyl)-p-cresol, toluene, 1008, Ar, 36 h, 45%. j) K2CO3,
THF/MeOH 1 : 1, 208, 2 h, 91%. k) KOH, THF, 208, 1 h, 79%.

Helvetica Chimica Acta ± Vol. 81 (1998)
1935
showed two signals of same intensity at 154.8 and 151.4 ppm corresponding to the two
diastereoisomers. In contrast to the original procedure [46], where a solution of PCl3
was added to a solution of (1R,2S,5R)-menthol, we found that inverse addition proved
to be crucial in obtaining the desired monomenthyl phosphorodichloridite in high yield.
By using the published conditions, significant formation of dimenthyl phosphorochlor-
idite arising from a second substitution of chloride by menthol was observed. It was also
of great importance to employ only 0.9 equiv. of menthyl phosphorodichloridite to
avoid the formation of products in which the OH groups of (Æ)-8 had reacted with
2 equiv. of the reagent. Under these conditions, diastereoisomerically pure ( )-9 (37%,
>99.5% de ( ˆ diastereoisomeric excess) [47]) was isolated after repeated recrystal-
lization from Et2O. The other diastereoisomer failed to crystallize from the filtrate even
after concentration.
After isolation, menthyl phosphite ( )-9 was hydrolyzed with K2CO3 in CHCl3/
MeOH to afford enantiomerically pure ( )-8 (97%). To establish the (R)-config-
uration of ( )-8, the diol was debrominated and benzylated to give ( )-10 (15% from
( )-8). The optical rotation of ( )-(R)-10 ([a]Dr:t:
ˆ
15.2 (c ˆ 0.5 (CH2Cl2))) was then
compared with that of (‡)-(S)-10 ([a]rD:t: ˆ‡ 15.2 (c ˆ 0.5 (CH2Cl2))) derived from
benzylation of (‡)-(S)-7,7'-bis(benzyloxy)-1,1'-binaphthalene-2,2'-diol, whose abso-
lute configuration had been previously determined [48]. Benzoylation of (R)-8 to give
(R)-11 (95%) was followed by Pd0-catalyzed Stille cross-coupling with 1-(trimethyl-
silyl)-2-(trimethylstannyl)ethyne [49] to give (R)-12. The yields for the formation of
(R)-12 after two rounds of chromatography (SiO2 H) proved to be very unreprodu-
cible; they could be as high as 45%, but usually less than 25%. Efforts to obtain the
desired dialkynylated product by a Stille or Sonogashira [50] cross-coupling reaction
with unprotected (R)-8 failed. Removal of the Me3Si groups in (R)-12 gave the
diethynyl derivative (R)-13 (91%), the direct precursor for the macrocyclization to
receptor (R,R,R)-1. Benzoyl-ester hydrolysis afforded the dialkynylated 1,1'-binaph-
thalene-2,2'-diol (R)-14 (69%) whose sugar-binding properties were also investigated
for comparison.
Oxidative Glaser-Hay coupling [51] of (R)-13 in CH2Cl2 proceeded rapidly and
afforded a product mixture from which cyclic trimeric (R,R,R)-15 (20%), tetrameric
(R,R,R,R)-16 (20%), and pentameric (R,R,R,R,R)-17 (4%) were isolated by careful
flash chromatography (Scheme 2). Fast-atom-bombardment (FAB) mass spectra with
positive-ion detection gave strong molecular ions indicating the size of the oligomers,
and the 13C-NMR spectra displayed the required 22 peaks for the D3-symmetrical cyclic
oligomers. Importantly, two signals were observed between 75 and 85 ppm, corre-
sponding to the C-atoms in the buta-1,3-diynediyl linkers. Further confirmation for the
formation of these linkers was provided by the IR spectra, which showed both
1
symmetric and antisymmetric stretches in the region between 2100 and 2250 cm . The
1H-NMR spectra of the three cyclic oligomers were very similar, except for the
aromatic signals corresponding to the benzoyl (Bz) protecting groups; presumably, the
observed differences in the positions of the Bz resonances reflect the different degrees
of steric crowding in the three cavities.
Benzoyl-ester hydrolysis of (R,R,R)-15 proceeded smoothly to afford the neutral
receptor (R,R,R)-1 in 90% yield. Attempts to prepare the target molecule by oxidative
macrocyclization of the free diol (R)-14 failed. Instead, 5-endo-dig cyclization [52] of

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Helvetica Chimica Acta ± Vol. 81 (1998)
Scheme 2. Synthesis of the Receptor (R,R,R)-1
a) CuCl, TMEDA, O2, CH2Cl2, 208, 20 min, 20% ((R,R,R)-15), 20% ((R,R,R,R)-16), 4% ((R,R,R,R,R)-17).
b) KOH, THF, 208, 30 min, 90%.
the OH groups with the adjacent ethynyl moieties occurred. Formation of products
containing naphtho[b]furan rings was deduced by the presence of a sharp singlet in the
1H-NMR spectrum (CDCl3) at 7.00 ppm for the H C(3) resonance of the furan ring.
An analogous reaction has been utilized for the efficient preparation of 2-substituted
benzo[b]furans by the reaction of 2-hydroxyaryl halides with a variety of alkynes in the
presence of a Pd0 catalyst and CuCl under mild conditions [53].
Considering the varying low yields of (R)-12 in the Stille coupling and the tedious
chromatographic product isolation, we sought to improve the yield and ease of isolation
of the dialkynylated 1,1'-binaphthalene precursor using the Sonogashira cross-coupling
reaction [50]. Since 3,3'-dibrominated 1,1'-binaphthalenes such as (Æ)-8 or (Æ)-11 were
found to be quite unreactive under these conditions, a corresponding 3,3'-diiodo
derivative was prepared. For this purpose, 6 was metallated and then reacted with I2 to
give 18 in 97% yield. Deprotection of the OH group at C(2) afforded 19 (97%), which
was coupled to give (Æ)-20 (63%) (Scheme 3). To our disappointment, (Æ)-20 did not
react with (1R,2S,5R)-menthyl phosphorodichloridite to form two diastereoisomeric
cyclic menthyl phosphites, probably as a result of the increased steric hindrance by the
bulky I substituents ortho to the OH groups at C(2) and C(2'). Furthermore, all other
attempts1) to resolve (Æ)-20 failed. In view of these problems, which are undoubtedly
associated with the presence of the I-atoms in (Æ)-20, we decided to introduce these
substituents only after optical resolution of the 1,1'-binaphthalene moiety.
1
)
The optical resolution was attempted by methods reported in [46][54]. For other resolutions of 1,1'-
binaphthalene-2,2'-diols, see [55]. For the synthesis of asymmetric 1,1'-binaphthalene-2,2'-diols, see [56].

Helvetica Chimica Acta ± Vol. 81 (1998)
Scheme 3. Synthesis of (Æ)-20
1937
a) t-BuLi, THF, 788, 30 min, then I2, 788 !208, 12 h, 97%, b) Conc. aq. HCl soln. (cat.), THF/MeOH 2 : 1,
708, 3 h, 97%. c) t-BuNH2, CuCl2, MeOH, 808, 1 h, 65%.
The direct electrophilic iodination [57] of enantiomerically pure 7,7'-bis(benzyl-
oxy)-1,1'-binaphthalene-2,2'-diol [48] or the ortho-lithiation of OH-protected deriva-
tives, followed by quenching with I2 [58], failed to yield enantiomerically pure 20. Most
conversions afforded complex product mixtures containing only traces of the desired
diiodinated compound, sometimes accompanied by reduced and higher iodinated
derivatives. Therefore, we decided to introduce the I substituents by a halogen-
exchange reaction after the optical resolution of (Æ)-8.
In a test run, diol (Æ)-8 was transformed into the MOM-protected derivative (Æ)-21
which, upon treatment with t-BuLi (3 equiv.) in THF at 788 followed by quenching
with I2, afforded (Æ)-22 (Scheme 4) in 93% yield. Repeating the reaction under exactly
the same conditions with the enantiomer (‡)-(S)-8 (obtained from menthyl phosphite
(‡)-9 prepared with (1S,2R,5S)-menthyl phosphorodichloridite as described above)
unfortunately was much less successful and yielded a mixture of the desired product
(S)-22 (less than 25%) together with mono- and bis-reduced side-products resulting
from Br/H exchange (ca. 20% each).
Deuterium isotope studies were performed in an effort to shed light on this
considerable difference in behavior between racemic and enantiomerically pure 21.
The enantiomer (S)-21 was dilithiated as described above at 788 and, after 1 h,
1
quenched at this temperature with CD3OD. The H-NMR spectrum of the crude
product showed a mixture of 3,3'-di- and 3-mono-deuterated 1,1'-binaphthalene
derivatives. Interestingly, one diastereotopic proton (either HR or HS ) in each of the
two benzylic CH2 groups was also found to be quantitatively substituted by a D-atom,
2
as illustrated by the H-NMR spectrum (CHCl3, 46 MHz) of the mixture. However,
when racemic (Æ)-21 was subjected to the same conditions, the benzylic H/D exchange
was insignificant and only deuteration at the 3,3'-positions was observed. These results
suggest that the 7,7'-bis(benzyloxy)-1,1'-binaphthalene molecules, with their large van
der Waals surfaces, aggregate at 788 in THFand that the steric accessibility to the base
(t-BuLi), and, therefore, the reactivity differs in the aggregates formed by the same
enantiomers (self-recognition in the conversion of (S)-21) and those formed by
different enantiomers (non-self-recognition in the conversion of (Æ)-21 (for an

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Helvetica Chimica Acta ± Vol. 81 (1998)
Scheme 4. Synthesis of (S,S,S)-1
a) MeOCH2Cl, K2CO3, MeCN, 208, 15 h, 96%. b) BuLi, TMEDA, THF, 788, 45 min, then I2, 15 min, 66%. c)
Me3SiCꢀCH, [PdCl2(dppf)] ´ CH2Cl2, CuI, Et2NH, toluene, 408, 4 h, 98%. d) K2CO3, THF/MeOH 1 : 1, 208,
2 h, 93%. e) CuCl, TMEDA, O2, CH2Cl2, 208, 3 h, 25%. f ) Conc. aq. HCl soln. (cat.), THF/MeOH 1 : 1, 208,
12 h, 77%.
example of different aggregations in solutions of racemates (non-self-recognition and
enantiomers (self-recognition, see [59]). A co-aggregation of the reagent can also not
be excluded. The X-ray crystal-structure analysis obtained for (S)-21 could possibly
suggest that coordination of the Li-atom in t-BuLi to the MOM moieties directs the
base in a proper orientation for intramolecular attack at the benzylic positions. The
monoclinic crystals obtained from AcOEt/hexane (P21/n, Z ˆ 2) contain (S)-21
arranged in two conformations, one (molecule 1) of which is depicted in Fig. 1. Both
molecules, in particular the one which is not shown (molecule 2), exhibit severe
disorder as a result of the flexible BnO and MOM residues. The torsion angle for
rotation about the chirality axis, C(6) C(1) C(23) C(24), in molecule 1 adopts a
value of 878, whereas it is significantly narrowed to 658 in molecule 2, illustrating the
well-known conformational flexibility of the 1,1'-binaphthalene moiety [60].
A satisfactory yield of (S)-22 (up to 66%) was finally obtained by treatment of (S)-
21 with 5 equiv. of BuLi in the presence of TMEDA in THF at 788, followed by
quenching with I2 at this temperature (Scheme 4). Sonogashira coupling [50] with
(trimethylsilyl)acetylene to give (S)-23 (98%) followed by alkyne deprotection
afforded the cyclization component (S)-24 (93%) in excellent yield. Among various Pd
catalysts, commercially available [1,1-bis(diphenylphosphino)ferrocene]dichloropalla-
dium(II) ´ CH2Cl2 ([PdCl2(dppf)] ´ CH2Cl2) gave the best yield in the shortest
conversion time (4 h) in the cross-coupling step. Glaser-Hay coupling of (S)-24
yielded, after gel-permeation chromatography (GPC), trimeric (S,S,S)-25 (25%), in
addition to higher oligomers which were not isolated. Acidic deprotection of (S,S,S)-25
under very dilute conditions to avoid naphtho[b]furan formation finally afforded
receptor (S,S,S)-1 in 77% yield.

Helvetica Chimica Acta ± Vol. 81 (1998)
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Fig. 1. X-Ray crystal structure of (S)-21. Only one of the two conformers (molecule 1) in the crystal is shown.
The vibrational ellipsoids are shown at the 30% probability level.
2.1.2. Synthesis of Receptors (S,S,S)- and (R,R,S)-2. The synthesis of these
receptors was greatly facilitated by starting from readily available, optically pure 1,1'-
binaphthalene-2,2'-diol ((R)-26 and (S)-26, resp.; Scheme 5). The resolution of (Æ)-26
on a large scale was performed by clathrate formation with N-benzylcinchonidinium
chloride [55e,g][61], yielding 10 ± 15 g of each enantiomer. After MOM protection of
(S)-26 to give (S)-27 (97%) [62], ortho-lithiation, followed by quenching with I2,
afforded (S)-28 in 65% yield. The optimal conditions for the iodination of
enantiomerically pure material differ from the published ones [58]: the most effective
method proved to be lithiation with 3.7 equiv. of BuLi and TMEDA in Et2O at room
temperature over 6.5 h, followed by addition of I2 in Et2O at 788. Sonogashira cross-
coupling using [PdCl2(PPh3)2] as the catalyst led to (S)-29 (90%), and protodesily-
lation provided (S)-30 (98%). Oxidative Glaser-Hay coupling yielded a mixture of
trimeric (S,S,S)-31 (37%), tetrameric (S,S,S,S)-32 (24%), and pentameric (S,S,S,S,S)-
33 (5%) which were separated by GPC. MOM Deprotection of the trimeric macrocycle
provided the target molecule (S,S,S)-2 (97%). The overall yield for the formation of
(S,S,S)-2 from (S)-26 was high (20%).
The construction of the macrocyclic skeleton in (R,R,S)-2 followed a stepwise
procedure (Scheme 6). The dialkynylated compound (R)-29 was prepared as described
above for its enantiomer, and slow mono-deprotection using borax (Na2B4O7) in THF/
H2O afforded (R)-34. When the reaction was quenched after 3.5 h, a mixture of starting
material (R)-29 (33%), desired product (R)-34 (42%), and doubly deprotected (R)-
30 (13%) was obtained. By repeating the reaction with recovered starting material
three times, the overall yield of (R)-34 was improved to 61%. Performing the same
reaction for 24 h led to (R)-30 in quantitative yield.
Dimerization of (R)-34 under Glaser-Hay conditions afforded (R,R)-35 (86%),
and alkyne deprotection gave (R,R)-36 (81%) which was subjected to a Glaser-Hay

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Scheme 5. Synthesis of (S,S,S)-2
a) MeOCH2Cl, NaH, THF, 208, 30 min, 97%. b) BuLi, TMEDA, Et2O, 208, 6.5 h, then I2, 788, 2 h, 65%. c)
Me3SiCꢀCH, [PdCl2(PPh3)2], CuI, Et3N, 408, 20 h, 90%. d) K2CO3, THF/MeOH 1 : 1, 208, 3 h, 98%. e) CuCl,
TMEDA, CH2Cl2, O2, 208, 2 h, 37% ((S,S,S)-31), 24% ((S,S,S,S)-32), 5% ((S,S,S,S,S)-33). f) Conc. aq. HCl
soln. (cat.), THF/MeOH 1 : 1, 208, 12 h, 97%.
cross-coupling with (S)-30. Slow addition of a solution of the two cyclization
components in CH2Cl2 to a solution of CuCl and TMEDA in CH2Cl2 under air
afforded diastereoisomeric mixtures of trimeric and tetrameric macrocyclic products,
from which pure (R,R,S)-31 (11%) and (S,S,S)-31 (4%) were isolated by GPC
followed by HPLC. The C2-symmetrical structure of (R,R,S)-31 was confirmed by its
1H- and 13C-NMR spectra which revealed three sets of naphthalene resonances of equal
intensity. Deprotection under mild acidic conditions finally led to the target compound
(R,R,S)-2 (79%).
2.1.3. Synthesis of Receptors (S,S,S)- and (S,S,R)-3. These macrocycles were also
synthesized starting from enantiomerically pure 1,1'-binaphthalene-2,2'-diol ((S)- or
(R)-26). Bromination of (S)-26 afforded the 6,6'-dibromo derivative (S)-37 (90%)
[63], and MOM protection led to (S)-38 (95%) (Scheme 7). The 2-phenylethyl groups
in (S)-39 were efficiently introduced (94%) by Suzuki cross-coupling [64] with B-(2-
phenylethyl)-9-borabicyclo[3.3.1]nonane (40), prepared in situ from styrene and 9-
borabicyclo[3.3.1]nonane (9-BBN) [65], using [PdCl2(dppf)] ´ CH2Cl2 as catalyst and
NaOH as base.
All other reaction steps were adopted from the sequence described above for the
preparation of (S,S,S)-2 and (R,R,S)-2 (Sect. 2.1.2) and proceeded in comparable
reaction times and yields. The D3-symmetrical receptor (S,S,S)-3 was formed by the
sequence (S)-39 !(S)-41 !(S)-42 !(S)-43 !(S,S,S)-44 (together with tetrameric
(S,S,S,S)-45) !(S,S,S)-3 (Scheme 8) in an overall yield of 13% (eight steps starting
from (S)-26). The C2-symmetrical counterpart (S,S,R)-3 was obtained by the sequence

Helvetica Chimica Acta ± Vol. 81 (1998)
Scheme 6. Synthesis of (R,R,S)-2
1941
a) Borax, THF/H2O, 208, 3.5 h, 42%. b) CuCl, TMEDA, CH2Cl2, O2, 208, 3 h, 86%. c) K2CO3, THF/MeOH 1:1,
208, 1.5 h, 81%. d) (S)-30, CuCl, TMEDA, CH2Cl2, O2, 208, 2 h, 11%. e) Conc. aq. HCl soln. (cat.), THF/MeOH
1:1, 208, 12 h, 79%.
Scheme 7. Synthesis of (S)-39
a) Br2, CH2Cl2, 788 !208, 3 h, 90%. b) MeOCH2Cl, K2CO3, DMF, 208, 12 h, 95%. c) [PdCl2(dppf)] ´ CH2Cl2,
NaOH, THF, 508, 15 h, 94%.
(S)-42 !(S)-46 !(S,S)-47 !(S,S)-48 !(S,S,R)-44 !(S,S,R)-3 (Scheme 9). All 2-
phenylethyl precursors to (S,S,S)-3 and (S,S,R)-3 are highly viscous oils, which
contrasts with the crystallinity of the 1,1'-binaphthalene precursors bearing BnO groups
in the 7,7'-positions or lacking functionality in the major groove.
2.2. Carbohydrate Recognition by the Synthetic Receptors 1 ± 3. CPK (Corey-
Pauling-Koltum)-model examinations and computer modeling (MacroModel V.5.5 and
V.6.0 [66]) suggested that the rigid, preorganized cavities with the six convergent H-
bonding sites in receptors 1 ± 3 would be complementary in size and shape to a
hexopyranose ring. Therefore, the complexation of octyl pyranosides was investigated
in the noncompetitive solvent CDCl3. The D3-symmetrical receptors are rather planar
in their overall shape, whereas the C2-symmetrical counterparts are much more
distorted from planarity (Fig. 2). Furthermore, the cavity of the latter is significantly

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Scheme 8. Synthesis of (S,S,S)-3
a) BuLi, TMEDA, Et2O, 208, 6.5 h, then I2, 788, 2 h, 73%. b) Me3SiCꢀCH, [PdCl2(PPh3)2], CuI, Et3N, 508,
2 h, 93%. c) K2CO3, THF/MeOH 1 : 1, 208, 3 h, 87%. d) CuCl, TMEDA, CH2Cl2, O2, 208, 1 h, 36% ((S,S,S)-44),
25% ((S,S,S,S)-45. e) Conc. aq. HCl soln. (cat.), THF/MeOH 1 : 1, 208, 12 h, 81%.
Scheme 9. Synthesis of (S,S,R)-3
a) Borax, THF/H2O, 208, 3.5 h, 28%. b) CuCl, TMEDA, CH2Cl2, O2, 208, 3 h. c) K2CO3, THF/MeOH 1:1, 208,
1.5 h, 76% from (S)-46. d) (R)-43, CuCl, TMEDA, CH2Cl2, O2, 208, 1 h, 23%. e) Conc. aq. HCl soln. (cat.),
THF/MeOH 1:1, 208, 12 h, 75%.

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narrowed. We expected that the reduced symmetry of the binding site and the tighter
host-guest fit provided by the C2-symmetrical receptors would translate into both
higher binding strength and enhanced substrate selectivity. As expected, the modeling
also showed that the size and shape of the receptor cavities are not affected by the
changes in peripheral functionality in 1 ± 3.
Fig. 2. Comparison of the energy-minimized structures of (R,R,R)-2 (left) and (S,S,R)-2 (right) (MacroModel
V.6.0, AMBER* force field, GB/SA solvation model for CHCl3). Similar binding sites are present in the
corresponding receptors 1 and 3.
2.2.1. 1H-NMR-Spectroscopic Investigations of the Complexation between 1-O-Octyl
Pyranosides and the D3-Symmetrical Receptors (R,R,R)-1 and (S,S,S)-1. The trimeric
receptors (R,R,R)-1/(S,S,S)-1 are highly soluble in CDCl3 (up to 20 mm) and do not
aggregate appreciably at concentrations below 5 mm, as determined by 1H-NMR
dilution experiments. Binding studies with 1-O-octyl pyranosides 49 ± 52 were carried
1
out at 300 K in dried CDCl3 by 500-MHz H-NMR titrations. The complexation-
induced downfield shift of the OH protons of the receptor, held at constant
concentration, was monitored as a function of the concentration of the guest. It was
experimentally impossible to approach the calculated shifts at saturation binding
(Ddsat) because of the overlap of the downfield-shifting OH signal with the aromatic
receptor resonances at higher degrees of complexation. Nevertheless, the maximum
observed degree of saturation (Ddmax obs up to 50 ± 60% of Ddsat) proved to be sufficient
1
in most assays for the reproducible determination of association constants Ka [l mol ]
1
and binding free enthalpies DG0 [kcal mol ] by nonlinear least-squares curve-fitting of

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the experimental titration data [67]. Other resonances of the receptors were not
affected by the addition of the carbohydrate guests.
The 1:1 complexes formed between (R,R,R)-1 or (S,S,S)-1, and pyranosides 49 ± 51
are of moderate stability, with association constants varying between Ka ˆ 110 and 370
1
1 mol 1 (Table 1). Diastereoselectivities of up to D(DG0) ˆ 0.7 kcal mol , and a small
1
enantioselectivity of D(DG0) ˆ 0.4 kcal mol was measured for the complexation of
octyl a-d- (49) and octyl a-l-pyranoside (50). Note that the binding free enthalpies
1
determined for the complexes of (S,S,S)-1 with 49 and 50 are 0.3 kcal mol more
negative than for the corresponding enantiomeric complexes formed by (R,R,R)-1.
Such a discrepancy between spectra measured more than three years apart could
originate from differences in the experimental titration conditions, such as the presence
of different amounts of residual H2O in the solvent [15][16]. In the titrations with
(R,R,R)-1, no residual H2O was present, whereas the 1H-NMR spectra recorded in the
titrations with (S,S,S)-1 displayed a small H2O peak at 1.54 ppm (c ꢁ 0.5 mm). Most
importantly, however, the enantioselectivities determined with the two enantiomeric
receptors are in complete agreement.
Table 1. Association Constants Ka [l mol 1] and Complexation Free Enthalpies DG0 [kcal mol 1] for 1:1
Complexes of Receptors (S,S,S)- and (R,R,R)-1 in CDCl3 (300 K). Also shown are the calculated and, in
parenthesis, the maximum observed complexation-induced upfield shifts Ddsat and Ddmax obs, of the receptor OH
protons.
Sugara)
Receptor
Kab) [l mol
]
DG0 [kcal mol
]
Ddsat (Ddmax obs)
1
1
49
50
51
49
50
51
(R,R,R)-1
(R,R,R)-1
(R,R,R)-1
(S,S,S)-1
(S,S,S)-1
(S,S,S)-1
210
110c)
370
170
350
240
3.2
2.8
3.5
3.1
3.5
3.3
2.01 (1.15)
2.29 (0.84)
2.48 (1.42)
2.09 (1.05)
1.90 (1.19)
2.03 (1.06)
a) Host concentration was constant at 0.5 mm, guest concentration varied between 0.5 ± 6.0 mm. b) Association
1
constants determined by nonlinear least-squares curve fitting of 500-MHz H-NMR titrations. Uncertainty in
Ka estimated at 20%. c) Higher uncertainty in Ka since only ca. 37% saturation binding reached.

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In control runs under the same conditions, no appreciable changes occurred in the
1H-NMR spectra of 1,1'-binaphthalene-2,2'-diol (R)-14 (c ˆ 0.5 mm) upon addition of
up to 12 equiv. of the pyranosides. This observation confirms that more than two OH
groups of the receptors (R,R,R)-1/(S,S,S)-1 contribute to the binding of the substrates
in the macrocyclic cavity.
The complexation of (R,R,R)-1 with a-d-mannoside 52 was also investigated, but a
broadening of the receptor OH signal at ambient temperature occurred, indicating an
intermediate host-guest exchange rate on the 1H-NMR time scale. This was confirmed
by variable-temperature studies. Fast exchange occurred at 330 K, whereas cooling to
240 K led to slow exchange and gave rise to a very complicated spectrum, since the low
symmetry of the pyranoside is imposed on the resonances of the receptor, with very
broad signals of bound host and guest. This slow host-guest exchange rate contrasts
with the rapid kinetics observed previously at similar binding strength for the
complexation of octyl pyranosides by open, cleft-type receptors [22a]. It supports a
complex geometry in which the sugar substrate fully penetrates into the macrocyclic
cavity rather than docking onto one of the two receptor faces.
1
2.2.2. H-NMR-Spectroscopic Investigations into the Sugar-Binding Ability of the
D3-Symmetrical Receptors (S,S,S)-2 and (S,S,S)-3. Like receptors (R,R,R)-1 and
(S,S,S)-1, the two trimeric macrocycles (S,S,S)-2 and (S,S,S)-3 are highly soluble in
CDCl3 and, at 300 K, do not aggregate at concentrations below 4 mm. When 1H-NMR
titration experiments with these receptors and octyl pyranosides at 300 K were
attempted, a strong broadening of all receptor proton signals occurred. This broadening
prevented determination of host-guest stoichiometries and association constants; it did,
however, provide evidence for sugar-receptor interactions. The OH resonance of the
receptors (0.5 mm) showed large downfield shifts upon addition of less than 1 equiv. of
carbohydrate. Due to the extreme broadening, however, it was impossible to follow this
signal over a meaningful titration range. Upon heating a solution of host and guest (c ˆ
0.5 mm) in CDCl2CDCl2 to 360 K, sharp signals were recovered; however, complex-
ation had vanished at this temperature. When a solution of (S,S,S)-3 (c ˆ 0.5 mm) and
49 (c ˆ 0.5 mm) in CDCl3 was cooled to 250 K, a spectrum at slow host-guest exchange
with sharp signals was obtained. Significant changes in the chemical shifts of the
aromatic receptor protons were observed, but the complexity of this spectrum
prevented the evaluation of the association strength by simple integration of signals of
free and bound macrocycle. The symmetry of the complex is reduced by the bound
pyranoside. The existence of different, energetically similar complex conformations
could further increase the number of resonances. Additionally, the stoichiometry of the
formed host-guest associations remained uncertain. Attempts to determine the
association strength by other methods (UV/VIS or circular dichroism (CD) titrations)
1
were unsuccessful. Also, the addition of co-solvents did not improve the H-NMR
titration results.
What causes the drastically different titration behavior of (S,S,S)-2 and (S,S,S)-3, as
compared to (R,R,R)-1 or (S,S,S)-1 for which the determination of association
constants from 1H-NMR binding titrations was quite straightforward (Sect. 2.2.1)? All
four receptors possess structurally identical cavity binding sites; they only differ by the
functionality attached to the major grooves of the 1,1'-binaphthalene spacers. Large
differences in the H-bonding donor-acceptor ability of the OH groups at the minor

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grooves of the 1,1'-binaphthalene spacers due to the differences in the major groove
functionality can be excluded with confidence. We assume that the strong signal
broadening observed at 300 K for solutions of receptors (S,S,S)-2 or (S,S,S)-3 and octyl
pyranosides does not reflect a stronger 1 :1 host-guest binding than had been observed
for the two D3-symmetrical enantiomers of 1 (Table 1). Rather, we suggest that it
originates from carbohydrate-induced aggregation and higher-order complexation. All
three D3-symmetrical receptors 1 ± 3 possess a rather flat macrocyclic framework with
three OH groups oriented to each face (see Fig. 2). A sandwich-type complexation
mode is conceivable, by which the sugar interacts with the OH groups on the interior
faces of two surrounding receptor molecules, leading to host-guest associations with
2 :1 stoichiometry and possibly even to more extended columnar aggregates ´´ H ´´ G ´´
H ´´ G ´´ H ´´ (H ˆ host, G ˆ guest). Apparently, the lateral BnO groups in receptor D3-
1 are efficient in preventing such higher-order complexation, and formation of cavity
inclusion complexes with 1 : 1 host-guest stoichiometry is observed. In contrast,
receptor D3-2 lacks any aggregation-preventing lateral functionality and the 2-
phenylethyl groups in D3-3 do not seem to be effective in preventing sandwich-type
complex geometries with higher stoichiometry.
2.2.3. 1H-NMR-Spectroscopic Investigations into the Sugar-Binding Ability of
(R,R,S)-2 and (S,S,R)-3. With their less planar geometries, the C2-symmetrical
receptors were not expected to undergo a sandwiching complexation of sugar
substrates, and this was confirmed in the binding studies. However, 1H-NMR titrations
with (R,R,S)-2 turned out to be impossible because of the insolubility of the receptor in
CDCl3. In contrast, the macrocycle (S,S,R)-3, with its flexible 2-phenylethyl groups at
the cavity periphery, proved to be readily soluble, and titrations at 300 K in CDCl3 were
not hampered by any signal broadening.
Octyl pyranosides and C2-symmetrical (S,S,R)-3 form 1:1 complexes with
association constants up to 10-fold higher (Table 2) than those measured for the
corresponding complexes of D3-symmetrical (R,R,R)- and (S,S,S)-1 (Table 1). In the
binding titrations at constant receptor concentration (c ˆ 0.5 mm), the small (Ddsat
<
0.1 ppm) but highly reproducible upfield changes in the chemical shift of the sharp
aromatic receptor signals of H C(4), H C(4'), and H C(4'') (for numbering, see
Scheme 9) upon addition of the monosaccharides were evaluated. Since the signals of
these three resonances appear at nearly identical chemical shift (Fig. 3), their averaged
Dd values were considered. Upon addition of a large excess of carbohydrate, values of
the maximum observed upfield shifts (Ddmax obs) very close to the calculated saturation
shifts (Ddsat) were measured. Other aromatic resonances of (S,S,R)-3 such as H C(8),
H
C(8'), and H C(8'') also displayed significant complexation-induced changes in
chemical shift (Fig. 3) which, due to the multiplicity of the resonances, could, however,
not be evaluated with the same accuracy. Analysis of the larger complexation-induced
downfield shifts of the receptor OH protons (Ddsat >> 1.0 ppm) was less informative,
because of the overlap with the aromatic signals over a significant part of the titration.
However, where measurement was possible, comparable association constants to those
obtained from the resonances of H C(4), H C(4'), and H C(4'') were obtained.
The selectivity in the complexation of octyl pyranosides by (S,S,R)-3 is remarkable:
1
diastereoselectivities up to 1.3 kcal mol were observed, and the enantioselectivity
1
(D(DG0) ˆ 0.9 kcal mol ) for the preferred binding of octyl a-l-glucoside (50) over

Helvetica Chimica Acta ± Vol. 81 (1998)
1947
Table 2. Association Constants Ka [l mol 1] and Complexation Free Enthalpies DG0 [kcal mol 1] for 1:1
Complexes of Receptor (S,S,R)-3 in CDCl3 (300 K). Also shown are the averaged calculated complexation-
induced upfield shifts Ddsat of the aromatic proton H C(4), H C(4'), and H C(4'').
Sugara)
Kab) [l mol
]
DG0 [kcal mol
]
Ddsat
H2O [mm]
1
1
49
49
50
51
51
51
53
1110
1190
4440
3260
2950
3360
560
4.1
4.2
5.0
4.8
4.7
4.8
3.7
0.049
0.048
0.036
0.048
0.050
0.049
0.051
0
3.0
0
0
1.5
6
0
a) Host concentration was constant at 0.5 mm, guest concentration varied between 0.5 ± 9.0 mm. b) Association
constants determined by nonlinear least-squares curve fitting of 500-MHz 1H-NMR titrations. Uncertainties in
Ka estimated at Æ20%.
Fig. 3. Part of the 1H-NMR spectrum of (S,S,R)-3 (0.5 mm) alone (a), and in the presence of 1.2 mm of 50 (b)
and 5.8 mm of 50 (c)

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Helvetica Chimica Acta ± Vol. 81 (1998)
octyl a-d-glucoside (49) is the highest so far observed for carbohydrate recognition
1
with synthetic receptors. When H-NMR titration experiments were performed with
octyl b-l-glucoside (54), the host-guest exchange rate became so slow that sharp signals
for unbound and bound receptor were visible at ambient temperature which, in this
case, is indicative of a very strong association. Unfortunately, signal assignments in the
complex and determination of quantitative binding data were unsuccessful. Never-
theless, it can be stated with confidence that (S,S,R)-3 has a higher affinity for l-
glucosides than for d-glucosides.
The observation of upfield shifts for several aromatic protons of (S,S,R)-3 indicates
that the receptor undergoes substrate-induced structural changes. This contrasts with
the results for (R,R,R)-1 and (S,S,S)-1, where only changes in the chemical shifts of the
OH protons were observed. Structural analysis by computer modeling indicated that
receptor (S,S,R)-3 not only contains a cavity with a smaller diameter (Fig. 2) than the
D3-symmetrical counterpart, but that the binding site is also more flexible. Monte Carlo
conformational searches (MacroModel V.6.0 [66], 4000 steps, AMBER*, GB/SA
solvation model for CHCl3) revealed for (S,S,R)-2 (as model for (S,S,R)-3) a total of six
conformers with 5 kcal mol 1 above the calculated global minimum structure, whereas
for (R,R,R)-2 only two conformers were found in this energy range.
The energy-minimized structure of the stable complex formed between (S,S,R)-2
and octyl a-l-glucoside (50) is depicted in Fig. 4. It shows clearly the tight host-guest fit
Fig. 4. The energy-minimized structure of the complex formed between (S,S,R)-2 (as a model for (S,S,R)-3) and
octyl a-l-glucoside (50) (MacroModel V.6.0, AMBER* force field, GB/SA solvation model for CHCl3). Shown
are the intermolecular H ´´´ O H-bonding distances in the complex.

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1949
in the inclusion complex with several short intermolecular H-bonds in which the sugar
OH groups participate cooperatively both as H-bond donors and acceptors. Exper-
imental evidence for such a tight fit was not only obtained by the large association
constants measured but also by the invariance of the complexation strength with
respect to small amounts of H2O in the titration solutions (Table 2). Bonar-Law and
Sanders [15] had observed higher binding strength when small amounts of H2O or
MeOH were added to solutions of carbohydrates and synthetic receptors in CDCl3.
Their receptors were too large to provide a tight fit to the substrate, and the co-solvents
were proposed to act as mortar and to enhance the associations by bridging the binding
partners via H-bonding. In our study, small amounts of H2O did not at all affect the
binding of pyranosides to (S,S,R)-3 (Table 2). The host-guest fit is already very tight in
the narrow cavity binding site, and there is no space to accommodate extra H2O
molecules.
3. Conclusions. ± Remarkable differences in the carbohydrate recognition proper-
ties were observed in the series of optically active D3-symmetrical ((S,S,S) and
(R,R,R)) and C2-symmetrical ((S,S,R) and (R,R,S)) macrocycles 1 ± 3. They all possess
a cavity lined with six convergent OH groups for H-bonding recognition and
complementary in size and shape to a monosaccharide. Whereas the D3-symmetrical
receptors possess, on average, quite planar geometries, the C2-symmetrical counter-
parts are much less planar. The recognition sites in the latter are also smaller and more
flexible, thereby providing a better fit to a complexed sugar guest.
The major difference in the series 1 ± 3 consists in the functional groups attached to
the periphery of the macrocycles. The BnO (in 1) and 2-phenylethyl (in 3) groups were
initially introduced to solubilize the receptors in the concentration ranges needed for
1H-NMR titrations in the noncompetitive solvent CDCl3. Whereas the solubility
properties of 1 and 3 were satisfactory, macrocycle (R,R,S)-2, lacking peripheral
functionality, was indeed found to be too insoluble for binding studies. An unexpected
advantage of the BnO groups in the 7,7'-positions of the 1,1'-binaphthalene spacers in 1
over the 2-phenylethyl groups in the corresponding 6,6'-positions in 3 only became
clear during the binding titrations. The flat D3-symmetrical macrocycle (S,S,S)-3 (as
well as (S,S,S)-2 without major-groove functionality) displayed a strong tendency to
form higher order, presumably sandwich-type complexes with the octyl pyranoside
substrates, and the determination of 1:1 host-guest association strength was, therefore,
not possible. In contrast, the 7,7'-BnO groups in (S,S,S)-1 and (R,R,R)-1 apparently
prevent this higher-order complexation mode effectively, and stoichiometric 1 :1
complexation could be investigated. No such higher-order complexation, which is
indicated by a very strong peak broadening in the 1H-NMR spectra, was observed with
the less planar macrocycle (S,S,R)-3. These findings underline in an impressive way the
relevance of a proper design of structural details not directly associated with the
binding interaction but ensuring solubility and preventing aggregation of a receptor.
The flat D3-symmetrical receptors (S,S,S)-1 and (R,R,R)-1 displayed only
moderate binding affinities and selectivities, whereas (S,S,R)-3 showed remarkable
association strength and selectivity. Aromatic OH groups are not the most efficient H-
bond donor and acceptor groups, yet the concerted binding of the sugar by a cyclic
1
array of these groups provides complex stabilities around DG0 ˆ 5.0 kcal mol .

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1
With diastereoselectivities up to D(DG0) ˆ 1.3 kcal mol and enantioselectivities of
1
D(DG0) ˆ 0.9 kcal mol , (S,S,R)-3 is among the most selective artificial carbohydrate
receptors known. Complexation occurs at present only in noncompetitive solvents such
as CDCl3. In future work, we hope to provide the necessary hydrophobic desolvation,
dispersion interactions, and C H ´´´ p interactions by attaching aromatic caps to the
receptor, to sandwich the saccharide guest bound to the cyclic array of OH groups in
the cavity. This may be a way to achieve complexation in competive protic solvents and,
ultimately, in H2O.
Experimental Part
General. All reactions were carried out under N2. Solvents and reagents were reagent-grade and
commercially available and used without further purification unless otherwise stated. THF and Et2O were
freshly distilled from sodium benzophenone ketyl. Evaporation in vacuo was conducted at H2O aspirator
pressure. Column chromatography (CC): SiO2 60 (230 ± 400 mesh, 0.040 ± 0.063 mm) from E. Merck (for
products containing MOM-protecting groups) or Fluka; visualization by UV light. M.p.: Büchi SMP-20;
uncorrected. IR Spectra (cm 1): Perkin-Elmer 1600-FT IR. NMR Spectra: Bruker AMX 500 or AMX 400, and
Varian Gemini 300 or 200 at 296 or 300 K, with solvent peak as reference. MS (m/z (%)): EI: VG TRIBRID
spectrometer at 70 eV; FAB: VG ZAB2-SEQ spectrometer with 3-nitrobenzyl alcohol (NOBA) as matrix;
MALDI-TOF-MS: Bruker Reflex spectrometer with 2-(4-hydroxyphenylazo)benzoic acid (HABA), a-cyano-
4-hydroxycinnamic acid (CCA), 2,4,6-trihydroxyacetophenone/diammonium citrate (THA/citrate) 2 :1, or
1,8,9-trihydroxyanthracene (dithranol) as matrix; positive-ion mode. Prep. gel-permeation chromatography
(GPC): Biobeads SX-1 or SX-3 from Biorad, eluent toluene or CH2Cl2; detection at 300 nm by UV detector
from Knauer. Elemental analyses were performed by the Mikrolabor at the Laboratorium für Organische
Chemie, ETH-Zürich.
Computer Modeling. For the simulations of receptors and host-guest complexes, Version 6.0 of Macro-
Model [66] was applied (Monte Carlo simulation, 4000 steps, AMBER* force field, GB/SA solvation model for
CHCl3). The AMBER* force field was modified to include buta-1,3-diyne parameters. For this purpose, an X-
ray crystal structure of 1,4-diphenylbuta-1,3-diyne [68] provided values for the bond distances and angles,
whereas stretching and bending force field constants adapted from AMBER* supplied C(sp2) CꢀC
parameters.
1H-NMR Binding Titrations. Quantitative binding data (Ka, DG0, Ddsat) were determined by nonlinear
least-squares curve fitting of 1H-NMR titration data (500 MHz, 300 K) in dry CDCl3 using the program
Associate V.1.6 [67]. Commercially available guests were used without further treatment. Pyranosides 50 [69]
and 54 [70] were prepared according to published procedures. The host concentration was kept constant at
0.5 mm, and a soln. of guest (and 0.5 mm host) was added in portions via microsyringe to the septum-capped
NMR tube containing the host and freshly activated, powdered 4-Š molecular sieves. After each addition, a
1H-NMR spectrum was taken. To obtain reproducible binding results, the solvent was carefully dried. Therefore,
CDCl3 was first allowed to stand over anh. K2CO3 and molecular sieves (4 Š) for at least 24 h prior to the
titration experiment. This served to both deacidify the CDCl3 and partially dry it. The remaining traces of H2O
1
(ca. 3 mm according to the H-NMR spectrum) in the decanted solvent were removed by the addition of just
enough freshly activated, powdered 4-Š molecular sieves to the NMR tube containing the titration soln., to
cause, in most cases, the disappearance of the H2O peak at 1.54 ppm (there should be no excess of sieves
present). Bonar-Law and Sanders had previously shown that these experimental conditions do not affect the
complexation of pyranosides [15].
6-Bromo-7-(methoxymethoxy)naphthalen-2-ol (5). To a degassed mixture of 3-bromonaphthalene-2,7-diol
(4) [41] (15.0 g, 62.7 mmol) and K2CO3 (7.5 g, 54.3 mmol) in dry MeCN (300 ml), MeOCH2Cl (MOMCl)
(6.5 ml, 6.9 g, 85.7 mmol) was added at 188 over 2 h via syringe pump. After stirring for 2 h, 0.1m aq. HCl soln.
(150 ml) was added, and the product extracted with AcOEt. The org. phase was washed with sat. aq. NaCl soln.,
dried (Na2SO4), and evaporated in vacuo. CC (hexane/AcOEt 5 : 1 with 0.5% Et3N) afforded 5 (8.9 g, 50%).
White solid. M.p. 107 ± 1088. IR (CHCl3): 3324s (br.), 2942w, 1624m, 1592w, 1501m, 1455w, 1437w, 1369m, 1200s,
1146s, 1078m, 1005m, 968m. 1H-NMR (300 MHz, CDCl3): 3.56 (s, 3 H); 5.13 (s, 1 H); 5.35 (s, 2 H); 6.99 (dd, J ˆ
8.7, 2.5, 1 H); 7.03 (d, J ˆ 2.5, 1 H); 7.31 (s, 1 H); 7.59 (d, J ˆ 8.7, 1 H); 7.98 (s, 1 H). 13C-NMR (50 MHz,
(CD3)2CO): 56.23; 95.48; 108.83; 110.06; 110.33; 117.92; 125.63; 129.05; 132.42; 135.89; 152.02; 156.82. EI-MS:

Helvetica Chimica Acta ± Vol. 81 (1998)
1951
‡
‡
282 (35, M , 79BrC12H11O3), 45 ([CH3OCH2] ). Anal. calc. for C12H11BrO3 (283.12): C 50.91, H 3.92, Br 28.22;
found: C 50.97, H 3.99, Br 28.37.
6-(Benzyloxy)-2-bromo-3-(methoxymethoxy)naphthalene (6). To
a degassed mixture of 5 (4.0 g,
14.1 mmol) and K2CO3 (4.0 g, 28.9 mmol) in dry DMF (40 ml), BnCl (2.0 ml, 2.2 g, 17.4 mmol) was added,
and the mixture was stirred at 808 for 1 h. The salts were removed by filtration through Celite. Evaporation in
vacuo afforded 6 (5.0 g, 94%). White solid (toluene). M.p. 114 ± 1158. IR (CHCl3): 3010m, 2935w, 1627s, 1594m,
1503s, 1454m, 1391m, 1244m, 1227m, 1152s, 1086m, 1015s, 976m, 884m. 1H-NMR (300 MHz, CDCl3): 3.57
(s, 3 H); 5.16 (s, 2 H); 5.36 (s, 2 H); 7.11 ± 7.15 (m, 2 H); 7.35 ± 7.49 (m, 6 H); 7.61 (d, J ˆ 9.7, 1 H); 7.98 (s, 1 H).
13C-NMR (75 MHz, CDCl3): 56.43; 70.03; 95.14; 106.48; 110.25; 110.93; 118.10; 125.64; 127.56; 128.10; 128.28;
‡
‡
128.68; 131.95; 134.72; 136.72; 151.74; 157.29. EI-MS: 374 (38, M , 79BrC19H17O3), 91 (100, [C7H7] ). Anal. calc.
for C19H17BrO3 (373.25): C 61.14, H 4.59, Br 21.41; found: C 61.08, H 4.68, Br 21.18.
7-(Benzyloxy)-3-bromonaphthalen-2-ol (7). A soln. of 6 (5.0 g, 13.4 mmol) and conc. aq. HCl soln. (37%,
5 ml) in THF/MeOH 2 :1 (100 ml) was heated to reflux for 3 h. After cooling to r.t., the mixture was quenched
with H2O (50 ml), extracted with CH2Cl2, and the org. phase washed with sat. aq. NaCl soln. Evaporation in
vacuo gave 7 (4.3 g, 98%). White solid (toluene). M.p. 153 ± 1548. IR (CHCl3): 3521s (br.), 3010w, 1630s, 1604m,
1505s, 1454m, 1439m, 1394m, 1267s, 1228m, 1199s, 1155m, 1011m, 882m. 1H-NMR (300 MHz, (CD3)2CO): 5.17
(s, 2 H); 7.07 (dd, J ˆ 9.0, 2.7, 1 H); 7.21 (d, J ˆ 2.7, 1 H); 7.31± 7.56 (m, 6 H); 7.68 (d, J ˆ 9.0, 1 H); 8.03 (s, 1 H);
9.24 (s, 1 H). 13C-NMR (75 MHz, (CD3)2CO): 70.51; 106.58; 110.29; 110.59; 117.92; 125.78; 128.56; 128.72;
‡
‡
129.14; 129.32; 132.68; 136.38; 138.20; 152.97; 158.50. EI-MS: 330 (19, M , 79BrC17H13O2), 91 (100, [C7H7] ).
Anal. calc. for C17H13BrO2 (329.20): C 62.03, H 3.98, O 9.72, Br 24.27; found: C 62.11, H 3.97, O 9.81, Br 24.32.
(Æ)-7,7'-Bis(benzyloxy)-3,3'-dibromo-1,1'-binaphthalene-2,2'-diol ((Æ)-8). Method A: A soln. of 7 (15 g,
46 mmol) and CuCl2 (12.6 g, 94 mmol) in MeOH (1.5 l) was degassed, saturated with Ar, and t-BuNH2 (21.0 ml,
14.6 g, 200 mmol) in MeOH (150 ml) was added slowly. The mixture was heated to reflux for 1 h, then cooled to
08, and quenched with 6m aq. HCl soln. (600 ml) to yield a yellow precipitate which was filtered and redissolved
in CHCl3. The org. phase was washed with H2O until neutral and evaporated in vacuo to afford (Æ)-8 (12.5 g,
84%). White powder (toluene).
Method B: To a soln. of CuCl(OH) ´ TMEDA [45] (56 mg, 2 mol-%) in CH2Cl2 (200 ml), 7 (3.8 g,
11.5 mmol) was added at 08. The mixture was stirred for 46 h at r.t., and then washed with 0.1m aq. NH3 soln. and
sat. aq. NaCl soln. Evaporation in vacuo gave (Æ)-8 (2.4 g, 64%). White crystalline solid (toluene). M.p. 207 ±
2088. IR (CHCl3): 3511m, 3022w, 1622s, 1494m, 1450w, 1378m, 1267m, 1194s, 1072w, 1028w. 1H-NMR (300 MHz,
CDCl3): 4.72 (d, AB, J ˆ 12.3, 2 H); 4.79 (d, AB, J ˆ 12.3, 2 H); 5.45 (s, 2 H); 6.38 (d, J ˆ 2.4, 2 H); 7.10 ± 7.27
(m, 12 H); 7.72 (d, J ˆ 9.0, 2 H); 8.15 (s, 2 H). 13C-NMR (75 MHz, CDCl3): 69.9; 104.8; 109.2; 113.6; 117.8;
‡
125.3; 127.5; 127.9; 128.5; 129.0; 132.4; 134.1; 136.1; 136.3; 148.5; 158.0. FAB-MS: 656 (100, M ). Anal. calc. for
C34H24Br2O4 (656.38): C 62.22, H 3.69, O 9.75, Br 24.35; found: C 62.32, H 3.97, O 9.55, Br 24.30.
Optical Resolution of (Æ)-8.
( )-[(R)-7,7'-Bis(benzyloxy)-3,3'-dibromo-1,1'-binaphthalene-2,2'-diyl]
[(1R,2S,5R)-5-Methyl-2-(1-methylethyl)cyclohexyl] Phosphite (( )-9). To PCl3 (1.12 ml, 1.76 g, 12.8 mmol)
in dry THF (15 ml) was added over 30 min at 08 a soln. of ( )-(1R,2S,5R)-menthol (2.97 g, 19.0 mmol) in THF
(15 ml). The mixture was cooled to 188, and dry Et3N (5.35 ml, 3.89 g, 38.4 mmol) was added. After stirring
for 15 min, a portion of this suspension (27 ml, 9.47 mmol) was added to (Æ)-8 (6.87 g, 10.47 mmol) in dry THF
(15 ml) at 188. The instantaneous disappearance of (Æ)-8 was monitored by TLC (toluene). The white
insoluble Et3NHCl was removed by filtration through Celite, and Et2O (200 ml) was added to the filtrate, and
the soln. evaporated in vacuo. Pure ( )-9 (3.23 g, 37%) was obtained by two recrystallizations at 188 from
Et2O. M.p. 181 ± 1828. [a]Dr:t:
ˆ
394.5 (c ˆ 1.0, CH2Cl2). IR (CHCl3): 2956m, 2922m, 2867m, 1622s, 1578w, 1500s,
1450m, 1383s, 1317w, 1217s, 978s, 883m, 844s. 1H-NMR (500 MHz, CDCl3): 0.83 ± 2.39 (m, 18 H); 4.20 ± 4.35
(m, 1 H); 4.53 (d, AB, J ˆ 11.8, 2 H); 4.60 (d, AB, J ˆ 11.8, 2 H); 6.55 (d, J ˆ 2.4, 1 H); 6.57 (d, J ˆ 2.4, 1 H);
7.00 ± 7.24 (m, 12 H); 7.71 (d, J ˆ 6.2, 1 H); 7.73 (d, J ˆ 6.2, 1 H); 8.13 (s, 1 H); 8.16 (s, 1 H). 13C-NMR
(125 MHz, CDCl3): 15.59; 15.62; 21.00; 22.07; 22.72; 24.96; 31.89; 34.03; 44.11; 44.14; 48.51; 48.53; 69.93; 78.22;
78.39; 106.89; 107.09; 113.24; 113.34; 119.12; 119.35; 123.17; 124.76; 124.80; 126.98; 127.17; 127.22; 127.41;
127.93; 127.95; 128.48; 128.82; 128.98; 132.21; 132.41; 132.47; 132.65; 136.26; 136.33; 144.89; 145.66; 157.22;
157.29 (There should be a total of 40 13C resonances; extra signals are caused by J(31P,13C) of 3 Hz.) 31P-NMR
‡
‡
(121.5 MHz, CDCl3): 155.1. FAB-MS: 841 (21, M ), 703 (100, [M C10H19] ). Anal. calc. for C44H41Br2O5P
(840.60): C62.87, H 4.92, O 9.52, Br 19.01, P 3.68; found: C 62.97, H 4.97, O 9.44, Br 18.84, P 3.59.
Compound (‡)-9 (679 mg, 24%) was obtained following the same procedure, starting with (‡)-(1S,2R,5S)-
menthol and (Æ)-8 (2.20 g, 3.35 mmol). [a]Dr:t: ˆ‡ 394.5 (c ˆ 1.0, CH2Cl2). 31P-NMR (121.5 MHz, CDCl3): 155.3.
Hydrolysis of ( )-9. Compound ( )-9 (2.0 g, 2.4 mmol) was stirred with K2CO3 (2.0 g, 14.5 mmol) in
CHCl3/MeOH 1:1 (200 ml) for 30 min. The reaction was quenched with H2O (100 ml), and the product

1952
Helvetica Chimica Acta ± Vol. 81 (1998)
extracted with CHCl3. Evaporation in vacuo yielded ( )-(R)-8 (1.5 g, 97%) which was further converted
without purification. A small amount was recrystallized from toluene to give a white solid with spectroscopic
data identical to those of the racemic material (Æ)-8 and [a]Dr:t:
ˆ
79.4 (c ˆ 1.0, CH2Cl2).
Compound (‡)-9 was converted to (‡)-(S)-8 ([a]rD:t: ˆ‡ 79.4 (c ˆ 1.0, CH2Cl2)) in the same way.
(
)-(R)-2,2',7,7'-Tetrakis(benzyloxy)-1,1'-binaphthalene (( )-(R)-10). A soln. of (R)-8 (50 mg, 76 mmol),
ammonium formate (167 mg, 2.6 mmol), and Pd/C (10%, 36 mg) in MeOH (5 ml) was heated to reflux. After
30 min, the mixture was filtered through Celite and evaporated in vacuo. The crude product was treated with
BnCl (100 ml, 110 mg, 0.87 mmol) and K2CO3 (0.48 g, 3.5 mmol) in DMF (10 ml) at 808 for 2 h, DMF was
removed, the product was purified by CC (hexane/AcOEt 4 :1), and then recrystallized from CH2Cl2 with
layered addition of hexane to afford (R)-10 (8 mg, 15%). [a]Dr:t:
ˆ
15.2 (c ˆ 0.5, CH2Cl2). 1H-NMR (300 MHz,
CDCl3): 4.65 (d, AB, J ˆ 11.7, 2 H); 4.71 (d, AB, J ˆ 11.7, 2 H); 4.91 (d, AB, J ˆ 12.6, 2 H); 4.98 (d, AB, J ˆ 12.6,
2 H); 6.90 ± 7.30 (m, 24 H); 6.52 (d, J ˆ 2.4, 2 H); 7.79 (d, J ˆ 9.0, 2 H); 7.84 (d, J ˆ 8.7, 2 H). 13C-NMR
(75 MHz, CDCl3): 69.6; 71.0; 105.4; 113.6; 116.8; 119.9; 125.1; 126.7; 127.2; 127.5; 127.7; 128.1; 128.4; 128.8;
‡
‡
129.4; 135.3; 136.8; 137.7; 154.6; 157.1. FAB-MS: 678 (22, M ), 91 (100, [C7H7] ).
(‡)-(R)-7,7'-Bis(benzyloxy)-3,3'-dibromo-1,1'-binaphthalene-2,2'-diyl Dibenzoate ((‡)-(R)-11). To a soln.
of (R)-8 (1.30 g, 2.0 mmol) in CH2Cl2 (100 ml), pyridine (0.33 ml, 0.32 g, 4.0 mmol), DMAP (0.49 g, 4.0 mmol),
and BzCl (0.58 ml, 0.64 g, 5.0 mmol) were added at 08. The mixture was stirred at r.t. for 2 h and then washed
with 0.02m aq. CuSO4 soln., 20% aq. NaHCO3 soln., and H2O. Evaporation in vacuo and purification by CC
(hexane/AcOEt 5 :1) afforded (R)-11 (1.64 g, 95%). White solid. M.p. 146 ± 1488. [a]rD:t: ˆ‡ 8.0 (c ˆ 1.0,
CH2Cl2). IR (CHCl3): 3181w, 3149w, 1742s, 1622m, 1584w, 1499m, 1452m, 1384m, 1260s, 1224s, 1178m, 1150w,
1078m, 1059m, 1039m, 930m. 1H-NMR (200 MHz, CDCl3): 4.71 (d, AB, J ˆ 12.0, 2 H); 4.89 (d, AB, J ˆ 12.0,
2 H); 6.60 (br. s, 2 H); 7.10 ± 7.60 (m, 18 H); 7.67 (d, J ˆ 9.1, 2 H); 7.81 (br. s, 4 H); 8.10 (s, 2 H). 13C-NMR
(75 MHz, CDCl3): 69.95; 106.17; 112.87; 120.38; 125.14; 127.62; 127.90; 127.97; 128.42 (2Â); 128.64; 128.77;
‡
‡
130.08; 132.52; 133.49 (2Â); 136.42; 145.11; 157.51; 163.81. FAB-MS: 864 (12, M ), 105 (100, [C7H5O] ). Anal.
calc. for C48H32Br2O6 (864.59): C 66.68, H 3.73, O 11.10, Br 18.48; found: C 66.52, H 3.88, Br 18.29.
(‡)-(R)-7,7'-Bis(benzyloxy)-3,3'-bis[(trimethylsilyl)ethynyl]-1,1'-binaphthalene-2,2'-diyl Dibenzoate ((‡)-
(R)-12). 1-(Trimethylsilyl)-2-(trimethylstannyl)ethyne (1.5 ml, 1.8 g, 6.7 mmol) [49], (R)-11 (2.0 g, 2.3 mmol),
[Pd(PPh3)4] (10 mol-%, 267 mg), and 2,6-di-(tert-butyl)-p-cresol (200 mg, 10% by weight) were added to dry
toluene (20 ml). The mixture was heated to 1008 under Ar for 36 h. The black precipitate was removed by
filtration through Celite, and the soln. washed with H2O. CC (Fluka SiO2-H; hexane/AcOEt 99.5 :0.5 !99 : 1),
followed by recrystallization from CH2Cl2 with layered addition of pentane, afforded (R)-12 (932 mg, 45%).
M.p. 170 ± 1728. [a]rD:t: ˆ‡ 1.6 (c ˆ 1.0, CH2Cl2). IR (CCl4): 3066w, 2960m, 2898w, 2155m, 1744s, 1621s, 1495m,
1
1452m, 1410w, 1389m, 1314w. H-NMR (300 MHz, CDCl3): 0.06 (s, 18 H); 4.75 (d, AB, J ˆ 12.0, 2 H); 4.92
(d, AB, J ˆ 12.0, 2 H); 6.69 (s, 2 H); 7.55 ± 7.71 (m, 18 H); 7.72 (d, J ˆ 9.0, 2 H); 7.86 (m, 4 H); 8.08 (s, 2 H).
13C-NMR (75 MHz, CDCl3): 0.51; 69.87; 99.03; 100.62; 106.13; 114.18; 119.72; 123.37; 126.53; 127.79 (2Â);
128.19; 128.37; 129.42; 129.48; 130.14; 133.08; 133.58; 134.54; 136.47; 148.28; 157.96; 164.16. FAB-MS: 899 (24,
‡
‡
M ), 105 (100, [C7H5O] ). Anal. calc. for C58H50O6Si2 (899.21): C 77.47, H 5.60; found: C 77.30, H 5.82.
(‡)-(R)-7,7'-Bis(benzyloxy)-3,3'-diethynyl-1,1'-binaphthalene-2,2'-diyl Dibenzoate ((‡)-(R)-13). To a soln.
of (R)-12 (310 mg, 0.35 mmol) in THF/MeOH 1:1 (64 ml), K2CO3 (320 mg, 2.32 mmol) was added, and the
mixture was stirred at r.t. for 2 h. CH2Cl2 (160 ml) was added, the org. phase washed with H2O, and concentrated
to yield (R)-13 (237 mg, 91%). White powder (CH2Cl2/hexane). M.p. 95 ± 978. [a]rD:t: ˆ‡ 26.6 (c ˆ 1.0, CH2Cl2).
1
IR (CCl4): 3312m, 3066w, 2957w, 2110w, 1742s, 1622m, 1495m, 1452m, 1387m, 1260m, 1262s, 1071m. H-NMR
(300 MHz, CDCl3): 3.12 (s, 2 H); 4.75 (d, AB, J ˆ 12.0, 2 H); 4.92 (d, AB, J ˆ 12.0, 2 H); 6.67 (br. s, 2 H); 7.10 ±
7.60 (m, 18 H); 7.73 (d, J ˆ 9.0, 2 H); 7.80 ± 7.85 (m, 4 H); 8.10 (s, 2 H). 13C-NMR (75 MHz, CDCl3): 69.92;
79.50; 81.28; 106.01; 113.30; 119.94; 123.48; 126.54; 127.69; 127.84; 128.27; 128.38; 129.15; 129.42; 129.98; 133.18;
‡
‡
134.30; 134.58; 136.39; 147.98; 158.12; 164.22. FAB-MS: 755 (27, M ), 105 (100, [C7H5O] ). Anal. calc. for
C52H34O6 (754.85): C 82.74, H 4.54; found: C 82.94, H 4.73.
(
)-(R)-7,7'-Bis(benzyloxy)-3,3'-diethynyl-1,1'-binaphthalene-2,2'-diol (( )-(R)-14). To a soln. of (R)-13
(70 mg, 9.3 mmol) in THF (40 ml), KOH (1.9m soln. in MeOH, 50 ml, 95 mmol) was added, and the mixture was
stirred for 1 h at r.t. The soln. was poured into Et2O (40 ml), washed with H2O (3 Â 100 ml), dried (Mg2SO4),
and evaporated to afford (R)-14 (40 mg, 79%). Cream-colored solid. M.p. 174 ± 1768. [a]Dr:t:
ˆ
50 (c ˆ 1.0,
CH2Cl2). IR (CCl4): 3528m, 3307m, 2100w, 1625s, 1497m, 1453w, 1380w, 1264m, 1220s, 1141m, 1020w. 1H-NMR
(300 MHz, CDCl3): 3.49 (s, 2 H); 4.72 (d, AB, J ˆ 12.0, 2 H); 4.80 (d, AB, J ˆ 12.0, 2 H); 5.60 (s, 2 H); 6.40
(d, J ˆ 9.0, 2 H); 7.08 ± 7.23 (m, 12 H); 7.75 (d, J ˆ 9.0, 2 H); 8.09 (s, 2 H). 13C-NMR (75 MHz, CDCl3): 69.8;
79.1; 83.2; 104.8; 108.3; 112.2; 117.5; 124.0; 127.6; 127.9; 128.5; 129.9; 134.1; 135.4; 136.3; 152.0; 158.6. FAB-MS:
‡
‡
546 (51, M ), 91 (100, [C7H7] ). Anal. calc. for C38H26O4 (546.63): C 83.50, H 4.79; found: C 83.27, H 4.97.

Helvetica Chimica Acta ± Vol. 81 (1998)
1953
Glaser-Hay Cyclization of (‡)-(R)-13. A soln. of CuCl (2.71 g, 27 mmol) and (R)-13 (150 mg, 0.2 mmol) in
CH2Cl2 (1 l) was stirred for 10 min under dry air, then TMEDA (4.21 ml, 3.24 g, 28 mmol) was added. After
20 min, the reaction was quenched with H2O (1 l), the org. phase washed with H2O, and concentrated. The
above procedure was repeated, and the cyclic oligomers were then isolated by CC (cyclohexane !cyclohexane/
AcOEt 4 : 1) to afford (R,R,R)-15 (62 mg, 20%), in addition to tetramer (R,R,R,R)-16 (62 mg, 20%), and
pentamer (R,R,R,R,R)-17 (5 mg, 4%).
(
)-(R,R,R)-Tris[2,2'-bis(benzoyloxy)-7,7'-bis(benzyloxy)-1,1'-binaphthalene-3,3'-diylbis(ethynyl)] (( )-
(R,R,R)-15). M.p. 168 ± 1728. [a]Dr:t:
ˆ
869.5 (c ˆ 1.0, CH2Cl2). IR (CHCl3): 3066w, 3033w, 2214m, 2144w,
1745s, 1620s, 1495m, 1451m, 1391m, 1237s, 1208m, 1140m, 1080m. 1H-NMR (300 MHz, CDCl3): 4.54 (d, AB, J ˆ
12.1, 6 H); 4.78 (d, AB, J ˆ 12.1, 6 H); 6.58 (d, J ˆ 2.4, 6 H); 6.78 ± 6.90 (m, 18 H); 7.12 ± 7.24 (m, 36 H); 7.61
(d, J ˆ 9.0, 6 H); 7.85 (dd, J ˆ 8.4, 1.2, 12 H); 7.93 (s, 6 H). 13C-NMR (75 MHz, (D8)THF): 70.54; 78.31; 79.19;
106.90; 114.09; 120.77; 124.60; 127.60; 128.24; 128.43 (2Â); 128.98; 129.06; 129.76; 130.62; 134.03; 134.66;
‡
135.39; 137.69; 150.05; 159.61; 164.91. FAB-MS: 2258 (100, M ). Anal. calc. for C156H96O18 (2258.49): C 82.96,
H 4.28; found: C 83.23, H 4.31.
(
)-(R,R,R,R)-Tetrakis[2,2'-bis(benzoyloxy)-7,7'-bis(benzyloxy)-1,1'-binaphthalene-3,3'-diylbis(ethynyl)]
(( )-(R,R,R,R)-16). M.p. 185 ± 1888. [a]Dr:t:
ˆ
855.6 (c ˆ 1.0, CH2Cl2). IR (CHCl3): 3066m, 2213w, 2144w,
1744s, 1620s, 1494m, 1451m, 1390m, 1238s, 1206m, 1178m, 1139w, 1055m, 1023m, 892w. 1H-NMR (300 MHz,
CDCl3): 4.69 (d, AB, J ˆ 12.0, 8 H); 4.89 (d, AB, J ˆ 12.0, 8 H); 6.60 (d, J ˆ 2.1, 8 H); 7.10 ± 7.30 (m, 72 H); 7.65
(d, J ˆ 9.3, 8 H); 7.71 (m, 16 H); 7.93 (s, 8 H). 13C-NMR (75 MHz, CDCl3): 69.9; 77.8; 77.9; 106.2; 113.0; 120.1;
123.4; 126.5; 127.6; 127.9; 128.2; 128.4; 129.0; 129.5; 130.0; 133.1; 134.6; 134.8; 136.3; 148.3; 158.4; 164.4. FAB-
‡
MS: 3011 (100, M ). Anal. calc. for C208H128O24 (3011.32): C 82.96, H 4.28; found: C 83.23, H 4.39.
(
)-(R,R,R,R,R)-Pentakis[2,2'-bis(benzoyloxy)-7,7'-bis(benzyloxy)-1,1'-binaphthalene-3,3'-diylbis(ethyn-
yl)] (( )-(R,R,R,R,R)-17). M.p. 205 ± 210. [a]Dr:t:
ˆ
838.8 (c ˆ 0.5, CH2Cl2). IR (CHCl3): 3060m, 2216w, 2143w,
1740s, 1619s, 1494m, 1451m, 1387m, 1315w, 1242s. 1H-NMR (200 MHz, CDCl3): 4.74 (d, AB, J ˆ 12.0, 10 H);
4.92 (d, AB, J ˆ 12.0, 10 H); 6.59 (d, J ˆ 2.4, 10 H); 7.10 ± 7.50 (m, 90 H); 7.64 (m, 30 H); 7.93 (s, 10 H).
13C-NMR (75 MHz, CDCl3): 70.0; 77.8; 78.1; 106.0; 113.1; 120.1; 123.4; 126.5; 127.6; 127.9; 128.2; 128.4; 129.0;
‡
129.4; 129.9; 133.1; 134.6; 135.0; 136.3; 148.0; 158.4; 164.2. FAB-MS: 3764 (100, M ). Anal. calc. for C260H160O30
(3764.16): C 82.96, H 4.28; found: C 82.82, H 4.17.
(
)-(R,R,R)-Tris[7,7'-bis(benzyloxy)-2,2'-dihydroxy-1,1'-binaphthalene-3,3'-diylbis(ethynyl)] (( )-(R,R,R)-
1). Compound (R,R,R)-15 (10 mg, 4.4 mmol) was dissolved in THF (20 ml), and the soln. degassed and
saturated with N2. After the addition of KOH (1.9m soln. in MeOH, 40 ml, 76 mmol), the mixture was stirred at
r.t. for 30 min, then AcOEt (20 ml) was added, the org. phase washed with H2O and evaporated in vacuo. The
above procedure was repeated four times, and the combined products were recrystallized from CH2Cl2 with
layered addition of hexane to yield (R,R,R)-1 (26 mg, 90%). Yellow solid. M.p. 2058 (dec.). [a]Dr:t:
ˆ
1114 (c ˆ
1.0, CH2Cl2). IR (CHCl3): 3520s, 3066m, 2928s, 2855m, 2203m, 2129m. 1H-NMR (300 MHz, CDCl3): 4.63
(d, AB, J ˆ 12.0, 6 H); 4.73 (d, AB, J ˆ 12.0, 6 H); 5.75 (s, 6 H); 6.41 (d, J ˆ 2.4, 6 H); 7.07 ± 7.23 (m, 36 H); 7.75
(d, J ˆ 9.3, 6 H); 8.08 (s, 6 H). 13C-NMR (75 MHz, (D8)THF): 70.24; 79.15; 80.61; 105.98; 111.19; 114.05;
‡
117.50; 124.83; 128.25; 128.37; 128.98; 130.60; 134.39; 137.15; 137.95; 156.28; 159.48. FAB-MS: 1633 (6, M ), 91
‡
(100, [C7H7] ). Anal. calc. for C114H72O12 (1633.84): C 83.81, H 4.44; found: C 84.11, H 4.69.
6-(Benzyloxy)-2-iodo-3-(methoxymethoxy)naphthalene (18). To a soln. of 6 (2.0 g, 5.4 mmol) in dry THF
(40 ml) at 788, t-BuLi (1.7m soln. in pentane, 4.8 ml, 7.5 mmol) was added, and the mixture was stirred for
30 min. A soln. of I2 (1.9 g, 8.2 mmol) in dry THF (10 ml) was added, and the mixture was left to warm to r.t.,
then stirred for 12 h. After hydrolysis with H2O (20 ml), the product was extracted with CH2Cl2, and the org.
phase was washed with 10% aq. Na2S2O5 soln. and H2O. Evaporation in vacuo afforded 18 (2.19 g, 97%). White
crystals (hexane). M.p. 93 ± 958. IR (KBr): 1624s, 1583m, 1500s, 1452s, 1424m, 1390s, 1366s, 1302m, 1272w,
1244m, 1217s, 1204s, 1151s, 1133m, 1086m, 1012s. 1H-NMR (300 MHz, CDCl3): 3.55 (s, 3 H); 5.16 (s, 2 H); 5.34
(s, 2 H); 7.08 ± 7.12 (m, 2 H); 7.30 (s, 1 H); 7.35 ± 7.49 (m, 5 H); 7.58 (d, J ˆ 9.7, 1 H); 8.23 (s, 1 H). 13C-NMR
(75 MHz, CDCl3): 56.55; 70.17; 85.16; 95.21; 106.68; 109.16; 118.09; 126.86; 127.78; 128.34; 128.39; 128.91;
‡
‡
135.75; 136.98; 139.03; 153.66; 157.98. EI-MS: 420 (100, M ); 91 (58, [C7H7] ). Anal. calc. for C19H17O3I
(420.25): C 54.30, H 4.08, I 30.20; found: C 54.46, H 3.88, I 29.95.
7-(Benzyloxy)-3-iodonaphthalen-2-ol (19). A soln. of 18 (3.0 g, 7.1 mmol) and conc. aq. HCl soln. (37%,
2.7 ml) in THF/MeOH 2 :1 (60 ml) was heated to reflux for 3 h. After cooling to r.t., the mixture was quenched
with H2O (30 ml), the product extracted in CH2Cl2, the org. phase washed with sat. aq. NaCl soln. and
evaporated in vacuo. The residue was suspended in hexane, filtered, and dried to give 19 (2.6 g, 97%). White
crystalline solid. M.p. 169 ± 1708. IR (KBr): 3393m, 1622s, 1588s, 1512m, 1472w, 1454m, 1420s, 1394m, 1372s,
1328w, 1289w, 1270w, 1217s, 1200s, 1161m, 1134m, 1078w, 1005s. 1H-NMR (300 MHz, CDCl3): 5.16 (s, 2 H); 5.38

1954
Helvetica Chimica Acta ± Vol. 81 (1998)
(s, 1 H); 7.25 (s, 1 H); 7.06 ± 7.10 (m, 2 H); 7.35 ± 7.50 (m, 5 H); 7.58 (d, J ˆ 8.7, 1 H); 8.15 (s, 1 H). 13C-NMR
(50 MHz, CDCl3): 67.64; 82.43; 103.41; 106.46; 115.32; 123.76; 125.28; 125.79; 125.89; 126.33; 133.82; 134.36;
‡
‡
135.63; 149.69; 155.56. EI-MS: 376 (10, M ), 91 (100, [C7H7] ). Anal. calc. for C17H13IO2 (376.20): C 54.28,
H 3.48; found: C 54.33, H 3.63.
(Æ)-7,7'-Bis(benzyloxy)-3,3'-diiodo-1,1'-binaphthalene-2,2'-diol ((Æ)-20). Compound (Æ)-20 (2.0 g, 65%)
was prepared from 19 (3.1 g, 8.2 mmol) using CuCl2 (2.2 g, 16.4 mmol) and t-BuNH2 (3.6 ml, 2.5 g, 34.3 mmol)
by Method A, described above for the synthesis of (Æ)-8. M.p. 1978. IR (KBr): 3444m, 1620s, 1578w, 1499s,
1449m, 1368s, 1217s, 1200s, 1161s, 1074m. 1H-NMR (300 MHz, CDCl3): 4.73 (d, AB, J ˆ 12.2, 2 H);
4.78(d, AB, J ˆ 12.2, 2 H); 5.35 (s, 2 H); 6.35 (d, J ˆ 2.2, 2 H); 7.08 ± 7.23 (m, 12 H); 7.70 (d, J ˆ 8.7, 2 H);
8.40 (s, 2 H). 13C-NMR (75 MHz, CDCl3): 158.56; 150.96; 140.14; 136.50; 134.85; 129.17; 128.75; 128.21; 127.75;
‡
126.56; 117.88; 111.94; 104.82; 82.88; 70.02. FAB-MS: 750 (100, M ). Anal. calc. for C34H24O4I2 (750.38):
C 54.42, H 3.22, I 33.82; found: C 54.22, H 3.04, I 33.66.
(‡)-(S)-7,7'-Bis(benzyloxy)-2,2'-bis(methoxymethoxy)-3,3'-dibromo-1,1'-binaphthalene ((‡)-(S)-21). To a
degassed mixture of (S)-8 (1.30 g, 2.0 mmol) and K2CO3 (1.7 g, 12.3 mmol) in dry MeCN (50 ml), MOMCl
(0.61 ml, 0.65 g, 8.0 mmol) was added at 08. The mixture was stirred for 15 h at r.t., then the salts were removed
by filtration through Celite. Evaporation in vacuo gave (S)-21 (1.43 g, 96%). White crystalline solid (hexane).
M.p. 1128. [a]rD:t: ˆ‡ 155.4 (c ˆ 1.0, CHCl3). IR (KBr): 3485m (br.), 2944w, 2889w, 1620s, 1496s, 1453m, 1380s,
1228s, 1205s, 1155s, 1088w, 1029m, 930s. 1H-NMR (300 MHz, CDCl3): 2.63 (s, 6 H); 4.49 (d, AB, J ˆ 5.4, 2 H);
4.66 (d, AB, J ˆ 12.6, 2 H); 4.69 (d, AB, J ˆ 5.4, 2 H); 4.70 (d, AB, J ˆ 12.6, 2 H); 6.40 (d, J ˆ 2.2, 2 H); 7.02 ±
7.05 (m, 4 H); 7.16 ± 7.20 (m, 8 H); 7.72 (d, J ˆ 8.7, 2 H); 8.16 (s, 2 H). 13C-NMR (300 MHz, CDCl3): 56.34;
69.82; 77.21; 98.87; 106.48; 114.66; 119.39; 126.34; 127.10; 127.28; 127.90; 128.54; 132.54; 134.25; 136.47; 150.43;
‡
157.32. FAB-MS: 744 (100, M ). Anal. calc. for C38H32O6Br2 (744.48): C 61.32, H 4.33, Br 21.47; found: C 61.34,
H 4.24, Br 21.22.
(Æ)-7,7'-Bis(benzyloxy)-2,2'-bis(methoxymethoxy)-3,3'-diiodo-1,1'-binaphthalene ((Æ)-22). To a soln. of
(Æ)-21 (1.07 g, 1.4 mmol) in dry THF (25 ml), t-BuLi (1.7m soln. in pentane, 2.5 ml, 4.3 mmol) was added at
788. The mixture was stirred for 30 min, and a soln. of I2 (1.10 g, 4.3 mmol) in dry THF (4.5 ml) was added.
After stirring at 788 for 2.5 h, the reaction was quenched with H2O (4 ml), the product extracted with CH2Cl2,
and the org. phase washed with 10% aq. Na2S2O5 soln. and H2O. Evaporation in vacuo gave (Æ)-22 (1.13 g,
93%). White crystals (CH2Cl2/hexane). M.p. 1328. 1H-NMR (300 MHz, CDCl3): 2.65 (s, 6 H); 4.32 (d, AB, J ˆ
5.3, 2 H); 4.63 (d, AB, J ˆ 5.3, 2 H); 4.63 (d, AB, J ˆ 12.4, 2 H); 4.70 (d, AB, J ˆ 12.4, 2 H); 6.38 (d, J ˆ 2.5, 2 H);
7.00 ± 7.20 (m, 12 H); 7.69 (d, J ˆ 9.0, 2 H); 8.41 (s, 2 H). 13C-NMR (50 MHz, CDCl3): 54.18; 67.48; 86.75;
96.65; 104.11; 116.78; 122.84; 124.81; 125.50; 125.57; 125.98; 126.17; 132.65; 134.08; 137.00; 150.07; 155.09. FAB-
‡
MS: 838 (100, M ). Anal. calc. for C38H32O6I2 (838.48): C 54.43, H 3.85, O 11.45; found: C 54.24, H 3.80,
O 11.56.
(‡)-(S)-7,7'-Bis(benzyloxy)-2,2'-bis(methoxymethoxy)-3,3'-diiodo-1,1'-binaphthalene ((‡)-(S)-22). To a
soln. of (S)-21 (500 mg, 0.7 mmol) in dry THF (40 ml), TMEDA (0.51 ml, 390 mg, 3.4 mmol) and BuLi (1.6m
soln. in hexane, 2.10 ml, 3.4 mmol) were added at 788. The mixture was stirred for 45 min, and a soln. of I2
(792 mg, 3.1 mmol) in dry THF (10 ml) was added. After 15 min, the reaction was quenched with 10% aq.
Na2S2O5 soln., the product extracted with CH2Cl2, the org. phase washed with H2O, and dried (Na2SO4).
Evaporation in vacuo gave the crude product which was purified by CC (hexane/AcOEt 3 : 1 containing 0.5%
Et3N) to give (S)-22 (369 mg, 66%). White powder with spectroscopic data identical to those of the racemic
material (Æ)-22 and [a]rD:t: ˆ‡ 91.6 (c ˆ 1.0, CHCl3).
(‡)-(S)-7,7'-Bis(benzyloxy)-2,2'-bis(methoxymethoxy)-3,3'-bis[(trimethylsilyl)ethynyl]-1,1'-binaphthalene
((‡)-(S)-23). To a degassed soln. of (S)-22 (559 mg, 0.67 mmol) in dry Et2NH (13 ml) and dry toluene (13 ml),
CuI (56 mg, 0.29 mmol), [PdCl2(dppf)] ´ CH2Cl2 (22 mg, 4 mol-%), and (trimethylsilyl)acetylene (0.3 ml,
209 mg, 2.16 mmol) were added, and the mixture stirred at 408 for 4 h. After evaporation of the solvent, the
residue was dissolved in CH2Cl2, the org. phase washed with sat. aq. NH4Cl soln. and H2O, dried (Na2SO4), and
evaporated in vacuo. CC (hexane/AcOEt 7: 5 containing 0.5% Et3N) afforded (S)-23 (509 mg, 98%). White
solid. M.p. 156 ± 1588. [a]rD:t: ˆ‡ 43.1 (c ˆ 1.0, CHCl3). IR (KBr): 3480s (br.), 2956w, 2891w, 2154m, 1618s,
1492m, 1376m, 1245s, 1221m, 1160m, 1071w, 983m, 950m, 888w, 843s, 759w. 1H-NMR (300 MHz, CDCl3): 0.26
(s, 18 H); 2.51 (s, 6 H); 4.62 (d, AB, J ˆ 12.1, 2 H); 4.68 (d, AB, J ˆ 12.1, 2 H); 4.80 (d, AB, J ˆ 5.9, 2 H); 4.94
(d, AB, J ˆ 5.9, 2 H); 6.40 (d, J ˆ 2.5, 2 H); 7.04 ± 7.07 (m, 4 H); 7.13 (dd, J ˆ 9.0, 2.5, 2 H); 7.17 ± 7.20 (m, 6 H);
7.71 (d, J ˆ 9.0, 2 H); 8.07 (s, 2 H). 13C-NMR (75 MHz, CDCl3): 0.08; 56.16; 69.86; 98.33; 98.75; 102.44;
106.60; 114.77; 119.03; 124.90; 125.88; 127.55; 127.99; 128.65; 129.35; 134.70; 135.38; 136.71; 154.15; 158.00.
‡
‡
FAB-MS: 779 (65, M ); 91 (100, [C7H7] ). Anal. calc. for C48H50O6Si2 (779.10): C 74.00, H 6.47; found: C 74.23,
H 6.31.

Helvetica Chimica Acta ± Vol. 81 (1998)
1955
(‡)-(S)-7,7'-Bis(benzyloxy)-2,2'-bis(methoxymethoxy)-3,3'-diethynyl-1,1'-binaphthalene ((‡)-(S)-24). To a
soln. of (S)-23 (330 mg, 0.42 mmol) in THF/MeOH 1:1 (70 ml), K2CO3 (385 mg, 2.79 mmol) was added, and
the mixture was stirred at r.t. for 2 h. After the addition of CH2Cl2 (160 ml), the org. phase was washed with H2O
and dried (Na2SO4). Evaporation in vacuo and CC (hexane/AcOEt 5 :1, 0.5% Et3N) afforded (S)-24 (249 mg,
93%). White powder. M.p. 160 ± 1628. [a]rD:t: ˆ‡ 71.4 (c ˆ 1.0, CHCl3). IR (KBr): 3279m, 3233m, 2821w, 2822w,
2089w, 1619s, 1493s, 1448m, 1379s, 1241s, 1220s, 1158s, 1099w, 1068m, 1026m, 940s (br.), 851w, 812w, 736m.
1H-NMR (500 MHz, CDCl3): 2.60 (s, 6 H); 3.30 (s, 2 H); 4.66 (d, AB, J ˆ 12.1, 2 H); 4.70 (d, AB, J ˆ 12.1, 2 H);
4.81 (d, AB, J ˆ 5.7, 2 H); 4.84 (d, AB, J ˆ 5.7, 2 H); 6.43 (d, J ˆ 2.5, 2 H); 7.05 ± 7.07 (m, 4 H); 7.14 ± 7.19
(m, 8 H); 7.74 (d, J ˆ 9.0, 2 H); 8.10 (s, 2 H). 13C-NMR (75 MHz, CDCl3): 56.13; 69.82; 80.81; 98.68; 106.37;
111.58; 113.74; 118.87; 124.65; 125.63; 127.28; 127.79; 128.41; 129.18; 134.73; 135.25; 136.34; 153.81; 157.85.
‡
FAB-MS: 634 (100, M ). Anal. calc. for C42H34O6 (634.74): C 79.48, H 5.40; found: C 79.24, H 5.29.
(‡)-(S,S,S)-Tris[7,7'-bis(benzyloxy)-2,2'-bis(methoxymethoxy)-1,1'-binaphthalene-3,3'-diylbis(ethynyl)]
((‡)-(S,S,S)-25). A mixture of (S)-24 (100 mg, 0.16 mmol) and CuCl (1.35 g, 14 mmol) in CH2Cl2 (500 ml) was
stirred for 10 min under dry air, then TMEDA (2.1 ml, 1.62 g, 14 mmol) was added. After 3 h, the reaction was
quenched with H2O (500 ml), the org. phase washed (H2O), and concentrated. CC (cyclohexane/AcOEt 4 :1)
yielded a mixture of cyclic oligomers, and separation by GPC (toluene) afforded (S,S,S)-25 (25 mg, 25%). M.p.
2728. [a]rD:t: ˆ‡ 445.2 (c ˆ 0.5, CHCl3). IR (KBr): 3059m, 2929m, 2200w, 2133w, 1617s, 1494m, 1450m, 1378m,
1261m, 1217s, 1156m, 1017m. 1H-NMR (200 MHz, CDCl3): 2.68 (s, 18 H); 4.62 (d, AB, J ˆ 12.0, 6 H); 4.71
(d, AB, J ˆ 12.0, 6 H); 4.77 (d, AB, J ˆ 5.6, 6 H); 4.87 (d, AB, J ˆ 5.6, 6 H); 6.52 (d, J ˆ 2.4, 6 H); 7.05 ± 7.24
(m, 36 H); 7.76 (d, J ˆ 9.0, 6 H); 8.09 (s, 6 H). 13C-NMR (50 MHz, CDCl3): 53.89; 67.45; 75.80; 77.61; 96.68;
104.02; 111.44; 116.59; 122.17; 123.25; 124.93; 125.54; 126.11; 127.25; 131.66; 133.03; 134.04; 153.25; 155.85.
‡
‡
MALDI-TOF-MS (dithranol): 1920 ([M ‡ Na] ), 1936 ([M ‡ K] ). Anal. calc. for C126H96O18 (1898.16):
C 79.73, H 5.10; found: C 79.86, H 5.31.
(‡)-(S,S,S)-Tris[7,7'-bis(benzyloxy)-2,2'-dihydroxy-1,1'-binaphthalene-3,3'-diylbis(ethynyl)] ((‡)-(S,S,S)-
1). To a soln. of (S,S,S)-25 (18 mg, 9.5 mmol) in THF/MeOH 1:1 (6 ml), conc. aq. HCl soln. (37%, 0.3 ml)
was added. After stirring for 12 h, the solid was filtered and dried to give (S,S,S)-1 (12 mg, 77%) with anal. data
identical to those of (R,R,R)-1 and [a]rD:t: ˆ‡ 554.3 (c ˆ 0.5, CHCl3).
(‡)-(S)-2,2'-Bis(methoxymethoxy)-3,3'-diiodo-1,1'-binaphthalene ((‡)-(S)-28). To a soln. of (S)-27 [62]
(1.60 g, 4.3 mmol) in dry Et2O (80 ml), TMEDA (2.39 ml, 1.85 g, 15.9 mmol) and BuLi (1.6m soln. in hexane,
9.8 ml, 15.7 mmol) were added at r.t. After stirring for 6.5 h, a soln. of I2 (5.09 g, 20.1 mmol) in Et2O (40 ml) was
slowly added at 788. The mixture was stirred for 2 h, then warmed to r.t., and quenched with 10% aq. Na2S2O5
soln. (15 ml). The product was extracted with AcOEt, the org. phase washed with H2O, and evaporated in
vacuo. CC (hexane/AcOEt 9 :1 containing 0.5% Et3N) afforded (S)-28 (1.75 g, 65%). White crystals. M.p. 928.
[a]rD:t: ˆ‡ 8.7 (c ˆ 1.0, THF). IR (KBr): 2922w, 2356w, 1383m, 1344m, 1180s, 994s, 956s. 1H-NMR (200 MHz,
CDCl3): 2.63 (s, 6 H); 4.72 (d, AB, J ˆ 5.4, 2 H); 4.83 (d, AB, J ˆ 5.4, 2 H); 7.18 ± 7.22 (dd, J ˆ 8.3, 0.8, 2 H);
7.29 ± 7.33 (m, 2 H); 7.36 ± 7.49 (m, 2 H); 7.80 (d, J ˆ 7.9, 2 H); 8.57 (s, 2 H). 13C-NMR (50 MHz, CDCl3):
54.09; 90.09; 97.03; 123.54; 123.92; 124.20; 124.43; 124.81; 129.92; 131.57; 137.73; 149.91. FAB-MS: 626 (16,
‡
‡
M ), 468 (100, [M
Compound ( )-(R)-28 ([a]Dr:t:
)-(S)-2,2'-Bis(methoxymethoxy)-3,3'-bis[(trimethylsilyl)ethynyl]-1,1'-binaphthalene (( )-(S)-29). To a
I
MeO] ). Anal. calc. for C24H20O4I2 (626.23): C 46.03, H 3.22; found: C 45.85, H 3.09.
ˆ
7.4 (c ˆ 1.0, THF)) was prepared in the same manner.
(
degassed soln. of (S)-28 (1.06 g, 1.7 mmol) in dry Et3N (29 ml), [PdCl2(PPh3)2] (58 mg, 5 mol-%), CuI (17 mg,
5 mol-%), and (trimethylsilyl)acetylene (1.0 ml, 0.69 g, 7.5 mmol) were added, and the mixture was stirred for
20 h at 408. The reaction was quenched with sat. aq. NaCl soln. (20 ml), the mixture filtered through Celite, and
the soln. extracted with CH2Cl2. The org. phase was washed with sat. aq. NaHCO3 soln., dried (Na2SO4), and
concentrated. CC (hexane/AcOEt 5 :1 containing 0.5% Et3N) afforded (S)-29 (0.86 g, 90%). White crystals
(hexane). M.p. 1708. [a]Dr:t:
ˆ
34.7 (c ˆ 01.0, THF). IR (KBr): 2956m, 2155m, 1426m, 1244s, 1158s, 1068s, 978s,
911m, 844s, 759m. 1H-NMR (300 MHz, CDCl3): 0.27 (s, 18 H); 2.44 (d, J ˆ 0.6, 6 H); 4.87 (dd, AB, J ˆ 6.2, 0.6,
2 H); 5.18 (dd, AB, J ˆ 6.2, 0.6, 2 H); 7.15 ± 7.18 (d, J ˆ 8.7, 2 H); 7.25 ± 7.30 (m, 2 H); 7.38 ± 7.43 (m, 2 H); 7.81
(d, J ˆ 8.1, 2 H); 8.17 (s, 2 H). 13C-NMR (75 MHz, CDCl3): 0.13; 56.06; 98.88; 99.29; 102.09; 117.26; 125.27;
‡
126.01; 126.79; 127.50; 127.75; 130.38; 134.14; 135.15; 153.66. FAB-MS: 566 (63, M ), 391 (100). Anal. calc. for
C34H38O4Si2 (566.85): C 72.04, H 6.76; found: C 72.00, H 6.55.
Compound (‡)-(R)-29 ([a]rD:t: ˆ‡ 35.4 (c ˆ 1.0, THF)) was prepared in the same manner.
(
)-(S)-2,2'-Bis(methoxymethoxy)-3-3'-diethynyl-1,1'-binaphthalene (( )-(S)-30). A soln. of (S)-29
(0.70 g, 1.2 mmol) and K2CO3 (1.17 g, 8.5 mmol) in MeOH/THF 1:1 (120 ml) was stirred at r.t. for 3 h. After
addition of CH2Cl2 (500 ml), the org. phase was washed with H2O, dried (Na2SO4), and concentrated. CC
(hexane/AcOEt 5 :1 containing 0.5% Et3N) afforded (S)-30 (0.51 g, 98%). White powder. M.p. 428. [a]Dr:t:
ˆ

1956
Helvetica Chimica Acta ± Vol. 81 (1998)
83.0 (c ˆ 1.0, THF). IR (KBr): 3280s, 2925m, 2100w, 1617w, 1490m, 1425m, 1392m, 1353m, 1240s, 1156s, 1064s,
9173s, 751s. 1H-NMR (500 MHz, CDCl3): 2.53 (s, 6 H); 3.33 (s, 2 H); 4.89 (d, AB, J ˆ 6.0, 2 H); 5.08 (d, AB, J ˆ
6.0, 2 H); 7.19 ± 7.21 (m, 2 H); 7.29 ± 7.32 (m, 2 H); 7.41 ± 7.44 (m, 2 H); 7.82 ± 7.84 (m, 2 H); 8.20 (s, 2 H).
13C-NMR (125 MHz, CDCl3): 56.05; 80.60; 81.52; 98.87; 116.24; 125.46; 125.59; 125.76; 127.49; 127.57; 130.11;
‡
‡
133.97; 135.23; 153.37. FAB-MS: 422 (36, M ), 391 (100, [M MeO] ). Anal. calc. for C28H22O4 ´ 0.5 H2O
(431.48): C 77.94, H 5.37; found: C 77.95, H 5.56.
Compound (‡)-(R)-30 ([a]rD:t: ˆ‡ 81.8 (c ˆ 1.0, THF)) was prepared in the same manner.
Glaser-Hay Cyclization of (S)-30. A soln. of (S)-30 (150 mg, 0.35 mmol) and CuCl (4.0 g, 40 mmol) in
CH2Cl2 (1.8 l) was stirred for 15 min, then TMEDA (6.0 ml, 4.6 g, 40 mmol) was added. The mixture was stirred
for 2 h under dry air, then quenched with H2O. The org. phase was washed (H2O), dried (Na2SO4), and
concentrated. Separation by GPC (toluene) afforded (S,S,S)-31 (55 mg, 37%) in addition to tetramer (S,S,S,S)-
32 (36 mg, 24%) and pentamer (S,S,S,S,S)-33 (8 mg, 5%).
(‡)-(S,S,S)-Tris[2,2'-bis(methoxymethoxy)-1,1'-binaphthalene-3,3'-diylbis(ethynyl)] ((‡)-(S,S,S)-31). M.p.
>3008. [a]rD:t: ˆ‡ 1287.8 (c ˆ 1.0, THF). IR (KBr): 2928m, 2202w, 2134w, 1618m, 1584m, 1490m, 1448m, 1426m,
1388m, 1349m, 1238m, 1200m, 1152s, 1067s, 969s, 914m. 1H-NMR (500 MHz, CDCl3): 2.59 (s, 18 H); 4.83
(d, AB, J ˆ 6.4, 6 H); 5.05 (d, AB, J ˆ 6.4, 6 H); 7.24 (d, J ˆ 8.7, 6 H); 7.30 ± 7.33 (m, 6 H); 7.42 ± 7.45 (m, 6 H);
7.84 (d, J ˆ 8.1, 6 H); 8.18 (s, 6 H). 13C-NMR (125 MHz, CDCl3): 56.23; 78.60; 79.95; 99.20; 116.25; 125.60;
‡
125.63; 126.47; 127.79; 127.94; 130.08; 134.14; 134.46; 154.86. MALDI-TOF-MS (dithranol): 1284 ([M ‡ Na] ),
‡
1303 ([M ‡ K] ). Anal. calc. for C84H60O12 (1261.41): C 79.98, H 4.79; found: C 79.73, H 4.77.
(‡)-(S,S,S,S)-Tetrakis[2,2'-bis(methoxymethoxy)-1,1'-binaphthalene-3,3'-diylbis(ethynyl)] ((‡)-(S,S,S,S)-32).
M.p. >3008. [a]rD:t: ˆ‡ 992.0 (c ˆ 1.0, THF). IR (KBr): 2950m, 2211w, 2138w, 1725m, 1616m, 1583m, 1489m,
1
1446m, 1428m, 1390m, 1353m, 1240m, 1155s, 1071m, 968s, 907m. H-NMR (300 MHz, CDCl3): 2.58 (s, 24 H);
4.90 (d, AB, J ˆ 6.3, 8 H); 5.13 (d, AB, J ˆ 6.3, 8 H); 7.20 (d, J ˆ 8.4, 8 H); 7.30 ± 7.35 (m, 8 H); 7.41 ± 7.46
(m, 8 H); 7.85 (d, J ˆ 8.1, 8 H); 8.24 (s, 8 H). 13C-NMR (125 MHz, CDCl3): 56.37; 78.29; 79.47; 99.40; 116.29;
125.97; 126.03; 126.76; 128.00; 128.08; 130.37; 134.48; 135.98; 154.26. MALDI-TOF-MS (HABA): 1705 ([M ‡
‡
Na] ). Anal. calc. for C112H80O16 ´ 3 H2O (1735.92): C 77.49, H 4.99; found: C 77.38, H 5.22.
(‡)-(S,S,S,S,S)-Pentakis[2,2'-bis(methoxymethoxy)-1,1'-binaphthalene-3,3'-diylbis(ethynyl)] ((‡)-(S,S,S,S,S)-
33). M.p. >3008. [a]Dr:t: ˆ‡ 339.8 (c ˆ 1.0, THF). IR (KBr): 2956m, 2207w, 2131w, 1731w, 1621m, 1586m, 1490m,
1
1446m, 1424m, 1394m, 1350m, 1258m, 1153s, 1079m, 969s, 912m. H-NMR (500 MHz, CDCl3): 2.60 (s, 30 H);
4.90 (d, AB, J ˆ 6.3, 10 H); 5.12 (d, AB, J ˆ 6.3, 10 H); 7.20 (d, J ˆ 8.7, 10 H); 7.30 ± 7.35 (m, 10 H); 7.42 ± 7.47
(m, 10 H); 7.85 (d, J ˆ 8.1, 10 H); 8.23 (s, 10 H). 13C-NMR (125 MHz, CDCl3): 56.38; 78.32; 79.62; 99.39;
116.27; 126.01 (2Â); 126.74; 127.97; 128.12; 130.40; 134.39; 136.19; 154.02. MALDI-TOF-MS (HABA): 2126
‡
([M ‡ Na] ).
(‡)-(S,S,S)-Tris[2,2'-dihydroxy-1,1'-binaphthalene-3,3'-diylbis(ethynyl)] ((‡)-(S,S,S)-2). To a soln. of (S,S,S)-
31 (22 mg, 1.7 mmol) in THF/MeOH 1 :1 (6 ml) was added conc. aq. HCl soln. (37%, 0.4 ml), and the mixture
was stirred for 12 h. After addition of H2O (35 ml), the precipitate was filtered and dried to afford (S,S,S)-2
(17 mg, 97%). M.p. 2608 (dec.). [a]rD:t: ˆ‡ 1663.5 (c ˆ 1.0 THF). IR (KBr): 3508s, 3056w, 2200w, 2140w, 1619s,
1494m, 1455m, 1430m, 1392m, 1349m, 1264s, 1240s, 1150s, 1097w, 889m. 1H-NMR (200 MHz, CDCl3): 5.75
(s, 6 H); 6.97 (d, J ˆ 8.3, 6 H); 7.13 ± 7.20 (m, 6 H); 7.31 ± 7.35 (m, 6 H); 7.82 ± 7.86 (d, J ˆ 7.9, 6 H); 8.14
(s, 6 H). 13C-NMR (50 MHz, CDCl3): 76.43; 77.45; 108.55; 111.00; 122.05; 122.90; 125.89; 126.14; 126.24;
‡
131.95; 132.14; 149.91. FAB-MS: 997 (100, M ). Anal. calc. for C72H36O6 ´ 2.5 H2O (1042.17): C 82.98, H 3.97;
found: C 82.81, H 4.25.
(‡)-(R)-2,2'-Bis(methoxymethoxy)-3-ethynyl-3'-[(trimethylsilyl)ethynyl]-1,1'-binaphthalene ((‡)-(R)-34).
A soln. of (R)-29 (535 mg, 0.94 mmol) and borax (1.45 g, 9.4 mmol) in THF (500 ml) and H2O (380 ml) was
stirred at r.t. for 3.5 h. After addition of H2O (380 ml), the mixture was extracted with CH2Cl2. The org. phase
was washed with sat. aq. NaCl soln., dried (Na2SO4), and concentrated. CC (hexane/AcOEt 7:1 containing
0.5% Et3N) afforded (R)-34 (196 mg, 42%). M.p. 1228. [a]rD:t: ˆ‡ 63.3 (c ˆ 1.0, THF). IR (KBr): 3245s, 2955m,
2155m, 1426m, 1241s, 1159s, 1069s, 975s, 914s, 843s, 756s. 1H-NMR (200 MHz, CDCl3): 0.29 (s, 9 H); 2.49
(s, 3 H); 2.54 (s, 3 H); 3.35 (s, 1 H); 4.88 (d, AB, J ˆ 6.0, 1 H); 4.92 (d, AB, J ˆ 6.2, 1 H); 5.11 (d, AB, J ˆ 6.0,
1 H); 5.19 (d, AB, J ˆ 6.2, 1 H); 7.18 ± 7.22 (m, 2 H); 7.27 ± 7.36 (m, 2 H); 7.39 ± 7.49 (m, 2 H); 7.82 ± 7.88
(m, 2 H); 8.19 (s, 1 H); 8.22 (s, 1 H). 13C-NMR (75 MHz, CDCl3): 0.14; 56.01; 56.21; 80.78; 81.65; 98.85;
99.08; 99.35; 102.05; 116.45; 117.29; 125.72; 125.80; 126.19 (2Â); 126.69; 126.77; 127.57; 127.66; 127.78 (2Â);
‡
‡
130.37 (2Â); 134.07; 134.30; 135.20; 135.39; 153.63; 153.68. FAB-MS: 494 (23, M ), 419 (100, [M C3H8O2] ).
Anal. calc. for C31H30O4Si (494.67): C 75.27, H 6.11; found: C 75.35, H 6.20.
(
)-(R,R)-3,3'-(Buta-1,3-diynediyl)bis{2,2'-bis(methoxymethoxy)-3'-[(trimethylsilyl)ethynyl]-1,1'-binaph-
thalene} (( )-(R,R)-35). A soln. of (R)-34 (132 mg, 0.27 mmol) and CuCl (1.00 g, 10 mmol) in CH2Cl2 (440 ml)

Helvetica Chimica Acta ± Vol. 81 (1998)
1957
was stirred for 15 min, then TMEDA (1.5 ml, 1.16 g, 10 mmol) was added, and stirring was continued for 3 h
under dry air. After addition of H2O, the org. phase was washed (H2O), dried (Na2SO4), and concentrated. CC
(hexane/AcOEt 5 :1 containing 0.5% Et3N) afforded (R,R)-35 (113 mg, 86%). M.p. 838. [a]Dr:t:
ˆ
125.1 (c ˆ
1.0, THF). IR (KBr): 2956m, 2144w, 1244m, 1158s, 1072m, 973s, 844s, 744m. 1H-NMR (200 MHz, CDCl3): 0.30
(s, 18 H); 2.52 (s, 6 H); 2.66 (s, 6 H); 4.90 (d, AB, J ˆ 6.2, 2 H); 4.95 (d, AB, J ˆ 6.2, 2 H); 5.12 (d, AB, J ˆ 6.2,
2 H); 5.22 (d, AB, J ˆ 6.2, 2 H); 7.20 ± 7.50 (m, 12 H); 7.85 (d, J ˆ 7.9, 2 H); 7.88 (d, J ˆ 7.9, 2 H); 8.21 (s, 2 H);
8.28 (s, 2 H). 13C-NMR (50 MHz, CDCl3): 2.64; 53.55; 53.86; 75.73; 77.23; 96.37; 96.75; 96.91; 99.48; 113.76;
114.78; 123.09; 123.22; 123.41; 123.79; 124.08; 124.30; 125.09; 125.28; 125.34; 125.47; 127.85; 128.55; 131.44;
‡
131.98; 132.74; 133.50; 151.12; 151.34. EI-MS: 987 (18, M ), 149 (100). Anal. calc. for C62H58O8Si2 ´ 0.5 H2O
(996.23): C 74.74, H 5.97; found: C 74.82, H 5.91.
(
)-(R,R)-3,3'-(Buta-1,3-diynediyl)bis[2,2'-bis(methoxymethoxy)-3'-ethynyl-1,1'-binaphthalene] (( )-(R,R)-
36). A soln. of (R,R)-35 (215 mg, 0.22 mmol) and K2CO3 (208 mg, 1.50 mmol) in MeOH/THF 1:1 (40 ml) was
stirred at r.t. for 1.5 h. After addition of CH2Cl2 (250 ml), the org. phase was washed (H2O), dried (Na2SO4),
and concentrated. CC (hexane/AcOEt 3 :2 containing 0.5% Et3N) afforded (R,R)-36 (148 mg, 81%). M.p. 828.
[a]rD:t:
ˆ
28.7 (c ˆ 1.0, THF). IR (KBr): 3278m, 2922w, 2143w, 2109w, 1240m, 1158s, 971s, 751m. 1H-NMR
(200 MHz, CDCl3): 2.55 (s, 6 H); 2.64 (s, 6 H); 3.34 (s, 2 H); 4.89 (d, AB, J ˆ 6.2, 2 H); 4.90 (d, AB, J ˆ 5.8,
2 H); 5.08 (d, AB, J ˆ 5.8, 2 H); 5.10 (d, AB, J ˆ 6.2, 2 H); 7.20 (d, J ˆ 8.7, 4 H); 7.28 ± 7.48 (m, 8 H); 7.85
(d, J ˆ 7.9, 4 H); 8.21 (s, 2 H); 8.28 (s, 2 H). 13C-NMR (50 MHz, CDCl3): 56.21; 56.37; 78.26; 79.70; 80.70; 81.79;
99.13; 99.29; 116.29; 116.45; 125.84; 125.90; 126.01; 126.16; 126.64; 126.77; 127.83; 127.87; 127.94; 128.10; 130.40
‡
(2Â); 134.15; 134.46; 135.59; 136.16; 153.68; 153.94. MALDI-TOF-MS (THA/citrate): 866 ([M ‡ Na] ). Anal.
calc. for C56H42O8 ´ 0.5 H2O (851.95): C 78.95, H 5.09; found: C 79.00, H 5.31.
(
)-(R,R,S)-Tris[2,2'-bis(methoxymethoxy)-1,1'-binaphthalene-3,3'-diylbis(ethynyl)] (( )-(R,R,S)-31). A
soln. of CuCl (1.35 g, 14 mmol) in CH2Cl2 (600 ml) was stirred for 15 min under dry air, then TMEDA (2.09 ml,
1.62 g, 14 mmol) was added. A soln. of (S)-30 (50 mg, 11.6 mmol) and (R,R)-36 (100 mg, 11.6 mmol) in CH2Cl2
(250 ml) was slowly added via syringe pump over 3 h. The mixture was stirred at r.t. for 24 h, then warmed to 308
for 2 h. The same workup as described for the synthesis of (S,S,S)-31 yielded a diastereoisomer mixture of
(R,R,S)-31 (16 mg, 11%) and (S,S,S)-31 (6 mg, 4%), which was separated by HPLC (Spherisorb SW, 5 mm;
toluene/AcOEt 99 :1). M.p. 2548 (dec.). [a]Dr:t:
ˆ
210.5 (c ˆ 1.0, THF). 1H-NMR (500 MHz, CDCl3): 2.54
(s, 6 H); 2.60 (s, 6 H); 2.61 (s, 6 H); 4.73 (d, AB, J ˆ 6.2, 2 H); 4.77 (d, AB, J ˆ 6.2, 2 H); 4.85 (d, AB, J ˆ 6.2,
2 H); 4.98 (d, AB, J ˆ 6.2, 2 H); 4.99 (d, AB, J ˆ 6.2, 2 H); 5.11 (d, AB, J ˆ 6.2, 2 H); 7.22 ± 7.48 (m, 18 H);
7.85 ± 7.91 (m, 6 H); 8.20 (s, 6 H). 13C-NMR (125 MHz, CDCl3): 56.16; 56.20; 56.29; 78.71; 78.74; 78.97; 80.08;
80.35; 80.49; 98.91; 99.18; 99.23; 116.11; 116.30; 116.33; 125.48; 125.55; 125.60; 126.42 (2Â); 126.55; 127.78;
127.90; 127.95; 128.20 (3Â); 129.03 (3Â); 130.07 (2Â); 130.15; 134.02; 134.05 (2Â), 134.10; 134.46; 134.62;
154.40; 154.81; 154.86.
Compound ( )-(R,R,S)-2 (18 mg, 79%) was prepared in the same manner as described for (S,S,S)-2
starting from (R,R,S)-31 (29 mg, 1.7 mmol) and conc. aq. HCl soln. (37%, 0.15 ml) in THF/MeOH 3 :2 (10 ml).
M.p. >3008. [a]Dr:t:
ˆ
611.1 (c ˆ 1.0, THF). 1H-NMR (200 MHz, (D8)THF): 6.99 ± 7.09 (m, 6 H); 7.15 ± 7.34
(m, 12 H); 7.80 ± 7.87 (m, 6 H); 8.11 (s, 2 H); 8.14 (s, 4 H). 13C-NMR (50 MHz, (D8)THF): 78.43 (2Â); 78.85;
79.64; 79.75; 80.02; 112.53; 112.64; 112.71; 113.98 (3Â); 123.16; 123.28; 123.37; 124.71 (3Â); 127.08; 127.19
(2Â); 127.68; 127.79 (2Â); 128.20; 128.27; 128.36; 133.22; 133.30; 133.66; 134.61; 134.71 (2Â); 154.17; 154.42 (2Â).
(
)-(S)-2,2'-Bis(methoxymethoxy)-6,6'-dibromo-1,1'-binaphthalene (( )-(S)-38). To a degassed soln. of
(S)-37 [63] (2.5 g, 5.6 mmol), MOMCl (1.7 ml, 1.80 g, 22.4 mmol) and K2CO3 (4.67 g, 33.8 mmol) were added in
DMF (50 ml) at 08, and the mixture was stirred at r.t. for 12 h. The salts were removed by filtration through
Celite, and evaporation in vacuo gave (S)-38 (2.8 g, 95%). White powder (cyclohexane). M.p. 1258. [a]Dr:t:
ˆ
16.3 (c ˆ 1.0, CHCl3). IR (KBr): 2957m, 2898m, 1586s, 1492s, 1344m, 1237s, 1188m, 1147m, 1077m, 1065m,
1019s, 954w, 917m, 896w, 863w, 806m. 1H-NMR (300 MHz, CDCl3): 3.16 (s, 6 H); 4.98 (d, AB, J ˆ 6.9, 2 H); 5.09
(d, AB, J ˆ 6.9, 2 H); 6.98 (d, J ˆ 9.0, 2 H); 7.29 (dd, J ˆ 9.0, 2.1, 2 H); 7.60 (d, J ˆ 9.0, 2 H); 7.87 (d, J ˆ 9.0,
2 H); 8.03 (d, J ˆ 9.02, 2 H). 13C-NMR (100 MHz, (D8)THF): 55.93; 95.60; 118.28; 118.75; 121.27; 128.07;
‡
‡
129.36; 130.15; 130.71; 131.90; 133.45; 154.34. EI-MS: 532 (62, M ), 456 ([M C3H8O2] ). Anal. calc. for
C24H20Br2O4 (532.23): C 54.16, H 3.79; found: C 53.89, H 3.85.
Compound (‡)-(R)-38 ([a]rD:t: ˆ‡ 19.7 (c ˆ 1.0, CHCl3)) was prepared in the same manner.
(
)-(S)-2,2'-Bis(methoxymethoxy)-6,6'-bis(2-phenylethyl)-1,1'-binaphthalene (( )-(S)-39). A soln. of styr-
ene (1.72 ml, 1.56 g, 15.0 mmol) in THF (10 ml) was slowly added to 9-BBN (0.5m soln. in THF, 30 ml,
15.0 mmol), and the mixture was heated to 608 for 5 h. This soln. (40 ml, 15.0 mmol) was then added to a
degassed soln. of (S)-38 (2.70 g, 5.1 mmol), [PdCl2(dppf)] ´ CH2Cl2 (135 mg, 3 mol-%), and 3m NaOH (10.0 ml,
30.0 mmol) in THF (100 ml), and the resulting mixture was warmed to 508 for 15 h. After filtration through

1958
Helvetica Chimica Acta ± Vol. 81 (1998)
Celite, H2O (300 ml) was added and the product extracted with CH2Cl2. The org. phase was stirred with 5% aq.
H2O2/NaOH soln. (200 ml) for 3 h and then washed (H2O and sat. aq. NaCl soln.). Evaporation in vacuo and
CC (hexane/AcOEt 5 : 1 containing 0.5% Et3N) afforded (S)-39 (2.80 g, 94%). Highly viscous oil. [a]Dr:t:
ˆ
2.7
(c ˆ 1.0, CHCl3). IR (neat): 2924s, 2853w, 1597m, 1497m, 1451w, 1355w, 1238m, 1197w, 1147m, 1070m, 1020s,
917w, 816w. 1H-NMR (200 MHz, CDCl3): 2.97 ± 3.05 (m, 8 H); 3.17 (s, 6 H); 4.99 (d, AB, J ˆ 6.6, 2 H); 5.10
(d, AB, J ˆ 6.6, 2 H); 7.10 ± 7.32 (m, 14 H); 7.60 (d, J ˆ 9.0, 2 H); 7.97 (s, 2 H); 7.90 (d, J ˆ 9.0, 2 H). 13C-NMR
(100 MHz, CDCl3): 37.65; 37.72; 55.75; 95.36; 117.54; 121.45; 125.63; 125.86; 126.35; 127.73; 128.29; 128.39;
‡
‡
128.81; 130.05; 132.56; 137.38; 141.77; 152.20. EI-MS: 582 (100, M ). HR-EI-MS: 582.2759 (M , C40H38O4; calc.
582.2770).
Compound (‡)-(R)-39 ([a]rD:t: ˆ‡ 3.4 (c ˆ 1.0, CHCl3)) was prepared in the same manner.
(‡)-(S)-2,2'-Bis(methoxymethoxy)-6,6'-bis(2-phenylethyl)-6,6'-diiodo-1,1'-binaphthalene ((‡)-(S)-41). Com-
pound (S)-41 (2.30 g, 73%) was prepared from (S)-39 (2.20 g, 3.8 mmol) in Et2O (70 ml) using BuLi (1.6m soln.
in hexane, 9.5 ml, 15.2 mmol), TMEDA (2.29 ml, 1.77 g, 15.2 mmol), and I2 (4.80 g, 18.9 mmol, soln. in 20 ml
Et2O) and following the same procedure as described for the synthesis of (S)-28. Highly viscous oil. [a]Dr:t:
ˆ
‡ 12.2 (c ˆ 1.0, CHCl3). IR (neat): 2921s, 2849w, 1736m, 1602w, 1562w, 1491m, 1453m, 1372m, 1233m, 1195w,
1
1159s, 1083m, 996m, 962m, 935m, 820w. H-NMR (200 MHz, CDCl3): 2.62 (s, 6 H); 2.97 ± 3.06 (m, 8 H); 4.69
(d, AB, J ˆ 5.6, 2 H); 4.84 (d, AB, J ˆ 5.6, 2 H); 7.13 ± 7.30 (m, 14 H); 7.52 (s, 2 H); 8.45 (s, 2 H). 13C-NMR
(100 MHz, CDCl3): 35.01; 35.26; 54.12; 90.21; 97.06; 123.03; 123.79; 123.95; 124.30; 126.11 (2Â); 126.17; 126.36;
‡
‡
‡
130.14; 137.06; 137.22; 139.12; 149.37. EI-MS: 834 (17, M ), 45 (100, [C2H5O] ). HR-EI-MS: 834.0685 (M ,
C40H36O4I2; calc. 834.0707).
Compound ( )-(R)-41 ([a]Dr:t:
ˆ
11.3 (c ˆ 1.0, CHCl3)) was prepared in the same manner.
(
)-(S)-2,2'-Bis(methoxymethoxy)-6,6'-bis(2-phenylethyl)-3,3'-bis[(trimethylsilyl)ethynyl]-1,1'-binaphtha-
lene (( )-(S)-42). To a suspension of (S)-41 (2.30 g, 2.8 mmol) in Et3N (40 ml), [PdCl2(PPh3)2] (100 mg, 5 mol-
%), CuI (27 mg, 5 mol-%), and (trimethylsilyl)acetylene (0.78 g, 1.12 ml, 8.4 mmol) were added, and the
mixture was heated to 508 for 2 h. After addition of sat. aq. NaCl soln. (30 ml) and filtration over Celite, the
product was extracted with CH2Cl2 and the solvent removed in vacuo. CC (hexane/AcOEt 12 :1 containing
0.5% Et3N) afforded (S)-42 (2.00 g, 93%). Highly viscous oil. [a]Dr:t:
ˆ
35.8 (c ˆ 1.0, CHCl3). IR (neat): 2956m,
2144m, 1591w, 1493m, 1250m, 1429m, 1243s, 1205m, 1154m, 1070m, 977m, 846m. 1H-NMR (200 MHz, CDCl3):
0.27 (s, 18 H); 2.44 (s, 6 H); 3.00 ± 3.06 (m, 8 H); 4.87 (d, AB, J ˆ 6.2, 2 H); 5.18 (d, AB, J ˆ 6.2, 2 H); 7.13 ± 7.32
(m, 14 H); 7.55 (s, 2 H); 8.08 (s, 2 H). 13C-NMR (75 MHz, CDCl3): 2.64; 34.95; 35.20; 53.51; 96.30; 96.52;
99.70; 114.62; 123.38; 123.66; 123.73; 124.27; 126.01; 126.14; 126.43; 127.95; 130.14; 132.04; 136.49; 139.19;
‡
‡
‡
150.58. EI-MS: 774 (9, M ), 73 (100, [Me3Si] ). HR-EI-MS: 774.3582 (M , C50H54O4Si2; calc. 774.3560).
Compound (‡)-(R)-42 ([a]rD:t: ˆ‡ 32.0 (c ˆ 1.0, CHCl3)) was prepared in the same manner.
(
)-(S)-2,2'-Bis(methoxymethoxy)-6,6'-bis(2-phenylethyl)-3,3'-diethynyl-1,1'-binaphthalene (( )-(S)-43).
Compound (S)-43 was prepared from (S)-42 (895 mg, 1.2 mmol) using K2CO3 (1.16 g, 8.4 mmol) in THF/
MeOH 1:1 (140 ml) and following the same procedure as described for (S)-30. CC (hexane/AcOEt 9 :1
containing 0.5% Et3N) afforded (S)-43 (630 mg, 87%). M.p. 458. [a]Dr:t:
ˆ
36.0 (c ˆ 1.0, CHCl3). IR (KBr):
2920s (br.), 2107w, 1731w, 1590m, 1492m, 1448m, 1430m, 1395w, 1373w, 1355w, 1236m, 1250m, 1156s, 1068m,
1011w, 966s, 905m, 816w. 1H-NMR (300 MHz, CDCl3): 2.53 (s, 6 H); 2.95 ± 3.12 (m, 8 H); 3.33 (s, 2 H); 4.89
(d, AB, J ˆ 5.7, 2 H); 5.08 (d, AB, J ˆ 5.7, 2 H); 7.12 ± 7.32 (m, 14 H); 7.58 (s, 2 H); 8.11 (s, 2 H). 13C-NMR
(100 MHz, CDCl3): 37.55; 37.76; 56.17; 80.89; 81.59; 99.06; 116.42; 125.98; 126.27; 126.40; 126.77; 128.62;
‡
‡
128.72; 129.28; 130.54; 132.80; 134.98; 139.30; 141.74; 153.18. EI-MS: 630 (58, M ), 45 (100, [C2H5O] ). Anal.
calc. for C44H38O4 (630.79): C 83.78, H 6.07; found: C 83.80, H 6.20.
Compound (‡)-(R)-43 ([a]rD:t: ˆ‡ 36.2 (c ˆ 1.0, CHCl3)) was prepared in the same manner.
Glaser-Hay Cyclization of (S)-43. A soln. of (S)-43 (240 mg, 0.38 mmol) and CuCl (3.5 g, 35 mmol) in
CH2Cl2 (1.2 l) was stirred for 10 min. After addition of TMEDA (5.3 ml, 4.1 g, 35 mmol) and stirring for 1 h
under dry air, H2O (400 ml) was added, the org. phase washed (H2O), dried (Na2SO4), and concentrated. CC
(hexane/AcOEt 3 :1 !1 : 1, containing 0.5% Et3N) and separation by GPC (CH2Cl2) afforded (S,S,S)-44
(85 mg, 36%), in addition to tetramer (S,S,S,S)-45 (59 mg, 25%).
(‡)-(S,S,S)-Tris[2,2'-bis(methoxymethoxy)-6,6'-bis(2-phenylethyl)-1,1'-binaphthalene-3,3'-diylbis(ethynyl)]
((‡)-(S,S,S)-44). M.p. 1728. [a]rD:t: ˆ‡ 792.3 (c ˆ 1.0, CHCl3). IR (KBr): 2920m, 2854w, 2206w, 2132w, 1585m,
1491m, 1446m, 1434m, 1368w, 1233w, 1200w, 1155s, 1069m, 971s, 922m, 898m, 816m. 1H-NMR (200 MHz,
CDCl3): 2.61 (s, 18 H); 2.98 ± 3.08 (m, 24 H); 4.95 (d, AB, J ˆ 6.3, 6 H); 5.07 (d, AB, J ˆ 6.3, 6 H); 7.15 ± 7.32
(m, 42 H); 7.60 (s, 6 H); 8.10 (s, 6 H). 13C-NMR (50 MHz, CDCl3): 35.04; 35.23; 53.80; 76.18; 77.70; 96.84;
113.86; 123.28; 123.73; 124.20 (2Â); 126.08; 126.17; 127.03; 127.92; 130.39; 131.63; 136.71; 139.12; 152.10.
‡
MALDI-TOF-MS (HABA): 1910 ([M ‡ Na] ). Anal. calc. for C132H108O12 (1886.33): C 84.05, H 5.77; found:
C 83.92, H 5.93.

Helvetica Chimica Acta ± Vol. 81 (1998)
1959
(‡)-(S,S,S,S)-Tetrakis[2,2'-bis(methoxymethoxy)-6,6'-bis(2-phenylethyl)-1,1'-binaphthalene-3,3'-diylbis-
(ethynyl)] ((‡)-(S,S,S,S)-45). M.p. 195 ± 1978. [a]rD:t: ˆ‡ 595.1 (c ˆ 1.0, CHCl3). IR (KBr): 2926m, 2232w, 2161w,
1587m, 1492m, 1445m, 1427m, 1372w, 1239w, 1204w, 1157s, 1071m, 968s, 929m, 908m, 817m. 1H-NMR
(300 MHz, CDCl3): 2.59 (s, 24 H); 2.95 ± 3.09 (m, 32 H); 4.89 (d, AB, J ˆ 6.3, 8 H); 5.12 (d, AB, J ˆ 6.3, 8 H);
7.11 ± 7.32 (m, 56 H); 7.58 (s, 8 H); 8.13 (s, 8 H). 13C-NMR (75 MHz, CDCl3): 37.54; 37.76; 56.37; 78.24; 79.60;
99.39; 116.27; 125.98; 126.29; 126.54; 126.81; 128.62; 128.72; 129.61; 130.54; 133.05; 135.41; 139.39; 141.69;
‡
153.79. MALDI-TOF-MS (HABA): 2539 ([M ‡ Na] ). Anal. calc. for C176H144O16 ´ 2 H2O (2551.13): C 82.86,
H 5.85; found: C 82.99, H 5.85.
(‡)-(S,S,S)-Tris[6,6'-bis(2-phenylethyl)-2,2'-dihydroxy-1,1'-binaphthalene-3,3'-diylbis(ethynyl)] ((‡)-
(S,S,S)-3). A soln. of (S,S,S)-44 (70 mg, 3.7 mmol) and conc. aq. HCl soln. (37%, 0.35 ml) in THF/MeOH 3 :2
(25 ml) was stirred at r.t. for 12 h. After concentration to 1/3 of the volume, reprecipitation with hexane (20 ml),
filtration, and drying afforded (S,S,S)-3 (45 mg, 75%). Yellow powder. M.p. >2508. [a]rD:t: ˆ‡ 1278.3 (c ˆ 1.0,
CHCl3). IR (KBr): 3502s (br.), 3027w, 2921m, 2853w, 2202w, 2132w, 1598m, 1492w, 1439m, 1376w, 1259m,
901m, 814m. 1H-NMR (400 MHz, CDCl3): 2.90 ± 2.97 (m, 24 H); 5.69 (br. s, 6 H); 6.90 (d, J ˆ 8.5, 6 H); 7.01
(d, J ˆ 8.5, 6 H); 7.16 ± 7.29 (m, 30 H); 7.58 (s, 6 H); 8.06 (s, 6 H). 13C-NMR (100 MHz, CDCl3): 37.57; 37.61;
78.90; 79.86; 110.85; 113.23; 125.37; 126.02; 126.96; 128.41; 128.44; 128.56; 129.55; 132.73; 133.93; 137.71; 141.58;
‡
151.69. MALDI-TOF-MS (HABA): 1645 ([M ‡ Na] ). Anal. calc. for C120H84O6 ´ H2O (1640.02): C 87.89,
H 5.29; found: C 87.83, H 5.21.
(
)-(S)-2,2'-Bis(methoxymethoxy)-6,6'-bis(2-phenylethyl)-3-ethynyl-3'-[(trimethylsilyl)ethynyl]-1,1'-bi-
naphthalene (( )-(S)-46). Compound (S)-46 was prepared from (S)-42 (2.0 g, 2.6 mmol) using borax (4.0 g,
26.0 mmol) in THF/H2O 4 :3 (1.4 l), following the same procedure as described for the synthesis of (R)-34. CC
(hexane/AcOEt 12 :1 containing 0.5% Et3N) afforded (S)-46 (520 mg, 28%) as a viscous oil besides starting
material ((S)-42) (1.11 g, 55%) and (S)-43 (90 mg, 6%). [a]Dr:t:
ˆ
45.1 (c ˆ 1.0, CHCl3). IR (KBr): 2922s (br.),
2148m, 1590w, 1494w, 1445w, 1428w, 1239m, 1203w, 1155s, 1067m, 970s, 843s. 1H-NMR (500 MHz, CDCl3): 0.27
(s, 9 H); 2.46 (s, 3 H); 2.50 (s, 3 H); 2.97 ± 3.06 (m, 8 H); 3.32 (s, 2 H); 4.84 (d, AB, J ˆ 6.1, 1 H); 4.88
(d, AB, J ˆ 6.2, 1 H); 5.07 (d, AB, J ˆ 6.1, 1 H); 5.15 (d, AB, J ˆ 6.2, 1 H); 7.10 ± 7.26 (m, 14 H); 7.53 (d, J ˆ 1.2,
1 H); 7.56 (d, J ˆ 1.2, 1 H); 8.06 (s, 1 H); 8.09 (s, 1 H). 13C-NMR (125 MHz, CDCl3): 0.13; 37.41; 37.45; 37.63;
37.65; 55.90; 56.10; 80.78; 81.31; 98.64; 98.86; 98.95; 102.05; 116.18; 117.02; 125.51; 125.88; 125.99 (2Â); 126.09;
126.11; 126.50; 126.58; 128.33; 128.34; 128.45 (2Â); 128.83; 128.93; 130.28 (2Â); 132.40; 132.63; 134.42; 134.60;
‡
‡
138.84; 138.96; 141.46 (2Â); 152.83; 152.88. EI-MS: 702 (15, M ), 91 (100, [C7H7] ). Anal. calc. for C47H46O4Si
(702.97): C 80.31, H 6.60; found: C 80.52, H 6.60.
(
)-(S,S)-3,3'-(Buta-1,3-diynediyl)bis[2,2'-bis(methoxymethoxy)-6,6'-bis(2-phenylethyl)-3'-ethynyl-1,1'-bi-
naphthalene] (( )-(S,S)-48). Compound (S,S)-47 was prepared from (S)-46 (590 mg, 0.84 mmol) using CuCl
(1.00 g, 10 mmol) and TMEDA (1.5 ml, 1.16 g, 10.0 mmol) in CH2Cl2 (600 ml) and following the same procedure
as described for the synthesis of (R,R)-35. The crude product was directly dissolved in THF/MeOH 1:1 (140 ml)
and converted to (S,S)-48 in the same manner as described for (R,R)-36, using K2CO3 (0.58 g, 4.2 mmol). CC
(hexane/AcOEt 9 :1 containing 0.5% Et3N) afforded (S,S)-48 (400 mg, 76% from (S)-46). M.p. 758. [a]Dr:t:
ˆ
59.7 (cˆ 1.0, CHCl3). IR (KBr): 2927s, 2855m, 2155w, 2112w, 1726s, 1588w, 1490w, 1450m, 1428w, 1369w,
1272m, 1236m, 1200w, 1156s, 1120w, 1066m, 968s, 816w. 1H-NMR (300 MHz, CDCl3): 2.55 (s, 6 H); 2.64 (s, 6 H);
2.99 ± 3.10 (m, 16 H); 3.35 (s, 2 H); 4.89 (d, AB, J ˆ 6.2, 2 H); 4.92 (d, AB, J ˆ 6.2, 2 H); 5.09 (d, AB, J ˆ 6.2,
2 H); 5.10 (d, AB, J ˆ 6.2, 2 H); 7.15 ± 7.35 (m, 28 H); 7.59 (s, 4 H); 8.12 (s, 2 H); 8.16 (s, 2 H). 13C-NMR
(125 MHz, CDCl3): 37.44; 37.66; 56.08; 56.23; 77.20; 78.04; 79.65; 80.67; 81.45; 98.90; 99.07; 116.03; 116.17;
125.54; 125.84; 126.00; 126.01; 126.17; 126.23; 126.45; 126.56; 128.35 (2Â); 128.45 (2Â); 129.07; 129.34; 130.28;
130.31; 132.46; 132.48; 132.76; 134.77; 135.32; 139.05; 139.16; 141.40; 141.44; 152.86; 153.14. MALDI-TOF-MS
‡
(HABA): 1283 ([M ‡ Na] ). Anal. calc. for C88H74O8 (1259.57): C 83.92, H 5.92; found: C 83.81, H 6.02.
(‡)-(S,S,R)-Tris[2,2'-bis(methoxymethoxy)-6,6'-bis(2-phenylethyl)-1,1'-binaphthalene-3,3'-diylbis(ethyn-
yl)] ((‡)-(S,S,R)-44). A soln. of (R)-43 (75 mg, 0.12 mmol), (S,S)-48 (150 mg, 0.12 mmol), and CuCl (3.2 g,
32 mmol) in CH2Cl2 (1.2 l) was stirred for 15 min. After addition of TMEDA (4.8 ml, 3.7 g, 32 mmol) and
stirring for 1 h under dry air, H2O (400 ml) was added, the org. phase washed (H2O), dried (Na2SO4), and
concentrated. CC (hexane/AcOEt 3 :1 !1 : 1 containing 0.5% Et3N) and GPC (CH2Cl2) afforded
a
diastereoisomer mixture of trimers (68 mg, 3.6 mmol, 30%). (S,S,R)-44 (52 mg, 2.8 mmol, 23%) was separated
from (S,S,S)-44 by HPLC (Spherisorb SW, 5 mm; toluene !toluene/AcOEt 95 : 5). M.p. 1758. [a]rD:t: ˆ‡ 241.9
(c ˆ 1.0, CHCl3). 1H-NMR (500 MHz, CDCl3): 2.51 (s, 6 H); 2.57 (s, 6 H); 2.59 (s, 6 H); 2.95 ± 3.08 (m, 24 H);
4.69 (d, AB, J ˆ 6.2, 2 H); 4.73 (d, AB, J ˆ 6.5, 2 H); 4.82 (d, AB, J ˆ 6.5, 2 H); 4.95 (d, AB, J ˆ 6.5, 2 H); 4.96
(d, AB, J ˆ 6.2, 2 H); 5.08 (d, AB, J ˆ 6.5, 2 H); 7.12 ± 7.30 (m, 42 H); 7.57 (s, 4 H); 7.60 (s, 2 H); 8.07 (s, 2 H);
8.08 (s, 4 H). 13C-NMR (125 MHz, CDCl3): 37.45 (2Â); 37.49; 37.66 (2Â); 37.69; 56.18; 56.22; 56.32; 78.68;

1960
Helvetica Chimica Acta ± Vol. 81 (1998)
78.73; 78.94; 80.27; 80.55; 80.69; 98.02; 99.17; 99.22; 116.17; 116.34; 116.37; 125.28; 125.31 (2Â); 125.44; 125.50;
125.60; 126.03 (2Â); 126.05; 126.46; 126.49; 126.60; 128.36 (2Â); 128.38; 128.46; 128.47; 128.48; 129.29 (2Â);
129.32; 130.27; 130.28; 130.35; 132.66; 132.68; 132.73; 133.57; 133.89; 134.06; 139.00 (2Â); 139.04; 141.42;
141.43; 141.44; 153.98; 154.39; 154.43.
Compound (‡)-(S,S,R)-3 (35 mg, 81%) was prepared in the same manner as described for (S,S,S)-3,
starting from (S,S,R)-44 (50 mg, 2.7 mmol) and conc. aq. HCl soln. (37 %, 0.23 ml) in THF/MeOH 3 :2 (15 ml).
M.p. >2508. [a]rD:t: ˆ‡ 381.7 (c ˆ 1.0, CHCl3). 1H-NMR (400 MHz, CDCl3): 2.94 ± 3.04 (m, 24 H); 5.80
(br. s, 6 H); 6.99 (d, J ˆ 8.7, 6 H); 7.04 (d, J ˆ 8.7, 6 H); 7.10 ± 7.31 (m, 30 H); 7.58 (s, 4 H); 7.60 (s, 2 H); 8.06
(s, 2 H); 8.08 (s, 4 H). 13C-NMR (100 MHz, CDCl3): 37.58 (3Â); 37.61 (3Â); 77.22 (3Â); 79.38; 79.48; 79.92;
80.07 (3Â); 110.83; 111.05 (2Â); 113.25; 113.27; 113.40; 125.34; 126.03 (2Â); 126.95; 127.00; 127.08; 128.40
(2Â); 128.42; 128.46 (2Â); 128.48; 128.71; 128.77; 128.80; 129.86; 129.90; 129.99; 132.75; 132.77; 132.94; 133.54;
133.67; 133.94; 137.96; 137.99 (2Â); 141.50; 141.53 (2Â); 151.45; 151.61; 151.79.
X-Ray Crystal Structure of (S)-21. Crystal data at 95 K for 2(C38H32O6Br2) (Mr 1488.91): monoclinic, space
group P21 (No. 4), 1calc. ˆ 1.488 g cm 3, Z ˆ 2, a ˆ 15.175(5) Š, b ˆ 10.348(5) Š, c ˆ 21.456(5) Š, b ˆ 99.41(2)8,
Vˆ 3324(2) Š3. Nonius CAD4 diffractometer, MoKa radiation, l ˆ 0.7107 Š. Single crystals were obtained by
diffusion of hexane to a AcOEt soln. The structure was solved by direct methods (SHELXS-86) and refined by
full-matrix least-squares analysis (SHELXL-93), using an isotropic extinction correction and w ˆ 1/[s2(Fo2) ‡
2
(0.111P)2 ‡ 15.51P], where P ˆ (Fo ‡ 2Fc2)/3. Both (independent) molecules, in particular molecule 2 (primed
(') atom labels) exhibit sever disorder, and as a result, the derived molecular geometry is not reliable. For some
atoms, the disorder could be resolved. For Br(2'), two sets of atomic parameters were refined anisotropically
with weights of 0.65 and 0.35, respectively. Three benzene rings (C(13) to C(18), C(13') to C(18'), C(35') to
C(40')) could be refined only by restraining the C C distances to ca. 1.39 Š. In addition, for the benzene ring
C(13') to C(18') and the fragment O(41) C(42) O(43) C(44), two different orientations were located and
refined isotropically with weights of 0.5 (for clarity, only one orientation is shown in Fig. 1). All other heavy
atoms were refined anisotropically (H-atoms neglected). Final R(F) ˆ 0.058, wR(F2) ˆ 0.150 for 798
parameters, 37 restraints, and 3703 reflections with I > 2s(I) and q < 248. Further details of the structure
analysis are available on request from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge
CB12 1EZ (UK), on quoting the full journal citation.
This work was supported by the Chiral-2 program of the Swiss National Science Foundation and
F. Hoffmann-La Roche AG, Basel. A. B. is grateful for a doctoral fellowship of the Fonds der Chemischen
Â
Industrie (Kekule-Stipendium), A. S. D. for a doctoral fellowship from the Stipendienfonds der Basler
Chemischen Industrie, and S. A. for a postdoctoral fellowship from the Royal Society (UK). We thank Dr.
Monika Sebova for NMR measurements and Thomas Mäder for HPLC separations.
REFERENCES
[1] a) N. Sharon, H. Lis, Sci. Am. 1993, 268 (1), 74; b) H. Lis, N. Sharon, Chem. Rev. 1998, 98, 637.
[2] G. Bock, S. Harnett, ꢀCarbonhydrate Recognition in Cellular Functionꢁ, Ciba Found, Symp. 1989, p. 145;
A. Kobata, Acc. Chem. Res. 1993, 26, 319; R. A. Dwek, Chem. Rev. 1996, 96, 683; A. Varki, Glycobiology
1993, 3, 97.
[3] R. U. Lemieux, Chem. Soc. Rev. 1989, 18, 347.
[4] R. A. Quiocho, Pure Appl. Chem. 1989, 61, 1293; N. Sharon, H. Lis, Science (Washington, D.C.) 1989, 246,
227; D. R. Bundle, N. M. Young, Curr. Opin. Struct. Biol. 1992, 2, 666; R. U. Lemieux, ꢀCarbohydrate
Antigensꢁ, Eds. P. J. Garegg and A. A. Lindberg, ACS Symp. Ser., Washington, D. C., 1993; T. Feizi,
D. Bundle, Curr. Opin. Struct. Biol. 1994, 4, 673; F. A. Quiocho, N. K. Vyas, Nature (London) 1984, 310, 381;
W. I. Weis, K. Drickamer, Annu. Rev. Biochem. 1996, 65, 441; K. Drickamer, Structure 1997, 5, 465.
[5] A. J. Sharff, L. E. Rodseth, S. Szmelcman, M. Hofnung, F. A. Quiocho, J. Mol. Biol. 1995, 246, 8; K. K.-
S. Ng, K. Drickamer, W. I. Weis, J. Biol. Chem. 1996, 271, 663; A. R. Kolatkar, W. I. Weis, ibid. 1996, 271,
6679; R. Sankaranarayanan, K. Sekar, R. Banerjee, V. Sharma, A. Surolia, M. Vijayan, Nature Struct. Biol.
1996, 3, 596; M. OꢁReilly, K. A. Watson, R. Schinzel, D. Palm, L. N. Johnson, ibid. 1997, 4, 405;
J. E. W. Meyer, G. E. Schulz, Protein Sci. 1997, 6, 1084; T. R. Transue, A. K. Smith, H. Mo, I. J. Goldstein,
M. A. Saper, Nature Struct. Biol. 1997, 4, 779; D. Forst, W. Welte, T. Wacker, K. Diederichs, ibid. 1998, 5, 37.
[6] K. H. Mortell, R. V. Weatherman, L. L. Kiessling, J. Am. Chem. Soc. 1996, 118, 2297.
[7] S. Elgavish, B. Shaanan, Trends Biochem. Sci. 1997, 22, 462.
[8] Y. Lee, R. Lee, Acc. Chem. Res. 1995, 28, 321.