Functionalized 3,3′,5,5′-tetraaryl-1,1′-biphenyls: Novel platforms for molecular receptors

Article abstract of DOI:10.1002/hlca.200390055

This paper describes the development of novel aromatic platforms for supramolecular construction. By the Suzuki cross-coupling protocol, a variety of functionalized m-terphenyl derivatives were prepared (Schemes 1-4). Macrolactamization of bis(ammonium sa

Full text of DOI:10.1002/hlca.200390055

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Helvetica Chimica Acta Vol. 86 (2003)
Functionalized 3,3',5,5'-Tetraaryl-1,1'-Biphenyls: Novel Platforms for
Molecular Receptors
by Roger Weltia), Yvonne Abela), Volker Gramlichb), and FranÁois Diederich*a)
a) Laboratorium f¸r Organische Chemie, ETH-Hˆnggerberg, HCI, CH-8093 Z¸rich (phone: (0)16322992;
fax: (0)16321109; e-mail: diederich@org.chem.ethz.ch)
b) Laboratorium f¸r Kristallographie, ETH-Zentrum, Sonneggstrasse 5, CH-8092 Z¸rich
This paper describes the development of novel aromatic platforms for supramolecular construction. By the
Suzuki cross-coupling protocol, a variety of functionalized m-terphenyl derivatives were prepared (Schemes 1
4). Macrolactamization of bis(ammonium salt) (S,S)-6 with bis(acyl halide) 7 afforded the macrocyclic receptor
(S,S)-2 (Scheme 1), which was shown by 1H-NMR titration studies to form −nesting× complexes of moderate
stability (Ka between 130 and 290 mÀ1, 300 K) with octyl glucosides 13 15 (Fig. 2) in the noncompetitive solvent
CDCl3. Suzuki cross-coupling starting from 3,3',5,5'-tetrabromo-1,1'-biphenyl provided access to a novel series
of extended aromatic platforms (Scheme 5) for cleft-type (Fig. 1) and macrotricyclic receptors such as (S,S,S,S)-
1. Although mass-spectral evidence for the formation of (S,S,S,S)-1 by macrolactamization between the two
1
functionalized 3,3',5,5'-tetraaryl-1,1'-biphenyl derivatives (S,S)-33 and 36 was obtained, the H- and 13C-NMR
spectra of purified material remained rather inconclusive with respect to both purity and constitution. The
versatile access to the novel, differentially functionalized 3,3',5,5'-tetrabromo-1,1'-biphenyl platforms should
ensure their wide use in future supramolecular construction.
1. Introduction. The design of efficient cleft-type or macrocyclic receptors for
host-guest complexation studies frequently relies on the use of rigid molecular
platforms that can be decorated with multiple convergent functional groups. An
incomplete list of examples for such platforms, recently used in the construction of
artificial receptors, includes meso-tetraarylporphyrins [1][2], hexasubstituted benzene
derivatives [3], cholic acid derivatives [4], and hexasubstituted triphenylenes [5].
During the course of our carbohydrate recognition studies with synthetic receptors [6],
we identified functionalized 3,3',5,5'-tetraarylated 1,1'-biphenyls as interesting new
platforms for incorporation into molecular receptors (Fig. 1). A literature search,
however, revealed that the preparation of such functionalized platforms had not been
previously described; only access to the parent scaffold had been reported [7]. Here, we
describe synthetic routes to 3,3',5,5'-tetraaryl-1,1'-biphenyls, suitably functionalized for
the targeted construction of macrotricycle (S,S,S,S)-1, which we had designed by
molecular modeling for the inclusion complexation of disaccharides such as maltose
(for a review on carbohydrate recognition with artificial receptors, see [8]). During the
course of this work, Davis and Wareham reported a related macrotricyclic receptor
featuring two 1,1'-biphenyl platforms linked by four amide bridges [9]. They observed
efficient inclusion complexation of monosaccharides in CDCl3/CD3OD mixtures
through H-bonding of the guest to the amide bridges and CÀH/p interactions between
the saccharide and the two sandwiching 1,1'-biphenyl moieties of the receptor;
noncovalent bonding interactions that are seen in the X-ray crystal structures of

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549
protein carbohydrate complexes [10][11]. We also hoped to see the beneficial effects
of these interactions in complexes formed with the new receptor (S,S,S,S)-1.
X
X
guest
X
X
R
R
R
R
Fig. 1. Schematic representation of guest recognition by functionalized 3,3',5,5'-tetraaryl-1,1'-biphenyl platforms.
X ˆ Recognition groups such as H-bonding donor and/or acceptor sites; R ˆ solubilizing and conformationally
enforcing residues.
O
O
HN
HN
O
O
HN
NH
NH
HN
O
O
O
O
HN
NH
(S,S,S,S)-1
2. Results and Discussion. 2.1. Synthesis and Complexation Behavior of a Model
Receptor. Macrocycle (S,S)-2 was selected as a first target to work out protocols for
linking m-terphenyl moieties (as in (S,S,S,S)-1) with peptidic bridges derived from l-
leucine (l-Leu) [12].
In the synthesis of (S,S)-2, Suzuki cross-coupling [13] between 3-nitrophenylbo-
ronic acid and 1,3-dibromobenzene afforded dinitro-m-terphenyl 3 [14], which was
reduced (H2, Pd/C) to diamine 4 [14] and subsequently transformed with N-Boc-l-Leu,
EDC ¥ HCl, and DMAP into diamide (S,S)-5 (Scheme 1). Boc-Deprotection with
CF3COOH afforded the macrocyclization precursor (S,S)-6. The second component, 7,
for the macrocyclization to (S,S)-2 was obtained starting from boronate 8 [15], which
was transformed by Suzuki cross-coupling into dicarbonitrile 9 [16]. Hydrolysis under
basic conditions afforded dicarboxylic acid 10, which was converted into bis(acyl

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Helvetica Chimica Acta Vol. 86 (2003)
HN
NH
O
O
NH
HN
O
O
(S,S)-2
halide) 7. By a similar route, 7 was also prepared starting from boronate 11 [17] via 12
and 10. Macrocyclization of (S,S)-6 with 7 under high-dilution conditions (c ˆ 1 mm) in
the presence of Et3N afforded the model system (S,S)-2 in good yield (60%).
Scheme 1. Synthesis of Macrocycle (S,S)-2
HO
OH
B
a)
c)
NO2
R
R
O
R
NH
O
NH
R
(S,S)-5 R = NHBoc
(S,S)-6 R = NH2·TFA
3 R = NO2
4 R = NH2
b)
d)
O
O
B
e)
a)
10 R = OH
CN
f)
CN
CN
COR
COR
8
9
7 R = Cl
g)
O
O
B
a)
h)
(S,S)-6 + 7
(S,S)-2
CO2Et
CO2Et
CO2Et
12
11
a) 1,3-Dibromobenzene, [Pd(dppf)Cl2] ¥ CH2Cl2, Na2CO3, PhH, EtOH, H2O, 808, 3 d; 85% (3), 60% (9), 62%
(12). b) H2 (4 bar), Pd/C, EtOH, r.t., 16 h; 98%. c) N-Boc-l-Leu, EDC ¥ HCl, DMAP, r.t., 1 d; 35%. d) TFA,
CH2Cl2, r.t., 4 h; 93%. e) NaOH, H2O, diethyleneglycol, D, 3.5 d, then 1m HCl, r.t.; 83%. f) SOCl2, D, 16 h. g) 2m
aq. LiOH, THF, r.t., 12 h; 76%. g) Et3N, THF, high dilution, D, 32 h, 60%. Dppf ˆ 1,1'-bis(diphenylphosphino)-
ferrocene; Boc ˆ (tert-butoxy)carbonyl; EDC ˆ 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide; DMAP ˆ
(4-dimethylamino)pyridine; TFA ˆ trifluoroacetic acid.

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551
1H-NMR binding titrations with the octyl glucosides 13 15 (Fig. 2), executed in
CDCl3 at 300 K and at constant concentration of (S,S)-2, showed that the model system
was able to complex a carbohydrate guest. Its cavity, however, is too small for
monosaccharide incorporation, and, correspondingly, the association is of moderate
strength only (Ka between 130 and 290 mÀ1, Table). We propose a −nesting× geometry for
the 1:1 host-guest complexes that are most probably stabilized by H-bonding of sugar
OH groups to the amide residues of the receptor and, possibly, by additional CÀH/p
interactions. The diastereoselectivity (D(DG) ˆ 0.5 kcal molÀ1) observed in the asso-
ciation of the stronger binding b- and the weaker binding a-anomer, 13 and 14,
respectively, is in good agreement with the one measured in previous investigations
[18]. It reflects the difference in energy of the intramolecular H-bonds in the two
anomers that are lost upon complexation. As expected for a conformationally flexible
receptor, no enantioselectivity was observed.
Fig. 2. Monosaccharides investigated as guests in this study
Table. Association Constants Ka [mÀ1] and Complexation Free Enthalpies DG [kcal molÀ1] Determined by
1H-NMR Titrations for the Complexes of Receptor (S,S )-2 with Monosaccharides 13 15 in CDCl3 (300 K)
b
Guesta)
Ka [mÀ1
]
DG ) [kcal molÀ1
]
Ddsatc) [ppm]
Degree of saturation (Ddmax. obs/Ddsat)
13
14
15
290
130
130
À 3.4
0.12
0.61
0.58
0.76
À 2.90.17
À 2.90.05
b
a) [Host]0 ˆ 10À3 m. ) Uncertainty in DG: Æ 0.1 kcal molÀ1
.
c) The downfield shift of the aromatic host
resonance at 8.1 ppm was monitored. Ddsat ˆ Shift at saturation binding; Ddmax. obs ˆ maximum shift reached in
the titration.
2.2. Synthetic Approaches towards Macrotricyclic Receptor (S,S,S,S)-1. 2.2.1.
Iodinated m-Terphenyls as Potential Precursors of 3,3',5,5'-Tetraaryl-1,1'-biphenyls.
Retrosynthetic analysis suggested two approaches for the preparation of the targeted
receptor. In route I, the macrotricyclic skeleton could be constructed in the final step by
four-fold amide bond formation, thereby generating the four bridges between the two
3,3',5,5'-tetraaryl-1,1'-biphenyl platforms (see below). In route II, two-fold aryl-aryl
homocoupling (for biaryl formation via homocoupling, see [19]) between two
molecules similar to (S,S)-2, but bearing iodo substituents in the meso-position of
the central m-terphenyl rings, would generate the receptor. Since the functionalized
platforms in route I could also be constructed by aryl-aryl coupling between iodinated
m-terphenyls, we focused our initial efforts at the preparation of such derivatives.

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For the construction of iodinated m-terphenyls by Suzuki cross-coupling as shown
in Scheme 1, we employed the diethyltriazene group as a masked iodo synthon [20].
Thus, 1-(3,5-dibromophenyl)-3,3-diethyltriaz-1-ene (16) [21] was coupled with 3-
nitrophenylboronic acid and the two boronates 8 and 11 to give triazenes 17 19,
respectively (Scheme 2). The X-ray crystal structure of dicarbonitrile 18 revealed the
presence of two conformers in the crystal lattice. In both structures, the absolute values
of the dihedral angles about the C(aryl)ÀC(aryl) bonds varied between 27.38 and 39.28
(Fig. 3).
Scheme 2. Synthesis of m-Terphenyls 17 19
Br
Br
a) or b) or c)
R
R
N3Et2
N3Et2
16
17 R = NO2
18 R = CN
19 R = CO2Et
a) c) [Pd(dppf)Cl2] ¥ CH2Cl2, 3-nitrophenylboronic acid (a), or 8 (b), or 11 (c), Na2CO3, PhH, EtOH, H2O,
808, 24 h; 80% (17), 67% (18), 84% (19).
Fig. 3. X-Ray crystal structure of 18 showing two conformers in the asymmetric unit. Arbitrary numbering.
Atomic displacement parameters obtained at 293 K are drawn at the 30% probability level. The absolute values
of the dihedral angles about the C(aryl)ÀC(aryl) bonds are 33.88 for C(9)ÀC(13), 39.28 for C(7)ÀC(1), 27.38
for C(9')ÀC(13'), and 36.68 for C(7')ÀC(1'). The angles were calculated from the least-squares planes through
the corresponding six-membered rings.
Starting from triazenyl-substituted m-terphenyl 17, the corresponding iodo
derivative 20 was readily obtained by heating with MeI in a sealed tube [22]
(Scheme 3). Reduction of 17 with H2 and Pd/C in AcOEt provided diamine 21, without
affecting the triazene moiety. Under standard peptide-coupling conditions (DCC/
BtOH), 21 reacted with 4-benzyl N-Boc-l-aspartate to give diamide (S,S)-22 and with

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553
N-Boc-l-Leu to afford (S,S)-23. However, the subsequent dialkyltriazene ! iodide
transformation proved to be problematic. Heating (S,S)-23 to reflux with MeI gave a
very polar product, possibly resulting from initial methylation of the amide N-atoms.
An alternative method for this transformation consists in heating the triazene with I2 in
ClCH2CH2Cl to 908 [23]. Although this reaction yielded the desired product (S,S)-24, it
was not possible to separate it from the reduced I-free by-product (S,S)-5.
Scheme 3. Conversions of Dinitro-m-terphenyl 17
N3Et2
N3Et2
R
b)
c)
NH2
NH2
HN
O
R
HN
BocHN
O
R
NO2
NO2
17 R = N3Et2
20 R = I
21
BocHN
a)
(S,S)-22 R = COOCH2C6H5
(S,S)-23 R = CHMe2
d)
R
HN
O
HN
O
BocHN
BocHN
(S,S)-24 R = I + (S,S)-5 R = H
(inseparable mixture)
a) MeI, sealed tube, 1308, 16 h; 88%. b) H2 (4 bar), Pd/C, AcOEt, r.t., 18 h; 83%. c) 4-Benzyl N-Boc-l-aspartate
or N-Boc-l-leucine, DCC, BtOH, THF, 08, 16 36 h; 51% (22), 61% (23). d) I2, ClCH2CH2Cl, 908, 7 h. DCC ˆ
dicyclohexylcarbodiimide; BtOH ˆ 1-hydroxy-1H-benzotriazole.
The preparation of the iodinated dicarboxylic acid 25, which we intended to cyclize
with (S,S)-24 (after removal of the Boc protecting groups), failed when starting from
dicarbonitriles 18 or 26 (Scheme 4), since both acidic and basic hydrolysis of the two
CN groups affected the dialkyltriazenyl (in 18) and I (in 26) substituents. However, the
desired diacid 25 was obtained by starting from diester 19. Ester hydrolysis did not
affect the triazenyl substituent, which allowed preparation of diacid 27. Also, after
conversion of 19 into iodide 28, hydrolysis readily afforded 25.
Initial attempts to prepare suitably functionalized 3,3',5,5'-tetraaryl-1,1'-biphenyl
platforms by homocoupling of iodinated m-terphenyls such as those shown in Scheme 4

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Helvetica Chimica Acta Vol. 86 (2003)
Scheme 4. Synthesis of Iodinated m-Terphenyldicarboxylic acid 25
N3Et2
I
a)
CN
CN
CN
CN
18
26
N3Et2
I
CO2H
CO2H
CO2H
CO2H
27
25
b)
b)
N3Et2
I
a)
CO2Et
CO2Et
CO2Et
CO2Et
28
19
a) MeI, sealed tube, 1308, 14 16 h; 96% (26), 95% (28). b) LiOH, THF, EtOH, r.t., 14 h; 45% (27), 89% (25).
failed, mainly due to the poor solubility of the starting materials in the commonly used
solvents. The m-terphenyl route was abandoned, when it proved to be more facile to
obtain the desired platforms starting from 3,3',5,5'-tetrabromo-1,1'-biphenyl (29).
2.2.2. Functionalized 3,3',5,5'-Tetraaryl-1,1'-biphenyls Starting from 3,3',5,5'-Tetra-
bromo-1,1'-biphenyl. When 3,3',5,5'-tetrabromo-1,1'-biphenyl (29), conveniently pre-
pared according to a literature procedure [24], was subjected to Suzuki cross-coupling
with 3-nitrophenylboronic acid (ca. 6 equiv.), tetra-arylated biphenyl 30 formed as a
precipitate and was isolated in 67% yield after recrystallization from 1,2-dichloroben-
zene (Scheme 5). Compound 30 is poorly soluble in almost all solvents, but could be
reduced with Sn in conc. HCl under heterogenous conditions. A reaction time of 2
weeks was required to obtain complete conversion to the more soluble tetramine 31,
which was isolated in 97% yield. Peptide coupling with N-Boc-l-Leu to (S,S)-32,
followed by N-deprotection, provided the readily soluble tetrakis(ammonium salt)
(S,S)-33, one of the two components for the macrocyclization to give (S,S,S,S)-1 (Route
I, see Sect. 2.2.1). 1H-NMR spectra of (S,S)-31 in CDCl3 featured strongly broadened
peaks, which we explain by the formation of H-bonding aggregates. In agreement with
this proposal, highly resolved spectra were obtained in (CD3)2SO in which H-bonding is
weakened due to solvent competition.

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Scheme 5. Synthesis of Functionalized 3,3',5,5'-Tetraaryl-1,1'-biphenyl Platforms
R
O
R
O
R
R
NH
NH
c)
(S,S)-32 R = NHBoc
(S,S)-33 R = NH2·TFA
d)
a)
R
30 R = NO2
31 R = NH2
R
HN
O
R
HN
O
R
b)
Br
Br
Br
Br
F
F
F
F
F
F
F
F
F
F
29
O
O
O
O
a)
R
R
f)
R
R
O
F
O
F
O
F
O
F
F
F
F
F
34 R = CO2Et
35 R = CO2H
36
e)
F
F
a) 3-Nitrophenylboronic acid or 11, [Pd(dppf)Cl2] ¥ CH2Cl2, Na2CO3, PhH, EtOH, H2O, 808, 72 h; 67% (29),
73% (33). b) Sn, conc. HCl, 1008, 2 weeks; 97%. c) N-Boc-l-Leu, EDC ¥ HCl, DMAP, 08, 48 h; 67%. d) TFA,
CH2Cl2, r.t., 4 h; 99%. e) LiOH, THF, H2O, D, 17 h; 87%. f) Pentafluorophenol, DCC, DMF, 08, 60 h; 51%.
Similarly, Suzuki cross-coupling of the tetrabromo derivative 29 with boronate 11
afforded the functionalized platform 34 (73% yield), which was soluble in THF
(Scheme 5). Ester hydrolysis gave tetracarboxylic acid 35, which was transformed into
the activated tetrakis(pentafluorophenyl ester) 36, the second cyclization component
on the way to the targeted macrotricycle.
First attempts to obtain the macrotricyclic receptor (S,S,S,S)-1 did not give
conclusive results. Macrolactamization of (S,S)-33 with activated ester 36 under high-
dilution conditions (c ˆ 1 mm, 18 h, 808) in THF in the presence of EtN(i-Pr)2 (8 equiv.)

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as a base (to transform salt (S,S)-33 into the free tetramine and to trap the
pentafluorophenol leaving group) afforded, after usual extractive workup (H2O/
CH2Cl2), a crude product that, according to analytical gel-permeation chromatography
(GPC, BioBeads S-X1, THF), contained a large amount of high-molecular weight by-
products. Purification by repeated GPC (BioBeads S-X1) and subsequent preparative
thin-layer chromatography (TLC, SiO2; CH2Cl2/MeOH 98 :2) provided 29 mg (13%)
of a colorless powder, which was a homogenous product according to analytical GPC
and TLC analysis. Its purity could not be further enhanced by HPLC. The analytical
characterization of this product, however, remains incomplete. The fast-atom-
bombardment mass spectrum (FAB-MS; matrix: 3-nitrobenzyl alcohol) clearly showed
‡
the molecular ion expected for (S,S,S,S)-1 as the parent ion at m/z 1534.1 (MH ,
‡
C100H93N8O8 ; calc. 1534.7). Besides a weak peak at m/z 1601.8, no major signals above
m/z 400 were observed. In the IR spectrum (KBr), bands expected for free carboxylate
and primary amine groups were absent. Nevertheless, the structure of the product
remains uncertain, since the 1H- and 13C-NMR analysis in solvents of different polarity
(CDCl3, (CD3)2SO) was not conclusive. The peaks were broadened, and, although in
the expected spectral regions, too many were observed. Since the spectra did not
change substantially upon heating to 393 K, it is uncertain whether the large number of
peaks is due to the presence of slowly exchanging conformational isomers. We also
cannot exclude the formation of two constitutional isomers, namely the one shown with
two parallel platforms and a second one, in which bridging occurs differently, leading to
a crossed array of the two platforms. This inability of fully characterizing the product
contrasts with our past success in purifying other complex macrotricyclic and
macrobicyclic spherical receptors [12][25][26].
3. Conclusions. A series of functionalized 3,3',5,5'-tetraaryl-1,1'-biphenyls were
prepared as aromatic −floor× and −ceiling× for incorporation into the targeted macro-
bicyclic disaccharide receptor (S,S,S,S)-1. These extended aromatic systems could also
serve as versatile platforms in a diversity of novel cleft-type receptors (as schematically
shown in Fig. 1). While approaches to these platforms involving the homocoupling of
iodinated m-terphenyls proved rather tedious, a straightforward access was available by
Suzuki cross-coupling to 3,3',5,5'-tetrabromo-1,1'-biphenyl. Although mass-spectral
evidence for formation of (S,S,S,S)-1 by macrolactamization between (S,S)-33 and 36
1
was obtained, the H- and 13C-NMR spectra of purified material remained rather
inconclusive with respect to both purity and constitution. With (S,S)-2, a macrocyclic
model receptor was prepared that forms −nesting× complexes of moderate stability (Ka
between 130 and 290 mÀ1, 300 K) with octyl glucosides 13 15 in the noncompetitive
solvent CDCl3. H-Bonding interactions between the sugar OH groups and the amide
residues of the receptor constitute the major driving force for the observed 1:1 host
guest complexation. Efforts are now underway to utilize other macrocyclization
protocols for introducing the novel platforms into macrotricyclic receptors such as
(S,S,S,S)-1.
We gratefully acknowledge the Stipendienfonds der Schweizerischen Chemischen Industrie and the Roche
Research Foundation for a graduate student fellowship (R. W.), and the Deutsche Forschungsgemeinschaft
(DFG) for a postdoctoral fellowship (Y. A. ) We thank Dr. Carlo Thilgen for help with the nomenclature, Boris
Thamberger for assistance with the synthesis, and Siefke Siefken for NMR measurements.

Helvetica Chimica Acta Vol. 86 (2003)
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Experimental Part
General. Solvents and reagents were reagent-grade and commercially available, and used without further
purification unless otherwise noted. CH2Cl2 was dried over CaH2, and PhMe and THF over Na. All solns. for Pd-
catalyzed cross-coupling reactions were carefully degassed and flushed with Ar. Evaporations and concen-
trations in vacuo were carried out at H2O-aspirator pressure. Drying of anal. samples occurred at 10À2 Torr.
Flash chromatography (FC): SiO2 60 (40 63 mm) from Fluka or Merck. Anal. TLC: Polygram SIL G/UV254 or
DURASIL-25 UV254 from Macherey-Nagel. Prep. TLC: PSC plates (2 mm SiO2 60 F254) from Merck. M.p.: B¸chi
Melting Point B-540, uncorrected. Optical rotations: Perkin-Elmer 241 polarimeter. IR Spectra [cmÀ1]: Perkin
Elmer 1600-FTIR; in CHCl3 or in KBr pellets. 1H- and 13C-NMR-spectra [ppm]: Bruker AMX-500, Varian
Gemini-200 and -300 at r.t. in CDCl3 or (CD3)2SO. The 13C-NMR resonances of the diethyltriazene moieties are
often very broad due to hindered rotation about the NÀN axis and could, therefore, not be detected. MS (m/z
(%)): EI: VG Tribrid mass spectrometer at 70 eV ionization energy; ESI-MS: Finnigan New Star FT/MS with 7-
T magnet; FAB-MS: VG ZAB2-SEQ spectrometer with 3-nitrobenzyl alcohol (3-NOBA) as matrix; FT-ICR-
MALDI-MS: Ion Spec Ultima FT-ICR-MS (337-nm N2-laser system, matrix: DHB (2,3-dihydroxybenzoic acid)
or DCTB ({(2E)-3-[4-(tert-butyl)phenyl]-2-methylprop-2-enylidenes} malononitrile). Elemental analyses were
performed by the Mikrolabor at the Laboratorium f¸r organische Chemie, ETH-Z¸rich.
1H-NMR Binding Titrations. Quant. binding data (Ka, DG, Ddsat) were determined by nonlinear least-
1
squares curve-fitting of H-NMR titration data (500 MHz, 300 K) with the program Associate V.1.6 [27]. Octyl
glucoside 15 was prepared according to published procedures [28]. Titration samples (CDCl3 dried over 4-ä
molecular sieves) were prepared by adding a soln. of guest in portions via microsyringe to the septum-capped
NMR tube while keeping the host at constant concentration. Concentration ranges: [host]0 ꢀ 1 mM, [guest]0 ꢀ
1
1
20 mm. After each addition, a H-NMR spectrum was recorded.
(À)-Di-(tert-butyl) N,N'-{1,1':3',1''-Terphenyl-3,3''-diylbis[(S)-iminocarbonyl)(2-methylpropyl)methyl]}di-
carbamate ((S,S)-5). Diamine 4 [14] (551 mg, 2.12 mmol), N-Boc-l-Leu (1.16 g, 4.65 mmol), and DMAP
(79mg, 0.65 mmol) were dissolved in dry THF (50 ml). After cooling to 0 8, EDC ¥ HCl (1.34 g, 4.65 mmol) was
added, and the mixture was stirred for 1 d at r.t. The solvent was evaporated in vacuo, and the residue was taken
up in CH2Cl2 and washed with sat. aq. NaHCO3 soln. (2Â), 1m HCl, and sat. aq. NaCl soln. The combined org.
layers were dried (MgSO4) and evaporated in vacuo. FC (SiO2; CH2Cl2/AcOEt 5 :1) gave (S,S)-5 (509mg,
35%). White powder. M.p. 2008. [a]2D3 ˆ À56.2 (c ˆ 1, CHCl3). IR (CHCl3): 3309w, 3032s, 1668s, 1612w, 1498m,
1431w, 1046m, 9 28m. 1H-NMR ((CD3)2SO, 300 MHz): 10.03 (s, 2 H); 7.9 2 (s, 2 H); 7.76 (s, 1 H); 7.68 7.63 (m, 2
H); 7.61 7.51 (m, 3 H); 7.46 7.34 (m, 4 H); 7.02-7.00 (m, 2 H); 4.14 4.08 (m, 2 H); 1.68 1.56 (m, 2 H); 1.55
1.38 (m, 4 H); 1.34 (s, 18 H); 0.87 (d, J ˆ 6.5, 12 H). 13C-NMR ((CD3)2SO, 75 MHz): 172.17; 155.66; 141.04;
140.75; 139.84; 129.81; 129.57; 126.07; 125.00; 121.90; 118.58; 117.69; 78.04; 53.60; 28.15; 24.31; 22.91; 21.48.
‡
‡
‡
FAB-MS: 685.4 (1, MH ), 586.5 (23, [MH À Boc] ), 487.4 (100, [MH À 2 Boc] ).
(‡)-N,N'-{1,1':3',1''-Terphenyl-3,3''-diylbis[(S)-iminocarbonyl)(2-methylpropyl)methyl]}diammonium
Bis(trifluoroacetate) ((S,S)-6). A soln. of (S,S)-5 (1.248 g, 1.82 mmol) in CH2Cl2 (7.5 ml) and TFA (5 ml) was
stirred for 4 h at r.t. After evaporation in vacuo, the residue was taken up in EtOH. Evaporation in vacuo
afforded (S,S)-6 (1.22 g, 93%), which was used without further purification. Slightly brownish powder. M.p.
136 1388. [a]2D3 ˆ ‡4.3 (c ˆ 1, CHCl3/EtOH 95 :5). IR (KBr): 3416 (br.), 3125 (br.), 1675m, 1400s, 1203m,
1140m, 839w, 800w. 1H-NMR ((CD3)2SO, 300 MHz): 10.77 (s, 2 H); 7.9 3 (s, 2 H); 7.79(br. s, 1 H); 7.70 7.65 (m, 2
H); 7.62 7.58 (m, 3 H); 7.51 7.44 (m, 4 H); 3.9 6 (m, 2 H); 1.67 (m, 6 H); 0.9 1 (d, J ˆ 3.1, 12 H). 13C-NMR
((CD3)2SO, 75 MHz): 168.33; 140.91; 140.83; 138.92; 129.84; 129.60; 126.19; 125.12; 122.82; 118.94; 118.06;
‡
51.80; 23.65; 22.57; 21.77. FAB-MS: 487.30 (100, [MH À 2 CF3COOH] ).
Ethyl 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (11). A soln of ethyl 3-iodobenzoate
(1.000 g, 3.6 mmol), AcOK (1.066 mg, 10.8 mmol), 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-1-yl)-4,4,5,5-
tetramethyl-1,3,2-dioxaborolane [29] (1.015 g, 4.0 mmol), and [Pd(dppf)Cl2] ¥ CH2Cl2 (50 mg, 68 mmol) was
flushed with Ar, then Me2SO (12 ml) was added, and the mixture was heated to 80 908 for 4.5 h. After cooling
to r.t., the soln. was diluted with PhMe (30 ml), and the org. layer was washed with H2O (3Â), dried (MgSO4),
and evaporated in vacuo. The remaining brown oil was purified by bulb-to-bulb distillation (<0.5 Torr 110
1208) to yield 11 (646 mg, 85%). Colorless oil. IR (CHCl3): 2979s, 2928m, 2873w, 1721s, 1606m, 1358s, 1320m,
1274m, 1254s, 1144m, 1092m, 1023m, 9 64m, 853m, 757m, 702m. 1H-NMR (200 MHz, CDCl3): 8.47 (m, 1 H);
8.18 8.09( m, 1 H); 8.03 7.94 (m, 1 H); 7.45 (dd, J ˆ 7.5, 7.5, 1 H); 4.39( q, J ˆ 7.0, 2 H); 1.41 (t, J ˆ 7.0, 3 H); 1.37
(s, 12 H). 13C-NMR (75 MHz, CDCl3): 167.0; 139.3; 135.9; 132.6; 132.5; 127.9; 84.2; 61.0; 24.9; 14.4. EI-MS: 276
‡
‡
(23, M ), 261 (41, [M À Me] ), 233 (100). Anal. calc. for C15H21BO4 (276.14): C 65.24, H 7.66; found: C 65.32 H
7.70.

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Helvetica Chimica Acta Vol. 86 (2003)
Diethyl 1,1':3',1''-Terphenyl-3,3''-dicarboxylate (12). A soln. of 11 (1.200 g, 4.34 mmol), 1,3-dibromoben-
zene (0.237 g, 1.97 mmol), and Na2CO3 (951 mg, 8.69 mmol) in PhH/EtOH (11:3, 20 ml) and H2O (13 ml) was
flushed with Ar for 1 h, then heated to 808. A spatula tip of [Pd(dppf)Cl2] ¥ CH2Cl2 was added, and the mixture
was heated to reflux for 3 d. After cooling to r.t., the org. solvents were evaporated in vacuo, and the residue was
extracted with CH2Cl2. Drying (MgSO4) and evaporation in vacuo left a residue, which was purified by FC
(SiO2; hexane/CH2Cl2 2 :1) to give 12 (463 mg, 62%). Colorless solid. M.p. 68 708. IR (KBr): 2977m, 2366w,
2333w, 1718s, 1588w, 1472m, 1299s, 1251s, 1230m, 1109m, 1077m, 1016w. 1H-NMR (200 MHz, CDCl3): 8.35 8.32
(m, 2 H); 8.07 (dd, J ˆ 7.8, 0.6, 2 H); 7.86 7.80 (m, 3 H); 7.65 7.61 (m, 2 H); 7.58 7.50 (m, 3 H); 4.41 (q, J ˆ 7.2,
4 H); 1.42 (t, J ˆ 7.2, 6 H). 13C-NMR (75 MHz, CDCl3): 166.8; 141.5; 141.2; 131.8; 129.7; 129.1; 128.8; 128.5;
‡
‡
126.8; 126.3; 61.2; 14.4. HR-MALDI-MS: 397.1412 (100, M , C24H22O4Na ; calc. 397.1415).
1,1':3',1''-Terphenyl-3,3''-dicarboxylic Acid (10). Method A: A mixture of 9 (1.38 g, 4.93 mmol) and finely
powdered NaOH (1.6 g, 39.43 mmol) in diethyleneglycol (30 ml) and H2O (0.5 ml) was heated to reflux for
3.5 d. After cooling to r.t., 1m HCl was added, and the formed precipitate was isolated by filtration and washed
with H2O (2Â). The solid was heated to reflux in EtOH (40 ml), and the precipitate formed upon cooling was
filtered off, washed with ice-cold EtOH (2Â), and dried to give 10 (1.3 g, 83%). Grey solid.
Method B: To a soln. of 12 (470 mg, 1.25 mmol) in THF (11 ml), LiOH (120 mg, 5.02 mmol) in H2O
(2.5 ml) was added, and the mixture was heated to reflux for 4 h. After cooling to r.t. and evaporation of the
solvent in vacuo, the residue was dissolved in sat. aq. Na2CO3 soln., which was washed with CH2Cl2. The aq.
phase was acidified (pH 1) by addition of conc. HCl, and the formed precipitate was isolated by filtration and
dried to give 10 (312 mg, 76%). Colorless powder. M.p. > 2508 (dec.). IR (KBr): 3000 2533 (br.), 1690s, 1601w,
1
1579w, 1440m, 1412m, 1384w, 1307s, 1262m, 1240m, 9 23m, 745s, 684m. H-NMR (200 MHz, (CD3)2SO): 13.08
(br. s, 2 H); 8.25 (m, 2 H); 8.11 7.88, 7.81 7.51 (2m, 10 H). 13C-NMR (75 MHz, (CD3)2SO): 167.5; 140.5; 140.4;
131.7; 131.6; 130.0; 129.5; 128.6; 127.7; 126.6; 125.5. ESI-MS: 349 (22, [M À H ‡ MeOH]À), 339(11, [ M À H ‡
Na]À), 317 (100, [M À H]À), 174 (8, [M À 2 H ‡ MeOH]2À), 158 (68, [M À 2 H]2À). HR-EI-MS: 318.0898 (100,
‡
‡
M , C20H14O , calc. 318.0898). Anal. calc. for C20H14O4 (318.33): C 75.46, H 4.43; found: C 73.77, H 4.71.
(6S,14S)-6,14-Bis(2-methylpropyl)-4,7,13,16-tetraaza-1,2,3,9,10,11(1,3)-hexabenzenacyclohexadecaphane-
5,8,12,15-tetraone ((S,S)-2). A soln. of 10 (310 mg, 0.97 mmol) in SOCl2 (10 ml) was heated to reflux for 16 h.
The excess of SOCl2 was removed by distillation, and the residue was dried at 10À2 Torr to yield crude 7. To a
soln. of (S,S)-6 (673 mg, 0.97 mmol) in dry THF (900 ml), Et3N (2 ml) was added, followed by crude 7 in dry
THF (60 ml). The mixture was stirred at r.t. for 24 h and at 808 for 8 h. Evaporation in vacuo left a residue, which
was purified by FC (SiO2; CH2Cl2/MeOH 20 :1) to give (S,S)-2 (458 mg, 60%). White powder. M.p. 302 3048
(dec.). [a]2D3 ˆ ‡1.4 (c ˆ 1, THF). IR (KBr): 3427m, 3306m, 3032w, 2956m, 2925m, 2879m, 2466w, 1669s, 1629s,
1534s, 1497m, 1437m, 1384m, 1384m, 1096m, 881w, 785m, 69 5m. 1H-NMR ((CD3)2SO, 500 MHz): 10.29( s, 2 H);
8.88 (d, J ˆ 7.7, 2 H); 8.45 (s, 2 H); 8.26 (s, 2 H); 8.18 (s, 1 H); 7.9 9 d(, J ˆ 7.8, 2 H); 7.85 (d, J ˆ 7.8, 2 H); 7.68 (d,
J ˆ 7.32, 2 H); 7.64 (s, 2 H); 7.64 7.52 (m, 5 H); 7.43 7.38 (m, 4 H); 7.34 7.32 (d, J ˆ 7.3, 2 H); 4.81 4.78 (m,
2 H); 1.87 1.78 (m, 2 H); 1.71 1.58 (m, 4 H); 0.9 0 (d, J ˆ 6.4, 6 H); 0.87 (d, J ˆ 6.4, 6 H). 13C-NMR ((CD3)2SO,
125 MHz): 171.44; 165.75; 141.20; 140.87; 140.71; 140.48; 139.64; 134.19; 130.10; 129.55; 129.48; 129.31; 128.94;
127.29; 126.53; 126.45; 126.37; 125.89; 124.15; 122.29; 118.54; 117.20; 52.77; 24.52; 22.83; 21.59. FAB-MS: 769.2
‡
(MH ). Anal. calc. for C50H48N4O4 (768.95): C 78.10, H 6.29; found: C 76.68, H 7.06.
3,3-Diethyl-1-(3,3''-dinitro-1,1':3',1''-terphenyl-5'-yl)triaz-1-ene (17). A degassed soln. of 3-nitrophenylbor-
onic acid (1.00 g, 5.99 mmol), 16 (0.912 g, 2.72 mmol), and Na2CO3 (1.15 g, 10.88 mmol) in PhH (39ml), EtOH
(11 ml), and H2O (50 ml) was heated to 808, then treated with a few mg of [Pd(dppf)Cl2] ¥ CH2Cl2. The mixture
was heated to reflux for 24 h, then the solvents were removed in vacuo, and the residue was dissolved in CH2Cl2
and washed with 1m NH4Cl. The org. layer was dried (MgSO4), and the solvent was evaporated in vacuo. FC
(SiO2; hexane/CH2Cl2 1:1) gave 17 (860 mg, 80%). Pale-red solid. M. p. 146.8 147.58. IR (KBr): 2974m, 2931m,
1586m, 1524s, 1449m, 1404m, 1351s, 1232m, 1113m, 9 00s, 878s, 819s. 1H-NMR (300 MHz, CDCl3): 8.58 8.56 (m,
2 H); 8.28 8.23 (m, 2 H); 8.08 8.03 (m, 2 H); 7.75 (d, J ˆ 1.7, 2 H); 7.71 7.63 (m, 2 H); 7.61 (t, J ˆ 1.7, 1 H); 3.87
(q, J ˆ 7.1, 4 H); 1.35 (t, J ˆ 7.1, 6 H ) . 13C-NMR (75 MHz, CDCl3): 153.06; 149.03; 142.95; 140.54; 133.50; 130.02;
‡
122.58; 122.35; 119.59. FAB-MS: 420.11 (100, MH ). Anal. calc. for C22H21N5O4: C 63.00, H 5.05, N 16.70;
found: C 63.01, H 5.10, N 16.87.
5'-(3,3-Diethyltriaz-1-enyl)-1,1':3',1''-terphenyl-3,3''-dicarbonitrile (18). According to the protocol for 17, 8
(2.439g, 10.6 mmol) and 16 (1.62 g, 4.8 mmol) in the presence of a few mg of [Pd(dppf)Cl2] ¥ CH2Cl2 reacted to
give, after FC (SiO2; hexane/AcOEt 9:1), 18 (2.69g, 67%). White solid. M.p. 110 113 8. IR (KBr): 3067w,
2967m, 2922m, 2866w, 2222s, 1572m, 1461m, 1400s, 1333s, 1250m, 1233s, 1105m, 867m, 789s, 683s. 1H-NMR
(300 MHz, CDCl3): 7.98 7.95 (m, 2 H); 7.94 7.88 (m, 2 H); 7.69 7.63 ( m, 4 H); 7.61 7.53 (m, 2 H); 7.47 (t, J ˆ
1.7, 1 H); 3.84 (q, J ˆ 7.1, 4 H); 1.32 (t, J ˆ 7.1, 6 H ) . 13C-NMR (75 MHz, CDCl3): 152.98; 142.53; 140.65; 131.85;

Helvetica Chimica Acta Vol. 86 (2003)
559
‡
131.21; 131.11; 129.88; 122.44; 119.36; 119.04; 113.23. FAB-MS: 380.11 (MH ). Anal. calc. for C24H21N5
(379.46): C 75.97, H 5.58, N 18.46; found: C 75.96, H 5.69, N 18.28. X-Ray: see Fig. 3.
Diethyl 5'-(3,3-Diethyltriaz-1-enyl)-1,1':3',1''-terphenyl-3,3''-dicarboxylate (19). According to the protocol
for 17, 11 (825 mg, 2.9mmol) and 16 (334 mg, 996 mmol) in the presence of a few mg of [Pd(dppf)Cl2] ¥ CH2Cl2
(44 mg, 60 mmol) reacted to give, after FC (SiO2; CH2Cl2/hexane 4 :1), 19 (396.8 mg, 84%). Yellow oil. IR
(NaCl): 2978w, 2929w, 1719s, 1578w, 1466w, 1449w, 1337m, 1283m, 1254m, 1221m, 1171w, 1110m, 1083w, 1020w,
870w, 753w. 1H-NMR (200 MHz, CDCl3): 8.35 (t, J ˆ 1.7, 2 H); 8.12 8.02, 7.95 7.86 (2m, 4 H); 7.72 (d, J ˆ 1.7, 2
H); 7.63 (t, J ˆ 1.7, 1 H); 7.56 (t, J ˆ 7.7, 2 H); 4.45 (q, J ˆ 7.0, 4 H); 3.85 (q, J ˆ 7.0, 4 H); 1.45 (t, J ˆ 7.0, 6 H); 1.34
(t, J ˆ 7.0, 6 H). 13C-NMR (75 MHz, CDCl3): 166.9; 152.6; 141.85; 141.80; 131.9; 131.3; 129.0; 128.7; 128.6; 123.0;
‡
‡
‡
119.0; 61.2; 14.4. EI-MS: 473 (9, M ), 428 (7, [M À C2H5O] ), 373 (100, [M À N3(C2H5)2] ), 300 (37), 272 (13,
‡
‡
‡
[M À N3(C2H5)2 À CO] ), 226 (24). HR-EI-MS: 473.2320 (M , C28H31N3O4 ; calc. 473.2314).
5'-Iodo-3,3''-dinitro-1,1':3',1''-terphenyl (20). A degassed soln. of 17 (100 mg, 0.23 mmol) in MeI (4 ml) in a
sealed tube was heated to 1308 for 16 h. The excess of MeI was removed by distillation, and FC (SiO2; CH2Cl2)
of the residue gave 20 (95 mg, 88%). White powder. M. p. 215.5 216.68. IR (KBr): 3077w, 2922m, 2855m, 1521s,
1355m, 1085s, 876m, 1495s, 79 8m, 734s, 677s. 1H-NMR (300 MHz, CDCl3): 8.50 8.48 (m, 2 H); 8.28 8.33 (m, 2
H); 8.04 (d, J ˆ 1.7, 2 H); 7.99 7.94 (m, 2 H); 7.81 (t, J ˆ 1.7, 1 H); 7.74 7.66 (m, 2 H). 13C-NMR (75 MHz,
‡
CDCl3): 149.09; 141.86; 141.06; 136.40; 133.39; 130.36; 125.77; 123.26; 122.34; 95.85. FAB-MS: 445.86 (100, M ).
Anal. calc. for C18H11IN2O4 (446.2): C 48.45, H 2.48, N 6.28; found: C 48.43, H 2.58, N 6.15.
5'-(3,3-Diethyltriaz-1-enyl)-1,1':3',1''-terphenyl-3,3''-diamine (21). To 17 (300 mg, 0.715 mmol) in AcOEt
(20 ml) under Ar, Pd/C (10%, 300 mg) was added, and the mixture was stirred under H2 (4 bar) for 18 h at r.t.
Filtration over Celite and concentration of the filtrate in vacuo, followed by recrystallization (CH2Cl2/hexane),
gave 21 (204 mg, 83%). Pale-yellow powder. M. p. 116 1188. IR (KBr): 3444m, 3355m, 3222w, 2978w, 2933m,
1622s, 1597s, 1578s, 1494m, 1466m, 1444m, 1400s, 1333s, 1311m, 1233m, 1161w, 1105m, 1077m, 9 89w, 856m, 783s,
694s. 1H-NMR (500 MHz, (CD3)2SO): 7.47 (t, J ˆ 1.7, 1 H); 7.45 (d, J ˆ 1.7, 2 H); 7.11 (t, J ˆ 7.8, 2 H); 6.93 (t, J ˆ
1.9, 2 H); 6.85 (ddd, J ˆ 7.6, 1.7, 1.0, 2 H); 6.58 (ddd, J ˆ 8.0, 2.2, 0.9, 2 H); 5.16 (br. s, 4 H); 3.78 (q, J ˆ 7.1, 4 H ) ;
1.24 (br. s, 6 H). 13C-NMR (75 MHz, (CD3)2SO): 151.77; 149.32; 142.35; 141.14; 129.57; 121.49; 117.06; 114.51;
‡
‡
113.44; 112.35. EI-MS: 359(12, M ), 260 (100), 259(90, [ M À N3(C2H5)2] ). Anal. calc. for C22H25N5 (359.48): C
73.51, H 7.01, N 19.48; found: C 73.39, H 7.08, N 19.56.
Dibenzyl (3S,3'S)-3,3'-({[(tert-Butyl)oxy]carbonyl}amino)-3,3'-[5'-(3,3-diethyltriaz-1-enyl)-1,1':3',1''-ter-
phenyl-3,3''-diylbis(iminocarbonyl)]dipropanoate ((S,S)-22). 4-Benzyl N-Boc-l-aspartate (440 mg, 1.36 mmol),
DCC (766 mg, 3.71 mmol), and BtOH (250 mg, 1.85 mmol) were dissolved in THF (1.5 ml) at 08. After the soln.
turned turbid, 21 (204 mg, 0.619mmol) was added, and the mixture was stirred at r.t. for 16 h. Filtration,
concentration of the filtrate in vacuo, and FC (SiO2, CH2Cl2/AcOEt 4 :1) afforded (S,S)-22 (308 mg, 51%).
Colorless oil. IR (CHCl3): 3316 (br.), 2976m, 2932m, 1733s, 1673s, 1611w, 1495m, 1163s, 867m, 787s, 69 7s.
1H-NMR (200 MHz, CDCl3): 8.02 7.92 (m, 2 H); 7.58 (m, 4 H); 7.36 7.25 (m, 17 H); 6.34 (m, 2 H); 5.15 (s, 4
H); 5.03 4.85 (m, 2 H); 3.82 (q, J ˆ 7.2, 4 H); 3.11 2.85 (m, 4 H); 1.42 (s, 18 H); 1.31 (t, J ˆ 7.2, 6 H). 13C-NMR
(75 MHz, CDCl3): 171.45; 170.24; 156.52; 152.23; 141.78; 141.31; 138.45; 135.83; 129.42; 128.76; 128.44; 123.10;
‡
118.92; 118.78; 118.29; 80.71; 66.92; 52.33; 36.77; 26.05; 25.53; 24.69. ESI-MS: 1008.6 (20, [M ‡ K] , 992.6 (85,
‡
‡
[M ‡ Na] , 871.6 (20, [M À N3Et2] ), 552.4 (100).
(‡)-Di(tert-butyl) N,N'-{5'-(3,3-Diethyltriaz-1-enyl)-1,1':3',1''-terphenyl-3,3''-diylbis[(S)-(iminocarbonyl)-
(2-methylpropyl)methyl]}dicarbamate ((S,S)-23). A soln. of 21 (238 mg, 663 mmol), EDC ¥ HCl (445 mg,
2.32 mmol), N-Boc-l-leucine (330 mg, 1.32 mmol), and DMAP (20.2 mg, 166 mmol) in dry THF (40 ml) was
stirred at r.t. for 1.5 d. After evaporation in vacuo, the residue was dissolved in CH2Cl2, and washed with 1m HCl,
sat. aq. NaHCO3 soln., and sat. aq. NaCl soln. The combined org. layers were dried (MgSO4), the solvent was
evaporated in vacuo, and the remaining oil was purified by FC (SiO2; CH2Cl2/AcOEt 6 :1). The pale-yellow
product foam was recrystallized from CH2Cl2/hexane to give (S,S)-23 (318 mg, 61%). Colorless needles. M.p.
156 1588 (CH2Cl2/hexane). [a]2D3 ˆ ‡44.6 (c ˆ 1, CHCl3). IR (KBr): 3312m, 2958m, 2867w, 1669s, 1611m,
1561m, 1528m, 1496m, 1361m, 1232m, 1164m, 1105w, 1049w, 870w, 785w, 69 7w. 1H-NMR (500 MHz, (CD3)2SO):
10.05 (br. s, 2 H), 7.9 5 (m, 2 H); 7.73 7.71 (m, 2 H), 7.57 (m, 1 H), 7.54 (m, 2 H); 7.45 7.41 (m, 4 H); 7.04 (d, J ˆ
6.0, 2 H); 4.17 4.13 (m, 2 H); 3.80 (q, J ˆ 6.9, 4 H); 1.68 1.64 (m, 2 H); 1.59 1.51 ( m, 4 H); 1.39 (s, 18 H); 1.26
(m, 6 H); 0.92 0.90 (m, 12 H). 13C-NMR (75 MHz, (CD3)2SO): 172.2; 155.7; 152.1; 141.7; 140.8; 139.8; 129.6;
‡
121.8; 121.6; 118.6; 117.6; 78.1; 53.7; 28.1; 24.3; 22.9; 21.5. ESI-MS: 825 (35, [ MH ‡ K] ), 809(100, [ MH ‡
‡
‡
‡
Na] ). HR-FAB-MS: 784.4752 (MH , C44H63N7O6 ; calc. 784.4761). Anal. calc. for C44H63N7O6 (786.03): C
67.24, H 8.08, N 12.21; found: C 67.33, H 7.86, N 12.35.
5'-Iodo-1,1':3',1''-terphenyl-3,3''-dicarbonitrile (26). A degassed soln. of 18 (100 mg, 0.26 mmol) in MeI
(4 ml) was heated to 1308 in a sealed tube for 16 h. The excess of MeI was removed by distillation, and FC (SiO2;

560
Helvetica Chimica Acta Vol. 86 (2003)
CH2Cl2) of the residue gave 26 (103 mg, 96%). White powder. M.p. 2668. IR (KBr): 3056m, 2222s, 1594m,
1
1572m, 1550s, 1478m, 1495s, 1317m, 867m, 783s, 722s, 686s. H-NMR (200 MHz, CDCl3): 7.67 7.58 (m, 2 H);
7.69( t, J ˆ 1.7, 1 H); 7.77 7.70 (m, 2 H); 7.88 7.82 (m, 2 H); 7.91 7.89 (m, 2 H); 7.9 7 (d, J ˆ 1.7, 2 H). 13C-NMR
(75 MHz, CDCl3): 142.01; 140.70; 136.17; 131.90; 131.77; 130.99; 130.17; 125.64; 118.63; 113.59; 95.77. EI-MS:
‡
406.0 (100, M ).
Diethyl 5'-Iodo-1,1':3',1''-terphenyl-3,3''-dicarboxylate (28). A soln. of 19 (63 mg, 133 mmol) and MeI (3 ml)
in a sealed tube was flushed with Ar and then stirred at 1308 for 16 h. After cooling and evaporation in vacuo, the
residue was purified by FC (SiO2; CH2Cl2/hexane 5 :1) to give 28 (63.5 mg, 95%). Colorless oil. IR (NaCl):
2978w, 1717s, 1583w, 1550w, 1444w, 1389w, 1367w, 1283m, 1250m, 1222m, 1172w, 1111m, 1083w, 1050w, 1022w,
867w, 816w, 750m, 689w. 1H-NMR (200 MHz, CDCl3): 8.29( m, 2 H); 8.15 8.06 (m, 2 H); 7.9 9 d(, J ˆ 1.7, 2 H);
7.85 7.77 (m, 3 H); 7.57 (t, J ˆ 7.8, 2 H); 4.45 (q, J ˆ 7.0, 4 H); 1.45 (t, J ˆ 7.0, 6 H). 13C-NMR (75 MHz, CDCl3):
‡
166.7; 143.2; 140.0; 135.6; 131.8; 131.6; 129.4; 129.3; 128.5; 125.9; 95.5; 61.4; 14.4. EI-MS: 500 (100, M ), 455 (48,
‡
‡
‡
‡
[M C2H5O] ); 427 (8, [M À C2H5O À CO] ); 300 (21, [M À C2H5O À I] ); 272 (36, [M À C2H5O À CO] ); 226
‡
‡
(45). HR-EI-MS: 500.0487 (M , C24H21IO4 ; calc. 500.0486).
5'-Iodo-1,1':3',1''-terphenyl-3,3''-dicarboxylic Acid (25). A soln. of 28 (59.6 mg, 119 mmol) and LiOH
(14.3 mg, 596 mmol) in EtOH (3 ml), H2O (2 ml), and THF (1 ml) was stirred at r.t. for 16 h, after which 1m HCl
was added. The mixture was extracted with AcOEt (2Â), the combined org. layers were dried (MgSO4), and the
solvent was evaporated in vacuo to yield 25 (47 mg, 89%). Colorless solid. M.p. 3008. 1H-NMR (200 MHz,
‡
(CD3)2SO): 13.13 (br. s, 2 H); 8.26 (m, 2 H); 8.11 7.97 (m, 7 H); 7.64 (t, J ˆ 7.7, 2 H). EI-MS: 444 (100, M ).
5',5''-Bis(3-nitrophenyl)-1,1':3',1'':3'',1'''-quaterphenyl (30). A soln. of 29 [24] (770 mg, 1.63 mmol), 3-
nitrophenylboronic acid (1.641 g, 9.83 mmol), and Na2CO3 (2.084 g, 19.66 mmol) in PhH/EtOH 11:3 (115 ml)
and H2O (77 ml) was flushed with Ar and heated to 808. Subsequently, [Pd(dppf)Cl2] (10 mg, 0.01 mmol) was
added, and the mixture was heated to reflux for 3 d. The precipitate was filtered off and recrystallized from 1,2-
dichlorobenzene to give 30 (703 mg, 67%). Pale-gray powder. M.p. > 3508 (dec.). IR (KBr): 3109m, 2923m,
2369s, 2339s, 1843m, 1771m, 1717m, 1689m, 1652m, 1538s, 1526s, 1346m, 867w, 802w, 736m, 665w. 1H-NMR
(200 MHz, CDCl3): 8.60 8.59( m, 4 H); 8.34 8.24 (m, 4 H); 8.12 8.04 (m, 4 H); 7.9 6 (d, J ˆ 2.1, 4 H); 7.93 7.91
(m, 2 H); 7.78 7.68 (m, 4 H). Due to the poor solubility of 30 in commonly used solvents, no 13C-NMR spectra
‡
could be obtained. DEI-MS: 638.58 (M ).
3,3',3'',3'''-(1,1'-Biphenyl-3,3',5,5'-tetrayl)tetrakis(benzenamine) (31).
A dispersion of 30 (800 mg,
1.25 mmol) and Sn (1.78 g, 15 mmol) in conc. HCl (40 ml) was heated to reflux for 2 weeks. After cooling to
r.t., the mixture was made basic (pH 14) with NaOH tablets. The soln. was diluted with H2O and extracted with
CH2Cl2 (4 Â 150 ml). The combined org. layers were dried (MgSO4), and the solvent was evaporated in vacuo to
give 31 (632 mg, 97%). Pale-yellow powder. M.p. 2848 (dec.). IR (KBr): 3336m, 3022m, 1927w, 1605s, 1580s,
1491m, 1401m, 1303w, 1204w, 1167w, 9 9 m2 , 863m, 782m, 701m. 1H-NMR (200 MHz, CDCl3): 7.86 (d, J ˆ 1.7, 4
H); 7.79( t, J ˆ 1.7, 2 H); 7.34 7.24 (m, 4 H); 7.11 7.10 (m, 4 H); 7.08 7.03 (m, 4 H); 6.77 6.72 (m, 4 H).
13C-NMR (75 MHz, (CD3)2SO): 149.39; 142.48; 141.70; 140.96; 129.63; 124.20; 114.78; 113.5; 112.53. DEI-MS:
‡
518.4 (100, M ).
Tetra(tert-butyl) N,N',N'',N'''-(1,1'-Biphenyl-3,3',5,5'-tetrayltetrakis{(S)-[(1,3-phenylene)iminocarbonyl](2-
methylpropyl)methyl})tetracarbamate ((S,S)-32). To a soln. of 31 (200 mg, 0.385 mmol), N-Boc-l-leucine
(504 mg, 2.02 mmol), and DMAP (20 mg, 0.16 mmol) in DMF (40 ml) and dioxane (10 ml) at 08, EDC ¥ HCl
(512 mg, 2.67 mmol) was added, and the mixture was stirred at r.t. over 2 d. More N-Boc-L-leucine (504 mg,
2.02 mmol) and additional EDC ¥ HCl (512 mg, 2.67 mmol) were added at 08. After stirring at r.t. for 3 d, the
solvent was evaporated in vacuo and the residue taken up in CH2Cl2. The org. layers were washed with 1m HCl
(2Â) and sat. aq. NaHCO3 soln. (3Â). The combined org. layers were dried (MgSO4), and FC (SiO2; CH2Cl2/
AcOEt 20 :1) afforded (S,S)-32 (342 mg, 67%). White solid. M.p. 2668. [a]2D3 ˆ ‡167 (c ˆ 1, CHCl3). IR (KBr):
3422w, 3314m, 2958m, 1670s, 1558m, 1550m, 1495m, 1367m, 1235w, 1164m, 1048w, 868w, 786w, 69 8w. 1H-NMR
(500 MHz, (CD3)2SO): 10.04 (br. s, 4 H); 7.97 (br. s, 8 H); 7.83 (br. s, 2 H); 7.77 7.75 (m, 4 H); 7.57 7.56 (m, 4
H); 7.46 7.43 (m, 4 H); 7.01 (d, J ˆ 8.1, 4 H); 4.14 4.10 (m, 4 H); 1.65 1.63 (m, 4 H); 1.52 1.50 (m, 4 H);
1.46 1.41 (m, 4 H); 1.35 (s, 36 H,); 0.88 (s, 24 H). 13C-NMR (125 MHz, (CD3)2SO): 171.89; 155.42; 141.80;
141.60; 140.39; 139.63; 129.40; 124.86; 124.36; 122.09; 118.60; 117.75; 77.96; 53.57; 28.14; 24.30; 22.92; 21.48. ESI-
‡
MS: 1395.1 (100, [M ‡ Na] ).
N,N',N'',N'''-(1,1'-Biphenyl-3,3',5,5'-tetrayltetrakis{(S)-[(1,3-phenylene)iminocarbonyl](2-methylpropyl)-
methyl})tetraammonium Tetrakis(trifluoroacetate) ((S,S-33). A soln. of (S,S)-32 (342 mg, 0.259mmol) in
CH2Cl2/TFA 1 :1 (40 ml) was stirred at r.t for 4 h under Ar. The mixture was evaporated in vacuo, EtOH was
added, and the solvent was again evaporated in vacuo to yield (S,S)-33 (364 mg, 99%). White powder. M.p. 2348.
[a]2D3 ˆ À18.4 (c ˆ 0.5, THF). IR (KBr): 3233m, 1964m, 1670s, 1488m, 1436m, 1391m, 1303w, 1202s, 1138s, 865m,

Helvetica Chimica Acta Vol. 86 (2003)
561
840m, 79 9m, 732m, 69 7m. 1H-NMR (500 MHz, (CD3)2SO): 10.76 (br. s, 4 H), 7.99 (br. s, 8 H); 7.85 (br. s, 2 H);
7.75 7.73 (m, 4 H); 7.66 7.64 (m, 4 H); 7.53 7.49( m, 4 H); 3.74 (br. s, 12 H); 3.9( m, 4 H); 1.68 (m, 12 H);
0.92 (s, 24 H). 13C-NMR (125 MHz, (CD3)2SO): 168.08; 141.83; 141.46; 140.57; 138.70; 129.69; 125.02;
‡
123.05; 119.05; 118.18; 51.78; 23.65; 22.63; 21.77. FAB-MS: 1200.45 (5, [M À 2 CF3COOH] ); 1086.27 (5,
‡
‡
[M À 3 CF3COOH] ); 971.49 (100, [M À 4 CF3COOH] ).
Tetraethyl 3,3',3'',3'''-(1,1'-Biphenyl-3,3',5,5'-tetrayl)tetrakis(benzenecarboxylate) (34). A degassed soln. of
11 (700 mg, 2.53 mmol), 29 (198 mg, 0.42 mmol), and Na2CO3 (535 mg, 5.05 mmol) in PhH (24 ml), EtOH
(6 ml), and H2O (20 ml) was heated to 808. Subsequently, [Pd(dppf)Cl2] ¥ CH2Cl2 (20 mg) was added, and the
mixture was heated to reflux for 3 d. After evaporation in vacuo, the residue was taken up in CH2Cl2, and the
soln. was washed with 1m NH4Cl. The org. layer was dried (MgSO4) and evaporated in vacuo. FC (SiO2; CH2Cl2)
gave 34 (251 mg, 73%). Slightly yellow solid. M.p. 1638. IR (KBr): 2978m, 1716s, 1581m, 1450w, 1366m, 1285s,
1224s, 1110m, 869w, 753s, 69 3m. 1H-NMR (300 MHz, CDCl3): 8.41 8.40 (m, 4 H); 8.12 8.08 (m, 4 H); 7.9 5
7.91 ( m, 8 H); 7.88 (t, J ˆ 1.6, 2 H); 7.61 7.55 (m, 4 H); 4.43 (q, J ˆ 7.2, 8 H); 1.42 (t, J ˆ 7.2, 12 H). 13C-NMR
(75 MHz, CDCl3): 160.50; 142.41; 141.86; 141.12; 131.80; 131.28; 129.03; 128.85; 128.48; 125.86; 125.70; 61.19;
‡
14.39. DEI-MS: 746.2 (M ).
3,3',3'',3'''-(1,1'-Biphenyl-3,3',5,5'-tetrayl)tetrakis(benzenecarboxylic Acid) (35). To 34 (251 mg,
0.336 mmol) in THF (25 ml), LiOH (100 mg, 4.18 mmol) in H2O (2.0 ml) was added, and the mixture was
heated to reflux for 17 h. The mixture was partitioned between sat. aq. K2CO3 soln. and CH2Cl2. The aq. soln.
was acidified with 1m HCl to pH 1, and the formed precipitate was filtered off and dried to yield 35 (175 mg,
87%). Pale-green solid. M.p. > 4008. IR (KBr): 3426m, 3032 (br.), 2655w, 2544w, 1700s, 1582m, 1450m, 1426m,
1388w, 1270m, 858w, 752m, 686m. 1H-NMR (300 MHz, (CD3)2SO): 13.03 (br. s, 4 H); 8.34 (m, 4 H); 8.20 8.11
(m, 8 H); 8.00 7.91 (m, 6 H); 7.66 7.57 (m, 4 H). 13C-NMR (125 MHz, (CD3)2SO): 167.26; 141.78; 141.2;
140.39; 131.88; 131.59; 129.23; 128.53; 127.89; 125.61; 124.97. ESI-MS: 634 (22, MÀ).
Tetrakis(pentafluorophenyl) 3,3',3'',3'''-(1,1'-Biphenyl-3,3',5,5'-tetrayl)tetrakis(benzenecarboxylate) (36).
To 35 (170 mg, 0.267 mmol) in dry DMF (7 ml) under Ar, pentafluorophenol (246 mg, 1.340 mmol) was added,
and the soln. was cooled to 08. After addition of DCC (332 mg, 1.608 mmol), the mixture was stirred at 08 for
60 h. Filtration over Celite and evaporation in vacuo provided a residue that was dissolved in PhMe and filtered
over Celite again. Evaporation in vacuo and FC (SiO2; CH2Cl2) gave 36 (178 mg, 51%). White solid. M.p. 2548.
IR (KBr): 3445 (br.), 2922w, 2666w, 2455w, 2360m, 1771s, 1593w, 1521s, 1271m, 1210m, 1146w, 1040m, 9 9 m7 ,
735m. 1H-NMR (300 MHz, CDCl3): 8.55 8.54 (m, 4 H); 8.28 8.25 (m, 4 H); 8.11 8.07 (m, 4 H); 7.9 9 d(, J ˆ
1.6, 4 H); 7.93 (t, J ˆ 1.6, 2 H); 7.94 7.68 (m, 4 H). 13C-NMR (75 MHz, CDCl3): 162.78; 143.25; 142.80; 141.86;
141.72; 139.86; 138.22; 136.57; 133.87; 130.25; 129.91; 129.78; 128.02; 126.43; 126.03. HR-MALDI-MS:
‡
‡
1321.0864 (100, [M ‡ Na] , C64H22F20O8Na ; calc. 1321.0893).
≈
X-Ray Crystal Structure of 18. Data for C24H21N5, Mr ˆ 379.46, at Tˆ 293 K: triclinic, space group P1 (No.
2), Dc ˆ 1.173 g cmÀ3, Z ˆ 4, a ˆ 8.343(6), b ˆ 14.306(11), c ˆ 18.797(12) ä, a ˆ 80.66(6), b ˆ 87.54(6), g ˆ
76.01(6)8, Vˆ 2148.1(3) ä3. Syntex diffractometer, MoKa radiation, l ˆ 0.7107 ä. A single crystal with linear
dimensions of ca. 0.5 Â 0.3 Â 0.3 mm was used. The structure was solved by direct methods and refined by full-
matrix least-squares analysis (SHELXTL). All heavy atoms were refined anisotropically, H-atoms fixed
isotropically with atomic positions based on stereochemical considerations. Final R(F) ˆ 0.049, wR(F2) ˆ 0.137
for 528 parameters and 2489reflections with I > 2s(I) and 2.2 < q < 20.08 (corresponding R values based on all
4002 reflections are 0.072 and 0.145, resp.). Crystallographic data (excluding structure factors) have been
deposited with the Cambridge Crystallographic Data Centre as supplementary publication No. CCDC-197055.
Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge
CB21EZ, UK (fax: (‡44)1223-336-033; e-mail: deposit@ccdc.cam.ac.uk).
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Received November 27, 2002