Synthesis of {242}- and {323}-p-octiphenyls

Article abstract of DOI:10.1002/hlca.200490198

The introduction of rigid-rod molecules as privileged scaffolds has opened routes to otherwise problematic supramolecular architecture like artificial β-barrels and functional supramolecules covering pores, hosts, sensors, and catalysts. The usefulness of

Full text of DOI:10.1002/hlca.200490198

Helvetica Chimica Acta Vol. 87 (2004)
2181
Synthesis of {242}- and {323}-p-Octiphenyls
by Yoann Baudry, Dawn Ronan, Damien Jeannerat, and Stefan Matile*
Department of Organic Chemistry, University of Geneva, 30, Quai Ernest Ansermet, CH-1211 Geneva
The introduction of rigid-rod molecules as privileged scaffolds has opened routes to otherwise problematic
supramolecular architecture like artificial b-barrels and functional supramolecules covering pores, hosts,
sensors, and catalysts. The usefulness of p-oligophenyls for the construction of functional barrel-stave
architecture has, however, been limited by uniform substitution along the rigid-rod scaffold. The objective of
this report is to overcome this obstacle for the synthesis of p-octiphenyls with orthogonally protected carboxylic
acid groups along the rigid-rod scaffold. In the reported {242}-p-octiphenyl 1, the two peripheral arene moieties
carry carboxylic acid groups protected as benzyl esters, whereas the four central carboxylic acid groups are
protected orthogonally as tert-butyl esters (Scheme 2). The complementary orthogonal protection of the three
peripheral and the two central arenes is achieved in the {323}-p-octiphenyl 2 (Scheme 3). The realized {242}-and
{323}-p-octiphenyls 1 and 2, respectively, provide a complete set for the general access to refined rigid-rod
barrel-stave architecture with maximized functional plasticity. The need for resolution-enhanced (aliased)
HMBC 2D-NMR spectroscopy to characterize these refined oligomers is described in the following publication
in this issue of Helv. Chim. Acta.
Introduction. In this report, we describe the synthesis of {242}-p-octiphenyl 1 and
{323}-p-octiphenyl 2 (Scheme 1). The carboxylic acid groups lining the scaffold of both
rigid-rod molecules carry orthogonal protecting groups. Benzyl esters, cleaved by
hydrogenolysis and resistant to CF3COOH, and the solubilizing [1] tert-butyl esters,
removed by CF3COOH and untouched by hydrogenolysis, were selected for
orthogonal protection in this study [2]. The design of refined rigid-rod oligomers 1
3
3
2
3
2
3
2
3
1
and 2 focused on maximal complementarity. The conventional 1 ,2 ,3 ,4 ,5 ,6 ,7 ,8 )
(ˆ 3,3',2'',3''',2'''',3''''',2'''''',3''''''') motif [3 6] of {242}-p-octiphenyl 1 was complement-
ed by the new 12,22,33,42,53,62,73,82 1) (ˆ2,2',3'',2''',2'''',3''''',2'''''') sequence in {323}-p-
octiphenyl 2. {242}-p-Octiphenyl 1 comprises compressed terminal 13,23 and 72,83
domains separated by an expanded central 32,43,52,63 domain, whereas {323}-p-
octiphenyl 2 features a compressed central 42,53 domain flanked by expanded 12,22,33
and 62,73,82 domains. Finally, the sequence of the same orthogonal protecting groups
was inverted from central tert-butyl esters and terminal benzyl esters in 1 to terminal
tert-butyl esters and central benzyl esters in 2.
With complementary {242}-rod 1 and {323}-rod 2 in hand, a comprehensive set of
general precursors for refined rigid-rod barrel-stave architecture is available. For
example, central and peripheral peptide strands of different sequences can be
selectively introduced in conjugates 3 and 4 to produce {242}- and {323}-rigid-rod
b-barrel pores [3], sensors [4][5], and catalysts [6] with central and peripheral domains
of different dimensions.
1
)
Arbitrary numbering; for systematic names, see Exper. Part.
¹ 2004 Verlag Helvetica Chimica Acta AG, Z¸rich

2182
Helvetica Chimica Acta Vol. 87 (2004)
and {323}-p-Octiphenyl with Carboxylic Acid Groups Carrying the
Scheme 1. {242}-p-Octiphenyl
1
2
Orthogonal Protecting Groups OPG1 and OPG2 along Their Scaffold Enable, e.g., the Introduction of
Chemically Distinct Peptide Strands for Self-Assembly of {242}- and {323}-b-Barrels with Partially or Fully
Contracted Active Sites
Results and Discussion. Many strategies for the synthesis of more-complex p-
oligophenyls and related rigid-rod scaffolds have been reported in the literature [7
44]. {242}-p-Octiphenyl 1 was prepared in ten steps from commercial biphenyl 5

Helvetica Chimica Acta Vol. 87 (2004)
2183
Scheme 2
a) KI, 70% [43]. b) 1. BuLi; 2. MeOH; 67% [42]. c) 1. BuLi, 2. CuCl2 ; 64% [42]. d) 1. t-BuLi, toluene; 2. I2;
46% [42]. e) BBr3; 85%. f) tert-Butyl bromoacetate, Cs2CO3; 89%. g) BBr3; 90%. h) Benzyl bromoacetate,
Cs2CO3; 87%. i) 4,4,5,5-Tetramethyl-1,3,2-dioxaborolane, [PdCl2(dppf)], Et3N. j) [Pd(PPh3)4], K2CO3, DMSO;
51% form 14.
(Scheme 2). The first four steps of the synthesis of the central p-quaterphenyl subunit
were accomplished according to [42][43]. Specifically, diazonium salt 5 was iodinated
with KI. One I-substituent in biphenyl 6 was removed non-selectively with BuLi. After
quenching with MeOH, the desired iodobiphenyl 7 could be isolated from a roughly
statistical mixture of biphenyls with either no or one (7) terminal I-substituent.
Oxidative coupling of iodobiphenyl 7 gave p-quaterphenyl 8. The same product was
prepared in similar yields by conversion of iodo compound 7 to the corresponding
boronic acid and subsequent Suzuki coupling (not shown). p-Quaterphenyl 8 was
regioselectively iodinated with t-BuLi and molecular I2. The p-quaterphenyl product 9
is the last compound of this sequence that was previously reported [42]. Multiple alkyl
ether cleavage in p-quaterphenyl 9 with BBr3 gave tetrol 10, which was treated with tert-
butyl bromoacetate to give the desired p-quaterphenyl subunit 11. This key
intermediate carries four lateral carboxylate handles protected as tert-butyl esters
and two terminal I-substituents for Suzuki coupling with the peripheral biphenyl
subunits 12.
The peripheral boronate 12 was accessible from diether 7 in three steps. Ether
exchange via diol 13 to dibenzyl ester 14 was as unproblematic as expected. The
homologous bis(4-nitrobenzyl) and di(tert-butyl) esters were prepared analogously for

2184
Helvetica Chimica Acta Vol. 87 (2004)
controls (not shown). Several conditions were tested to optimize the preparation of
boronate 12. Best substrate conversion was observed by reacting dibenzyl ester 14 with
pinacolborane (ˆ4,4,5,5-tetramethyl-1,3,2-dioxalorolane), Et3N, and [PdCl2(dppf)] in
MeCN at 858 for 3 h (dppf ˆ 1,1'-bis(diphenylphosphino)ferrocene). Less-satisfactory
results were obtained, in our hands, with bis(4-nitrobenzyl) instead of dibenzyl ester 14
as the starting material. Less-satisfactory results were further obtained with bis(pina-
colato)diboron [41 43] instead of pinacolborane [45], KOAc instead of Et3N as base,
and DMSO or dioxane instead of MeCN as solvents. Boronate 12 was used as the crude
product for the next reaction to avoid unnessesary losses due to product decomposition
during purification on silica gel and, less pronounced, on alox.
Suzuki coupling [46 52] of the central p-quaterphenyl subunit 11 carrying lateral
tert-butyl esters and the peripheral biphenyl subunits 12 carrying orthogonal benzyl
esters gave the desired {242}-p-octiphenyl 1 in 51% yield. This reaction was
complicated by the need for aprotic solvents to avoid ester hydrolysis or trans-
esterification. For instance, the use of aqueous Cs2CO3 as the base of choice in many
examples [46][47] resulted in partial loss of the benzyl esters. The presence of MeOH
as in some of McClure×s fluorine-mediated couplings resulted in transesterification
[48]. Good yields of up to 44% were achieved with Fu×s fluorine-mediated Suzuki
coupling in THF [49]. A maximal yield, i.e., 51%, was obtained with a procedure based
on [Pd(PPh3)4] and K2CO3 in DMSO, adapting insights from several reports [48 51] to
the excellent conditions published last year by Yoburn and Van Vranken [52].
The synthesis of {323}-p-octiphenyl 2 in eight steps from commercial biphenyl 5 has
been communicated previously and is summarized here only briefly for comparison and
completion (Scheme 3) [7]. The central biphenyl subunit 15 was readily accessible from
diiodo compound 6 by transetherification via diol 16. The synthesis of the peripheral p-
terphenyl subunit 17 from biphenyl 6 was more demanding. Slow addition of boronic
acid 18 to an excess of biphenyl 6 was the key for controlled Suzuki coupling to afford
p-terphenyl 19 as the main product; routine conditions afforded overreacted p-
quaterphenyl and unreacted biphenyl 6 together with traces of terphenyl 19. Side-chain
introduction by ether exchange via triol 20 was straightforward. Conversion of the
tri(tert-butyl) ester 21 to boronate 17 worked best under the conditions used in the
synthesis of 1, i.e., pinacolborane, [PdCl2(dppf)], and Et3N in MeCN. The instability of
benzyl esters in basic protic solvents prevented the application of many routine
conditions for the final Suzuki coupling of central and terminal p-oligophenyls 15 and
17, respectively. In agreement with the results for rod 1, the modified conditions of
Yoburn and Van Vranken [52] proved best in our hands, providing access to pure {323}-
p-octiphenyl 2 in 48% yield. The synthesis of the homologous {323}-p-octiphenyl with
4-methoxybenzyl (4-MeOBn) rather than benzyl protection has been reported [7].
Because preliminary results from selective deprotection confirmed the orthogonality of
Bn/t-Bu pairs as superior to 4-MeOBn/t-Bu pairs, we focused our attention on Bn/t-Bu-
{323}-rod 2.
The purities and structures of the final {242}-p-octiphenyl 1 and {323}-p-octiphenyl 2
were confirmed by conventional spectroscopic and analytical methods as described in
the Exper. Part. The characterization of refined oligomers by NMR spectroscopy,
however, is notoriously problematic. The similar chemical shifts of several nearly
identical ring moieties result in signal clusters that are challenging to separate and to

Helvetica Chimica Acta Vol. 87 (2004)
2185
Scheme 3
a) KI; 70%. b) BBr3, 100%. c) Benzyl bromoacetate, Cs2CO3; 84%. d) [Pd(PPh3)4], K2CO3, acetone/H2O 5 :1;
37%. e) BBr3; 92%. f) tert-Butyl bromoacetate, Cs2CO3; 90%. g) Pinacolborane, [PdCl2(dppf)], Et3N, MeCN.
h) [Pd(PPh3)4], K2CO3, DMSO; 48% from 21 [7].
assign. At worst, these signal clusters are detected as the broad, unresolved signals
known from the corresponding polymers. Satisfactory interpretation of the 1H-as well
as the 13C-NMR spectra of {242}-rod 1 and {323}-rod 2 was not possible by conventional
NMR techniques including DEPT, COSY, HMBC, and HSQC. High-resolution
(aliased) HSQC and HMBC NMR spectroscopy, however, were confirmed as user-
friendly methods for complete characterization of complex oligomers. The application
of this somewhat underappreciated method for full interpretation of both 1H-as well as
the 13C-NMR spectra of {242}-rod 1 and {323}-rod 2 is described in the following
publication [53].
Preliminary studies confirmed orthogonal deprotection of {242}-p-octiphenyl 1 and
{323}-p-octiphenyl 2 in practice. Namely, the benzyl esters could be cleaved selectively
by hydrogenolysis without cleavage of the tert-butyl esters, whereas the tert-butyl esters
could be cleaved selectively with CF3COOH without cleavage of the benzyl esters.
Efforts to synthesize refined peptideÀp-octiphenyl conjugates 3 and 4 and to study
their self-assembly into multifunctional {242}- and {323}-b-barrel pores are ongoing and
will be reported in due course.
We thank A. Pinto and J.-P. Saulnier for NMR measurements, P. Perrottet and the group of F. G¸laÁar for
MS measurements, H. Eder for elemental analyses, and the Swiss National Science Foundation for financial
support (200020-101486 and National Research Program Supramolecular Functional Materials 4047-057496).

2186
Helvetica Chimica Acta Vol. 87 (2004)
Experimental Part
General. Reagents for synthesis were purchased either from Aldrich, Fluka, or Acros. Solvents were
distilled and dried before use. All reactions were performed under Ar. Column chromatography (CC): silica gel
60 (Fluka; 40 63 mm). Anal. and prep. TLC: silica gel 60 (Fluka; 0.2 mm) and silica gel GF (Analtech;
1
1000 mm), resp. IR Spectra: Perkin-Elmer-Spectrum-One-FT-IR spectrometer; solid samples; nÄ cmÀ1. H-and
13C-NMR Spectra1): Bruker-300, -400, or -500 spectrometer; chemical shifts d in ppm relative to SiMe4
(ˆ0 ppm), coupling constants J in Hz; assignments with the aid of additional information from 2D NMR
spectra (1H,1H-COSY, HSQC, HMBC) [53]; ESI-MS and Atmospheric-pressure chemical-ionization (APCI)
MS: Finnigan-MAT-SSQ-7000 instrument; in m/z (rel. %). HR-MS: VG analytical 7070E.
14,44-Diiodo-13,23,32,43-tetramethoxy-p-quaterphenyl (ˆ4,4'''-Diiodo-3,3',2'',3'''-tetramethoxy-1,1':4'',1'''-
quaterphenyl; 9). Intermediate 9 was prepared from biphenyl 5 in overall four steps as described in [42]
(Supporting Information).
14,44-Diiodo-tetrol-p-quaterphenyl-13,23,32,43 (ˆ4,4'''-Diiodo[1,1'':4''-,1'''-quaterphenyl]-2'',3,3',3'''-tetrol;
10). To a soln. of 9 (130 mg, 0.19 mmol) in dry CH2Cl2 (10 ml), 1m BBr3 in CH2Cl2 (1.5 ml) was added at
À 788. This soln. was allowed to warm to r.t. over 14 h. Then, H2O was added at À 788. After warming to 58, the
soln. was washed with brine, dried (Na2SO4), and evaporated, and the crude product purified by CC (CH2Cl2/
MeOH 15 :1): pure 10 (100 mg, 85%). Colorless solid. TLC (CH2Cl2/MeOH 15 :1): Rf 0.22. M.p. > 2308. IR:
3370s, 2972m, 2931m, 1697m, 1584m, 1545m, 1489w, 1469m, 1399s, 1175s, 1130s. 1H-NMR (500 MHz, CD3OD):
7.68 (d, 3J ˆ 8.2, HÀC(15), HÀC(45)); 7.28 (d, 3J ˆ 7.9, HÀC(25), HÀC(36)); 7.16 (d, 4J ˆ 1.7, HÀC(22),
HÀC(33)); 7.1 (dd, 3J ˆ 7.90, 4J ˆ 1.7, HÀC(26), HÀC(35)); 7.1 (d, 4J ˆ 2.0, HÀC(12), HÀC(42)); 6.9 (dd, 3J ˆ
8.2, 4J ˆ 2.0, HÀC(16), HÀC(46)). 13C-NMR (125 MHz, CD3OD): 158.2 (s, C(13), C(43)); 155.3 (s, C(23),
C(32)); 143.5 (s, C(11), C(41)); 141.9 (s, C(21), C(34)); 140.6 (d, C(15)); 133.1 (d, C(25)); 126.6 (s, C(24), C(31));
120.8 (d, C(16), C(46)); 119.9 (d, C(26), C(35)); 115.4 (d, C(22), C(33)); 113.9 (d, C(12), C(42)); 83.5 (s, C(14),
‡
‡
C(44)). HR-MS: 621.9173 (M , C24H16O4I2 ; calc. 621.9138).
2,2',2'',2'''-[(14,44-Diiodo-p-quaterphenyl-13,23,32,43-tetrayl)tetrakis(oxy)]tetrakis[acetic Acid] Tetra(tert-bu-
tyl Ester] (ˆ2,2',2'',2'''-[(4,4'''-Diiodo[1,1':4',1'':4'',1'''-quaterphenyl]-2'',3,3',3'''-tetrayl)tetrakis(oxy)]tetrakis-
[acetic Acid] Tetra(tert-butyl Ester); 11). To a soln. of 10 (100 mg, 0.16 mmol) in dry acetone (25 ml) was
added Cs2CO3 (420 mg, 1.3 mmol). The resulting suspension was stirred at r.t. for 30 min. Then, tert-butyl
bromoacetate (190 ml, 1.3 mmol) was added, and the mixture was stirred for an additional 3 h. The mixture was
then evaporated, the residue dissolved in AcOEt, washed with brine, dried (MgSO4), and evaporated, and the
crude product purified by CC (CH2Cl2/petroleum ether 4 :1, then CH2Cl2/AcOEt 120 :1): anal. pure 11 (165 mg,
96%). Colorless solid. TLC (CH2Cl2/AcOEt 120 :1): Rf 0.44. M.p. 48 498; IR: 2979m, 2918m, 1752s, 1737s,
1606w, 1473m, 1393m, 1241s, 1156s, 631s, 539s. 1H-NMR (500 MHz, CD2Cl2): 7.87 (d, 3J ˆ 8.0, HÀC(15),
4
HÀC(45)); 7.45 (d, 3J ˆ 7.8, HÀC(25), HÀC(36)); 7.25 (dd, 3J ˆ 7.8, J ˆ 1.7, HÀC(26), HÀC(35)); 7.02 (d, 4J ˆ
1.7, HÀC(22), HÀC(33)); 7.02 (dd, 3J ˆ 8.0, 4J ˆ 1.9, HÀC(16), HÀC(46)); 6.96 (d, 4J ˆ 1.9, HÀC(12), HÀC(42));
4.66 (s, CH2OÀC(13), CH2OÀC(43)); 4.57 (s, CH2OÀC(23), CH2OÀC(32)); 1.51 (s, 2t-Bu (rings 1 and 4)); 1.46
(s, 2 t-Bu (rings 2 and 3)). 13C-NMR (125 MHz, CD2Cl2): 168.1 (s, COCH2OÀC(23), COCH2OÀC(32)); 167.5
(s, COCH2OÀC(13), COCH2OÀC(32)); 157.5 (s, C(13), C(43)); 156.2 (s, C(23), C(32)); 143.0 (s, C(11), C(41));
141.2 (s, C(21), C(34)); 140.3 (d, C(15), C(45)); 132.6 (d, C(25), C(36)); 127.2 (s, C(24), C(31)); 122.4 (d, C(16),
C(46)); 120.2 (d, C(26), C(35)); 111.4 (d, C(12), C(42)); 111.1 (d, C(22), C(33)); 85.4 (s, C(14), C(44)); 82.8
(s, 2 Me3C (rings 1 and 4)); 82.4 (s, 2 Me3C (rings 2 and 3)); 67.0 (t, CH2OÀC(13), CH2OÀC(43)); 66.6
(t, CH2OÀC(23), CH2OÀC(32)); 28.2 (q, 2 Me3C (rings 1 and 4)); 28.1 (q, 2 Me2C (rings 2 and 3)). APCI-MS
(acetone/N(CH2CH2OH)3; neg.): 1113 (100, [M ‡ Cl]À). APCI-MS (acetone/N(CH2CH2OH)3; pos.): 1228 (100,
‡
[M ‡ N(CH2CH2OH)3] ).
4-Iodo-3,3'-dimethoxy-1,1'-biphenyl (7). Intermediate 7 was prepared from biphenyl 5 in overall two steps
as described in [42] (Supporting Information).
4-Iodo[1,1'-biphenyl]-3,3'-diol (13). To a soln. of 7 (60 mg, 0.18 mmol) in dry CH2Cl2 (10 ml) was added 1m
BBr3 in CH2Cl2 (0.72 ml) at À 788. This soln. was allowed to warm to r.t. over 14 h. Then, H2O was added at À
788 to quench the reaction. After warming to 58, the soln. was washed with brine (3Â), dried (Na2SO4), and
evaporated and the crude product purified by CC (CH2Cl2/MeOH 20 :1): anal. pure 13 (49 mg, 90%). Colorless
solid. TLC (CH2Cl2/MeOH 12 :1): Rf 0.50. M.p. 134 1358. IR: 3338m, 2921m, 1613w, 1589m, 1567s, 1481m,
1339s, 1309s, 1184s, 1172s, 939s. 1H-NMR (500 MHz, CD3OD): 7.68 (d, 3J ˆ 8.2, HÀC(15)); 7.2 (t, 3J ˆ 7.8,
HÀC(25)); 7.0 (d, 4J ˆ 2.1, HÀC(12)); 7.01 (ddd, 3J ˆ 7.9, 4J ˆ 2.2, 4J ˆ 1.0, HÀC(24)); 6.98 (dd, 4J ˆ 2.2, 2.4,
HÀC(22)); 6.80 (dd, 3J ˆ 8.2, 4J ˆ 2.1, HÀC(16)); 6.77 (ddd, 3J ˆ 7.9, 4J ˆ 1.0, 2.4, HÀC(26)). 13C-NMR
(125 MHz, CD3OD): 158.8 (s, C(23)); 158.2 (s, C(13)); 144.2 (s, C(11)); 142.9 (s, C(21)); 140.5 (d, C(15)); 130.9

Helvetica Chimica Acta Vol. 87 (2004)
2187
(d, C(25)); 120.9 (d, C(16)); 119.0 (d, C(24)); 115.6 (d, C(26)); 114.5 (d, C(22)); 114.1 (d, C(12)); 83.3 (s, C(14)).
‡
‡
APCI-MS (acetone): 347 (22, [M ‡ Cl]À), 311 (50, [M À H]À). HR-MS: 311.9656 (M , C12H9O2I ; calc.
311.9647).
2,2'-[(4-Iodo[1,1'-biphenyl]-3,3'-diyl)bis(oxy)]bis[acetic Acid] Dibenzyl Ester (14). To a soln. of 13
(120 mg, 0.39 mmol) in dry acetone (25 ml) was added Cs2CO3 (757 mg, 2.34 mmol). The resulting suspension
was stirred at r.t. for 10 min. Then benzyl bromoacetate (182 ml, 1.17 mmol) was added, and the suspension was
stirred for an additional hour. The mixture was evaporated, the residue dissolved in AcOEt, the soln. washed
with brine, dried (MgSO4), and evaporated and the crude product purified by CC (CH2Cl2/petroleum ether 4 :1,
then CH2Cl2): anal. pure 14 (206 mg, 87%). Colorless solid. TLC (CH2Cl2): Rf 0.53. M.p. 89 908. IR: 3035w,
2914w, 1716s, 1593m, 1561m, 1474m, 1455m, 1395m, 1233s, 1071s, 968m. 1H-NMR (300 MHz, CD2Cl2): 7.86
(d, 3J ˆ 8.1, HÀC(15)); 7.42 7.30 (m, 2 PhCH2, HÀC(25)); 7.13 (ddd, 3J ˆ 7.7, 4J ˆ 1.5, 1.5, HÀC(26)); 7.07
(dd, 4J ˆ 1.9, 1.5, HÀC(22)); 6.96 (dd, 3J ˆ 8.1, 4J ˆ 1.9, HÀC(16)); 6.91 (d, 4J ˆ 1.9, HÀC(12)); 6.90 (ddd, 3J ˆ 7.7,
4J ˆ 1.5, 1.5, HÀC(24)); 5.25 (s, PhCH2 (ring 1)); 5.24 (s, PhCH2 (ring 2)); 4.81 (s, CH2OÀC(13)); 4.74
(s, CH2OÀC(23)). 13C-NMR (75 MHz, CD2Cl2): 168.9 (s, COCH2OÀC(23)); 168.4 (s, COCH2OÀC(13)); 158.6
(d, C(23)); 157.3 (d, C(13)); 142.9 (s, C(11)); 142.0 (s, C(21)); 140.4 (d, C(15)); 135.8 (s, 2 Cipso (Bn)); 130.4
(d, C(25)); 129.0 128.6 (6d, 4 Co, 4 Cm, 2 Cp (all Bn)); 122.7 (d, C(16)); 120.8 (d, C(26)); 114.0 (d, C(22)); 114.0
(d, C(24)); 111.6 (d, C(12)); 85.5 (s, C(14)); 67.4 (t, 2 PhCH2); 66.7 (t, CH2OÀC(13)); 65.8 (t, CH2OÀC(23)).
APCI-MS (acetone; neg.): 643 (5, [M ‡ Cl]À), 517 (24, [M À I ‡ Cl]À), 459 (100, [M À 2 Bn ‡ Cl]À). APCI-MS
‡
‡
‡
‡
(acetone; pos.): 608 (12, [M] ), 482 (100, [M À I] ), 391 (47, [M À Bn À I] ). HR-MS: 608.0739 (M ,
‡
C30H25O6I ; calc. 608.0696).
{424}-p-Octiphenyl 1 (ˆ2,2',2'',2''',2'''',2''''',2'''''',2'''''''-[[1,1':4',1'':4'',1''':4''',1'''':4'''',1'''''.4''''',1'''''':4'''''',1'''''''-
Octiphenyl-2'',2'''',2'''''',3,3',3''',3''''',3'''''''-octayloctakis(oxy)]octakis[acetic Acid] 01,01',01'''''',01'''''''-Tetrabenzyl
01'',01''',01'''',01'''''-Tetra(tert-butyl) Ester). To a soln. of 14 (300 mg, 0.49 mmol) in degassed MeCN (9 ml) were
added [PdCl2(dppf)] (3 mol-%), Et3N (412 ml, 3.0 mmol) and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(ˆ pinacolborane) (430 ml, 3.0 mmol). The soln. was heated at 808 for 3 h. Benzene (8 ml) was then added
and the soln. washed with brine, dried (MgSO4), and evaporated: intermediate 12.
a) Crude 12 (68 mg, 0.11 mmol) was then added to a soln. of 11 (20 mg, 0.019 mmol), [Pd(PPh3)4] (6 mol-
%) and K2CO3 (15 mg, 0.11 mmol) in degassed DMSO (3 ml). The soln. was heated at 908 for 14 h. After
cooling to r.t., CHCl3 (40 ml) was added, the mixture washed with H2O, dried (MgSO4), and evaporated, and the
crude product purified by prep. TLC (CH2Cl2/AcOEt 120 :1, double elution): anal. pure 1 (17 mg, 51%).
Colorless solid.
b) Crude 12 (68 mg, 0.11 mmol) was added to a soln. of 11 (20 mg, 0.019 mmol), [Pd(PPh3)4] (6 mol-%),
and CsF (17 mg, 0.11 mmol) in degassed THF (3 ml). The soln. was heated to reflux for 14 h. Workup and
purification as in a) gave anal. pure 1 (13.5 mg, 44%). Colorless solid. TLC (CH2Cl2/AcOEt 120 :1): Rf 0.27.
1H-NMR (500 MHz, CD2Cl2): 7.52 (d, 3J ˆ 7.9, HÀC(45), HÀC(56)); 7.47 (d, 3J ˆ 7.7, H ÀC(25), HÀC(76)); 7.46
(d, 3J ˆ 7.1, H ÀC(36), HÀC(65)); 7.38 (m, HÀC(15), HÀC(85)); 7.36 (m, 4 Ho (Bn, rings 1 and 8), 4 Hm (Bn,
rings 1 and 8)); 7.35 (m, 2 Hp (Bn, rings 1 and (8));7.34 (m, HÀC(46), HÀC(55)); 7.33 (m, HÀC(35), HÀC(66));
7.31 (m, 4 Ho (Bn, rings 2 and 7)); 7.30 (m, 2 Hp (Bn, rings 2 and 7), 4 Hm (Bn, rings 2 and 7)); 7.29 (dd, 3J ˆ 7.7,
4J ˆ 1.6, HÀC(26), HÀC(76)); 7.23 (ddd, 3J ˆ 7.7, 4J ˆ 1.7, 0.8, HÀC(16), HÀC(86)); 7.16 (dd, 4J ˆ 2.5, 1.7,
HÀC(12), HÀC(82)); 7.14 (d, 4J ˆ 1.6, HÀC(42), HÀC(53)); 7.09 (d, 4J ˆ 1.7, HÀC(33), HÀC(62)); 7.09 (d, 4J ˆ
4
1.6, HÀC(22), HÀC(73)); 6.91 (ddd, 3J ˆ 8.2, J ˆ 2.5, 0.8, HÀC(14), HÀC(84)); 5.25 (s, 2 PhCH2 (rings 1 and
8)); 5.20 (s, 2 PhCH2 (rings
2
and 7)); 4.77 (s, CH2OÀC(23), CH2OÀC(72)); 4.76 (s, CH2OÀC(13),
CH2OÀC(82); 4.62 (s, CH2OÀC(43), CH2OÀC(52)); 4.56 (s, CH2OÀC(32), CH2OÀC(63)); 1.49 (s, 2 tBu (rings
4
and 5)); 1.47 (s, 2 tBu (rings
3
and 6)). 13C-NMR (125 MHz, CD3OD): 169.2 (s, COCH2ÀC(23),
COCH2ÀC(72)); 169.0 (s, COCH2ÀC(13), COCH2ÀC(83)); 168.2 (s, COCH2ÀC(43), COCH2ÀC(83)); 168.2
(s, COCH2ÀC(32), COCH2ÀC(63)); 158.7 (s, C(13), C(83); 156.3 (s, C(43), C(52)); 156.2 (s, C(32), C(63)); 156.2
(s, C(23), C(72)); 142.9 (s, C(11), C(81)); 142.1 (s, C(34), C(61)); 142.0 (s, C(41), C(54)); 141.9 (s, C(21), C(74));
135.9 (s, 4 Cipso (Bn, rings 1, 2, 7 and 8)); 132.7 (d, C(25), C(76)); 132.6 (d, C(45), C(56)); 132.5 (d, C(36), C(65));
130.4 (d, C(15), C(85)); 129.0 (d, 4 Cm (Bn, rings 1 and 8)); 129.0 (d, 4 Cm (Bn, rings 2 and 7)); 128.9 (d, 2 Cp (Bn,
rings 1 and 8)); 128.8 (d, 2 Cp (Bn, rings 2 and 7)); 128.7 (d, 4 Co (Bn, rings 1 and 8)); 128.7 (d, 4 Co (Bn, rings 2
and 7)); 127.3 (s, C(24), C(71)); 127.1 (s, C(44), C(51)); 126.9 (s, C(31), C(64)); 121.0 (d, C(16), C(86)); 120.7
(d, C(26), C(75)); 120.4 (d, C(46), C(55)); 120.4 (d, C(35), C(66)); 114.0 (d, C(12), C(82)); 113.8 (d, C(14), C(84));
111.6 (d, C(22), C(73)); 111.4 (d, C(42), C(53)); 111.3 (d, C(33), C(52)); 82.4 (s, 4 Me3C (rings 3 5)); 67.3
(t, 2 PhCH2 (rings 1 and 8)); 67.2 (t, 2 PhCH2 (rings 2 and 6)); 66.7 (t, CH2OÀC(43), CH2OÀC(52)); 66.6
(t, CH2OÀC(32), CH2OÀC(63)); 66.5 (t, CH2OÀC(23), CH2OÀC(72)); 65.9 (t, CH2OÀC(13), CH2OÀC(83));

2188
Helvetica Chimica Acta Vol. 87 (2004)
28.3 (q, 2 Me3C (rings 4 and 5)); 28.2 (q, 2 Me3C (rings 3 and 6)). ESI-MS (CH2Cl2/MeOH 9 :1): 1811 (100,
‡
[M ‡ Na] ), 917 (81, [M ‡ 2 Na]2‡).
{323}-p-Octiphenyl 2 (ˆ2,2',2'',2''',2'''',2''''',2'''''',2'''''''-[[1,1':4',1'':4'',1''':4''',1'''':4'''',1'''''.4''''',1'''''':4'''''',1'''''''-
Octiphenyl-2'',2'''',2'''''',3,3',3''',3''''',3'''''''-octayloctakis(oxy)]octakis[acetic Acid] 01''',01''''-Dibenzyl 01,01',01'',
01''''', 01'''''', 01'''''''-Hexa(tert-butyl) Ester). Compound 2 was prepared from biphenyl 5 in overall eight steps
as described in [7] (Supporting Information).
REFERENCES
[1] N. Sakai, N. Majumdar, S. Matile, J. Am. Chem. Soc. 1999, 121, 4294.
[2] T. W. Green, P. G. M. Wuts, −Protective Groups in Organic Synthesis×, 3rd edn., Wiley, New York, 1999.
[3] N. Sakai, S. Matile, Chem. Commun. 2003, 2514.
[4] G. Das, P. Talukdar, S. Matile, Science (Washington, D.C.) 2002, 298, 1600.
¬
[5] N. Sorde, G. Das, S. Matile, Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 11964.
¬
[6] N. Sakai, N. Sorde, S. Matile, J. Am. Chem. Soc. 2003, 125, 7776.
[7] D. Ronan, Y. Baudry, D. Jeannerat, S. Matile, Org. Lett. 2004, 6, 885.
[8] P. F. H. Schwab, M. D. Levin, J. Michl, Chem. Rev. 1999, 99, 1863.
[9] M. D. Levin, P. Kaszynski, J. Michl, Chem. Rev. 2000, 100, 169.
[10] K. M¸llen, G. Wegner, −Electronic Materials: The Oligomer Approach×, Wiley-VCH, Weinheim, 1998.
[11] M. J. E. Resendiz, J. C. Noveron, H. Disteldorf, S. Fischer, P. J. Stang, Org. Lett. 2004, 6, 651.
[12] Z. H. Li, M. S. Wong, Y. Tao, M. D×Iorio, J. Org. Chem. 2004, 69, 921.
¬
[13] L. O. Peres, F. Guillet, G. Froyer, Org. Biomol. Chem. 2004, 2, 452.
[14] F. Maya, J. M. Tour, Tetrahedron 2004, 60, 81.
[15] B. Li, J. Li, Y. Fu, Z. Bo, J. Am. Chem. Soc. 2004, 126, 3430.
[16] J. J. Michels, M. J. O×Connell, P. N. Taylor, J. S. Wilson, F. Cacialli, H. L. Anderson, Chem. Eur. J. 2003, 9,
6167.
[17] K. Tsubaki, M. Miura, H. Morikawa, H. Tanaka, T. Kawabata, T. Furuta, K. Tanaka, K. Fuji, J. Am. Chem.
Soc. 2003, 125, 16200.
[18] Y. Geng, A. Trajkovska, S. W. Culligan, J. J. Ou, H. M. P. Chen, D. Katsis, S. H. J. Chen, J. Am. Chem. Soc.
2003, 125, 14032.
[19] N. Aratani, H. S. Cho, T. K. Ahn, S. Cho, D. Kim, H. Sumi, A. Osuka, J. Am. Chem. Soc. 2003, 125, 9668.
[20] X. Deng, C. Cai, Tetrahedron Lett. 2003, 44, 815.
[21] M. S. Wong, X. L. Zhang, D. Z. Chen, W. H. Cheung, Chem. Commun. 2003, 138.
[22] O. Deeg, P. Bauerle, Org. Biomol. Chem. 2003, 1, 1609.
[23] J. T. Ernst, O. Kutzki, A. K. Debnath, S. Jiang, H. Lu, A. D. Hamilton, Angew. Chem., Int. Ed. 2002, 41, 278.
[24] X. Deng, A. Mayeux, C. Cai, J. Org. Chem. 2002, 67, 5279.
[25] T. E. O. Screen, J. R. G. Thorne, R. G. Denning, D. G. Bucknall, H. L. Anderson, J. Am. Chem. Soc. 2002,
124, 9712.
[26] K. Fuji, T. Furuta, K. Tanaka, Org. Lett. 2001, 3, 169.
[27] J. R. Nitschke, T. D. Tilley, J. Am. Chem. Soc. 2001, 123, 10183.
[28] I. K. Spiliopoulos, J. A. Mikroyannidis, Macromolecules 2001, 34, 5711.
[29] J. W. Park, M. D. Ediger, M. M. Green, J. Am. Chem. Soc. 2001, 123, 49.
[30] V. Deimede, J. K. Kallitsis, T. Pakula, J. Polym. Sci., Polym. Chem. 2001, 39, 3168.
[31] M. Ciaris, K. G. Gravalos, P. Lianos, Opt. Mater. 2001, 18, 351.
[32] M. W. Read, J. O. Escobedo, D. M. Willis, P. A. Beck, R. M. Strongin, Org. Lett. 2000, 2, 3201.
[33] J. P. Navak, D. L. Feldheim, J. Am. Chem. Soc. 2000, 122, 3979.
[34] S. B. Heidenhain, Y. Sakamoto, T. Suzuki, A. Miura, H. Fujikawa, T. Mori, S. Tokito, Y. Taga, J. Am. Chem.
Soc. 2000, 122, 10240.
[35] B. Schlinke, L. De Cola, P. Belser, V. Balzani, Coord. Chem. Rev. 2000, 208, 267.
[36] V. Hensel, A. D. Schl¸ter, Chem. Eur. J. 1999, 5, 421.
[37] J. M. Kauffman, Synthesis 1999, 6, 918.
[38] P. N. W. Baxter, J.-M. Lehn, G. Baum, D. Fenske, Chem. Eur. J. 1999, 5, 102.
[39] D. Gosztola, M. P. Niemczyk, M. R. Wasielewski, J. Am. Chem. Soc. 1998, 120, 5118.
[40] S. Iijima, Nature (London) 1991, 354, 56.
[41] N. Sakai, D. Gerard, S. Matile, J. Am. Chem. Soc. 2001, 123, 2517.

Helvetica Chimica Acta Vol. 87 (2004)
[42] B. Baumeister, N. Sakai, S. Matile, Org. Lett. 2001, 3, 4229.
2189
[43] F. Robert, J.-Y. Winum, N. Sakai, D. Gerard, S. Matile, Org. Lett. 2000, 2, 37.
[44] N. Sakai, K. C. Brennan, L. A. Weiss, S. Matile, J. Am. Chem. Soc. 1997, 119, 8726.
[45] M. Murata, S. Watanabe, Y. Matsuda, J. Org. Chem. 1997, 62, 6458.
[46] A. Suzuki, J. Organomet. Chem. 1999, 576, 147.
[47] N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457.
[48] S. W. Wright, D. L. Hageman, L. D. McClure, J. Org. Chem. 1994, 59, 6095.
[49] A. F. Littke, C. Dai, G. C. Fu, J. Am. Chem. Soc. 2000, 122, 4020.
[50] J. P. Wolfe, S. L. Buchwald, Angew. Chem., Int. Ed. 1999, 38, 2413.
[51] J. P. Wolfe, R. A. Singer, B. H. Yang, S. L. Buchwald, J. Am. Chem. Soc. 1999, 121, 9550.
[52] J. C. Yoburn, D. L. Van Vranken, Org. Lett. 2003, 5, 2817.
[53] D. Jeannerat, D. Ronan, Y. Baudry, A. Pinto, J.-P. Saulnier, S. Matile, Helv. Chim. Acta 2004, 87, 2190.
Received April 27, 2004