Enantioselective synthesis of binaphthyl polymers using chiral asymmetric phenolic coupling catalysts: Oxidative coupling and tandem glaser/oxidative coupling

Article abstract of DOI:10.1021/jo070636+

(Chemical Equation Presented) A series of functionalized and optically active polybinaphthyls have been synthesized from achiral substrates by asymmetric oxidative phenolic coupling using a chiral 1,5-diaza-cis-decalin copper catalyst. In most cases, a copper tetrafluoroborate catalyst was found to be superior to the copper iodide catalyst, as ortho-iodination of the substrates could be prevented. Three methods for the formation of chiral polymers are described. In the first method, two 2-naphthols linked together at C-6 are subjected to the optimized asymmetric oxidative phenolic coupling conditions to form chiral polynaphthyls. A combination of NMR and HPLC measurements secured the selectivity of the asymmetric coupling. In the second method, substrates containing only one naphthalene were utilized. By incorporating a 2-naphthol and a terminal alkyne, the chiral copper catalysts effect both Glaser-Hay coupling of the alkyne and oxidative asymmetric coupling of the 2-naphthol with remarkable chemoselectivity. The relative reaction rates of various moieties with the chiral catalysts follows the order: benzyl cyanides ? aryl alkynes > electron-rich 2-naphthols > electron-deficient 2-naphthols > alkyl alkynes. Because of high chemoselectivity, this approach is useful for the organized assembly of multifunctional substrates in a single operation. In all cases, no cross-coupling is observed between the alkyne and the 2-naphthol. This approach was thus applied to a set of highly functionalized precursors. In this third case, the biaryl coupling was performed first and a Glaser-Hay coupling was performed in a separate step to generate a highly functionalized polymer. In some cases, the resultant chiral polymers exhibit very large optical rotations.

Full text of DOI:10.1021/jo070636+

Enantioselective Synthesis of Binaphthyl Polymers Using Chiral
Asymmetric Phenolic Coupling Catalysts: Oxidative Coupling and
Tandem Glaser/Oxidative Coupling
Barbara J. Morgan, Xu Xie, Puay-Wah Phuan, and Marisa C. Kozlowski*
Department of Chemistry, Roy and Diana Vagelos Laboratories, UniVersity of PennsylVania,
Philadelphia, PennsylVania 19104
marisa@sas.upenn.edu
ReceiVed April 3, 2007
A series of functionalized and optically active polybinaphthyls have been synthesized from achiral
substrates by asymmetric oxidative phenolic coupling using a chiral 1,5-diaza-cis-decalin copper catalyst.
In most cases, a copper tetrafluoroborate catalyst was found to be superior to the copper iodide catalyst,
as ortho-iodination of the substrates could be prevented. Three methods for the formation of chiral polymers
are described. In the first method, two 2-naphthols linked together at C-6 are subjected to the optimized
asymmetric oxidative phenolic coupling conditions to form chiral polynaphthyls. A combination of NMR
and HPLC measurements secured the selectivity of the asymmetric coupling. In the second method,
substrates containing only one naphthalene were utilized. By incorporating a 2-naphthol and a terminal
alkyne, the chiral copper catalysts effect both Glaser-Hay coupling of the alkyne and oxidative asymmetric
coupling of the 2-naphthol with remarkable chemoselectivity. The relative reaction rates of various moieties
with the chiral catalysts follows the order: benzyl cyanides . aryl alkynes > electron-rich 2-naphthols
> electron-deficient 2-naphthols > alkyl alkynes. Because of high chemoselectivity, this approach is
useful for the organized assembly of multifunctional substrates in a single operation. In all cases, no
cross-coupling is observed between the alkyne and the 2-naphthol. This approach was thus applied to a
set of highly functionalized precursors. In this third case, the biaryl coupling was performed first and a
Glaser-Hay coupling was performed in a separate step to generate a highly functionalized polymer. In
some cases, the resultant chiral polymers exhibit very large optical rotations.
Introduction
version and high doped conductivity.2 The 2,2′-linked polycar-
bonates-polynaphthyls have a stable helical conformation in
solution.3 Optically active polybinaphthyls have also found
utility as catalysts for asymmetric transformations.4 For example,
several of the 3,3′-linked polymers display excellent enantio-
Optically active polybinaphthyls are important chiral materials
with high thermal and configurational stability. Typically, chiral
polynaphthyls are polymerized at 2,2′-, 3,3′-, 4,4′-, and 6,6′-
positions (Figure 1).1 Potential applications for optically active
polybinaphthyls include liquid crystalline materials, optically
nonlinear materials, soluble high-temperature materials, elec-
trochemical sensors, and polarized light emitters. For instance,
the 6,6′-linked poly(arylenevinylene)-polynaphthyls exhibit
higher fluoescence quantum yields relative to the racemic
(2) (a) Hu, Q.; Vitharana, D.; Liu, G.; Jai, V.; Wagaman, M. W.; Zhang,
L.; Lee, T. R.; Pu, L. Macromolecules 1996, 29, 1082-1084. (b) Tsubaki,
K.; Miura, M.; Nakamura, A.; Kawabata, T. Tetrahedron Lett. 2006, 47,
1241-1244.
(3) (a) Hu, Q.; Huang, W.; Vitharana, D.; Zheng, X.; Pu, L. J. Am.
Chem. Soc. 1997, 119, 12454-12464. (b) Pieraccini, S.; Ferrarine, A.; Fuji,
K.; Gottarelli, G.; Lena, S.; Tsubaki, K.; Spada, G. P. Chem. Eur. J. 2006,
12, 1121-1126.
(4) For reviews see: (a) Pu, L. Tetrahedron: Asymmetry 1998, 9, 1457-
1477. (b) Pu, L. Chem. Eur. J. 1999, 5, 2227-2232.
(1) For a review on polynaphthyls, see: Pu, L. Chem. ReV. 1998, 98,
2405-2494.
10.1021/jo070636+ CCC: $37.00 © 2007 American Chemical Society
Published on Web 07/13/2007
J. Org. Chem. 2007, 72, 6171-6182
6171

Morgan et al.
FIGURE 1. Chiral 1,1′-binaphthalene polymers derived from chiral monomers.
selectivity as catalyst in the asymmetric addition of Et2Zn to a
broad range of aldehydes.5 One advantage of the polymer
catalysts is ready recovery and reuse without loss of selectivity.
Because of the importance of chiral binaphthyls, many methods
have been developed for the preparation: condensation of
functionalized binaphthyl monomers,6 the polymerization of
binaphthyls containing olefin groups,7 the ring-opening polym-
erization of binaphthyl carbonates,8 and transition metal-
catalyzed cross-couplings.9 Notably, the majority of the optically
active polybinaphthyls reported have been made by polymeri-
zation of the optically active binaphthyl monomers.10
Because of the important properties that optically active
polybinaphthyls exhibit as well as their successful application
to asymmetric catalysis, the synthesis of binaphthyl polymers
with different functionality and the development of new methods
for more efficient polymerizations are important. The majority
of prior reports of the preparation of chiral binaphthyl polymers
begin with chiral 1,1′-binaphthyl monomers. Previously, we
reported the first enantioselective synthesis of functionalized
chiral polybinaphthyls from achiral starting materials.11 Since
then, other methods have been reported for the asymmetric
(5) (a) Huang, W.; Hu, Q.; Zheng, X.; Anderson, J.; Pu, L. J. Am. Chem.
Soc. 1997, 119, 4313-4314. (b) Hu, Q.; Zheng, X.; Pu, L. J. Org. Chem.
1996, 61, 5200-5201. (c) Huang, W.; Hu, Q.; Pu, L. J. Org. Chem 1998,
63, 1364-1365. (d) Hu, Q.; Huang, W.; Pu, L. J. Org. Chem 1998, 63,
2798-2799. (e) Arai, T.; Hu, Q.; Zheng, X.; Pu, L.; Sasai, H. Org. Lett.
2000, 2, 4261-4263. (f) Yu, H.; Hu, Q.; Pu, L. J. Am. Chem. Soc. 2000,
122, 6500-6501.
(6) (a) Schulz, R. C.; Jung, R. H. Makromol. Chem. 1968, 116, 190-
202. (b) Tamai, Y.; Matsuzaka, Y.; Oi, S.; Miyano, S. Bull. Chem. Soc.
Jpn. 1991, 64, 2260-2265. (c) Mi, Q.; Gao, L.; Ding, M. Macromolecules
1996, 29, 5758-5759.
(7) (a) Kakuchi, T.; Yokota, K. Makromol. Chem. Rapid Commun. 1985,
6, 551-555. (b) Kakuchi, T.; Sasaki, H.; Yokota, K. Makromol. Chem.
1988, 189, 1279-1285. (c) Yokota, K.; Kakuchi, T.; Sasaki, H.; Ohmori,
H. Makromol Chem. 1989, 190, 1269-1275. (d) Yokota, K.; Kakuchi, T.;
Yamamoto, T.; Hasegawa, T.; Haba, O. Makromol. Chem. 1992, 193, 1805-
1813. (e) Kakuchi, T.; Hasegawa, T.; Sasaki, H.; Ohmori, H.; Yamaguchi,
K.; Yokota, K. Makromol. Chem. 1989, 190, 2091-2097. (f) Nakano, T.;
Sogah, D. Y. J. Am. Chem. Soc. 1995, 117, 534-535. (g) Puts, R. D.; Sogah,
D. Y. Macromolecules 1995, 28, 390-392.
(8) (a) Takata, T.; Furusho, Y.; Murakawa, K.-i.; Endo, T.; Matsuoka,
H.; Hirasa, T.; matsuo, J.; Sisido, M. J. Am. Chem. Soc. 1998, 120, 4530-
4531. (b) Tanaka, T.; Matsuoka, H.; Endo, T. Chem. Lett. 1991, 2091-
2094.
(9) (a) Bedworth, P. W.; Tour, J. M. Macromolecules 1994, 27, 622-
624. (b) Hu, Q.; Vitharana, D. R.; Pu, L. In Electrical, Optical, and Magnetic
Properties of Organic Solid State Materials III; Jen, A. K.-Y., Lee, C. Y.-
C., Dalton, L. R., Rubner, M. F., Wnek, G. E., Chiang, L. Y., Eds.; MRS:
Pittsburgh, 1996; p 621. (c) Ma, L.; Hu, Q.-S.; Musick, K.; Vitharana, D.
R.; Wu, C.; Kwan, C. M. S.; Pu, L. Macromolecules 1996, 29, 5083-
5090. (d) Ma, L.; Hu, Q.-S.; Pu, L. Tetrahedron: Asymmetry 1996, 7, 3103-
3106. (e) Cheng, H.; Ma, L.; Hu, Q.; Zheng, X.; Anderson, J.; Pu, L.
Tetrahedron: Asymmetry 1996, 7, 3083-3086. (f) Hu, Q.; Vitharana, D.
R.; Liu, G.; Jain, V.; Pu, L. Macromolecules 1996, 29, 5075-5082. (g)
Huang, W. S.; Hu, Q.-S.; Zheng, X. F.; Anderson, J.; Pu, L. J. Am. Chem.
Soc. 1997, 119, 4313-4314. (h) Song, J.; Cheng, Y.; Chen, L.; Zou, X.;
Zhiliu, W. Eur. Polym. J. 2006, 42, 663-669.
(10) Examples of polymerizations via diastereoselective oxidative biaryl
couplings of chiral BINOL derivatives have been reported: (a) Habaue,
S.; Seko, T.; Okamoto, Y. Macromolecules 2002, 35, 2437-2439. (b)
Habaue, S.; Seko, T.; Isonaga, M.; Ajiro, H.; Okamoto, Y. Polym. J. 2003,
35, 592-597.
6172 J. Org. Chem., Vol. 72, No. 16, 2007

EnantioselectiVe Synthesis of Binaphthyl Polymers
SCHEME 1. Preparation of a 6,6′-Binaphthene-2,2′diol and
Oxidative Polymerization
polymerization of naphthalene units, but most processes resulted
in low to moderate yields and enantioselectivities.12 The
stereoselective polymerization of chiral binaphthalene deriva-
tives as a monomeric unit has also been reported recently, where
the polymerizations proceed under ligand control regardless of
the monomer stereostructure.13 In addition, optically active
polymers have been synthesized in high diastereoselectivity via
second-order asymmetric transformations of chiral oligonaph-
thalene derivatives (from dimer to hexadecamer) as a monomeric
unit.14
Overall, asymmetric C-C bond forming catalysis has proven
efficient for the synthesis of optically active small molecules
but has been utilized less frequently in asymmetric polymeriza-
tions.15 We have developed an efficient method to prepare chiral
1,1′-binaphthols utilizing 1,5-diaza-cis-decalin copper complexes
such as 2 (eq 1) for the oxidative coupling of 2-naphthol
derivatives (eq 2; 85% yield, 93% ee).16 Herein, we disclose
the full results from our investigation of these copper catalysts
in the asymmetric polymerization of achiral 2-naphthol com-
pounds.
both stannylation and cross-coupling are effected.17 With methyl
ester monomer 7 in hand, this material was treated with the
CuCl(OH)TMEDA (9) complex to afford a yellow solid 10
(Table 1, entry 1). Although 10 was not soluble in organic
solvents, the corresponding acid was soluble in basic aqueous
solutions. However, the 1H NMR signals in D2O/NaOD
remained broadened and detailed structural information could
not be obtained. To increase solubility, we turned to the n-hexyl
ester analogue 8 which was prepared in the same manner as 7.
Application of the achiral CuCl(OH)TMEDA catalyst to 8
(Table 1, entry 2) yielded two fractions after column chroma-
tography, 11a and 11b, with different molecular weight distribu-
tions as judged by GPC (Mw ) 4800, Mn ) 3100 vs Mw
)
1
8500, Mn ) 5800). From the H NMR spectra, two sets of
aromatic peaks were identified in both 11a and 11b which
correspond to the internal repeat units and the termini units,
respectively. The number average molecular weights (Mn)
deduced from the NMR integrations correlated with the GPC
data. To achieve a higher degree of polymerization, 8 was treated
with the same catalyst at 80 °C. A jellylike material was
obtained, and the soluble fraction contained only one set of
aromatic peaks, indicating a higher degree of polymerization
(>20:1 internal:terminal).
Results and Discussion
When 8 was subjected to polymerization with the CuI 1,5-
diaza-cis-decalin catalysts (R,R)-2b and (S,S)-2b under similar
conditions, a slight lower molecular weight 11c was obtained
(Table 1, entries 3 and 4). The optical rotations of 11c from the
two enantiomeric catalysts were comparable and of the opposite
sign. Interestingly, the sign of the optical rotation of polymer
(R)-11c (-73) is opposite that of the isolated binaphthyl unit
(R)-4b (+101, eq 1). In other studies, similar phenomenon have
been observed and attributed to the countervailing higher order
structure of the polymeric form.7,18 However, the sign of the
optical rotation of the dimer from 8, (R)-11e (-60) is the same
as that of polymer (R)-11c (-73). We believe that this type of
comparison is more valid, as the polymer end groups are present
in dimer 11e but not in 4b. Thus, the higher order structure in
polymer 11c does not reverse the optical rotation. Unfortunately,
purification of 11c was complicated by the formation of
byproducts. We speculated that these byproducts arose from
Asymmetric Polymerization of Naphthol Dimers. The
polymerization precursors 7 and 8 were efficiently prepared from
the corresponding 6-bromonaphthoate with hexamethylditin and
catalytic Pd(PPh3)4 (Scheme 1). In this novel one-pot procedure,
(11) Xie, X.; Phuan, P.-W.; Kozlowski, M. Angew. Chem., Int. Ed. 2003,
42, 2168-2170.
(12) (a) Habaue, S.; Seko, T.; Okamoto, Y. Macromolecules 2003, 36,
2604-2608. (b) Habaue, S.; Murakami, S.; Higashimura, H. J. Polym.
Sci: Part A: Polym. Chem. 2005, 43, 5872-5878.
(13) Habaue, S.; Ajiro, H.; Yoshii, Y.; Hirasa, T. J. Polym. Sci: Part
A: Polym. Chem. 2004, 42, 4528-4534.
(14) (a) Tsubaki, K.; Miura, M.; Morikawa, H.; Tanaka, H.; Kawabata,
T.; Furuta, T.; Tanaka, K.; Fuji, K. J. Am. Chem. Soc. 2003, 125, 16200-
16201. (b) Tsubaki, K.; Tanaka, H.; Takaishi, K.; Miura, M.; Morikawa,
H.; Furuta, T.; Tanaka, K.; Fuji, K.; Sasamori, T.; Tokitoh, N.; Kawabata,
T. J. Org. Chem. 2006, 71, 6579-6587.
(15) For some examples of asymmetric polymerization: (a) Coates, G.;
Waymouth, R. M. J. Am. Chem. Soc. 1993, 115, 91-98. (b) Brookhart,
M.; Wagner, M. I. J. Am. Chem. Soc. 1994, 116, 3641-3642. (c) Nozaki,
K.; Sato, N.; Tonomura, Y.; Yasutomi, M.; Takaya, H.; Hiyama, T.;
Matsubara, T.; Koga, N. J. Am. Chem. Soc. 1997, 119, 12779-12795. (d)
Kenichi, K.; Itsuno, S.; Ito, K. Chem. Commun. 1999, 35-36. (e) Nozaki,
K.; Kawashima, Y.; Oda, T.; Hiyama, T. Macromolecules 2002, 35, 1140-
1142.
(17) For related biaryl coupling see: (a) Grigg, R.; Teasdale, A.;
Sridharan, V. Tetrahedron Lett. 1991, 32, 3859-3862. (b) Kelly, T. R.;
Li, Q.; Bhushan, V. Tetrahedron Lett. 1990, 31, 161-164.
(18) For similar structural effects with related polybinaphthyls, see: (a)
Wyatt, S. R.; Hu, Q.-S.; Yan, X.-L.; Bare, W. D.; Pu, L. Macromolecules
2001, 34, 7983-7988. (b) Ma, L.; White, P. S.; Lin, W. J. Org. Chem.
2002, 67, 7577-7586.
(16) Li, X.; Yang, J.; Kozlowski, M. C. Org. Lett. 2001, 3, 1137-
1140.
J. Org. Chem, Vol. 72, No. 16, 2007 6173

Morgan et al.
int:term
TABLE 1. Treatment of 7 and 8 with Selected Copper Catalysts (Scheme 1)
catalyst
R1
mol %
no.
time
T (°C)
products
yield, %
Mw
Mn
Mw/Mn
[R]rDt
GPCa
NMR
a
a
a
entry
1
2
Me
n-Hx
9
9
4 d
4 d
40
40
10
11a
11b
(S)n-11c
(R)n-11c
NA
NA
NA
+82
-73
+78
-89
NA
10
37
25
52
50
74
78
28
9
11
7
31
7
4800
8500
2800
2600
10 500
12 300
3100
5800
2200
2100
4900
5400
1.6
1.5
1.3
1.2
2.1
2.3
4.7:1
9.6:1
3.1:1
2.9:1
8.1:1
8.9:1
NA
NA
NA
NA
NA
4.5:1
9:1
3
4
5
6
7
n-Hx
n-Hx
n-Hx
n-Hx
n-Hx
10
10
10
20
10
(R,R)-2b
(S,S)-2b
(R,R)-2d
(S,S)-2d
9
4 d
4 d
5 d
2 d
1 h
40
40
60
80
60
2.3:1
2.4:1
>20:1
>20:1
1:1
2:1
1:2
2:1
1:1
(S)n-11d
(R)n-11d
11e (n ) 1)
11f (n ) 2)
(S)-11e (n ) 1)
(S,S)-11f (n ) 2)
(R)-11e (n ) 1)
(R,R)-11f (n ) 2)
NA
8
9
n-Hx
n-Hx
10
10
(R,R)-2d
(S,S)-2d
1 d
3 h
60
60
+50
+69
-60
-71
NA
2:1
a Measured by gel permeation chromatography (GPC) using a polystyrene standard.
ortho-iodination of 8 by the iodide present in catalyst 2b. As
To determine the degree of asymmetric induction introduced
in these polymerizations, 8 was treated with (S,S)-2d under
milder conditions (Table 1, entry 9) to provide a mixture of
recovered 8 (46%), dimer (R)-11e (n ) 1, 31%), and trimer
(R)-11f (n ) 2, 7%) after chromatography. Similarly, racemic
dimer 11e and trimer 11f were prepared by treating of 8 with
CuCl(OH)TMEDA under milder conditions (Table 1, entry 7).
HPLC analysis (Chiralpak AD) of the corresponding n-hexyl
ethers 12 (Scheme 1) indicated that dimer (R)-11e was formed
with 85% ee which is similar to the selectivity observed for 4b
(87% ee, eq 2). While HPLC resolution of the corresponding
trimer, 11f, was not possible, the 1H NMR spectra of the trimer
permitted assignment of the diastereomeric excess. Different
values were observed for the chemical shifts of the internal
aromatic protons of the diastereomers of 11f (a-d and a′-d′,
Figure 3 and Figure 4). From integration of these signals, a
70-75% diastereomeric excess is measured for the trimer 11f
formed from (S,S)-2d. An 85% ee in each biaryl coupling would
give a 72% de [85.5% (R,R)-11f, 14.0% (S,R)-11f, 0.5% (S,S)-
11f] consistent with this NMR measurement. On this basis, it
appears that each biaryl coupling in the polymerization proceeds
independently with 85% ee and that an optically active polymer
is formed when chiral 2d is employed.
such, we explored other catalysts (2c-e), which do not contain
a halide counterion. Catalysts 2d,e were readily generated from
the chloride precursor 2a via exchange with the corresponding
silver(I) salt (eq 1). It was necessary to carry out the counterion
exchange with the Cu(II) oxidation state, since the Cu(I) adducts
with 1,5-diaza-cis-decalin underwent oxidation when treated
with Ag(I) salts because of Ag(I) f Ag(0) redox chemistry.
The CuOTf, CuBF4, and CuSbF6 complexes 2c-e all catalyze
the dimerization of 3a (eq 2) with enantioselectivity (89-94%
ee) similar to the CuI complex 2b. In addition, the byproducts
observed with 2b were eliminated with 2c-e. The rates with
the different catalysts did vary considerably (Figure 2). Both
the CuOTf and CuSbF6 catalysts were relatively slow. While
the CuBF4 catalyst is slightly slower initially than the CuI
catalyst, the CuBF4 catalyst ultimately forms 4a to a greater
extent since ortho-halogenation does not compete.
FIGURE 2. Rate profiles for catalyst 2b-e (eq 1) in the formation of
4a (eq 2).
With the optimal catalyst in hand, 8 was again subjected to
polymerization (Table 1, entries 5-6). Not only was the yield
(74-78%) of polymerized material (11d) higher, but the degree
of polymerization was also higher (Mw ) 10 500-12 300, Mn
) 4900-5400). The optical rotations of 11d from the two
enantiomeric catalysts again were approximately the same
magnitude but of opposite signs indicating that chiral polymers
were indeed being formed.
FIGURE 3. 1H NMR patterns which allow differentiation of (R,R)-
and (S,S)-11f from (S,R)-11f (see Figure 4).
The CD and UV spectra of the dimers and trimers derived
from 11 are shown in Figures 5 and 6. The UV spectra of the
6174 J. Org. Chem., Vol. 72, No. 16, 2007

EnantioselectiVe Synthesis of Binaphthyl Polymers
FIGURE 4. 1H NMR spectra of the trimer 11f generated from (S,S)-2d and from CuCl(OH)TMEDA (9).
FIGURE 5. UV spectra of 1.7 × 10-4 M (R)-11e, (R,R)-11f, (S)-11e,
FIGURE 6. CD spectra of (R)-11e, (R,R)-11f, (S)-11e, (S,S)-11f, and
(S)n-11d in CH2Cl2 at ambient temperature. 1.7 × 10-4 M except (S)n-
and (S,S)-11f, in CH2Cl2 at ambient temperature.
11d which was 1.7 × 10-5 M.
dimer 11e and trimer 11f are very similar (same maxima and
minima) except for a more intense signal due to the greater
number of naphthalenes18 (Figure 5). The CD spectra of the
enantiomeric dimers (11e) and trimers (11f) show mirror Cotton
effects (Figure 6). Upon generation of dimer (S)-11e and the
trimer (S,S)-11f under the conditions in entry 8 of Table 1,
additional oligomeric material was observed (S)n-11d. The CD
spectra of the polymers 11d from the enantiomeric catalysts
also displayed a mirror Cotton effect except for a more intense
signal.
one set of these linkages is already formed. A more efficient
method for preparing such polymers would be to form both sets
of linkages at the same time from monomers containing two
sites, which react in the presence of copper oxidants. We
proposed monomers 14 and 15 (eq 3, eq 4) as suitable for this
purpose since each compound contains two sites that can react
in the presence of copper oxidants, the alkyne terminus and C1
of the 2-naphthol. The self-reactivity of each site is high and
the cross-reactivity is low, enabling formation of a well-defined
polymer chain. The alkyne containing monomers 14 and 15 are
Tandem Glaser-Hay Coupling and Asymmetric Oxida-
tive Coupling. Typically, the main chain poly-1,1′-binaphthyls
are polymerized via the 2,2′-,5-8 3,3′-,19,4 4,4′-,9a and 6,6′9b-9f
-
(19) (a) Li, C.-J.; Slaven, W. T.; IV.; John, V. T.; Banerjee, S. J. Chem.
Soc., Chem. Commun. 1997, 1569-1570. (b) Li, C.-J.; Wang, D.; Slaven,
W. T., IV. Tetrahedron Lett. 1996, 37, 4459-4462.
positions. In prior reports and the work described above, the
polybinaphthyls are formed from “monomer” units in which
J. Org. Chem, Vol. 72, No. 16, 2007 6175

Morgan et al.
int:ter m
TABLE 2. Treatment of 14-16, 19 with Selected Copper Catalysts
catalyst
entry
SM
mol %
no.
time
T (°C)
products
yield, %
Mw
Mn
Mw/Mn
[R]rDt
GPCa
NMR
1
2
3
4
5
6
7
14
16
14
14
19
15
15
10
20
20
20
10
10
20
9
3 d
2 d
2 d
2 d
2 d
2 d
4 d
rt
16
77
90
80
86
86
61
60
NA
-248
-168
+174
+238
NA
(S,S)-2d
(S,S)-2d
(R,R)-2d
9
80
80
80
80
rt
(R)n-17a
(R)n-17b
(S)n-17b
(S)n-17c
20
12 900
9200
15 100
11 000
4400
4900
6800
5100
2.9
1.9
2.2
2.2
6.4:1
7.3:1
10.5: 1
7.6:1
5.7:1
5.6:1
9.1:1
7.4:1
9
(R,R)-2d
70
(S)n-21
10 300
3900
2.6
-180
6.3:1
NA
a Measured by gel permeation chromatography (GPC) using a polystyrene standard.
SCHEME 2. Sequential and Tandem Glaser-Hay
Coupling/Oxidative Coupling from Alkynyl Naphthol 14
readily prepared from bromonaphthoate 6 (eq 3) and 3-hydroxy-
2-naphthoic acid (eq 4), respectively.
isolate each biaryl coupling site, we infer that a similar level of
enantioselectivity is exercised at each biaryl coupling during
the polymerization resulting in an optically active polymer.
Furthermore, the silyl group of 18 was removed to produce
the terminal alkyne 19 which was subjected to 10 mol % CuCl-
(OH)TMEDA to obtain the polymer 17c with identical optical
rotation as 17b (Scheme 3, Table 2, entry 5). As both the UV
and CD spectra support, the structure of the resultant product
was identical to that of polymer 17 from 14 or 16 (Figure 7
and Figure 8) even though the termini are alkynyl instead of
naphthalenyl. Therefore, we deduce that the one-pot asymmetric
polymerizations from 14 were accomplished with ∼73% ee.
Upon treatment of 14 with 10 mol % of the achiral CuCl-
(OH)TMEDA catalyst at room temperature, the Glaser-Hay
coupling20 was found to occur very rapidly resulting in formation
of bisalkyne 16 in good yield (77%) (Scheme 2, Table 2, entry
1). Further reaction via phenolic coupling was accomplished
by subjecting bisalkyne 16 to 20 mol % (S,S)-2d at 80 °C for
2 d to provide polymer (R)n-17a in 90% yield. When monomer
14 was subjected to these same conditions (Table 2, entry 3),
the material obtained, (R)n-17b, was very similar to the (R)n-
17a obtained from 16 (Table 2, entry 2). Thus, we conclude
that the polymerization occurs via tandem alkynyl and phenolic
couplings. When the enantiomeric (R,R)-2d catalyst was em-
ployed with 14, the enantiomeric polymer (S)n-17b was observed
(Table 2, entry 4). These enantiomeric polymers exhibit
comparable optical rotations of opposite signs (-168 and 174),
which are only slightly lower than that of 17a (-248).
The UV and CD spectra of polymer 17 generated from 14 or
16 were identical (Figure 7 and Figure 8), indicating that catalyst
2d can effect both the alkynyl and phenolic coupling cleanly.
No cross-coupling and no interference by alkynyl copper
intermediates on the stereochemical course of the biaryl coupling
was observed.
In order to determine the stereochemical fidelity in the
polymerization of 14 to 17, silylated substrate 13 was examined
in the oxidative biaryl coupling (Scheme 3). With the same
CuBF4 catalyst used in the polymerizations, 18 was obtained
with 73% ee. Since the alkyne spacer units of 16 essentially
FIGURE 7. UV spectra of 2 × 10-5 M 9 in CH2Cl2at ambient
(20) For, a review see: Siemsen, P.; Livingston, R. C.; Diederich, R.
F. Angew. Chem., Int. Ed. 2000, 39, 2632-2657.
temperature.
6176 J. Org. Chem., Vol. 72, No. 16, 2007

EnantioselectiVe Synthesis of Binaphthyl Polymers
SCHEME 4. Tandem Oxidative Coupling/Glaser-Hay
Coupling to Generate Polynaphthols with 1,1′- and
3.3′-Linkages 4. Synthesis of a Highly Functionalized
Naphthol
FIGURE 8. CD spectra of 2 × 10-5 M 9 in CH2Cl2at ambient
temperature.
SCHEME 3. Stepwise Oxidative Coupling and Glaser-Hay
Coupling from Alkynyl Naphthol 13
the optical rotation of polymer (S)-21 is negative while the
optical rotation of the related polymer (S)-17 (Scheme 3) is
positive (Table 2). Even though both compounds possess the
same binaphthol configurations, as they were prepared from the
same chiral catalyst, the overall polymer architectures are
substantially different.
The CD and UV spectra of the dimer and oligomers derived
from 15 are shown in Figures 9 and 10. The spectra of the dimer
(S)1-21 and oligomer (S)n-21 are very similar (same maxima
and minima) except for a more intense signal due to the greater
number of naphthalenes, indicating no higher order structure.
Surprisingly, when the other alkyne monomer 15, with the
alkyne attached via C3 ester instead of the directly to the
naphthalene as in 14, was subjected to the same conditions (10
mol % CuCl(OH)TMEDA), the phenolic coupling occurred first
to provide the biaryl coupling product 20 (61%) along with
recovering starting material (15%) (Scheme 4, Table 2, entry
6). From this experiment we conclude that the rate of Glaser-
Hay coupling for aryl-substituted alkynes is greater than that
of alkyl-substituted alkynes and the rate of oxidative phenolic
coupling of 3-carboxy-2-naphthols is intermediate to these two
rates. Regardless of the relative rates, the chemoselectivity of
each coupling is remarkably high and to date we have not
observed any of the cross-coupled materials. The polymer of
the alkynyl ester monomer 15, (S)-21, could be prepared directly
by subjecting monomer 15 to 20 mol % (R,R)-2d under more
forcing conditions (Scheme 4, Table 2, entry 7). Interestingly,
FIGURE 9. UV spectra of 2 × 10-5 M (S)1-21 and (S)n-21 in CH2Cl2
at ambient temperature.
Tandem Strategy with Highly Functionalized Substrates.
In further work, we studied whether a similar strategy could
be executed to generate highly functionalized versions of these
polymers. To this end, 7-bromonaphthalene 25 was efficiently
prepared from the corresponding phenyl acetic acid (Scheme
5).21
(21) Mulrooney, C. A.; Xiaolin, L.; DiVirgilio, E. S.; Kozlowski, M.
C. J. Am. Chem. Soc. 2003, 125, 6856-6857.
J. Org. Chem, Vol. 72, No. 16, 2007 6177

Morgan et al.
SCHEME 7. Formation of a Chiral 1,1′-Binaphthalene with
7,7′-Cross-Linking Groups
FIGURE 10. CD spectra of 2 × 10-5 M (S)1-21 and (S)n-21 in CH2-
Cl2 at ambient temperature.
SCHEME 8. Glaser-Hay Coupling To Generate
Polynaphthols with 1,1′- and 7,7′-Linkages
SCHEME 5. Synthesis of a Highly Functionalized Naphthol
SCHEME 6. Tandem Oxidative Coupling/Glaser-Hay
Coupling to Generate Polynaphthols with 1,1′- and
7,7′-linkages
to the achiral and chiral copper catalysts to afford racemic 30
and (R)-30, respectively (Scheme 7). Though previously the
CuBF4 catalyst was found to be more reactive and as selective
as the CuI catalyst, the same reactivity pattern did not follow
for this substrate. The enantioselective coupling of the highly
functionalized naphthol using the CuI catalyst gave 85% yield
and 82% ee as compared to 35% yield and 64% ee with the
CuBF4 catalyst. In a one-pot sequence after coupling, the alkynyl
silyl group was cleaved, the phenolic acetates were hydrolyzed,
and the phenols were methylated to furnish polymerization
precursor 32 (Scheme 7).
Upon treatment of 32 with the CuCl‚TMEDA catalyst (9),
the polymerization was affected by the Glaser-Hay coupling
of terminal aryl alkynes (Scheme 8). In order to isolate lower
molecular weight polymers, the polymerization of the racemic
biaryl was stopped after 17 h, and the resultant materials were
characterized.
Precursor 27 was synthesized from 25 via Sonagashira
coupling, silyl deprotection, and selective C2-acetate cleavage
(Scheme 6). Initial attempts to affect the oxidative biaryl
coupling in tandem with Glaser-Hay coupling produced 28 as
an insoluble, yellow precipitate.
Because of the intractable nature of 28, the two copper-
catalyzed procedures were undertaken in a stepwise manner.
Since solubilization was planned by alkylation of the phenols,
the biaryl coupling was undertaken first, as the free phenol is
need for this oxidative coupling. Thus, the protected alkyne 29,
which cannot undergo the Glaser-Hay coupling, was subjected
The number-average molecular weights Mn from integration
of the NMR signals for the terminal alkynes and the methyl
ethers correlate with the data from matrix-assisted laser desorp-
tion ionization time-of-flight (MALDI-TOF) spectrometry analy-
sis (Table 3), indicating that cyclic species are not predominant.
To achieve a higher degree of polymerization, (R)-32 was
subjected to the copper catalyst for 4 d. Because of the
broadening of the signals as the polymer size increased, an
accurate weight could not be determined for the chiral polymers
(R)-33d and (R)-33e from NMR integration, but the Mn was
established using MALDI-TOF (Table 3). MALDI-TOF was
6178 J. Org. Chem., Vol. 72, No. 16, 2007

EnantioselectiVe Synthesis of Binaphthyl Polymers
TABLE 3. Materials Obtained from Glaser-Hay Reaction of 32 and (R)-32
entry
product
yield (%)
Mn (NMR)
Mn (GPC)a
Mw/Mn (GPC)
Mn (MALDI)
[R]2D0
1
2
3
4
5
dimer 33a
trimer 33b
tetramer 33c
(R)-33d
15
5
32
38
45
1195
1792
2388
710
1160
1780
2390
6770
1.1
1.1
1.3
1.6
1.6
1219 (MNa+)
1887 (MNa+‚THF)
2387
3623 (MK+)
7786 (MNa+)
-708
-1135
(R)-33e
a Measured by gel permeation chromatography (GPC) using a polystyrene standard.
FIGURE 11. UV spectra of 5 µM (R)-30, 32, (R)-33d, (R)-33e in
THF at ambient temperature.
FIGURE 13. Concentration dependence in the CD spectra in THF at
ambient temperature: (a) (R)-33d; (b) (R)-33e.
notable feature in going from the binaphthols to the chiral
polymers is a shift in the longer wavelength region from 320
nm to 355/380 nm. These same differences are observed in the
CD spectra (Figure 12). Under dilute conditions (5 µM), the
CD spectra of chiral polymers (R)-33d and (R)-33e are identical
except for their intensity due to the greater number of binaphthyl
units in (R)-33e. Furthermore, the CD spectra of the shorter
polymer (R)-33d (6 binaphthol units) exhibit a linear dependence
upon concentration (Figure 13a). However, the CD spectra of
the longer polymer (R)-33e (13 binaphthol units) vary nonlin-
early with concentration (Figure 13b). In particular, the negative
Cotton effects at 355 and 380 nm decrease as the concentration
increases. Also, at 310 nm there is a switch from a positive
Cotton effect at 5 µM to a negative Cotton effect at 10 and 25
µM. These data indicate additional structuring at higher
concentrations that is consistent with aggregation of the longer
polymer (R)-33e under these conditions.
FIGURE 12. CD spectra of (R)-30, (R)-33d, (R)-33e in THFat ambient
temperature.
accurate with the racemic polymers, and the chiral MALDI-
TOF data correlated with the GPC data in the same manner as
the racemic polymers.
To our surprise, the functionalized chiral polymers (R)-33d
and (R)-33e gave much higher optical rotations (Table 3) in
comparison to the unfunctionalized polymers described in the
preceding sections. On a per binaphthyl basis, the optical
rotations are also much higher than that of the corresponding
binaphthyl monomer (R)-30 ([R]2D0 -40.0) indicating some
type of higher order structure. To investigate this possibility
further, the UV and CD spectra were measured. The UV spectra
(Figure 11) of the binaphthols (R)-30 and 32 are similar as are
those of the chiral polymers (R)-33d and (R)-33e. The most
J. Org. Chem, Vol. 72, No. 16, 2007 6179

Morgan et al.
Polymer (S)n-11d. To a mixture of 8 (0.054 g, 0.10 mmol) in
ClCH2CH2Cl (2 mL) and DMF (0.05 mL) was added the CuBF4·
(R,R)-1,5-diaza-cis-decalin catalyst (0.006 g, 0.02 mmol). The
resultant solution was stirred at 60 °C for 5 d and then cooled to
room temperature. After removal of the solvent, the resultant solid
was washed with MeOH to remove the catalyst. The dried solid
was dissolved in CH2Cl2 and precipitated with MeOH. This
procedure was repeated three times. After removal of trace solvent
in Vacuo, the remaining material consisted of 11d which was
obtained as a yellow solid in 74% (0.040 g) yield: [R]rDt +78 (c
0.13, CH2Cl2); GPC (THF, polystyrene standard) Mw ) 10 600,
Mn ) 4900 (PDI ) 2.2); UV-vis(CH2Cl2) λmax 325 nm; 1H NMR
and 13C NMR spectra are similar to those of 11a.
Dimer 11e and Trimer 11f. These materials were obtained by
halting the reaction prior to completion. To a mixture of 8 (0.054
g, 0.10 mmol) in ClCH2CH2Cl (2 mL) was added CuCl(OH)-
TMEDA (0.046 g, 0.02 mmol). The resultant mixture was stirred
at 60 °C for 1 h. After removal of the solvent, the residue was
chromatographed (50-80% CH2Cl2/hexanes) which provided re-
covered 8 (0.022 g, 41%), 11e (0.015 g, 28%), and 11f (0.005 g,
9%).
Dimer 11e. 1H NMR (500 MHz, CDCl3) δ 0.91-0.97 (m, 12H),
1.25-1.54 (m, 24H), 1.85-1.90 (m, 8H), 4.42-4.51 (m, 8H),
7.33-7.35 (m, 4H), 7.74 (dd, J ) 8.9, 1.8 Hz, 2H), 7.79 (d, J )
8.7 Hz, 2H), 7.87 (dd, J ) 8.7, 1.8 Hz, 2H), 8.09 (s, 2H), 8.25 (d,
J ) 1.4 Hz, 2H), 8.55 (s, 2H), 8.79 (s, 2H), 10.58 (s, 2H), 10.92
(s, 2H); 13C NMR (125 MHz, CDCl3) δ 14.0, 14.1, 22.5, 22.6,
25.6, 25.7, 28.5, 28.6, 31.4, 31.5, 66.0, 66.2, 111.6, 114.8, 114.9,
116.8, 125.5, 126.9, 127.0, 127.3, 127.5, 128.7, 129.0, 132.5, 132.9,
135.3, 135.8, 136.1, 136.3, 137.0, 154.4, 156.5, 169.8, 170.1; IR
(film) 3206, 2929, 1677 cm-1; Elemental analysis (C68H74O12) calcd
C 75.39, H 6.89, found C 75.85, H 7.27.
Trimer 11f. 1H NMR (500 MHz, CDCl3) δ 0.92-0.95 (m, 18H),
1.38-1.53 (m, 36H), 1.85-1.89 (m, 12H), 4.42-4.50 (m, 12H),
7.31-7.34 (m, 6H), 7.70-7.74 (m, 4H), 7.78 (d, J ) 8.7 Hz, 2H),
7.86 (dd, J ) 8.7, 1.7 Hz, 2H), 8.08 (s, 2H), 8.22 (d, J ) 1.7 Hz,
1H), 8.23 (d, J ) 1.7 Hz, 1H), 8.24 (d, J ) 1.5 Hz, 2H), 8.54 (s,
2H), 8.76 (s, 1H), 8.77 (s, 1H), 8.78 (s, 2H), 10.57 (s, 2H), 10.90
(s, 4H); 13C NMR (125 MHz, CDCl3) δ 13.99, 14.02, 22.52, 22.56,
25.66, 25.70, 28.56, 28.62, 31.44, 31.48, 66.00, 66.18, 111.6, 115.0
(2C), 116.9, 125.4, 126.9, 127.0, 127.3, 127,5, 128.7, 129.0, 129.1,
132.5, 133.0, 136.0, 136.1, 136.3, 136.8, 154.5, 156.7, 169.9, 170.2;
IR (film) 3206, 2929, 1677 cm-1; Elemental analysis (C102H110O18)
calcd C 75.44, H 6.83, found C 75.63, H 7.19.
Concluding Remarks
In conclusion, we report the full results from the first
enantioselective approach to functionalized chiral polybinaph-
thyls from achiral starting materials. Chiral copper catalysts
effect enantioselective oxidative biaryl coupling and tandem
Glaser-Hay/enantioselective oxidative biaryl coupling of 2-naph-
thols. Since the functional group tolerance is high,22 a large
number of structures are accessible using this method. This
concept was demonstrated with the synthesis of highly func-
tionalized polybinaphthyls. The CD and UV spectra of the
functionalized polybinaphthyls support the formation of chiral
polybinaphthyls, with different linking units giving rise to
different overall structures. The relative reaction rates of various
substrates with the chiral catalysts follows the order: benzyl
cyanides23 . aryl alkynes20 > electron-rich 2-naphthols >
electron-deficient 2-naphthols > alkyl alkynes.20 Since the
chemoselectivity of each coupling is remarkably high, substrates
can be selected which assemble in a defined order under a single
set of reaction conditions exposing selected terminal groups,
allowing selective cross-linking, or generating more complex
architectures.
Experimental Section
For general procedures as well as preparation of catalysts and
monomers, see the Supporting Information.
Poly(dihexyl 6,6′-dihydroxy-2,2′-binaphthalene-7,7′-dicar-
boxylate (11a and 11b). A mixture of 8 (0.108 g, 0.2 mmol) and
CuCl(OH)TMEDA (0.005 g, 0.02 mmol) in CH2Cl2 (2 mL) was
stirred at 40 °C under O2 for 5 d. The mixture was concentrated to
give a brown solid which was washed with MeOH and then
chromatographed (CH2Cl2) to give 11a (0.04 g) in 37% yield as
yellow crystals. The silica gel from the column was then extracted
with CH2Cl2 and concentrated to give 11b (0.027 g) in 25% yield
as orange crystals. 11a: GPC (THF, polystyrene standard) Mw
)
4,800, Mn ) 3,100, PDI ) 1.6; 1H NMR (500 MHz, CDCl3, 4.5:1
of two sets of peaks) δ1(internal) 0.91-0.95 (m, 6H), 1.41-1.54
(m, 12H), 1.85-1.90 (m, 4H), 4.44-4.47 (m, 4H), 7.31-7.34 (m,
2H), 7.69-7.73 (m, 2H), 8.19-8.24 (m, 2H), 8.75-8.77 (m, 2H),
10.88-10.90 (m, 2H); δ2(terminal) 0.91-0.95 (m, 6H), 1.41-1.54
(m, 12H), 1.85-1.90 (m, 4H), 4.09 (br, 4H), 7.34 (s, 2H), 7.79 (d,
J ) 8.6 Hz, 2H), 7.87 (d, J ) 8.2 Hz, 2H), 8.10 (s, 2H), 8.56 (s,
2H) 10.57 (s, 2H); 13C NMR (125 MHz, CDCl3) δ1(internal)14.0,
22.53, 25.67, 28.59, 31.43, 66.12, 115.0, 116.9, 125.4, 126.8, 127.5,
129.0, 133.0, 136.0, 136.3, 154.5, 170.1; δ2(terminal) 13.96, 22.50,
25.64, 28.54, 31.40, 65.95, 115.0, 111.6, 127.0, 127.3, 127.5,
128.95, 132.5, 135.95, 137.0, 156.7, 169.9; IR (film) 3206, 2929,
1677 cm-1; Elemental analysis (C34H38O6) calcd C 75.25, H 7.06,
found C 75.44, H 6.92. 11b: GPC (THF, polystyrene standard)
Mw ) 8500, Mn ) 5800, PDI ) 1.5; 1H NMR and 13C NMR spectra
are similar to those of 11a.
Dimer (R)-11e and Trimer (R,R)-11f. These materials were
obtained by halting the reaction prior to completion. To a mixture
of 8 (0.054 g, 0.1 mmol) in ClCH2CH2Cl (2 mL) and DMF (0.05
mL) was added the CuBF4·(S,S)-1,5-diaza-cis-decalin catalyst (0.006
g, 0.02 mmol). The resultant mixture was stirred at 60 °C for 3 h.
After removal of the solvent, the residue was chromatographed (50-
80% CH2Cl2/hexanes) which provided recovered 8 (0.025 g, 46%),
11e (0.017 g, 31%), and 11f (0.004 g, 7%).
Dimer (R)-11e. [R]Drt -60 (c 0.05, CH2Cl2); UV-vis (CH2Cl2)
1
λ
max270 nm; H NMR spectrum is the same as that of 11e (see
Polymer (S)n-11c. To a mixture of 8 (0.054 g, 0.10 mmol) in
CH2Cl2 (1 mL) was added the CuI·(R,R)-1,5-diaza-cis-decalin
catalyst (0.003 g, 0.01 mmol). After being stirred at 40 °C under
O2 for 4 d, the mixture was concentrated to give a brown solid
which was washed with MeOH. Chromatography (7.5% EtOAc/
hexanes, then CH2Cl2) provided (S)-11c (0.028 g) in 52% yield as
yellow crystals: [R]rDt +82 (c 1.4, CHCl3); GPC (THF, polysty-
above).
Trimer (R,R)-11f. [R]rt -71 (c 0.095, CH2Cl2); UV-vis (CH2-
Cl2) λmax 270 nm; 1H NMDR δ 0.92-0.95 (m, 18H), 1.38-1.53 (m,
36H), 1.85-1.89 (m, 12H), 4.42-4.50 (m, 12H), 7.27-7.34 (m,
6H), 7.70-7.74 (m, 4H), 7.78 (d, J ) 8.7 Hz, 2H), 7.86 (dd, J )
8.7, 1.8 Hz, 2H), 8.08 (s, 2H), 8.22 (d, J ) 1.7 Hz, 0.3H), 8.23 (d,
J ) 1,7 Hz, 1.7H), 8.24 (d, J ) 1.7 Hz, 2H), 8.54 (s, 2H), 8.76 (s,
0.5H), 8.77 (s, 1.5H), 8.78 (s, 2H), 10.57 (s, 2H), 10.90 (s, 4H).
(R)n-17a from Glaser Coupled Bisalkyne 16. To a mixture of
16 (0.059 g, 0.1 mmol) in ClCH2CH2Cl (2 mL) and DMF (0.05
mL) was added the CuBF4·(S,S)-1,5-diaza-cis-decalin catalyst (0.012
g, 0.04 mmol). The resultant mixture was stirred at 80 °C for 2 d.
After removal of the solvent, the residue was chromatographed
(10% MeOH/CH2Cl2) to yield a solid which was precipitated with
1
rene standard) Mw ) 2800, Mn ) 2200, PDI ) 1.3); H NMR
spectrum is similar to that of 11a.
(22) Xiaolin, L.; Hewgley, J. B.; Mulrooney, C. A.; Yang, J.; Kozlowski,
M. C. J. Org. Chem 2003, 68, 5500-5511.
(23) Our copper complex 2b catalyzes the benyzl cyanide couplings
described by de Jongh in ∼5 min at -78 °C: de Jongh, H. A. P.; de Jongh,
R. H. I.; Mijs, W. J. J. Org. Chem. 1971, 36, 3160-3168.
6180 J. Org. Chem., Vol. 72, No. 16, 2007

EnantioselectiVe Synthesis of Binaphthyl Polymers
MeOH to afford (R)n-17a as a yellow solid in 90% yield: [R]rt
10.64 (s, 2H); 13C NMR (125 MHz, CDCl3) δ 169.6, 169.2, 156.5,
153.0, 147.7, 132.3, 131.0, 122.6, 119.2, 115.1, 108.8, 102.1, 100.7,
100.5, 56.2, 53.5, 21.3, 0.2; HRMS (ESI) calcd for C40H42O12Si2
(MNa+) 793.2100, found 793.2098; CSP HPLC (Chiralpak AD,
1.0 mL/min, 90:10 hexanes:i-PrOH) tR(R)) 8.1 min, tR(S))12.5
min; 82% ee.
Dimethyl 1,1′,3,3′,7,7′-Hexamethoxy-6,6′-diethynyl-1,1′-bi-
naphthalene-2,2′-dicarboxylate (32). To a solution of 30 in THF
(4 mL) was added TBAF (0.34 mL, 0.34 mmol). After being stirred
for 15 min at room temperature under argon, the solvent was
evaporated in vacuo. The resultant brown solid was dissolved in
EtOAc and washed with brine. The organics were dried, and the
solvent was evaporated in vacuo. The yellow solid, 31, was carried
on to the next step without further purification.
D
)
-248 (c 0.1, CH2Cl2); GPC (THF, polystyrene standard) Mw
1
12 900, Mn ) 4400, PDI ) 2.9; H NMR (500 MHz, CDCl3, 6:1
ratio of two sets of peaks) δ1(internal) 0.89-0.96 (m, 6H), 1.30-
1.52 (m, 12H), 1.84-1.89 (m, 4H), 4.42-4.47 (m, 4H), 7.10 (d, J
) 8.9 Hz, 2H), 7.40 (d, J ) 8.6 Hz, 2H), 8.14 (s, 2H), 8.63 (s,
2H), 10.98 (s, 2H); δ2(terminal) 7.29 (s, 2H), 7.54 (d, J ) 8.6 Hz,
2H), 7.64 (d, J ) 8.5 Hz, 2H), 8.05 (s, 2H), 8.44 (s, 2H), 10.68 (s,
2H); 13C NMR (125 MHz, CDCl3) δ1(internal)14.0, 22.5, 25.6, 28.5,
31.4, 66.3, 74.5, 81.8, 115.3, 116.8, 117.2, 124.9, 126.6, 131.8,
132.8, 134.8, 136.7, 155.5, 169.8; small peaks from the termini
were observed at δ2(terminal)66.1, 74.4, 81.8, 112.0, 117.0, 124.8,
126.4, 126.7, 131.4, 132.2, 134.3, 137.5, 155.7, 169.6; IR (film)
2929, 1680 cm-1; Elemental analysis (C38H38O6) calcd C 77.27, H
6.48, found C 75.69, H 5.06.
To a solution of 31 in DMF (5 mL) were added NaH (60% in
oil, 100 mg, 2.4 mmol) and MeI (0.35 mL, 5.1 mmol). After being
stirred for 4 h at room temperature under argon, the mixture was
quenched with 1 N HCl. The aqueous phase was extracted with
EtOAc, and the combined organics were washed with 1 N HCl (3
× 20 mL) and brine (2 × 20 mL). The organics were dried (Na2-
SO4), and after the solvent was evaporated, the residue was
chromatographed (50% EtOAc/hexanes) to give 32 as a clear resin
(95 mg) in 95% yield over the three steps: Rf ) 0.43 (50% EtOAc/
hexanes); IR (thin film) 3285, 2945, 2926, 2853, 2108, 1733, 1590
(R)n-17b from Monomer 14. To a mixture of 14 (0.059 g, 0.2
mmol) in ClCH2CH2Cl (2 mL) and DMF (0.05 mL) was added the
CuBF4·(S,S)-1,5-diaza-cis-decalin catalyst (0.012 g, 0.04 mmol). The
resultant mixture was stirred at 80 °C for 2 d. After removal of the
solvent, the residue was chromatographed (10% MeOH/CH2Cl2)
to yield a solid which was precipitated with MeOH to afford 17b
as a yellow solid in 80% yield: [R]rDt -168 (c 0.1, CH2Cl2); GPC
(THF, polystyrene standard) Mw ) 9200, Mn) 4900, PDI ) 1.9;
1H NMR and 13C NMR are similar to those of (R)n-17a obtained
from bisalkyne 16.
1
cm-1; H NMR (500 MHz, CDCl3) δ 3.26 (s, 2H), 3.35 (s, 6H),
3.99 (s, 6H), 4.04 (s, 6H), 4.14 (s, 6H), 7.30 (s, 2H), 7.48 (s, 2H);
13C NMR (125 MHz, CDCl3) δ 167.1, 157.4, 153.6, 152.2, 132.5,
129.8, 126.2, 121.8, 119.6, 115.4, 101.1, 82.8, 79.9, 62.9, 62.3,
56.3, 53.0; HRMS (ESI) calcd for C34H30O10 (MNa+) 621.1700,
found 621.2802.
(S)n-17c from Dimer (S)-19. To a solution of 19 (59 mg, 0.1
mmol) in ClCH2CH2Cl (2 mL) was added CuCl(OH)TMEDA (2
mg, 0.01 mmol). The resultant mixture was stirred at 80 °C under
O2 for 2 d. After removal of the solvent, the residue was precipitated
17c as a yellow resin (51 mg) in 86% yield: [R]rDt 238 (c 0.08,
CH2Cl2); GPC (THF, polystyrene standard) Mw ) 11 000, Mn )
(R)-Dimethyl 1,1′,3,3′,7,7′-Hexamethoxy-6,6′-diethynyl-1,1′-
binaphthalene-2,2′-dicarboxylate ((R)-32). (R)-31 was prepared
in the same manner as 31 above and was obtained as a yellow
solid and carried on to the next step without further purification.
(R)-32 was prepared in the same way as 32 and was obtained as
1
5100, PDI ) 2.2; H NMR (500 MHz, CDCl3) δ 0.93-0.96 (m,
6H), 1.40-1.52 (m, 12H), 1.85-1.90 (m, 4H), 4.45-4.48 (m, 4H),
7.10 (d, J ) 8.8 Hz, 2H), 7.39 (d, J ) 9.0 Hz, 2H), 8.16 (s, 2H),
8.62 (s, 2H), 10.96 (m, 2H); 13C NMR (125 MHz, CDCl3) δ14.0,
22.5, 25.7, 28.6, 31.4, 66.3, 74.5, 81.9, 115.3, 116.9, 117.3, 124.9,
126.6, 131.8, 132.8, 134.8, 136.7, 155.5, 169.8; Elemental analysis
(C38H36O6) calcd C 77.53, H 6.16, found C 76.35, H 5.87.
1
a clear resin in 95% yield. H NMR and 13C NMR are similar to
those of 32.
Dimer 33a, Trimer 33b, and Tetramer 33c. These materials
were obtained by halting the reaction prior to completion. To a
mixture of 32 (0.095 g, 0.16 mmol) in CH2Cl2 (5 mL) was added
CuCl(OH)TMEDA (0.008 g, 0.032 mmol). The resultant mixture
was stirred at room temperature for 17 h under an oxygen
atmosphere. The reaction was quenched with 1 N HCl, and the
aqueous phase was extracted with CH2Cl2. The organics were dried
(Na2SO4), and after the solvent was evaporated, the residue was
chromatographed (50-80% EtOAc/hexanes) to yield 33a (0.015
g, 16%), 33b (0.005 g, 5%), and 33c (0.030 g, 32%).
(S)-21. To a mixture of 15 (0.120 g, 0.45 mmol) in 1,2-
dichloroethane (4 mL) and DMF (0.05 mL) was added catalyst
(R,R)-2d. After being stirred at 70 °C for 4 d under O2, the mixture
was cooled and concentrated. The residue was washed with MeOH
to remove the catalyst, and the residual solvent was removed in
vacuo. The resultant solid was dissolved in CH2Cl2 and precipitated
with MeOH. This procedure was repeated three times to provide
an orange solid (0.072 g) in 60% yield: [R]rDt -180 (c 0.05, CH2-
Cl2); GPC (THF, polystyrene standard) Mw )10 300, Mn ) 3900,
Dimer 33a. Rf ) 0.08 (50% EtOAc/hexanes); Mn,NMR ) 1195,
1
1
Mn,GPC ) 710, Mw/Mn ) 1.1, Mn,MALDi-TOF ) 1219(MNa+); H
PDI ) 2.6; H NMR (500 MHz, CDCl3) δ 1.76-1.78 (m, 2H),
2.00 (br, 2H), 2.40-2.41 (m, 2H), 4.46 (br, 2H), 7.25-7.16 (m,
1H), 7.31 (br, 2H), 7.93 (br, 1H), 8.67 (s, 1H), 10.75 (s, 1H); 13C
NMR (125 MHz, CDCl3) δ 18.9, 24.9, 27.7, 65.3, 66.0, 76.9, 114.2,
117.0, 123.9, 124.7, 127.2, 129.4, 132.7, 137.2, 154.1, 170.1; IR
(CHCl3 solution) 1678, 1280 cm-1; Elemental analysis (C34H30O6)
calcd C 76.67, H 5.30, found C 73.40, H 5.04.
NMR (500 MHz, CDCl3) δ 3.23 (s, 2H), 3.34 (s, 6H), 3.36 (s,
6H), 3.98 (s, 6H), 3.99 (s, 12H), 4.04 (s, 6H), 4.12 (s, 6H), 4.15 (s,
6H), 7.26 (s, 2H), 7.28 (s, 2H), 7.43 (s, 2H), 7. 48 (s, 2H); 13C
NMR (125 MHz, CDCl3) δ 166.8, 166.7, 157.5, 157.2, 153.5, 153.3,
152.0, 151.9, 132.9, 132.1, 129.6, 129.5, 126.1, 126.0, 121.6, 119.3,
119.2, 115.2, 114.9, 100.9, 100.7, 82.4, 79.7, 79.0, 78.7, 62.7, 62.6,
62.0, 61.9, 56.1, 56.0, 52.7, 52.6; IR (film) 3277, 2926, 2853, 2212,
1733, 1590 cm-1
(R)-Dimethyl 1,1′-Diacetoxy-3,3′-dihydroxy-7,7′-dimethoxy-
6,6′-(di-2-(trimethylsilyl)ethynyl)-1,1′-binaphthalene-2,2′-dicar-
boxylate ((R)-30). To a solution of 29 (200 mg, 0.52 mmol) in
CH2Cl2 (3 mL) and ClCH2CH2Cl (2 mL) was added the CuI·(S,S)-
1,5-diaza-cis-decalin catalyst (36 mg, 0.10 mmol). After being
stirred for 3 d under oxygen, the solution was quenched with 1 N
HCl. The aqueous phase was extracted with CH2Cl2, the organics
were washed with brine and dried (Na2SO4), and the solvent was
evaporated in vacuo. The resultant resin was chromatographed (60%
EtOAc/hexanes) to give (R)-30 (170 mg) as a yellow solid in 85%
Trimer 33b. Rf ) 0.17 (2.5% MeOH/CH2Cl2); Mn,NMR ) 1792,
Mn,GPC ) 1160, Mw/Mn ) 1.1, Mn,MALDi-TOF ) 1887(MNa+‚THF);
1H NMR (500 MHz, CDCl3) δ 3.23 (br s, 2H), 3.33 (s, 6H), 3.35
(s, 3H), 3.34 (s, 3H), 3.35 (s, 6H), 3.97 (s, 6H), 3.98 (s, 6H), 3.99
(s, 18H), 4.03 (s, 3H), 4.04 (s, 3H), 4.12 (s, 6H), 4.13 (s, 6H), 4.14
(s, 6H), 7.23 (s, 2H), 7.25 (s, 1H), 7.25 (s, 1H), 7.28 (s, 2H), 7.42
(s, 2H), 7.43 (s, 2H), 7. 48 (s, 2H); 13C NMR (125 MHz, CDCl3)
δ 166.8, 166.7, 166.6, 157.5, 157.4, 157.2, 153.4, 153.3, 152.0,
151.9, 132.9, 132.8, 132.1, 129.6, 129.5, 126.2, 126.0, 121.6, 119.3,
119.2, 115.2, 115.0, 114.9, 100.9, 100.8, 82.4, 79.7, 79.1, 79.0,
78.7, 78.6, 62.7, 62.6, 62.0, 61.9, 56.0, 55.9, 52.7, 52.6; IR (film)
3296, 2961, 2926, 2853, 2212, 1729, 1590 cm-1
yield: Rf ) 0.31 (50% EtOAc/hexanes); mp 254-257 °C; [R]20
D
-40.0;I R (thin film) 3177, 2961, 2922, 2853, 2154, 1776, 1675,
1
1621, 1571 cm-1; H NMR (500 MHz, CDCl3) δ 0.08 (s, 18H),
2.54 (s, 6H), 3.96 (s, 6H), 4.03 (s, 6H), 7.11 (s, 2H), 7.26 (s, 2H),
J. Org. Chem, Vol. 72, No. 16, 2007 6181

Morgan et al.
Tetramer 33c. Rf ) 0.14 (2.5% MeOH/CH2Cl2); Mn,NMR ) 2388,
Mn,GPC ) 1780, Mw/Mn ) 1.3, Mn,MALDi-TOF ) 2387; 1H NMR (500
MHz, CDCl3) δ 3.23 (s, 2H), 3.33 (br s, 18H), 3.35 (s, 6H), 3.98
(br m, 42H), 4.02 (br s, 6H), 4.12 (br m, 24H), 7.21 (br m, 6H),
7.25 (br s, 2H), 7.42 (br m, 6H), 7. 47 (br s, 2H); 13C NMR (125
MHz, CDCl3) δ 167.1, 167.0, 166.9, 157.8, 157.4, 153.7, 153.7,
153.5, 152.3, 152.2, 152.2, 133.1, 133.0, 132.3, 129.9, 129.8, 129.8,
126.4, 126.3, 126.3, 122.1, 122.1, 121.8, 119.6, 119.5, 119.5, 115.5,
115.2, 101.1, 101.0, 82.7, 80.0, 79.4, 78.9, 63.0, 62.2, 56.3, 52.8;
115.3, 101.1, 79.4, 79.0, 62.9, 62.2, 56.2, 52.8; IR (film) 3204,
2926, 2853, 2212, 1733, 1586 cm-1
.
(R)-33e. Rf ) 0.09 (2.5% MeOH/CH2Cl2); Mn,GPC ) 6770, Mw/
Mn ) 1.6, Mn,MALDi-TOF ) 7786 (MNa+); [R]D20 -1135.0; 1H NMR
(500 MHz, CDCl3) δ 3.32 (br s, 6H), 3.97 (br s, 12H), 4.11 (br m,
6H), 7.21 (br m, 2H), 7.42 (br m, 2H); 13C NMR (125 MHz, CDCl3)
δ 166.6, 157.5, 153.4, 151.9, 132.7, 129.5, 126.1, 121.8, 119.2,
115.0, 100.9, 79.1, 78.6, 62.7, 61.9, 56.0, 52.6; IR (film) 3204,
2999, 2926, 2853, 2212, 1733, 1586 cm-1
.
IR (film) 3293, 2999, 2949, 2845, 2212, 1733, 1590 cm-1
.
(R)-33. To a mixture of (R)-32 (0.080 g, 0.13 mmol) in CH2Cl2
(3 mL) was added CuCl(OH)TMEDA (0.006 g, 0.027 mmol). The
resultant mixture was stirred at room temperature for 4 d under an
oxygen atmosphere. The reaction was quenched with 1 N HCl, and
the aqueous phase was extracted with CH2Cl2. The organics were
dried (Na2SO4), and after the solvent was evaporated, the residue
was chromatographed (1-10% MeOH/CH2Cl2) to yield (R)-33d
(30 mg, 38%) and (R)-33e (36 mg, 45%) as the main fractions.
(R)-33d. Rf ) 0.11 (2.5% MeOH/CH2Cl2); Mn,GPC ) 2390, Mw/
Acknowledgment. Financial support was provided by the
University of Pennsylvania Research Foundation, the National
Science Foundation (CHE-0616885), and the National Institutes
of Health (CA-109164). We thank Andres Dulcey, Jonathon
Ruddick, Janine Ladislaw, and Prof. Virgil Percec for assistance
with the polymer characterization.
Supporting Information Available: Experimental details and
characterization of all new compounds. This material is available
free of charge Via the Internet at http://pubs.acs.org.
20
1
Mn ) 1.6, Mn,MALDi-TOF ) 3623 (MK+); [R]D -707.8; H NMR
(500 MHz, CDCl3) δ 3.33 (br s, 6H), 3.97 (br s, 12H), 4.12 (br m,
6H), 7.22 (br m, 2H), 7.42 (br m, 2H); 13C NMR (125 MHz, CDCl3)
δ 166.9, 157.8, 153.6, 152.2, 133.0, 129.8, 126.4, 122.1, 119.5,
JO070636+
6182 J. Org. Chem., Vol. 72, No. 16, 2007