Highly enantioselective oxidative couplings of 2-naphthols catalyzed by chiral bimetallic oxovanadium complexes with either oxygen or air as oxidant

Article abstract of DOI:10.1021/ja074322f

The chiral bimetallic oxovanadium complexes have been designed for the enantioselective oxidative coupling of 2-naphthols bearing various substituents at C6 and/or C7. The chirality transferring from the amino acid to the axis of the biphenyl in oxovanadium complexes 2 was found to occur with the use of UV and CD spectra and DFT calculation. The homo-coupling reaction with oxygen as the oxidant was promoted by 5 mol % of an oxovanadium complex derived from L-isoleucine and achiral biphenol to afford binaphthols in nearly quantitative yields with high enantioselectivities of up to 98% ee. An oxovanadium complex derived from L-isoleucine and H₈-binaphthol is highly efficient at catalyzing the air-oxidized coupling of 2-naphthols with excellent enantioselectivities of up to 97% ee. ⁵¹V NMR study shows that the oxovanadium complexes have two vanadium(V) species. Kinetic studies, the cross-coupling reaction, and HRMS spectral studies on the reaction have been carried out and illustrate that two vanadium(V) species are both involved in catalysis and that the coupling reaction undergoes a radical-radical mechanism in an intramolecular manner. Quantum mechanical calculations rationalize the importance of the cooperative effects of the axial chirality matching S-amino acids on the stereocontrol of the oxidative coupling reaction. The application of the transformation in the preparation of chiral ligands and conjugated polymers confirms the importance of the current process in organic synthesis.

Full text of DOI:10.1021/ja074322f

Published on Web 10/23/2007
Highly Enantioselective Oxidative Couplings of 2-Naphthols
Catalyzed by Chiral Bimetallic Oxovanadium Complexes with
Either Oxygen or Air as Oxidant
Qi-Xiang Guo,†,§ Zhi-Jun Wu,‡ Zhi-Bin Luo,† Quan-Zhong Liu,† Jian-Liang Ye,|
Shi-Wei Luo,*, Lin-Feng Cun,† and Liu-Zhu Gong*,†,
Contribution from the Hefei National Laboratory for Physical Sciences at the Microscale and
Department of Chemistry, UniVersity of Science and Technology of China, Hefei 230026, China,
Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China,
Chengdu Institute of Biology, Chengdu 610041, China, Department of Chemistry, College of
Chemistry and Chemical Engineering, Xiamen UniVersity, Xiamen, Fujian 361005, P.R. China,
and Graduate School of Chinese Academy of Sciences, Beijing, China
Received June 14, 2007; E-mail: gonglz@ustc.edu.cn; luosw@ustc.edu.cn
Abstract: The chiral bimetallic oxovanadium complexes have been designed for the enantioselective
oxidative coupling of 2-naphthols bearing various substituents at C6 and/or C7. The chirality transferring
from the amino acid to the axis of the biphenyl in oxovanadium complexes 2 was found to occur with the
use of UV and CD spectra and DFT calculation. The homo-coupling reaction with oxygen as the oxidant
was promoted by 5 mol % of an oxovanadium complex derived from L-isoleucine and achiral biphenol to
afford binaphthols in nearly quantitative yields with high enantioselectivities of up to 98% ee. An oxovanadium
complex derived from L-isoleucine and H8-binaphthol is highly efficient at catalyzing the air-oxidized coupling
of 2-naphthols with excellent enantioselectivities of up to 97% ee. 51V NMR study shows that the
oxovanadium complexes have two vanadium(V) species. Kinetic studies, the cross-coupling reaction, and
HRMS spectral studies on the reaction have been carried out and illustrate that two vanadium(V) species
are both involved in catalysis and that the coupling reaction undergoes a radical-radical mechanism in an
intramolecular manner. Quantum mechanical calculations rationalize the importance of the cooperative
effects of the axial chirality matching S-amino acids on the stereocontrol of the oxidative coupling reaction.
The application of the transformation in the preparation of chiral ligands and conjugated polymers confirms
the importance of the current process in organic synthesis.
bone.3 More importantly, optically pure binaphthyl-based small
molecules and polymers have also been extensively applied to
Introduction
Axially chiral compounds play very important roles in the
history of asymmetric synthesis, in particular, asymmetric
catalysis.1 Optically pure 1,1′-binaphthol and its derivatives have
been evaluated as versatile chiral auxiliaries and ligands in
asymmetric transformations.2 Many biologically active natural
products, for example, bioxanthracene (-)-ES-242-4, cer-
cosporin and calphostins A-D contain the binaphthol back-
the preparation of organic materials such as second nonlinear
optics, organic light-emitting devices (OLED), and chiral
sensers.4 The wide scope of applications of such compounds in
organic synthesis request efficient methods for their preparation.
The oxidative coupling of 2-naphthols is a straightforward
pathway to approach the binaphthols. Consequently, a large
number of transition metal-based homogeneous5 and heteroge-
neous6 catalysts have been discovered for the oxidative coupling
reactions to access racemic BINOL derivatives. As for the
synthesis of optically active binaphthols, optical resolution of
† Chengdu Institute of Organic Chemistry.
‡ Chengdu Institute of Biology.
§ Graduate School of Chinese Academy of Sciences.
| Xiamen University.
University of Science and Technology of China.
(3) For a review, see: (a) Coleman, R. S.; Madaras, M. L. In The Chemical
Synthesis of Natural Products; Hale, K. J., Ed; CRC Press: Sheffield, 2000;
Chapter 6, pp 144-179.
(1) (a) Kocˇovsky´, P.; Vyscocˇil, Sˇ.; Sm´rcina, M. Chem. ReV. 2003, 103, 3213.
(b) Chelucci, G.; Thummel, R. P. Chem. ReV. 2002, 102, 3129. (c) Solomon,
E. I.; Sundaram, U. M.; Machonkin, T. E. Chem. ReV. 1996, 96, 2563.
(2) (a) Noyori, R. Asymmetric Catalysis in the Organic Synthesis; Wiley: New
York, 1994. (b) Noyori, R.; Takaya, H. Acc. Chem. Res. 1990, 23, 345. (c)
Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds. ComprehensiVe Asymmetric
Catalysis; Springer-Verlag: Berlin, Heidelberg, 1999. (d) Noyori, R.
Tetrahedron 1994, 50, 4259. (e) Trost, B. M. Pure Appl. Chem. 1992, 64,
315. (f) Hayashi, T.; Kudo, A.; Ozawa, F. Pure Appl. Chem. 1992, 64,
421. (g) Mikami, K.; Shimizu, M. Chem. ReV. 1992, 92, 1021. (h) Kagan,
H. B.; Riant, O. Chem. ReV. 1992, 92, 1007. (i) Blaser, H.-U. Chem. ReV.
1992, 92, 935. (j) Rosini, G.; Franzini, L.; Raffaelli, A.; Salvadori, P.
Synthesis 1992, 503. (k) Chen, Y.; Yekta, S.; Yudin, A. K. Chem. ReV.
2003, 103, 3155. (l) Brunel, J. M. Chem. ReV. 2005, 105, 857.
(4) For reviews, see: (a) Pu, L. Chem. ReV. 1998, 98, 2405. (b) Pu, L. Chem.
ReV. 2004, 104, 1687. For leading representative original researches, see:
(c) Irie, M.; Yorozu, T.; Hayashi, K. J. Am. Chem. Soc. 1978, 100, 2236.
(d) James, T. D.; Sandanayake, K. R. A. S.; Shinkai, S. Nature 1995, 374,
345. (e) Akagi, K.; Piao, G.; Kaneko, S.; Sakamaki, K.; Shirakawa, H.;
Kyotani, M. Sciences 1998, 282, 1683. (f) Zheng, L.; Urian, R. C.; Liu,
Y.; Jen, A. K. Y.; Pu, L. Chem. Mater. 2000, 12, 13. (g) Pugh, V. J.; Hu,
Q. S.; Pu, L. Angew. Chem., Int. Ed. 2000, 39, 3638. (h) Gong, L. Z.; Hu,
Q. S.; Pu, L. J. Org. Chem. 2001, 66, 2358. (i) Lin, J.; Hu, Q. S.; Xu, M.
H.; Pu, L. J. Am. Chem. Soc. 2002, 124, 2088. (j) Cui, Y.; Evans, O. R.;
Ngo, H. L.; White, P. S.; Lin, W. B. Angew. Chem., Int. Ed. 2002, 41,
1159.
9
10.1021/ja074322f CCC: $37.00 © 2007 American Chemical Society
J. AM. CHEM. SOC. 2007, 129, 13927-13938
13927

A R T I C L E S
Guo et al.
racemic binaphthols is a conventional method and has been used
for the scalemic preparation of optically pure BINOL.7 Kinetic
resolution of BINOL derivatives by palladium-catalyzed alco-
holysis has very recently been developed as an alternative
method to approach optically active binaphthols and biphenols.8
The use of a chiral pool method to prepare optically active
BINOLs has also been investigated; however, it suffers from
the stoichiometric amounts of chiral sources as chiral resolution
does.9 In sharp contrast to well-developed catalytic synthesis
of racemic BINOLs, the asymmetric catalytic preparation of
chiral binaphthols develops much more slowly. The oxidative
couplings of 2-naphthols in the presence of catalytic amounts
of copper complexes of chiral amines have provided several
promising results,10 and their applications to the synthesis of
various poly(2,3-dihydroxy-1,4-naphthylene) derivatives with
main-chain chirality have been attempted.11 Very recently,
Kozlowski and co-workers disclosed a general approach to
optically active perylenequinones via an enantioselective oxida-
tive coupling reaction catalyzed by the complex of CuI and
(S,S)-1,5-diaza-cis-decalin.12 However, the copper-catalyzed
asymmetric oxidative biaryl coupling reaction cannot provide
the high enantioselectivity for 2-naphthols without a coordinat-
ing functional group to copper. A photoactivated chiral (NO)-
RuII-salen complex catalyzes the aerobic oxidative coupling
of 2-naphthols with 33-71% ee.13 Chiral vanadyl complexes
are another class of promising catalysts for the oxidative
coupling of 2-naphthols. The studies in this area started with
similar works from Chen14 and Uang15 whose groups indepen-
Figure 1. The oxovanadium complexes evaluated in this study.
dently designed similar oxovanadium complexes of chiral Schiff
bases for the asymmetric oxidative coupling of 2-naphthols with
moderate enantioselectivities. Subsequently, oxovanadium com-
plexes prepared from chiral Schiff bases with an additional
stereogenic center close to the reactive site were discovered with
an improved enantioselectivity over that observed with the
catalyst containing a single stereogenic center.16 Very recently,
chiral self-dimerized vanadium complexes on SiO2 were de-
veloped for the oxidative coupling of 2-naphthols with a
maximum enantioselectivity of 90% ee.17
The known monometallic chiral vanadyl complexes always
provided moderate enantioselectivity for the oxidative coupling
of most 2-naphthols. To overcome the low stereocontrol inherent
in these monovanadyl complexes, we have designed bimetallic
oxovanadium complexes 1 with multiple stereogenic centers,
which catalyzed the oxidative coupling of 2-naphthols and
derivatives with excellent enantioselectivity (up to 98% ee).18
In our further development, achiral biphenol-derived diastere-
omeric oxovanadium complexes 2 with an induced axial
chirality have been disclosed for the reaction also with excellent
enantioselectivity.19 In this contribution, we report the full results
of these studies, together with the discovery of new chiral
catalysts 3 with improved catalytic performance and their
applications in an efficient air-oxidized coupling of 2-naphthols
(Figure 1).
(5) (a) Sharma, V. B.; Jain, S. L.; Sain, B. Tetrahedron Lett. 2003, 44, 2655.
(b) Noji, M.; Nakajima, M.; Koga, K. Tetrahedron Lett. 1994, 35, 7983.
(c) Hwang, D.-R.; Chen, C.-P.; Uang, B.-J. Chem. Commun. 1999, 1207.
(d) Yadav, J. S.; Reddy, B. V. S.; Gayathri, K. U.; Prasad, A. R. New J.
Chem. 2003, 27, 1684. (e) Umare, P. S.; Tembe, G. L. React. Kinet. Catal.
Lett. 2004, 82, 173. (f) Gupta, R.; Mukherjee, R. Tetrahedron Lett. 2000,
41, 7763. (g) Nishino, H.; Satoh, H.; Yamashita, M.; Kurosawa, K. J. Chem.
Soc., Perkin Trans. 2 1999, 1919. (h) Ding, K.; Wang, Y.; Zhang, L.; Wu,
Y.; Matsuura, T. Tetrahedron 1996, 52, 1005. (i) Dewar, M. J. S.; Nakaya,
T. J. Am. Chem. Soc. 1968, 90, 7134.
(6) (a) Prasad, M. R.; Kamalakar, G.; Kulkarni, S. J.; Raghavan, K. V. J. Mol.
Catal. A: Chem. 2002, 180, 109. (b) Armengol, E.; Corma, A.; Garc´ıa,
H.; Primo, J. Eur. J. Org. Chem. 1999, 1915. (c) Kantam, M. L.; Kavita,
B.; Figueras, F. Catal. Lett. 1998, 51, 113. (d) Mastrorilli, P.; Muscio, F.;
Suranna, G. P.; Nobile, C. F.; Latronico, M. J. Mol. Catal. A: Chem. 2001,
165, 81. (e) Sakamoto, T.; Yonehara, H.; Pac, C. J. Org. Chem. 1997, 62,
3194. (f) Iwai, K.; Yamauchi, T.; Hashimoto, K.; Mizugaki, T.; Ebitani,
K.; Kaneda, K. Chem. Lett. 2003, 32, 58. (g) Fujiyama, H.; Kohara, I.;
Iwai, K.; Nishiyama, S.; Tsuruya, S.; Masai, M. J. Catal. 1999, 188, 417.
(h) Matsushita, M.; Kamata, K.; Yamaguchi, K.; Mizuno, N. J. Am. Chem.
Soc. 2005, 127, 6632.
(7) For resolution of binaphthols, see: (a) Feringa, B.; Wynberg, H. Bioorg.
Chem. 1978, 7, 397. (b) Toda, F.; Tanaka, K. J. Org. Chem. 1988, 53,
3607. (c) Pirkle, W. H.; Schreiner, J. L. J. Org. Chem. 1981, 46, 4988. (d)
Hu, Q. S.; Vitharana, D.; Pu, L. Tetrahedron: Asymmetry 1995, 6, 2123.
(e) Cai, D.; Hughes, D. L.; Verhoeven, T. R.; Reider, P. J. Tetrahedron
Lett. 1995, 36, 7991.
(8) Aoyama, H.; Tokunaga, M.; Kiyosu, J.; Iwasawa, T.; Obora, Y.; Tsuji, Y.
J. Am. Chem. Soc. 2005, 127, 10474.
(9) (a) Toda, F.; Tanaka, K.; Miyamoto, H.; Koshima, H.; Miyahara, I.; Hirotsu,
K. J. Chem. Soc., Perkin Trans. 1997, 2, 1877. (b) Delogu, G.; Fabbri, D.;
Dettori, M. A.; Forni, A.; Casalone, G. Tetrahedron: Asymmetry 2000,
11, 4417.
Results and Discussion
Binaphthol-Based Bimetallic Chiral Oxovanadium Com-
plexes. In the catalyst system based on monometallic oxova-
nadium complexes of chiral Schiff bases, the stereochemical
discrimination just depended on the chirality in the amino acid.
We initially reasoned that the stereocontrol would be improved
by introducing another suitable chiral center close to the
naphthoxy or phenoxy in the complex 4.14,15 On the basis of
this idea, we have designed novel oxovandium complexes 1
and 5, which contain two chiral centers in amino acids and an
axial chirality in the binaphthyl unit (Figure 2). The complexes
1 and 5 differ in the absolute configuration of the axial chirality
of the binaphthyl moiety. In principle, the catalysts with matched
chirality show better catalytic performance than those with
(10) (a) Nakajima, M.; Miyoshi, I.; Kanayama, K.; Hashimoto, S.-I.; Noji, M.;
Koga, K. J. Org. Chem. 1999, 64, 2264. (b) Li, X.; Yang, J.; Kozlowski,
M. C. Org. Lett. 2001, 3, 1137. (c) Gao, J.; Reibenspies, J. H.; Martell, A.
E. Angew. Chem., Int. Ed. 2003, 42, 6008. (d) Li, X.; Hewgley, J. B.;
Mulrooney, C. A.; Yang, J.; Kozlowski, M. C. J. Org. Chem. 2003, 68,
5500.
(11) (a) Habaue, S.; Seko, T.; Okamoto, Y. Macromolecules 2002, 35, 2437.
(b) Habaue, S.; Seko, T.; Okamoto, Y. Macromolecules 2003, 36, 2604.
(c) Tsubaki, K.; Miura, M.; Morikawa, H.; Tanaka, T.; Kawabata, T.; Furuta,
T.; Tanaka, K.; Fuji, K. J. Am. Chem. Soc. 2003, 125, 16200. (d) Xie, X.;
Phuan, P.-W.; Kozlowski, M. C. Angew. Chem., Int. Ed. 2003, 42, 2168.
(12) Mulrooney, C. A.; Li, X.; DiVirgilio, E. S.; Kozlowski, M. C. J. Am. Chem.
Soc. 2003, 125, 6856.
(15) Hon, S.-W.; Li, C.-H.; Kuo, J.-H.; Barhate, N. B.; Liu, Y.-H.; Wang, Y.;
Chen, C.-T. Org. Lett. 2001, 3, 869.
(16) (a) Barhatre, N. B.; Chen, C.-T. Org. Lett. 2002, 4, 2529. (b) Chu, C.-Y.;
Uang, B.-J. Tetrahedron: Asymmetry 2003, 14, 53.
(17) (a) Tada, M.; Taniike, T.; Kantam, L. M.; Iwasawa, Y. Chem. Commun.
2004, 2542. (b) Tada, M.; Kojima, N.; Izumi, Y.; Taniike, T.; Iwasawa, Y.
J. Phys. Chem. B 2005, 109, 9905.
(18) Luo, Z.; Liu, Q.; Gong, L.; Cui, X.; Mi, A.; Jiang, Y. Z. Chem. Commun.
2002, 914.
(19) Luo, Z. B.; Liu, Q. Z.; Gong, L. Z.; Cui, X.; Mi, A. Q.; Jiang, Y. Z. Angew.
Chem., Int. Ed. 2002, 41, 4532.
(13) Irie, R.; Masutani, K.; Katsuki, T. Synlett 2000, 1433.
(14) Chu, C.-Y.; Hwang, D.-R.; Wang, S.-K.; Uang, B.-J. Chem. Commun. 2001,
980.
9
13928 J. AM. CHEM. SOC. VOL. 129, NO. 45, 2007

Entioselective Oxidative Couplings of 2-Naphthols
A R T I C L E S
Figure 2. General strategy for the design of bimetallic oxovanadium
complexes with multiple stable stereogenic centers.
Scheme 1. Preparation of Bimetallic Oxovanadium Complexes
Figure 3. 51V NMR spectrum of 1c.
Table 1. Oxidative Coupling of 2-Naphthol with Bimetallic
Oxovanadium Complexes 1a-d and 5a,b
time
yield
(%)b
ee
(%)c
entry
catalyst
(days)
mismatched chirality. Thus, complexes 1 and 5 must exhibit
different abilities at catalyzing the oxidative coupling of
2-naphthols.
1
2
3
4
5
6
1a
1b
1c
1d
5a
5b
5
8
6
8
5
5
<20
70
93
63
70
50
81
83
71
6d
Oxovanadium complexes 1 are prepared by condensations
of (R)-3,3′-diformyl-2,2′-dihydroxy-1,1-binaphthol20 with (S)-
amino acids (7) and vanadyl sulfate according to the previous
procedure21 (Scheme 1). The condensations proceeded smoothly
to provide crude complexes 1 as a dark-green solid. Oxovana-
dium complexes 5 were prepared from (S)-3,3′-diformyl-2,2′-
dihydroxy-1,1-binaphthol through the same procedure as that
for the preparation of 1. However, the reaction took a prolonged
time and gave the target complexes in comparably low yields.
Oxovandium complexes 1 and 5 were identified by high-
resolution mass spectra (HRMS) and FT-IR. In HRMS spectra,
the observed exact molecular weight of either of 1a-d or 5a,b
is consistent with the calculated one and thus suggests that the
structures shown in 1 and 5a,b are most likely correct.
51V NMR spectroscopy has been a powerful probe for studies
of complexes in solution, and the vanadium nucleus is particu-
75
10d
a The reaction was carried out in CCl4. b Isolated yield. c The ee values
were determined by HPLC on a Kromasil CHI-TBB column, and the
absolute configuration is R. d Reactions were conducted at RT.
coupling reaction of 2-naphthol was conducted with 10 mol %
of either oxovanadium complexes 1 or 5 at 0 °C using carbon
tetrachloride as a solvent with an intension to clarify the effect
of the substituent of the vanadyl catalyst on enantioselectivity
and the contribution of the axial chirality to stereoselection
(Table 1). Catalysts bearing aliphatic substituents such as 1b-d
exhibit higher catalytic activity and enantioselectivity than their
benzyl-substituted counterpart 1a. Catalyst 1c with a sec-butyl
substituent provided the best result.
A significant decrease in the enantioselectivity was observed
in the reaction catalyzed by complexes 5a,b in comparison with
the reaction catalyzed by their related diastereomers 1a,b (entries
1-2 and 5-6), demonstrating that the (R)-configuration of the
axial chirality matches (S)-amino acids to favor the stereocontrol
of the oxovanadium complex.
larly suitable for studies of vanadium (V) complexes.22 The 51
V
NMR spectrum of oxovanadium complex 1c was measured with
VOCl3 as a standard in DMSO. A strong signal at -584 ppm
was observed (Figure 3), indicating that the vanadium is
vanadium (V) and the structures shown in the oxovanadium
complexes 1 are most reasonable.
The use of 1c to catalyze the oxidative coupling of 7-sub-
stituted-2-naphthol derivatives was investigated. The reaction
was performed under 1 atm oxygen with 10 mol % of the
oxovanadium complex 1c, and proceeded after 7 days to give
the homo-coupling product in high yields. Excellent enantiose-
lectivities ranging from 92% to 98% ee were observed for all
of the 7-substituted-2-naphthols tested (Table 2). In general, the
stereochemical outcome does not rely on the size of the
substituents. Variation of the substituent at C7 from methoxy
In our preliminary studies, we have observed a remarkable
dependence of the enantioselectivity on the reaction temperature
and found that 0 °C is an optimal reaction temperature in terms
of reactivity and enantioselectivity.18 Therefore, the oxidative
(20) (a) Brunner, H.; Schiessling, H. Bull. Soc. Chim. Belg. 1994, 103, 119. (b)
Zhang, H. C.; Huang, W. S.; Pu, L. J. Org. Chem. 2001, 66, 481.
(21) (a) Theriot, L. J.; Carlisle, G. O.; Hu, H. J. J. Inorg. Nucl. Chem. 1969,
31, 2841. (b) Frausto da Silva, J. J. R.; Wootton, R.; Gillard, R. D. J. Chem.
Soc. A 1970, 3369.
(22) Tracey, A. S. Coord. Chem. ReV. 2003, 237, 113.
9
J. AM. CHEM. SOC. VOL. 129, NO. 45, 2007 13929

A R T I C L E S
Guo et al.
Figure 4. General strategy for the design of bimetallic chiral oxovanadium complexes with flexible axial chirality.
Table 2. Oxidative Coupling of 2-Naphthols Catalyzed by
Oxovanadium Complex 1ca
yield
(%)b
ee
(%)c
entry
products
R1
R2
1
2
3
4
5
6
7
9b
9c
9d
9e
9f
H
H
H
H
H
H
H
OCH2CHdCH2
OMe
98
88
99
95
93
91
96
95
98
93
96
94
92
96
OEt
OnBu
OnC8H17
OnC12H25
OBn
9g
9h
Figure 5. 51V NMR spectrum of oxovanadium complex 2f.
Scheme 2. Preparation of Oxovanadium Complexes 2
a The reactions are carried out at 0 °C in the presence of 10 mol % of
catalyst 1c using CCl4 as solvent. b Isolated yields. c The ee values are
determined by HPLC on a Kromasil CHI-TBB or Chiralpak AD column.
to other alkoxy’s does not lead to much change in the
enantioselectivity.
Achiral Biphenol-Based Bimetallic Chiral Oxovanadium
Complexes. An achiral ligand with a biphenyl backbone, once
coordinated to a chiral transition-metal complex, will become
axially chiral and thus lead to the formation of a chiral catalyst
with the amplified chiral environment. Such a strategy is called
“asymmetric activation” and becomes a powerful platform for
discovering new and efficient chiral catalysts.23 The utility of
this method to evaluate an efficient chiral catalyst with a
conformationally flexible biphenyl moiety has been demon-
strated by a large number of successful examples.24
Oxovanadium complexes 2 are structurally similar to 1 except
that the binaphthyl unit of 1 is replaced with a conformationally
flexible biphenyl unit (Figure 4). In principle, diastereomeric
complexes will be generated when 3,3′-diformyl-2,2′-dihydroxy-
1,1′-phenol (10) is condensed with (S)-amino acids (7) and
vanadyl sulfate because of the increased rotation barrier in 2
(Figure 4). The diastereomers with matching chirality between
the chiral centers of the amino acid units and the induced axially
chiral biphenyl unit should provide high enantioselectivity for
the oxidative coupling; otherwise low enantioselectivity will
result.
Oxovanadium complexes 2 were prepared by condensations
of 3,3′-diformyl-2,2′-dihydroxy-2-phenol (10)20b with (S)-amino
acids (7) and vanadyl sulfate following a similar procedure for
the preparation of 1 (Scheme 2). All the complexes 2 obtained
are dark-green. As with the vanadium complexes 1, it is difficult
to obtain pure samples for most of complexes 2 for the NMR
measurement; thus, these were preliminarily characterized by
HRMS and IR. Fortunately, the complex 2f was obtained in an
1
analytically pure form. The H NMR and 13C NMR spectra of
2f are in agreement with those of the structure of 2f (See
Supporting Information). The 51V NMR spectrum of 2f was also
measured with VOCl3 as a standard (Figure 5). A signal at -600
ppm is assigned to vanadium(V).
The use of circular dichroism (CD) to investigate the axial
chirality of the biaryl compounds has been extensively studied.25
To estimate the flexible propagated chirality that exists in
vanadium complexes 2, optical spectroscopy studies on 2f and
their analogues 1c, 2f′, 3, and 11 were carried out. Vanadium
complexes 2f′, 3, and 11 were synthesized in a manner similar
to that for the synthesis of 1a-d and 2a-h. The UV-vis
(23) (a) Mikami, K.; Terada, M.; Korenaga, T.; Matsumoto, Y.; Ueki, M.;
Angelaud, R. Angew. Chem., Int. Ed. 2000, 39, 3532. (b) Mikami, K.;
Terada, M.; Korenaga, T.; Matsumoto, Y.; Matsukawa, S. Acc. Chem. Res.
2000, 33, 391. (c) Mikami, K.; Yamanaka, M. Chem. ReV. 2003, 103, 3369.
(d) Faller, J. W.; Lavoie, A. R.; Parr, J. Chem. ReV. 2003, 103, 3345. (e)
Ding, K.; Du, H.; Yuan, Y.; Long, J. Chem. Eur. J. 2004, 10, 2872.
(24) Walsh, P. J.; Lurain, A. E.; Balsells, J. Chem. ReV. 2003, 103, 3297.
(25) Berova, N., Nakanishi, K., Woody, R. W., Eds. Circular Dichroism:
Principles and Applications; Wiley-VCH: New York, 2000.
9
13930 J. AM. CHEM. SOC. VOL. 129, NO. 45, 2007

Entioselective Oxidative Couplings of 2-Naphthols
A R T I C L E S
the absolute configuration of the axis bond, were observed. The
complexes 2f and 2f′ were prepared from L- and D-isoleucines,
respectively. A clearly negative Cotton effect was seen at 320
nm in the spectrum of 2f. In contrast to this, a positive Cotton
effect was observed at 320 nm in the spectrum of 2f′. These
CD spectra indicate that complexes 2f and 2f′ are mirror images
and the chirality does transfer from D- or L-isoleucines to axis
of the biphenyl moiety. No Cotton effect was found at the
similar absorption area in the CD spectrum of 11, indicating
no or very little occurrence of the chirality transfer from
L-isoleucine due to the free rotation of the axis bond. A negative
Cotton effect was also seen at 340 nm, tailed toward 450 nm in
the CD spectrum of 3. Comparison of the CD spectra of 3 and
2f implies that the absolute configuration of the axis bond in 3
seems the same as that arising from the chirality transfer from
L-isoleucine in 2f.
The complexes 2a-h possibly exist as diastereomeric mix-
tures in solution, of which, as indicated by the CD study, (S,R)-
diastereomers might be predominant. Although it is difficult to
separate these diastereomers, these diastereomeric mixtures are
found to be efficient for the asymmetric oxidative coupling of
2-naphthols. The oxidative coupling of 2-naphthol is employed
as a model reaction to investigate the effects of the substituents
of amino acids and the catalyst loading on the reactivity and
enantioselectivity (Table 3). It is found that both the reactivity
and enantioselectivity are dependent on the substituent R of the
amino acids. Complex 2a, derived from (S)-phenylalanine gives
a high yield of 77% and a fairly good enantioselectivity of 80%
ee (entry 1). However, catalysts 2b and 2c that were prepared
from 4-methoxyphenylalanine and 4-fluorophenylalanine, re-
spectively, exhibit much lower enantioselectivities (entries 2 and
3) compared to that of their structural analogue 2a (entry 1).
The complex 2d with a â-naphthyl group shows the lowest
enantioselectivity (entry 4). The highest yield of 89% and
enantioselectivity of 89% ee are observed with catalyst 2f that
contains two sec-butyl substituents (entry 6). A decrease in
enantioselectivity was found upon replacement of the sec-butyl
group with other alkyl substituents (entries 5, 7, and 8).
Figure 6. UV-vis spectra of vanadium complexes; (blue line) with 1c;
(black line) with 2f′; (red line) with 3; (red/yellow double line) with 11;
(dark blue line) with 2f.
Figure 7. CD spectra of vanadium complexes; (blue line) with 1c; (black
line) with 2f′; (red line) with 3; (red/yellow double line) with 11; (dark
blue line) with 2f.
absorption spectra of 1c, 2f, 2f′, 3, and 11 were obtained with
a concentration of the complexes at 1.0 × 10-5 M in CH2Cl2,
which are shown in Figure 6. Two absorption bands were
observed in spectra of the complexes. One strong band is around
250-320 nm, which arises from the phenylene. The other one
is around 320-420 nm, which stems from the conjugated double
bonds in the azomethyne and phenylene in the complexes.26
Even though employed as diastereomeric mixtures, 2e-g still
give higher or comparable enantioselectivities in comparison
with their 1,1′-binaphthyl analogues 1b-d. These results,
together with the CD study, indicate that the major diastereomers
in 2 might have an axial chirality similar to that of the 1,1′-
binaphthyl unit of (R,S)-1, which matches the chirality of the
(S)-amino acid unit to be responsible for the high enantiose-
lectivity.
The generality of the process catalyzed by 2f was then
examined. A wide range of 2-naphthols was coupled in the
presence of 5 mol % of 2f under the optimized conditions with
oxygen as oxidant. Table 4 shows the results. The reaction is
quite sensitive to the substituent position on the 2-naphthols.
Generally, much higher enantioselectivities for 7-substituted
2-naphthols (94-97% ees, entries 1-7) than those for the
2-naphthols with similar substituents at C6 (36% and 44% ees,
entries 10 and 11) were observed. The enantioselectivity does
not depend on the size of the substituent. Thus, variation of the
substituent at C7 from methoxy to other alkoxy groups hardly
changed the enantioselectivities (entries 1-7). However, the
electron nature of the substituent impinges to some degree on
the enantioselectivity. In the cases of 2-naphthols substituted
Figure 7 shows the circular dichroism (CD) of the vanadium
complexes. The CD maxima at 320-340 nm, which are
correlated with the absorptions of the conjugated double bonds
in the azomethyne of the vanadium complexes and thus reflect
(26) (a) Tada, M.; Kojima, N.; Izumi, Y.; Taniike, T.; Iwasawa, Y. J. Phys.
Chem. B 2005, 109, 9905. (b) Pessoa, J. C.; Cavaco, I.; Correia, I.; Duarte,
M. T.; Gillard, R. D.; Henriques, R. T.; Higes, F. J.; Madeira, C.; Tomaz,
I. Inorg. Chim. Acta 1999, 293, 1.
9
J. AM. CHEM. SOC. VOL. 129, NO. 45, 2007 13931

A R T I C L E S
Guo et al.
Table 3. Oxidative Coupling of 2-Naphthol with Oxovanadium
Complexes 2
Table 5. Comparison of the Ability of 3, 1c, and 2f at Catalyzing
the Oxidative Coupling of 8b
yield
(%)a
ee
(%)b
entry
catalyst
R
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
Bn
77
38
64
69
42
89
56
73
80
51
67
50
79
89
79
70
4-MeOC6H4CH2
4-FC6H4CH2
â-naphthyl
i-Pr
sec-Bu
t-Bu
time
yield
(%)a
TOF
ee
1
entry
catalyst
oxidant
(days)
(d-
)
(%)b
2g
2h
n-Bu
1
2
3
4
3
3
1c
2f
O2
1.5
2
2
92
99
51
25
6.1
5.0
2.5
1.3
91
93
96
89
Air
Air
Air
isolated yield. c The ee values were determined by HPLC on a Kromasil
CHI-TBB column, and the absolute configuration is R.
a
2
Table 4. Oxidative Coupling of 2-Naphthols in the Presence of 5
mol % 2fa
a Isolated yields. b The ee values are determined by HPLC on a
Kromasil CHI-TBB or Chiralpak AD column, the configurations of products
are R.
and 16). A much lower enantioselectivity but a high yield were
provided for 9v that has two 4-fluorophenyl substituents, a much
bulkier group than bromide, at C6 and C6′. These results, in
the combination with those for 6-substituted binaphthols 9k and
9l, suggest that the C6 substituent of 2-naphthols has a
remarkable impact on the stereochemistry, but has little influence
on the reactivity.
H8-BINOL-Based Bimetallic Chiral Oxovanadium Com-
plexes and Oxidative Coupling Using Air as Oxidant. Our
interest to investigate the ability of the H8-BINOL-based
vanadium complexes for catalyzing the oxidative coupling of
2-naphthols stemmed from the fact that most chiral ligands with
a H8-binaphthyl backbone show higher efficiencies and enan-
tioselectivities than those with binaphthyl in many cases.l,2k,27
The complex 3, which was synthesized by a similar procedure
for the preparation of 1 and 2, was also characterized by IR
and HRMS. It did not give an improved enantioselectivity for
the coupling of 8b compared with its structural analogues 1c
and 2f. However, upon using air as the oxidant, the vanadium
complex 3 is much more efficient than both 1c and 2f (Table
5, entries 2-4). Interestingly, faster reaction and higher enan-
tioselectivity were seen by using 3 as a catalyst under 1 atm air
(Table 5).
time
yield
(%)b
ee
entry
products
R1
R2
(days)
(%)c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
9b
9c
9d
9e
9f
9g
9h
9i
9j
9k
9l
9m
9n
9o
9p
9q
9r
9s
H
H
H
H
H
H
H
H
H
OCH2CHdCH2
OMe
4
7
4
4
4
4
6
6
6
5
5
4
6
6
6
6
6
6
6
6
6
99
95
99
99
99
94
80
92
>99
>99
93
98
97
95
95
96
94
94
97
95
86
85
36
44
90
96
97
98
98
89
91
90
OEt
OnBu
OnC8H17
OnC12H25
OBn
Ph
4-FC6H4
H
OCH2CHdCH2
OnPr
Br
Br
Br
Br
Br
Br
Br
Br
H
H
OMe
OEt
95
OCH2CHdCH2
>99
>99
96
OnBu
OnC5H11
OnC6H13
OnC8H17
OBn
97
9t
9u
9v
95
Br
96 96d
4-FC6H4
OnBu
96
48
This result is very important because air is the most plentiful
oxidant source and is safe and environmentally benign. The air-
oxidized homocouplings of 2-naphthols in the presence of
transition-metal complexes in either asymmetric or racemic
manner were attempted;6b,10a however, the reactions proceeded
with unsatisfactory results. Although the asymmetric oxidative
coupling of 2-naphthols using air as oxidant catalyzed by a
bimetallic vanadium complex in chloroform solvent proceeded
successfully to give the product in high yield, a lower enanti-
oselectivity relative to the reaction using molecular oxygen in
CCl4 was observed.28 So far, there is no efficient chiral catalyst,
which shows high catalytic activity and enantioselectivity for
the oxidative coupling of 2-naphthols with air as the oxidant.
The ability of vanadium complex 3 at catalyzing the oxidative
coupling of various 2-naphthols bearing a substituent at C7 or
two substituents at both C6 and C7 using air as oxidant was
examined (Table 6). The reaction was performed following a
a The reactions are carried out under 1 atm oxygen. b Isolated yields.
c The ee values are determined by HPLC on a Kromasil CHI-TBB or
Chiralpak AD column, the configurations of products are R. d Using toluene/
CCl4 ) 1:3 as the solvent.
with an aromatic group at C7, much decreased enantioselec-
tivites were provided (entries 8 and 9). The best result for the
oxidative coupling of 6-substitued 2-naphthols was seen in the
case of 6-bromo-2-naphthol, which gave rise to the product with
90% ee (entry 12).
Also conducted were symmetric oxidative couplings of
2-naphthols bearing two substituents at C6 and C7, respectively-
(entries 13-21). The size of the substituent at C7 somewhat
affects the enantioselectivity. The increase in the size of
substituent at C7 by varying that from hydrogen to n-butoxy
leads to a slightly improved enantioselectivity (entries 12-16).
However, the enantioselectivity gradually drops by a small
amount as the substituent size at C7 increases. Very high
enantioselectivities were observed for 9p and 9q, which bear
two butoxy and allyloxy substituents, respectively (entries 15
(27) Tang, W.; Zhang, X. Chem. ReV. 2003, 103, 3029.
(28) Somei, H.; Asano, Y.; Yoshida, T.; Takizawa, S.; Yamataka, H.; Sasai, H.
Tetrahedron Lett. 2004, 45, 1841.
9
13932 J. AM. CHEM. SOC. VOL. 129, NO. 45, 2007

Entioselective Oxidative Couplings of 2-Naphthols
A R T I C L E S
Table 6. Oxidative Coupling of 2-Naphthols with Air as Oxidant in the Presence of 3a
time
yield
(%)b
ee
(%)c
entry
products
R1
R2
(days)
1
2
3
4
5
6
7
8
9
9a
9c
9d
9e
9g
9o
9p
9q
9r
9s
H
H
H
H
H
4
2
1.5
1.5
2
2
2
2
2
58
94
99
97
85
96
92
90
90
89
88
82
60
92
93
93
89
97
95
97
96
93
96
86
OMe
OEt
OnBu
OC12H25
OEt
H
Br
Br
Br
Br
Br
Br
Br
OCH2CH2dCH2
OnBu
OnC5H11
OnC6H13
OnC8H17
H
10
11
12
2
2
2
9t
9m
a The reactions are carried out under 1 atm air. b Isolated yields. c The ee values are determined by HPLC on a Kromasil CHI-TBB or Chiralpak AD
column.
procedure similar to that for a coupling reaction catalyzed by
6-methoxy-2-naphthol (8w) would be oxidized to a cation, which
attacks another molecule of more nucleophilic 8w, giving 9x
as a major product. Since 8m is much less nucleophilic and
more difficult to be oxidized than 6-methoxy-2-naphthol, 9m
and the cross-coupled 9w would be generated the least.
In the presence of 5 mol % of 2f, the competitive coupling
reaction proceeded to give a mixture of cross-coupled 9w,
homocoupled 9m, and 9x. The ratio of 9m/9w/9x is 1:2.2:5.2,
which is statistically in agreement with the radical-radical
coupling mechanism.6h,10d
A kinetic study was carried out on the oxidative coupling of
7-allyloxy-2-naphthol (8b) in the presence of 10 mol % of either
of these catalysts, 11, 2f, 1c, and 3, with molecular oxygen as
oxidant. As shown in Figure 8, these catalysts exhibit dramati-
cally different catalytic activity. Of them, 3 is the most
catalytically active and provided an 8 times faster reaction than
11. The catalytic activity of these vanadium complexes decreases
in an order of 3 > 1c > 2f . 11. The monovanadium complex
11 is much less catalytically active than the bis-vanadium ones.
Recently, Sasai and co-workers also observed a similar tendency
in this issue.28
2f with the exception of using air to replace oxygen as the
oxidant. Most of reactions proceeded to completion within 2
days even though the oxidative couplings were catalyzed by 5
mol % of 3 under 1 atm air. In most cases (entries 2-8, 12),
the enantioselectivities that were obtained were comparable with
those observed for the similar 2f-catalyzed reactions with
molecular oxygen as the oxidant (entries 2-4, 6, 12, and 14-
16, Table 4). However, the air-oxidative coupling of 2-naphthol
afforded a moderate yield and enantioselectivity (entry 1). It is
noteworthy that the coupling reactions proceeded to generate
9r-t with higher enantioselectivities (entries 9-11) than those
observed with 2f (Table 4, entries 17-19). This process
represents the most efficient and enantioselective oxidative
coupling of 2-naphthols with air as oxidant.
Mechanistic Aspect. It has been reported that the oxidative
coupling generally proceeds via three possible mechanisms: (1)
the radical-radical coupling, (2) the radical-anion coupling,
and (3) the heterolytic coupling of cationic species with
2-naphthol. The ruthenium-6h and copper-10dcatalyzed oxidative
coupling reactions of 2-naphthols have been proven to possibly
proceed through a radical-radical coupling pathway. To make
clear the exact mechanism for the present reaction, a cross-
coupling of 6-bromo-2-naphthol (8m) and 6-methoxy-2-naphthol
(8w) was attempted in the presence of 2f (Scheme 3). In
principle, a radical-radical coupling should give a mixture of
products, and the ratios of these compounds should be in
agreement with the relative reactivities. Because the redox
potential of 8m is higher than that of 8w, the 6,6′-dimethoxy-
2,2′-binaphthol (9x) will be produced in the majority. Theoreti-
cally, the radical-anion coupling will preferentially form a
cross-coupling product since the radical would form from a more
oxidizable 8w and then attack a more stable anion generated
from 8m. In the heterolytic coupling, the electron-richer
The oxidative coupling of 7-allyloxy-2-naphthol (8b) in the
presence of various amounts of vanadium complex 2f under
argon were carried out. As shown in Figure 9, the conversion
is linearly correlated to the amount of the vanadium complex
2f. The observed data are consistent with the calculated ones
in that one molecule of bimetallic vanadium complex 2f can
9
J. AM. CHEM. SOC. VOL. 129, NO. 45, 2007 13933

A R T I C L E S
Guo et al.
Figure 8. Kinetic studies on the oxidative coupling of 7-allyloxy-2-naphthol. (blue ×) with 11. (red 9) with 2f. (yellow 2) with 1c. (dark blue 9)
with 3.
of 2-naphthol to generate a complex I, which reacts with another
molecule of 2-naphthol to give a complex II and to release one
molecule of water. Two intramolecular oxidations take place
in II to form a double-free radical species III, and vanadium-
(V) is reduced into vanadium(IV). The intermediate III proceeds
an enantioselective intramolecular radical-radical coupling
reaction to give IV, which undergoes an isomerization to afford
an intermediate V. After a decoordination and subsequent
oxidation with molecular oxygen, (R)-BINOL was released, and
the vanadium catalyst 2f was regenerated from the intermediate
V. In these steps, the intramolecular radical-radical coupling
reaction is aggregately supported by the results of kinetic study,
the oxidative coupling of 8b under argon, and cross-coupling
between 8m and 8w. The proposed mechanism is therefore
reasonable to account for the observed results.
The reaction mechanism was further studied by high-
resolution mass spectroscopy (HRMS) with ESI source (Figure
10). The coupling reaction catalyzed by 2f was monitored off-
line in negative ion mode. Surprisingly, the radical anion [2f]•-
Figure 9. Oxidative coupling of 8b with various amounts of 2f under argon.
(black 9) Theoretical data; (red 9) experimental data.
(m/z 614) of the catalyst was observed. It has been reported
Scheme 3. Catalytic Cross-Coupling of 6-Bromo-2-naphthol and
that ESI is able to directly transfer ions from solution to gas
phase;30 thereby the radical anion (m/z 614) of the catalyst is
another piece of evidence to support the radical reaction
mechanism that we propose (Scheme 4). After 5 h, we observed
four peaks at m/z 757, 780, 884, and 907, of which the peaks
at m/z 884, 907 are assigned to the intermediates [II]•- and [II
+ Na]•-, respectively, and those at m/z 757 [I-2H]- and 780
[I-H+Na]•- are assigned to the intermediate I formed by the
coordination of the catalyst 2f with one molecule of 2-naphthol.
The intermediate I reacts with another molecule of 2-naphthol
to release one molecule of H2O, generating the intermediate II.
After the reaction has performed for 23 h, the peaks at m/z 882
and 883 are observed, which are probably formed through losing
H atoms from the intermediate V. Meanwhile, the peak at m/z
285 that is assigned to the product BINOL was also detected
(see Supporting Information for the whole spectra). The relative
intensity of the peak at m/z 884 vs that at m/z 882 became
weaker gradually as the reaction proceeded (Figure 10). After
154 h, all intermediates could not be detected, indicating the
reaction proceeded completely. All these observed MS data,
6-Methoxy-2-naphthol
oxidize two 7-allyloxy-2-naphthol (8b) to generate the coupling
product. These results indicate that both vanadiums(V) of 2f
are involved in simultaneous oxidative coupling.29
On the basis of the experimental data and literatures, a
reaction mechanism has been proposed (Scheme 4). The
bimetallic vanadium complex 2f first reacts with one molecule
(29) The oxidation reaction of stoichiometic amounts of homochiral chloro-
vanadate with (S)-ethyl mandelate under unaerobic conditions has been
used for the mechanistic investigation, see: Radosevich, A. T.; Musich,
C.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 1090.
(30) de la Mora, J. F.; Van Berkel, G. J.; Enke, C. G.; Cole, R. B.; Martinez-
Sanchez, M.; Fenn, J. B. J. Mass Spectrom. 2000, 35, 939.
9
13934 J. AM. CHEM. SOC. VOL. 129, NO. 45, 2007

Entioselective Oxidative Couplings of 2-Naphthols
A R T I C L E S
Scheme 4. Proposed Mechanism for the Oxidative Coupling of 2-Naphthol Catalyzed by Bimetallic Vanadium Complexes
together with precedent experiments, are consistent with the
proposed mechanism.
2f and (S,S)-2f. The catalytic results and CD studies indicated
that (R,S)-2f is possibly predominant. To further estimate the
flexible propagated chirality that exists in vanadium complex
2f, theoretical calculations were first performed on (R,S)-2f and
(S,S)-2f. The calculated most stable structures are shown in
Figure 11. The parameters of bond length involving vanadium
of (R,S)-2f and (S,S)-2f obtained from the DFT modeled
structures are in agreement with the crystallographic structural
data (Table 7).33
The most stable structure of (R,S)-2f was predicted to be much
more favorable than that of (S,S)-2f by a calculated energy of
4.43 kcal/mol, indicating that the diastereomer (R,S)-2f is easier
to be formed than (S,S)-2f. The greater stability of the (R,S)-
diastereomer of the oxovanadium complex 2f results from the
(R)-axial chirality of biphenyl matching the (S)-configuration
of R-amino acids because the sec-butyl group is perpendicular
to the azomethyne of the complex. However, in (S,S)-2f, the
(S)-axial chirality of biphenyl makes the sec-butyl group of the
(S)-R-amino acid take a coplanar orientation with the azom-
ethyne. This eclipsed conformation of sec-butyl group causes a
significantly repulsive interaction between H1-H3 with a
Theoretical Studies on the Stereochemistry. Theoretical
calculations were performed to explore the intrinsic factors for
the asymmetric oxidative coupling of 2-naphthol catalyzed by
the oxovanadium complex 2f. All the structures were completely
optimized by using the gradient-corrected hybrid density func-
tion theory B3LYP method as implemented in the G03 program
package.31 A basis set of valence double-ê quality was used.
Relativistic effects were addressed implicitly by the use of
relativistic effective core potentials (RECPs) for V. The standard
Dunning-Hay D95V basis was used for C, H, O, and N atoms.
This basis set/RECP combination is commonly denoted by the
acronym “LANL2DZ”.32
Oxovanadium complexes 2f have a conformationally flexible
biphenyl unit, leading to the existence of diastereomers (R,S)-
(31) Frisch, M. J.; et al. Gaussian 03, revision C.02; Gaussian, Inc.: Wallingford
CT, 2004.
(32) (a) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 299. (b) Dunning, T.
H.; Hay, P. J. In Modern Theoretical Chemistry; Schaefer, H. F., Ed.;
Plenum: New York, 1976; Vol. 3, p 1. (c) Ehlers, A. W.; Bohme, M.;
Dapprich, S.; Gobbi, A.; Hollwarth, A.; Jonas, V.; Kohler, K. F.; Stegmann,
R.; Veldkamp, A.; Frenking, G. Chem. Phys. Lett. 1993, 208, 111. (d)
Hollwarth, A.; Bohme, M.; Dapprich, S.; Ehlers, A. W.; Gobbi, A.; Jonas,
V.; Kohler, K. F.; Stegmann, R.; Veldkamp, A.; Frenking, G. Chem. Phys.
Lett. 1993, 208, 237.
(33) Rehder, D.; Schulzke, C.; Dau, H.; Meinke, C.; Hanss, J.; Epple, M. J.
Inorg. Biochem. 2000, 80, 115.
9
J. AM. CHEM. SOC. VOL. 129, NO. 45, 2007 13935

A R T I C L E S
Guo et al.
Figure 10. Reaction process detected by ESI-MS. (a) ESI-MS spectrum was obtained after the reaction was performed after 5 h; (b) after 23 h; (c) after
34 h; (d) after 80 h; (e) after 106 h; (f) after 130 h; (g) after 154 h.
Table 7. Parameters of Bond Length Involving Metal Vanadium
by DFT Calculations and X-ray Crystallography of ref 33 (in Å)
Among the four structures of the intermediate IV formed from
the (R,S)-2f-catalyzed coupling of 2-naphthols (Figure 12), the
shell
(R,S)-2f
(S,S)-2f
X-raya
most favorable one was predicted to be (R,S,R)-IV-1, which
corresponds to the experimental major product. (R,S,R)-IV-2,
an alternative assembly to give (R)-BINOL, was predicted to
be much less stable than (R,S,R)-IV-1 by about 4.28 kcal/mol
due to the different arrangement of the two coordinated
2-naphtholates. In (R,S,R)-IV-1, the two naphthyl rings take a
parallel orientation and are away from the metal centers with
an anti-conformation. The (VO)C-C-C-C(OV) dihedral angle
(along with the forming C-C bond) was predicted to be about
141° to minimize the sterical repulsion during the whole
coupling procedure, whereas in (R,S,R)-IV-2, the crosswise
section of two naphthyl rings with a perpendicular π-π stacking
makes the structure distorted, leading to an eclipsed conforma-
tion. The (VO)C-C-C-C(OV) dihedral angle was predicted
to be about 26° so that the steric strength was significantly
enhanced as the located 1H-8′H distance is about 2.04 Å in
(R,S,R)-IV-2. Both (R,S,S)-IV-1 and (R,S,S)-IV-2, which will
give the (S)-BINOL, were predicted to be much less stable than
(R,S,R)-IV-1 by about 13 kcal/mol. The destabilization resulted
from the peculiar arrangement of two naphthyl rings, which took
a crosswise configuration with the top pointing down and the
bottom stretching up so that the steric interaction was increased.
Thus, the coupling reaction catalyzed by 2f occurred through
VdO
V-N
V-O
V-OCO
V-Oph
1.589
2.117
1.775
1.863
1.851
1.588
2.126
1.775
1.861
1.847
1.589
2.043
2.008
1.975
1.921
a The bond lengths are from X-ray crystallography of ref 33.
distance of about 1.987 Å in (S,S)-2f (Figure 11). The calculation
once again proved that (R,S)-2f is the predominant diastereomer.
To gain insights into the origin of the enantioselectivity of
the oxidative coupling, further calculations were undertaken on
the catalytic performance of the asymmetric oxidative coupling
of 2-naphthol in the presence of (R,S)-2f. The four possible
structures of the intermediate IV, which principally offer the
final products, were successfully modeled by DFT calculations
as shown in Figure 12. The two 2-naphtholates respectively
coordinated to vanadiums can take an orientation either of two
naphthyl rings parallel to each other or of a crosswise section
with the top coordinated 2-naphtholate pointing down and the
bottom one stretching up. While the coupling reaction takes
place, the H atoms connected to two carbon atoms where the
coupling takes place can take an orientation either toward or
away from the central vanadium.
9
13936 J. AM. CHEM. SOC. VOL. 129, NO. 45, 2007

Entioselective Oxidative Couplings of 2-Naphthols
A R T I C L E S
Figure 11. Structures of oxovanadium complex 2f modeled by DFT, relative enthalpy in kcal/mol. Legend is as follows: (yellow) vanadium; (gray) carbon;
(red) oxygen; (blue) nitrogen; (cyan) hydrogen. For clarity just key hydrogen atoms are shown.
Figure 12. Structures of intermediate IV modeled by DFT, relative enthalpy in kcal/mol and H-H distance in Å. Legend is as follows: (yellow) vanadium;
(gray) carbon; (red) oxygen; (blue) nitrogen; (cyan) hydrogen; (light green) top naphthyl of BINOL; (dark green) down naphthyl of BINOL. For clarity just
key hydrogen atoms are shown.
excellent enantioselectivity.34 Referring to the general procedure
for the preparation of BINAP and related chiral ligands,
Scheme 5. Preparation of 7,7′-Disubstituted BINOLs and BINAPs
Based on the Oxidative Coupling
compounds 12 were transformed into 7,7′-disubstituted BINAP
13 (Scheme 5). The rhodium complexes of 13 have been used
to catalyze the conjugated addition of arylboronic acids to
unsaturated ketones with high enantioselectivity.35
Optically active binaphthol-based conjugated polymers have
extensive application in asymmetric catalysis2 and in the creation
of organic materials.4a,b An optically active conjugated polymer
17 was readily prepared starting with an oxidative coupling of
8q, which furnished 9q in quantitative yield with 98% ee
(Scheme 6). Protection of 9q by treatment with methoxy-
methylchloride (MOMCl) and sodium hydride (NaH) afforded
14 in more than 95% yield. After a Suzuki coupling with 15
and a subsequent hydrolysis, chiral conjugated polymer 17 was
obtained in 80% yield. Compared with similar polymers reported
previously,4a,b this polymer has a substituent at C7 of its
binaphthol repeating unit, and thus its dihedral angle is tunable.
The effect of the dihedral angle on the secondary structure and
optical properties of the polymer could be investigated further.
the most favorable intermediate (R,S,R)-IV-1 to predominantly
give (R)-BINOL.
Application of Oxidative Coupling Reactions. The current
process is quite synthetically useful. The oxidative coupling of
8b to generate 9b is very reproducible and can be easily scaled
up with no loss of the enantioselectivity. After several conve-
nient synthetic steps, 9b was transformed into a family of 7,7′-
disubstituted 2,2′-binaphthols (12), which were used in the
titanium-catalyzed phenylacetylene addition to aldehydes with
(34) Liu, Q.-Z.; Xie, N.-S.; Luo, Z.-B.; Cui, X.; Cun, L.-F.; Gong, L.-Z.; Mi,
A.-Q.; Jiang, Y.-Z. J. Org. Chem. 2003, 68, 7921-7924.
(35) Yuan, W.-C.; Cun, L.-F.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z. Tetrahedron
Lett. 2005, 46, 509.
9
J. AM. CHEM. SOC. VOL. 129, NO. 45, 2007 13937

A R T I C L E S
Guo et al.
Scheme 6. Preparation of Chiral Conjugated Polymer Based on Oxidative Coupling
Conclusion
lecular manner. Theoretical studies on the intermediates of the
reaction revealed the origin of the stereochemistry and suggested
that the cooperative effects of the axial chirality and the
matching S-amino acids would have stereocontrol of the catalytic
oxidative coupling of 2-naphthols. The usefulness of this
efficient oxidative coupling reaction has been demonstrated by
the synthesis of chiral ligands and conjugated polymers.
Chiral, bimetallic vanadium complexes derived from optically
pure binaphthol, H8-binaphthol, and achiral biphenol were
prepared and evaluated for catalyzing the enantioselective
catalytic oxidative coupling of 2-naphthols. In the oxovanadium
complexes derived from binaphthol, the R-configuration of the
axial chirality matches S-amino acids to favor stereocontrol.
Spectral and experimental studies demonstrated that the axial
chirality of the vanadium complex that is derived from biphenol
is transferred from the amino acids and is crucial for the
stereocontrol. Excellent enantioselectivities of 90-97% ee, and
almost perfect yields are provided by the presence of 5 mol %
of the optimal catalyst 2f for a large number of monosubstituted
and bisubstituted 2-naphthols. Oxidative coupling of 2-naphthols
catalyzed by the H8-binaphthol-based oxovanadium complex
with air as the oxidant proceeded smoothly to give homo-
coupling products in nearly quantitative yields with very high
enantioselectivities. Kinetic studies, cross-coupling experiments,
and HRMS spectral studies on the reaction all indicate that the
radical-radical coupling reaction takes place in an intramo-
Acknowledgment. We are grateful for financial support from
National Natural Science Foundation of China (projects
203900505 and 20325211). We thank the USTC-HP Laboratory
of High-performance Computing in providing computing re-
sources.
Supporting Information Available: Experimental details and
characterization of new compounds, calculated energies and
Cartesian coordinates of the calculated structures, and complete
ref 31. This material is available free of charge via the Internet
at http://pubs.acs.org.
JA074322F
9
13938 J. AM. CHEM. SOC. VOL. 129, NO. 45, 2007