Catalytic asymmetric oxidative couplings of 2-naphthols by tridentate N-ketopinidene-based vanadyl dicarboxylates

Article abstract of DOI:10.1021/ol026156g

(Matrix presented) A series of oxovanadium(IV) complexes derived from tridentate N-ketopinidene-α-amino acids were synthesized. They serve as efficient catalysts for the enantioselective oxidative couplings of various 3-, 6-, or 7-substituted 2-naphthols. The best scenario involves the use of a vanadyl complex arising from L-tert-leucine in CCl₄. The asymmetric couplings of 2-naphthols can be conducted smoothly at 40-45 °C under a stream of gaseous oxygen, leading to 2,2′dihydroxy-1,1′-binaphthyls in good yields (61-99%) and with enantioselectivities of up to 87%.

Full text of DOI:10.1021/ol026156g

ORGANIC
LETTERS
2002
Vol. 4, No. 15
2529-2532
Catalytic Asymmetric Oxidative
Couplings of 2-Naphthols by Tridentate
N-Ketopinidene-Based Vanadyl
Dicarboxylates
Nivrutti B. Barhate and Chien-Tien Chen*
Department of Chemistry, National Taiwan Normal UniVersity, Taipei, Taiwan
chefV043@scc.ntnu.edu.tw
Received May 8, 2002
ABSTRACT
A series of oxovanadium(IV) complexes derived from tridentate N-ketopinidene-r-amino acids were synthesized. They serve as efficient catalysts
for the enantioselective oxidative couplings of various 3-, 6-, or 7-substituted 2-naphthols. The best scenario involves the use of a vanadyl
complex arising from L-tert-leucine in CCl4. The asymmetric couplings of 2-naphthols can be conducted smoothly at 40−45 °C under a stream
of gaseous oxygen, leading to 2,2′-dihydroxy-1,1′-binaphthyls in good yields (61−99%) and with enantioselectivities of up to 87%.
Axially dissymmetric 1,1′-bi-2-naphthol (BINOL) and its
derivatives are important chiral auxiliaries in asymmetric
syntheses and catalyses.1 In addition, their facile conversions
to the corresponding 2,2′-bis(diphenylphosphino)-1,1′-bi-
naphthyls (BINAP) have further expanded their synthetic
utilities in various domains of asymmetric catalyses.2 In light
of the comprehensive applications in asymmetric transforma-
tions, their preparation in optically pure form has remained
under intense attention over the past 2 decades.3
is a topic of imminent research.4 Seminal studies of
Brussee3h,5 and Kocˇovsky´6 on the syntheses of scalemic
BINOLs involved Cu(II)-amine complex mediated oxidative
couplings of 2-naphthols. However, in most instances,
second-order asymmetric transformation was observed rather
than asymmetric couplings. Nakajima and co-workers7a have
demonstrated the first successful enantioselective variant by
(3) (a) Toda, F.; Tanaka, K. Chem. Commun. 1997, 1087. (b) Cai, D.;
Hughes, D. L.; Verhoeven, T. R.; Reider, P. J. Tetrahedron Lett. 1995,
7991. (c) Osa, T.; Kashiwagi, Y.; Yanagisawa, Y.; Bobbitt, J. M. J. Chem.
Soc., Chem. Commun. 1994, 2535. (d) Kawashima, M.; Hirata, R. Bull.
Chem. Soc. Jpn. 1993, 66, 2002. (e) Shindo, M.; Koga, K.; Tomioka, K. J.
Am. Chem. Soc. 1992, 114, 8732. (f) Kawashima, M.; Hirayama, A. Chem.
Lett. 1990, 2299. (g) Toda, F.; Tanaka, K. J. Org. Chem. 1988, 53, 3607.
(h) Brussee, J.; Groenendijk, J. L. G.; te Koppele, J. M.; Jansen, A. C. A.
Tetrahedron 1985, 41, 3313. (i) Yamamoto, K.; Fukushima, H.; Yumioka,
H.; Nakazaki, M. Bull. Chem. Soc. Jpn. 1985, 58, 3633. (j) Miyano, S.;
Kawahara, K.; Inoue, Y.; Hashimoto, H. Tetrahedron Lett. 1987, 355. (k)
Feringa, B.; Wynberg, H, Bioorg. Chem. 1978, 7, 397.
In recent years, asymmetric synthesis of BINOLs by
catalytic enantioselective means to complement the needs
of stoichiometric resolving agents and chiral chromatography
(1) (a) Ishihara, K.; Nakamura, H.; Yamamoto, H. J. Am. Chem. Soc.
1999, 121, 7720. (b) Kobayashi, S.; Komiyama, S.; Ishitani, H. Angew.
Chem., Int. Ed. Engl. 1998, 37, 979. (c) Noyori, R. Asymmetric Catalysis
in Organic Synthesis; Wiley and Sons: New York, 1994. (d) For a recent
review, see: Pu, L. Chem. ReV. 1998, 98, 2405. (e) Rosini, C.; Franzini,
L.; Raffaelli, A.; Salvadori, P. Synthesis 1992, 503. (f) Kagan, H. B.; Riant,
O. Chem. ReV. 1992, 92, 1007. (g) Mikami, K.; Shimizu, M. Chem. ReV.
1992, 92, 1021. (h) ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer-Verlag: Berlin, Heidelberg, 1999.
(i) Bolm C.; Hildebrand, J. P.; Muniz, K.; Hermanns, N. Angew. Chem.,
Int. Ed. 2001, 40, 3285.
(4) Stinson, S. C. Chiral Chemistry. Chem. Eng. News 2001, 70 (20),
45-57.
(5) Brussee, J.; Jansen, A. C. A. Tetrahedron Lett. 1983, 24, 3261.
(6) (a) Smrcˇina, M.; Lorenc, M.; Hanusˇ, V.; Sedmera, P.; Kocˇovsky´, P.
J. Org. Chem. 1992, 57, 1917. (b) Smrcˇina, M.; Pola´kowa´, J.; Vyskocˇil,
S.; Kocˇovsky´, P. J. Org. Chem. 1993, 58, 4534. (c) Smrcˇina, M. Vyskocˇil,
S.; Macˇa, B.; Pola´sˇek, M.; Claxton, T. A.; Abbott, A, P.; Kocˇovsky´, P. J.
Org. Chem. 1994, 59, 2156.
(2) (a) Noyori, R. Chem. ReV. 1989, 18, 187. (b) Noyori, R.; Takaya, H.
Acc. Chem. Res. 1990, 23, 345.
10.1021/ol026156g CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/26/2002

applying L-proline-derived diamine-Cu(I) complex to effect
the couplings of 3-carboalkoxy-2-naphthols in up to 78%
ee. Subsequent study by Kozlowski further improved the
catalytic protocol to 93% ee by using Cu(I)-1,5-diaza-
decaline complexes.7b Notably, these two complexes were
specifically active and enantioselective for 3-carboalkoxy-
2-naphthols, presumably as a result of facile bidentate
coordination of the substrates.
specifically active toward nucleophilic acyl substitution of
anhydrides and oxidative couplings of 2-naphthols. We
thought to examine the reactivity and enantioselectivity
profiles of new chiral vanadyl dicarboxylates derived from
(+)-ketopinic acid, a uniquely stable chiral â-keto acid, and
R-amino acids in asymmetric oxidative couplings of 2-naph-
thols. Herewith, we describe the preliminary results of this
work.
As part of our continuing research interests toward vanadyl
complex-mediated catalysis in our laboratory,8 we have
recently developed the first successful enantioselective
oxidative couplings of 2-naphthols catalyzed by N-sali-
cylidene-R-amino acid based vanadyl complexes (e.g., 1a
and 1b, Figure 1). Various 3-, 6-, and 7-substituted BINOLs
The targeted vanadyl dicarboxylates (2a-e) were prepared
by combining vanadyl sulfate with in situ generated Schiff
bases from (+)-ketopinic acid and respective R-amino acids.
Mass analyses of these complexes by the FAB technique
indicate that they are mainly composed of tetradentate
monomers and pentadentate dimers.12 To gain insights into
their R-substituent (R) and chirality influences on enantio-
controls of the coupling processes, five natural (L-form)
R-amino acids and D-valine were first examined in a model
coupling of 2-naphthol. The model reactions were carried
out by following a reaction protocol similar to that for
catalyst 1a or 1b (10mol %, O2, ambient temperature in
CCl4). It was found that the coupling rates and enantio-
selectivities were highly dependent on the steric bulks of R,
Table 1.
Figure 1. Vanadyl complexes derived from 2-hydroxy-1-naph-
thaldehyde or (+)-ketopinic acid with R-amino acids.
Table 1. Effects of R-Amino Acids in 2 on Catalytic
Asymmetric Coupling of 2-Naphthol in CCl4
were furnished in excellent yields and with fair enantio-
selectivities of up to 68%.8b,9 Notably, the preliminary
searches for chiral vanadyl complexes have revealed that the
carboxylate functionality in the chiral template is essential
for the coupling activity.10
Very recently, Gong and co-workers have further extended
this concept.11 Oxovanadium(V) complexes derived from
R-amino acids and a chiral salicylidene-based template, 3,3′-
diformyl-2,2′-dihydroxy-1,1′-bi-2-naphthyl, could achieve a
similar enantioselectivity (57% ee) in the oxidative coupling
of 2-naphthol under our previously reported reaction condi-
tions (10 mol %, 20 °C).8b More significantly, the enantio-
selectivities in the oxidative couplings of the parent, 6-
bromo-, and 7-methoxy-2-naphthol were further improved
to a range of 82% to 98% at a lower temperature of 0 °C.
More than 1 year ago, we identified a new category of
vanadyl species, namely, vanadyl dicarboxylates, which were
catalyst/R
time, d
yield,a
%
ee,b,c
%
PhCH2 (2a )
i-Pr (2b)
i-Prd (2b′)
s-Bu (2c)
i-Bu (2d )
t-Bu (2e)
7
10
10
7
9
15
96
77
69
90
77
65
28
52
-8
40
3
87
a Isolated yields after flash column purification. b Determined by HPLC
on Chiralcel AD or OJ column. c Defined as (%S - %R)/(%S + %R) ×
d
100%. D-Valine was used.
(7) (a) Nakajima, M.; Miyoshi, I.; Kanayanma, 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) These complexes were specifically active
for the couplings of 3-substituted 2-naphthols. Unfortunately, in the case
of parent 2-naphthol, BINOL was produced in significantly poorer ee’s (13-
18%). For details see ref 7a and b.
(8) (a) Chen, C.-T.; Hon, S.-W.; Weng, S.-S. Synlett 1999, 816. (b) 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. (c) Chen, C.-T.; Kuo, J.-H.; Li, C.-H.; Barhate,
N. B.; Hon, S.-W.; Li, T.-W.; Chao, S.-D.; Liu, C.-C.; Li, Y.-C.; Chang,
I.-H.; Lin, J.-S.; Liu, C.-J.; Chou, Y.-C. Org. Lett. 2001, 3, 3729.
(9) For couplings mediated by photoactivated chiral (NO)Ru(II)-Salen
complex, see: Irie R.; Masutani, K.; Katsuki, T. Synlett 2000, 1433.
(10) For additive effects, see: Chu, C.-Y.; Hwang, D.-R.; Wang, S.-K.;
Uang, B.-J. Chem. Commun. 2001, 980.
In general, vanadyl complexes (2b and 2c) bearing
isopropyl and sec-butyl substituents (i.e., with 1′ branching
points) led to scalemic BINOL-3a with enantioselectivities
significantly higher (52% and 40%) than those catalyzed by
2a and 2d bearing 2′-branched (R ) PhCH2 and i-Bu)
substituents (28% and 3% ee). More satisfactory enantio-
selective coupling of 2-naphthol was observed for catalyst
2e with the sterically most demanding substituent (R ) t-Bu),
where 3a was isolated after 15 days in 87% ee but in 65%
yield. To our knowledge, this was one of the most enantio-
(11) Luo, Z.; Liu, Q.; Gong, L.; Cui, X.; Mi, A.; Jiang, Y. Chem.
Commun. 2002, 914.
(12) See the Supporting Information for details.
2530
Org. Lett., Vol. 4, No. 15, 2002

selective preparations of the parent BINOL by metal complex
catalyzed asymmetric coupling techniques. It should be noted
that the asymmetric induction (-8% ee vs 52% ee) in the
coupling was reversed but to a lesser extent upon using
vanadyl complex 2b′ derived from D-valine instead of
L-valine.
Table 3. Effects of Substrates on the Catalytic Asymmetric
Couplings Mediated by 2ea
To improve the coupling yields with intact enantioselection
in the test reaction by 2e,13 we further examined a couple of
key factors such as O2 pressure and temperature in rate
controls. The coupling rate was greatly enhanced by more
than 6 times (from 15 days to 60 and 52 h, respectively)
under an oxygen pressure of 75 and 130 psi, respectively.
However, a significant drop in ee by 26% and 33%,
respectively, for BINOL-3a was observed (entries 1-3, Table
2).
entry
time, d
product
yield,b %
ee,c %
1
2
3
4
5
6
7
7
8
8
10e
8
3a
3b
3c
3d
3e
3f
99 (95d)
86 (99)
99 (100)
95 (- - -)
99 (88)
96 (- - -)
61 (98)
84 (83)
42 (88)
64 (39)
59 (- - -)
85 (98)
87 (- - -)
76 (35)
Table 2. Effects of Pressure, Temperature, and Catalyst
Loading on Catalytic Asymmetric Coupling of 2-Naphthol by 2e
7
10e
3g
entry
loading/T
time/pressure
yield,a
%
ee,b %
a All reactions were carried out with 3 mol % of salt-free catalyst 2e at
40-45 °C. b Isolated yields after flash column purification. c Determined
by HPLC analysis on Chiralpak AD or AS or Chiralcel OD column. d The
numbers in parentheses correspond to the most selective results reported in
refs 8b and 11. e Carried out in toluene.
1
2
3
4
5
6
7
8
9
10 m ol %/r t
10 mol %/rt
10 mol %/rt
15 d /- - -
2.5 d/75 psi
2.2 d/130 psi
10 d/- - -
7 d /- - -
3 d/- - -
2 d/- - -
7 d /- - -
11 d/30 psi
7 d /- - -
65
88
80
71
95
99
99
99
97
99
87
83
87
61
54
83
81
62
61
83
64
84
76
62
10 mol %/40 °C
10 m ol %/45 °C
10 mol %/50 °C
10 mol %/70 °C
5 m ol %/45 °C
5 mol %/45 °C
3 m ol %c/45 °C
2 mol %/45 °C
1 mol %/45 °C
of the coupling products by 25-41% was attained when
catalyst 2e was employed.
Among three substrate classes examined, poorer asym-
metric inductions were observed in the couplings of 6-sub-
stituted-2-naphthols (42-64% ee, entries 2-4), where the
electron-withdrawing 6-Br case led to the least enantio-
selectivity (42% ee).14 So far, more promising enantioselec-
tive substrates for the couplings were 7-methoxy- and
7-benzyloxy-2-naphthol. BINOL-3e and -3f were furnished
in 85% and 87% ee, respectively, and in essentially quantita-
tive yields in 8 days (entries 5 and 6). In comparison with
Gong’s results, BINOL-3e provided by our catalytic system
(85% ee) exhibits lower enantioselectivity by 13%, although
with slightly higher chemical yield (by 11%, entry 5).
10
11
12
7 d/- - -
9 d/- - -
a Isolated yields after flash column purification. b Determined by HPLC
on Chiralcel AD or OJ column. c A salt free catalyst was employed.
A similar trend was observed by conducting the coupling
at 70 °C (entry 7). Further trials at different elevated
temperatures (entries 4-7) led to an optimal working
temperature range of 40-45 °C, where virtually quantitative
formation of 3a can be achieved in 81% ee in 7 days (entry
5). In addition, the catalyst loading can be reduced down to
3 mol % (entries 8-12, Table 2) without compromising
yields and enantioselectivities in the model coupling reaction.
With the optimized catalytic protocol in hand, we further
explored its generality toward substrate scope. As shown in
Table 3, moderate to good enantioselectivities (42-87% ee)
were achieved for asymmetric couplings of 2-naphthols with
varying C(3), C(6), or C(7) appendages. For comparison,
the best results obtained earlier from our catalysts8b or very
recently from Gong’s are included in parentheses. In all cases
except 6,6′-dibromo- and 7,7′-dimethoxy-BINOL, 3b and 3e
(entries 2 and 5), good improvement in enantiomeric excesses
In comparison, the coupling reactions of 3-substituted-2-
naphthols were either far less enantioselective (e.g., ca. 10%
ee for R1 ) CH2OAc and OCH2Ph) or inactive (e.g., R1 )
Br, CO2R). The only example with a satisfactory level of
enantioselectivity is 3-(1-hydroxy-1,1-diphenylmethyl)-2-
naphthol. After 10 days of reaction in toluene, its coupling
product 3g was obtained in 76% ee with 61% yield. Notably,
the X-ray crystallographic analysis of this potentially useful
new chiral auxiliary 3g shows delicate topological C2
symmetry around the four phenyl units.12
In conclusion, we have presented a new catalytic asym-
metric oxidative coupling protocol for 2-naphthols by chiral
vanadyl dicarboxylates. When combined with vanadyl sul-
fate, they can be readily prepared from ketopinic acid and
R-amino acids. The couplings proceed smoothly at 40-45
(13) Among five different solvent classes (chloroalkanes, ethers, nitriles,
nitroalkanes, alcohols, and arenes) screened, better asymmetric inductions
were observed for the coupling reactions conducted in CCl4 (87% ee) and
toluene (53% ee) albeit still with moderate yields (65-67%) at ambient
temperature. As to co-oxidant effects, the reaction was complete in 40 h at
0 °C with trityl hydroperoxide and BINOL-3a was isolated in 80% with
significant drop in ee by 17%.
(14) As a detour to solve this problem, 3b may also be prepared directly
from 3a by double bromination: Castro, P. P.; Diederich, F. Tetrahedron
Lett. 1991, 32, 6277.
Org. Lett., Vol. 4, No. 15, 2002
2531

°C under O2 with 3 mol % of catalyst loading, leading to
various BINOLs with good to high enantioselectivities of
up to 87%. To our knowledge, Gong’s and our new catalytic
systems represent one of the best enantioselective couplings
of 2-naphthols to date and complement the systems devel-
oped by Nakajima and Kozlowski.7 In addition, the concep-
tually new catalytic system of the stable, chiral â-keto acid
based vanadyl dicarboxylates might open a new entry to
search for better catalysts in order to achieve even higher
levels of asymmetric oxidative couplings of 2-naphthols, as
well as other domains of asymmetric catalysis. The ready
availability for either antipodes of ketopinic acid and R-amino
acids, as well as easy catalyst preparation and product
purification, augur well for their potential applications in
organic synthesis and practical uses.
Acknowledgment. We are grateful to the National
Science Council of the Republic of China for a generous
support of this research.
Supporting Information Available: Optimal procedures
for the preparation of catalyst 2e and for its mediated
coupling of 2-naphthol and full spectroscopic characterization
of 3a-g in PDF format; X-ray data for 3g in CIF format.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL026156G
2532
Org. Lett., Vol. 4, No. 15, 2002