A new synthetic route to enantiomerically pure axially chiral 2,2′-bipyridine N,N′-dioxides. Highly efficient catalysts for asymmetric allylation of aldehydes with allyl(trichloro)silanes

Article abstract of DOI:10.1021/jo0300800

New axially chiral 2,2′-bipyridine N,N′-dioxides 1 were obtained in an enantiomerically pure form by way of cyclic diesters 6 or 7 which were formed by the esterification of diols 2 with (R)-2,2′-bis(chlorocarbonyl)-1,1′-binaphthalene (5). Epimerization of the kinetic products at the ester formation (R_nap,S_pyr)-6 to the thermodynamically stable isomers (R_nap,R_pyr)-7 was observed in refluxing toluene or in the presence of trifluoroacetic acid. One of the N,N′-dioxides 1a which is substituted with phenyl groups at the 6 and 6′ positions was found to be highly catalytically active and enantioselective for the asymmetric allylation of aldehydes with allyl(trichloro)silane giving homoallyl alcohols.

Full text of DOI:10.1021/jo0300800

A New Syn th etic Rou te to En a n tiom er ica lly P u r e Axia lly Ch ir a l
2,2′-Bip yr id in e N,N′-Dioxid es. High ly Efficien t Ca ta lysts for
Asym m etr ic Allyla tion of Ald eh yd es w ith Allyl(tr ich lor o)sila n es
Toyoshi Shimada, Asato Kina, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, J apan
thayashi@kuchem.kyoto-u.ac.jp
Received March 5, 2003
New axially chiral 2,2′-bipyridine N,N′-dioxides 1 were obtained in an enantiomerically pure form
by way of cyclic diesters 6 or 7 which were formed by the esterification of diols 2 with (R)-2,2′-bis-
(chlorocarbonyl)-1,1′-binaphthalene (5). Epimerization of the kinetic products at the ester formation
(Rnap,Spyr)-6 to the thermodynamically stable isomers (Rnap,Rpyr)-7 was observed in refluxing toluene
or in the presence of trifluoroacetic acid. One of the N,N′-dioxides 1a which is substituted with
phenyl groups at the 6 and 6′ positions was found to be highly catalytically active and
enantioselective for the asymmetric allylation of aldehydes with allyl(trichloro)silane giving
homoallyl alcohols.
CHART 1
In tr od u ction
Some of the enantiomerically pure molecules based on
the axially chiral biaryl skeleton have been used suc-
cessfully as powerful chiral ligands or catalysts in
catalytic asymmetric reactions,1 and the development of
their preparation method has been one of the recent
topics in the chiral technology because of the great utility
of the enantiomerically pure axially chiral compounds.1
The method for the preparation so far reported involves
their asymmetric synthesis by enantioselective2 and
diastereoselective3 coupling between two aryl groups,
desymmetrization of symmetrically substituted biaryls,4,5
and enantioselective ring-opening of cyclic substrates
fixing axial chirality.6,7 Of the axially chiral compounds,
2,2′-bipyridine N,N′-dioxide derivatives have recently
attracted considerable attention due to their high ability
as a chiral Lewis base which catalyzes the asymmetric
allylation of aldehydes with allyl(trichloro)silanes,8,9
asymmetric aldol reaction with trichlorosilyl enol ethers,10
asymmetric conjugate addition of thiols,11 and asym-
metric ring-opening of epoxides.12 The first example of
the axially chiral 2,2′-bipyridine N,N′-dioxide reported
by Nakajima was prepared by optical resolution of the
racemate (Chart 1).13 Other N-oxides used by Kocovsky9
and Denmark10 are substituted with chiral moieties other
than bipyridine axial chirality. In a preliminary com-
munication, we have reported14 a new, efficient method
(1) (a) Noyori, R.; Takaya, H. Acc. Chem. Res. 1990, 23, 345. (b)
Rosini, C.; Franzini, L.; Raffaelli, A.; Salvadori, P. Synthesis 1992, 503.
(c) Pu, L. Chem. Rev. 1998, 98, 2405. (d) Hayashi, T. Acc. Chem. Res.
2000, 33, 354. (e) McCarthy, M.; Guiry, P. J . Tetrahedron 2001, 57,
3809.
(2) (a) Hayashi, T.; Hayashizaki, K.; Kiyoi, T.; Ito, Y. J . Am. Chem.
Soc. 1988, 110, 8153. (b) Hayashi, T.; Hayashizaki, K.; Ito, Y.
Tetrahedron Lett. 1989, 30, 215. (c) Cammidge, A. N.; Cre´py, K. V. L.
Chem. Commun. 2000, 1723. (d) Yin, J .; Buchwald, S. L. J . Am. Chem.
Soc. 2000, 122, 12051. (e) Castanet, A. S.; Colobert, F.; Broutin, P. E.;
Obringer, M. Tetrahedron: Asymmetry 2002, 13, 659.
(3) (a) Miyano, S.; Tobita, M.; Hashimoto, H. Bull. Chem. Soc. J pn.
1981, 54, 3522. (b) Nelson, T. D.; Meyers, A. I. J . Org. Chem. 1994,
59, 2655. (c) Nicolaou, K. C.; Li, H.; Boddy, C. N. C.; Ramanjulu, J .
M.; Yue, T. Y.; Natarajan, S.; Chu, X. J .; Bra¨se, S.; Ru¨bsam, F. Chem.
Eur. J . 1999, 5, 2584. (d) Kamikawa, K.; Uemura, M. Synlett 2000,
938. (e) Watanabe, T.; Shakadou, M.; Uemura, M. Synlett 2000, 1141.
(4) Hayashi, T.; Niizuma, S.; Kamikawa, T.; Suzuki, N.; Uozumi,
Y. J . Am. Chem. Soc. 1995, 117, 9101.
(5) (a) Tuyet, T. M. T.; Harada, T.; Hashimoto, K.; Hatsuda, M.; Oku,
A. J . Org. Chem. 2000, 65, 1335. (b) Harada, T.; Tuyet, T. M. T.; Oku,
A. Org. Lett. 2000, 2, 1319.
(6) (a) Bringmann, G.; Breuning, M.; Tasler, S. Synthesis 1999, 525.
(b) Bringmann, G.; Wuzik, A.; Ku¨mmel, J .; Schenk, W. A. Organome-
tallics 2001, 20, 1692.
(8) Nakajima, M.; Saito, M.; Shiro, M.; Hashimoto, S. J . Am. Chem.
Soc. 1998, 120, 6419.
(9) Malkov, A. V.; Orsini, M.; Pernazza, D.; Muir, K. W.; Langer,
V.; Meghani, P.; Kocovsky, P. Org. Lett. 2002, 4, 1047.
(10) Denmark, S. E.; Fan, Y. J . Am. Chem. Soc. 2002, 124, 4233.
(11) Saito, M.; Nakajima, M.; Hashimoto, S. Tetrahedron 2000, 56,
9589.
(12) Nakajima, M.; Saito, M.; Uemura, M.; Hashimoto, S. Tetrahe-
dron Lett. 2002, 43, 8827.
(13) Nakajima, M.; Sasaki, Y.; Shiro, M.; Hashimoto, S. Tetrahe-
dron: Asymmetry 1997, 8, 341.
(7) Shimada, T.; Cho, Y.-H.; Hayashi, T. J . Am. Chem. Soc. 2002,
124, 13396.
(14) Shimada, T.; Kina, A.; Ikeda, S.; Hayashi, T. Org. Lett. 2002,
4, 2799.
10.1021/jo0300800 CCC: $25.00 © 2003 American Chemical Society
Published on Web 07/17/2003
J . Org. Chem. 2003, 68, 6329-6337
6329

Shimada et al.
SCHEME 1
SCHEME 2a
of obtaining enantiomerically pure 2,2′-bipyridine N,N′-
dioxides 1. The chiral axis of configurationally labile 2,2′-
bipyridinediol 2 is fixed by the formation of cyclic diesters
with (R)-1,1′-binaphthalene-2,2′-dicarboxylic acid and
oxidation of bipyridine nitrogens giving N,N′-dioxides
followed by hydrolysis to remove the dicarboxylic acid
give axially chiral 2,2′-bipyridine N,N′-dioxides 1 whose
axis is not labile. At the cyclic diester formation, we
observed an interesting phenomenon that the kinetic
product can be isomerized into the thermodynamically
more stable epimeric isomer by heating. Taking advan-
tage of this epimerization, both enantiomers of N,N′-
dioxide 1 were obtained in an enantiomerically pure form
using a single enantiomer of the dicarboxylic acid. Here,
we wish to report a full description of the experiments
on the epimerization including its kinetic studies and the
results obtained for the asymmetric allylation of alde-
hydes catalyzed by the 2,2′-bipyridine N,N′-dioxides 1.
a
Reaction conditions: (i) Et3N, CHCl3, rt, 8 h; (ii) PhMe, reflux,
48 h.
An interesting epimerization was observed on heating
the crude product obtained by the esterification of diol
2a (Scheme 2, lower equation). Thus, the crude mixture
consisting of (Rnap,Spyr)-6a and (Rnap,Rpyr)-7a in a ratio of
1
17:1 was heated in refluxing toluene for 48 h. H NMR
studies showed that there was no detectable amount of
the isomer 6a and all of 6a was isomerized into its epimer
7a . It follows that the isomer 6a is the kinetic product
formed at the esterification and it can be isomerized into
thermodynamically more stable isomer 7a upon heating
in toluene. After this isomerization procedure, the iso-
merically pure 7a was isolated in 75% yield. The absolute
configuration of the bipyridine axis of these isomers was
determined by X-ray crystallography of the esters 6a and
7a . As can be seen from the ORTEP drawings shown in
Figure 1, the kinetic product 6a has the S configuration
on its bipyridine axis while thermodynamically stable
isomer 7a has the R configuration. The complete epimer-
ization of bipyridine axis from S to R on heating was also
observed for the cyclic diesters 6b, 6c, and 6d , which gave
(Rnap,Rpyr)-7b-d in 83%, 87%, and 59% isolated yields,
respectively. This epimerization will be discussed in
detail in the next section.
Both the kinetic products (Rnap,Spyr)-6a -d and the
thermodynamic products (Rnap,Rpyr)-7a -d were readily
converted into the axially chiral bipyridine N,N′-dioxides
1a -d without loss of the axial chirality of the bipyridine
moiety (Scheme 3). For example, oxidation of the bipyr-
idine moiety in (Rnap,Spyr)-6a with m-chloroperbenzoic
acid gave N,N′-dioxide (Rnap,Spyr)-8a in 63% yield. The
formation of N,N′-dioxide fixes the axial chirality of
bipyridine moiety and does not allow the rotation about
the bipyridine axis even after the removal of the chiral
diacid. Alkaline hydrolysis of 8a gave 85% yield of (S)-
3,3′-bis(hydroxymethyl)-6,6′-diphenyl-2,2′-bipyridine N,N′-
dioxide (1a ), whose enantiomeric purity determined by
HPLC analysis was >99% ee. The chiral source, 1,1′-
binaphthalene-2,2′-dicarboxylic acid, was recovered quan-
titatively. Starting from the thermodynamic isomer
(Rnap,Rpyr)-7a , the oxidation and alkaline hydrolysis gave
(R) isomer of the bipyridine N,N′-dioxide 1a . Thus, the
achiral bipyridine diol 2a can be converted into either
enantiomer of the axially chiral N,N′-dioxide 1a in an
enantiomerically pure form simply by choosing the reac-
Resu lts a n d Discu ssion
P r epar ation of Axially Ch ir al 2,2′-Bipyr idin e N,N′-
Dioxid es. The bipyridinediols 2a -d , which contain
substituents at the 6 and 6′ positions, were readily
prepared from the corresponding 2,9-disubstituted 1,10-
phenanthrolines 315 by a sequence of reactions consisting
of oxidation with potassium permanganate and sodium
periodate, esterification of the carboxylic acids, and
reduction of esters 4 with lithium aluminum hydride
(Scheme 1). The formation of cyclic diesters of 1,1′-
binaphthalene-2,2′-dicarboxylate proceeded at room tem-
perature with high selectivity to give one of the two
possible diastereomeric isomers in a ratio of over 5:1 for
all the bipyridinediols 2 (Scheme 2, upper equation).
Thus, treatment of 3,3′-bis(hydroxymethyl)-6,6′-diphenyl-
2,2′-bipyridine (2a ) with an excess of (R)-2,2′-bis(chloro-
carbonyl)-1,1′-binaphthalene (5)16 in the presence of
triethylamine in chloroform at room temperature for 8 h
gave a high yield of cyclic diester which consists of
diastereomeric isomers (Rnap,Spyr)-6a and (Rnap,Rpyr)-7a
in a ratio of 17:1, which was determined by 1H NMR
studies. Isomerically pure (Rnap,Spyr)-6a was obtained in
67% isolated yield by a chromatography on silica gel
followed by GPC purification. The preferential formation
of the isomer (Rnap,Spyr)-6 was also observed in the
esterification of other diols with (R)-5, the ratio of
(Rnap,Spyr)-6 to (Rnap,Rpyr)-7 being 24/1, 20/1, and 5/1 for
the diols 2b, 2c, and 2d , which are substituted with
methyl, hydrogen, and tert-butyl, respectively.
(15) Dietrich-Buchecker, C. O.; Marnot, P. A.; Sauvage, J . P.
Tetrahedron Lett. 1982, 23, 5291.
(16) Ohta, T.; Ito, M.; Inagaki, K.; Takaya, H. Tetrahedron Lett.
1993, 34, 1615.
6330 J . Org. Chem., Vol. 68, No. 16, 2003

Axially Chiral 2,2′-Bipyridine N,N′-Dioxides
SCHEME 3
SCHEME 4a
a
Reaction conditions: (i) PhMe, reflux; (ii) trifluoroacetic acid,
PhMe.
TABLE 1. Activa tion P a r a m eter s for Th er m a l
Isom er iza tion of (Rn a p,Spyr )-6a -d Ca lcu la ted fr om
Ar r h en iu s P lot
∆Gq
k103°C
(h-1
∆Hq
∆Sq
103°C
103°C
(kJ ‚mol-1
103°C
(kJ ‚mol-1
ligand
)
)
)
(J ‚K-1mol-1
)
(Rnap,Spyr)-6a
(Rnap,Spyr)-6b
(Rnap,Spyr)-6c
(Rnap,Spyr)-6d
104
104
102
102
2.91 × 10-2
2.29 × 10-2
5.87 × 10-2
5.43 × 10-2
111
162
141
116
18.6
154
104
F IGURE 1. Ortep drawings for (Rnap,Spyr)-6a (upper) and
(Rnap,Rpyr)-7a (lower). Thermal ellipsoids are shown at the 30%
probability level. The solvent molecules and all hydrogens are
omitted for simplicity.
37.2
tion procedures, oxidation of the bipyridine moiety before
or after the epimerization. Similarly, cyclic diesters
(Rnap,Spyr)-6b-d and (Rnap,Rpyr)-7b-d gave the corre-
sponding bipyridine N,N′-dioxides (S)-1b-d and (R)-1b-
d , respectively.
termined in a similar manner (Table 1). The activation
free energy for all the derivatives (Rnap,Spyr)-6a -d are
almost the same irrespective of the substituents at 6 and
6′ positions. It is likely that the epimerization proceeds
via a transition state which involves a bipyridine of
planar conformation. Activation barrier is considered to
be determined by the repulsion between methylene
protons, the repulsion between lone pairs of pyridine
nitrogens, and the stabilization of bipyridine by π-con-
jugation. The repulsion between methylene protons is
probably the most decisive factor, because the substitu-
ents at the 6 and 6′ positions did not affect the activation
free energy of epimerization.
Addition of trifluoroacetic acid greatly accelerated the
epimerization (Table 2). The rate constant of epimeriza-
tion of (Rnap,Spyr)-6a in the presence of 1 equiv of tri-
fluoroacetic acid at 33 °C was 0.23 h-1, much larger than
that in the absence of trifluoroacetic acid. Comparing this
rate constant with the value estimated by the extrapola-
tion of the Arrhenius plot in the absence of acid to 33
°C, the epimerization in the presence of acid is 23 000
times faster than that in the absence of acid. It is known
Kin etic Stu d ies on th e Ep im er iza tion of Cyclic
Diester s. Epimerization of (Rnap,Spyr)-6a to (Rnap,Rpyr)-
7a proceeded thermally, and the activation parameters
were determined to be ∆Gq
) 104 kJ ‚mol-1, ∆Hq
103°C
103°C
) 111 kJ ‚mol-1, and ∆Sq103°C ) 19 J ‚mol-1K-1, which were
measured by monitoring the ratio of (Rnap,Spyr)-6a to
1
(Rnap,Rpyr)-7a by use of H NMR spectroscopy (Scheme
4, Table 1). Plotting ln([(Rnap,Spyr)-6a ]/[(Rnap,Spyr)-6a ]0)
versus time gave a straight line (R2 g 0.99), indicating
that the epimerization is first order in [(Rnap,Spyr)-6a ]. The
rate constant of epimerization at 103 °C is 2.91 × 10-2
h-1. Other species were not detected during the epimer-
ization reaction. The isomer (Rnap,Rpyr)-7a is much more
stable than its epimer (Rnap,Spyr)-6a , because a detectable
amount of (Rnap,Spyr)-6a was not observed after heating
the isomerically pure (Rnap,Rpyr)-7a in refluxing toluene.
The activation parameters of (Rnap,Spyr)-6b-d were de-
J . Org. Chem, Vol. 68, No. 16, 2003 6331

Shimada et al.
TABLE 2. Ra te Con sta n t a n d Activa tion F r ee En er gy
for P r oton -P r om oted Isom er iza tion of (Rn a p,Spyr )-6a -d
SCHEME 6
+
+
a
a
+
∆Gq
kH
∆Gq
k33°C
(h-1
kH
/
H
33°C
33°C
33°C
33°C
ligand
(kJ ‚mol-1
)
(h-1
)
(kJ ‚mol-1
)
)
k33°C
(Rnap,Spyr)-6a
(Rnap,Spyr)-6b
(Rnap,Spyr)-6c
(Rnap,Spyr)-6d
79
89
81
77
0.23
1.0 × 102 1.0 × 10-5 2.3 × 104
0.0042 1.2 × 102 1.7 × 10-7 2.5 × 104
0.11
0.40
1.1 × 102 1.9 × 10-6 5.5 × 104
1.0 × 102 1.3 × 10-5 3.1 × 104
a
These values are estimated by the extrapolation of the
Arrhenius plot in the absence of acid to 33 °C.
SCHEME 5
TABLE 3. Asym m etr ic Allyla tion of Ald eh yd es 10 w ith
Allyl(tr ich lor o)sila n e Ca ta lyzed by 0.1 m ol % of (R)-1a a
% eec
[R]20
D
yieldb (%) of 11
of 11
entry
aldehyde 10
of 11
(config) (c in C6H6)
1
2
3
4
5
6
7
8
9
4-MeOC6H4CHO (10a )
3,4-(MeO)2C6H3CHO (10b) 95 (11b) 98 (S) -37.8 (1.9)
4-n-BuOC6H4CHO (10c)
4-t-BuC6H4CHO (10d )
4-MeC6H4CHO (10e)
PhCHO (10f)
96 (11a ) 94 (S) -32.7 (1.0)
93 (11c) 94 (S) -23.2 (2.6)d
93 (11d ) 89 (S) -24.1 (1.0)d
94 (11e) 89 (S) -43.4 (1.1)
95 (11f) 84 (S) -48.9 (1.0)
90 (11g) 81 (S) -84.1 (1.0)
93 (11h ) 76 (S) -68.4 (1.0)
83 (11i) 56 (S) -18.1 (1.9)
that unsubstituted 2,2′-bipyridine exists in a trans
conformation in organic solvent, and it takes a stable cis
conformation in an acidic solution.17 The protonation of
pyridine nitrogen is proposed to accelerate the epimer-
ization by stabilizing the planar transition state.
1-NapCHO (10g)
2-MeOC6H4CHO (10h )
4-CF3C6H4CHO (10i)
10 (E)-PhCHdCHCHO (10j) 95 (11j) 60 (S) +10.9 (1.0)d
a
The allylation was carried out with (R)-1a (0.1 mol %),
Ap p lica tion of Axia lly Ch ir a l 2,2′-Bip yr id in e N,N′-
Dioxid es 1 to Asym m etr ic Allyla tion w ith Allyl-
(tr ich lor o)sila n es. As reported in our previous paper,14
the bipyridine dioxide (R)-1a which contains two phenyl
groups at the 6 and 6′ positions has high catalytic activity
as well as high enantioselectivity for the asymmetric
allylation with allyl(trichloro)silanes. For example, the
reaction of 4-methoxybenzaldehyde (10a ) with allyl-
(trichloro)silanes (1.2 equiv) in acetonitrile at -45 °C was
completed within 2.5 h even in the presence of 0.1 mol
% of (R)-1a to give 96% yield of the corresponding
homoallyl alcohol 11a , which is an (S) isomer of 94% ee
(Scheme 5). The high catalytic activity of (R)-1a observed
here makes a remarkable contrast to the much lower
catalytic activity of other chiral Lewis acid and base
catalysts used so far in the asymmetric reactions,18 where
1-10 mol % of the catalyst is usually required for a
reasonable reaction rate. The other bipyridine oxides
1b-d were not so effective as 1a for the asymmetric
allylation of aldehydes.14
It has been proposed that bidentate N-oxide attaches
to the silicon atom to generate a pentacoordinate cationic
silicate, which activates the carbonyl moiety of aldehyde
as Lewis acid8,12,19 and the nucleophilic attack to carbonyl
carbon takes place at the γ position of allyl group via six-
membered cyclic chairlike transition structure to give the
corresponding homoallyl alcohol.20 Our catalyst system
is consistent with the proposed mechanism. Crotylation
catalyzed by (R)-1a gave only γ-allylated homoallyl
alcohol, whose relative configuration is syn from Z-crotyl-
allyl(trichloro)silane (1.2 equiv), and diisopropylethylamine (3
b
equiv) in 1.0 M acetonitrile solution at -45 °C for 2.5 h. Isolated
yield. c Determined by GLC analysis with CP-Chirasil-Dex for
11a ,b,d ,e, by HPLC analysis with Chiralcel OD-H for 11c,f,g,h ,j,
d
and by HPLC analysis with Chiralcel OJ for 11i. Specific rotation
in Et2O.
(trichloro)silane while anti from E-crotyl(trichloro)silane,
both in perfect regio- and diastereoselectivity (Scheme
6). These results support the six-membered ring chairlike
transition states.
In the presence of 0.1 mol % of (R)-1a , Lewis base-
catalyzed allylation of various aromatic aldehydes pro-
ceeded smoothly in acetonitrile at -45 °C to give the
corresponding homoallyl alcohols in high yield (Table 3).
The enantioselectivity was strongly dependent on the
substituents on the phenyl ring, being higher with more
electron donating groups. The highest enantioselectivity
(98% ee) was observed in the reaction of 3,4-dimethoxy-
benzaldehyde (10b). High catalytic activity was also
observed for an R,â-unsaturated aldehyde, although
aliphatic aldehydes were not good substrates, showing
poor reactivity and enantioselectivity.
Con clu sion
New axially chiral 2,2′-bipyridine N,N′-dioxides 1 were
obtained by a new method which does not require any
procedures for the separation of enantiomers or diaste-
reoisomers. The present method involves the formation
of a diastereomeric chiral cyclic diester as a key step,
where an interesting epimerization from the kinetic
product to the thermodynamically stable isomer was
observed. Either enantiomer of the dioxides, (R)-1 or (S)-
1, can be obtained in an enantiomerically pure form by
choosing the reaction procedures. One of the dioxides,
which is substituted with phenyl groups at 6 and 6′
positions, exhibited extremely high catalytic activity for
(17) Howard, S. T. J . Am. Chem. Soc. 1996, 118, 10269.
(18) Yanagisawa, A. In Comprehensive Asymmetric Catalysis; J a-
cobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer-Verlag:
Heidelberg, Germany, 1999; Chapter 27.
(19) Denmark, S. E.; Fu, J . J . Am. Chem. Soc. 2000, 122, 12021.
(20) (a) Kobayashi, S.; Nishio, K. Tetrahedron Lett. 1993, 34, 3453.
(b) Denmark, S. E.; Coe, D. M.; Pratt, N. E.; Griedel, B. D. J . Org.
Chem. 1994, 59, 6161.
6332 J . Org. Chem., Vol. 68, No. 16, 2003

Axially Chiral 2,2′-Bipyridine N,N′-Dioxides
3,3′-Bis(h yd r oxym et h yl)-6,6′-d i-ter t-b u t yl-2,2′-b ip yr i-
d in e (2d ). A mixture of 2,9-di-tert-butyl-1,10-phenanthroline
(3d ) (1.79 g, 6.13 mmol), potassium carbonate (2.5 g, 18 mmol),
sodium periodate (10 g, 49 mmol), potassium permanganate
(1.3 g, 8.5 mmol), tert-butyl alcohol (200 mL), and water (300
mL) was refluxed vigorously for 9.5 h. The black precipitate
was removed from the resulting mixture by filtration, and the
filter cake was washed with chloroform (ca. 100 mL). tert-Butyl
alcohol was removed from the filtrate, and the resulting
solution was acidified with concentrated hydrochloric acid and
extracted with chloroform three times. The combined organic
layer was washed with aqueous sodium chloride, dried over
anhydrous sodium sulfate, and evaporated under reduced
pressure. To the residue was added thionyl chloride (13 mL,
0.18 mol); the reaction mixture was refluxed for 7 h. Thionyl
chloride was evaporated under reduced pressure. To the
residue was added methanol (10 mL, 0.25 mol), followed by
triethylamine dropwise at 0 °C. The reaction mixture was
stirred at room temperature for 8 h. Methanol was removed
from the mixture. The residue was dissolved to chloroform,
the mixture was washed with 0.5 N hydrochloric acid, satu-
rated aqueous NaHCO3, aqueous sodium chloride, dried over
anhydrous sodium sulfate, and evaporated under reduced
pressure, and the residue was passed through silica gel column
to give the mixture of starting material 3d and 3,3′-bis-
(methoxycarbonyl)-6,6′-di-tert-butyl-2,2′-bipyridine (4d ) (1.76
g, 3d /4d ) 0.6/1), which was used for the next reaction
immediately. 3d : 1H NMR (CDCl3) δ 1.60 (s, 18H), 7.70 (s,
2H), 7.71 (d, J ) 8.5 Hz, 2H), 8.13 (d, J ) 8.5 Hz, 2H). 4d : 1H
NMR (CDCl3) δ 1.34 (s, 18H), 3.72 (s, 6H), 7.38 (d, J ) 8.0 Hz,
2H), 8.08 (d, J ) 8.0 Hz, 2H).
To the mixture (1.76 g) in tetrahydrofuran (46 mL) under
nitrogen atmosphere was added lithium aluminum hydride
(176 mg, 4.63 mmol) at -78 °C. The reaction mixture was
stirred at room temperature for 2 h, quenched with water (0.34
mL), stirred for additional 30 min, and filtered through Celite.
The filtrate was dried over anhydrous sodium sulfate and
evaporated under reduced pressure, and the residue was
chromatographed on silica gel (hexane/ethyl acetate ) 1/1) to
give starting material (3d ) (422 mg, 24% recovery) and 3,3′-
bis(hydroxymethyl)-6,6′-dimethyl-2,2′-bipyridine (2d ) (634 mg,
43% yield): 1H NMR (CDCl3) δ 1.41 (s, 18H), 4.37 (d, J ) 6.9
Hz, 4H), 5.43 (t, J ) 6.9 Hz, 2H), 7.47 (d, J ) 8.1 Hz, 2H),
7.84 (d, J ) 8.1 Hz, 2H); 13C NMR (CDCl3) δ 30.1, 37.3, 62.8,
119.8, 133.5, 139.7, 156.1, 167.4. Anal. Calcd for C20H28N2O2:
C, 73.14; H, 8.59. Found: C, 73.42; H, 8.42.
the asymmetric allylation of aldehydes with allyl(trichlo-
ro)silane giving homoallyl alcohols. The low catalyst
loading realized here (0.01-0.1 mol %) is unprecedented
for the Lewis base-catalyzed asymmetric reactions.
Exp er im en ta l Section
Gen er a l Meth od s. All moisture-sensitive manipulations
were carried out under a nitrogen atmosphere. Nitrogen gas
was dried by passage through P2O5. Chemical shifts are
reported in δ ppm referenced to an internal tetramethylsilane
standard or residual peak of toluene-d8 (δ 2.32 of methyl
proton) for 1H NMR and chloroform-d (δ 77.0 ppm) for 13C
NMR.
Ma ter ia ls. 2,9-Diphenyl-1,10-phenanthroline (3a ),15 2,9-di-
tert-butyl-1,10-phenanthroline (3d ),15 3,3′-bis(methoxycarbon-
yl)-6,6′-dimethyl-2,2′-bipyridine (4b),21 and 3,3′-bis(hydroxy-
methyl)-2,2′-bipyridine (2c)22 were prepared according to the
reported procedures.
3,3′-Bis(m et h oxyca r b on yl)-6,6′-d ip h en yl-2,2′-b ip yr i-
d in e (4a ). A mixture of 2,9-diphenyl-1,10-phenanthroline (3a )
(4.43 g, 13.3 mmol), potassium carbonate (5.3 g, 38 mmol),
sodium periodate (22 g, 0.10 mol), potassium permanganate
(2.7 g, 17 mmol), tert-butyl alcohol (340 mL), and water (510
mL) was refluxed vigorously for 14 h. The black precipitate
was removed from the resulting mixture by filtration, and the
filter cake was washed with chloroform (ca. 100 mL). The
filtrate was concentrated to ca. 200 mL under reduced pres-
sure, and the starting material was recovered by filtration in
39% (1.72 g). The filtrate was acidified with concentrated
hydrochloric acid to give white precipitate by filtration. After
the precipitate was dried under reduced pressure at 40 °C for
3 h, the suspension of bipyridine derivative in diethyl ether
(300 mL) was treated with diazomethane, quenched with acetic
acid, and adjusted to pH 8 with saturated aqueous NaHCO3.
The aqueous layer was extracted with chloroform three times.
The combined organic layer was washed with aqueous sodium
chloride, dried over anhydrous sodium sulfate, and evaporated
under reduced pressure to give 3,3′-bis(methoxycarbonyl)-6,6′-
diphenyl-2,2′-bipyridine (4a ) (1.99 g, 35% yield): 1H NMR
(CDCl3) δ 3.65 (s, 6H), 7.45 (m, 6H), 7.87 (d, J ) 8.3 Hz, 2H),
8.06 (d, J ) 8.7 Hz, 4H), 8.33 (d, J ) 8.3 Hz, 2H); 13C NMR
(CDCl3) δ 52.3, 118.9, 125.1, 127.3, 128.8, 129.8, 138.0, 138.8,
158.1, 167.5. Anal. Calcd for C26H20N2O4: C, 73.57; H, 4.75.
Found: C, 73.39; H, 4.69.
3,3′-Bis(h yd r oxym eth yl)-6,6′-d ip h en yl-2,2′-bip yr id in e
(2a ). To a solution of 3,3′-bis(methoxycarbonyl)-6,6′-diphenyl-
2,2′-bipyridine (4a ) (2.36 g, 5.55 mmol) in tetrahydrofuran (55
mL) under nitrogen atmosphere was added lithium aluminum
hydride (347 mg, 9.15 mmol) at -78 °C. The reaction mixture
was stirred at room temperature for 2 h, quenched with water
(0.42 mL), stirred for additional 30 min, and filtered through
Celite. The filtrate was dried over anhydrous sodium sulfate
and evaporated, and the residue was chromatographed on
silica gel (ethyl acetate/hexane/chloroform ) 1/1/1) to give 3,3′-
bis(hydroxymethyl)-6,6′-diphenyl-2,2′-bipyridine (2a ) (1.79 g,
88% yield): 1H NMR (CDCl3) δ 4.49 (d, J ) 7.1 Hz, 4H), 5.56
(t, J ) 7.1 Hz, 2H), 7.45 (t, J ) 7.3 Hz, 2H), 7.50 (t, J ) 7.3
Hz, 4H), 7.83 (d, J ) 8.1 Hz, 2H), 7.89 (d, J ) 8.7 Hz, 4H),
8.02 (d, J ) 8.1 Hz, 2H); 13C NMR (CDCl3) δ 62.9, 121.6, 127.1,
129.1, 129.4, 135.2, 138.6, 140.6, 156.0, 157.1. Anal. Calcd for
Cyclic d iester ((Rn a p,Spyr )-6a ). To a solution of (R)-2,2′-
bis(chlorocarbonyl)-1,1′-binaphthalene ((R)-5) (1.08 g, 2.85
mmol) in chloroform (19 mL) under nitrogen atmosphere was
added dropwise a solution of 2a (700 mg, 1.90 mmol) and
triethylamine (1.1 mL, 7.6 mmol) in chloroform (19 mL) at 0
°C. The reaction mixture was stirred at room temperature for
21 h. It was diluted with chloroform and washed with water,
0.1 N hydrochloric acid, saturated aqueous NaHCO3, and
aqueous sodium chloride. The organic layer was dried over
anhydrous sodium sulfate and evaporated under reduced
pressure. The residue was chromatographed on silica gel
(benzene/ethyl acetate ) 20/1) and purified by GPC to give
(Rnap,Spyr)-6a (860 mg, 67% yield): [R]20 +115.1 (c 0.25,
D
CHCl3); 1H NMR (CDCl3) δ 4.89 (d, J ) 12.0 Hz, 2H), 5.19 (d,
J ) 12.0 Hz, 2H), 7.10 (d, J ) 8.6 Hz, 2H), 7.27 (t, J ) 8.5 Hz,
2H), 7.40 (t, J ) 7.3 Hz, 2H), 7.46 (t, J ) 7.3 Hz, 4H), 7.51 (t,
J ) 7.5 Hz, 2H), 7.84 (d, J ) 8.6 Hz, 2H), 7.87 (d, J ) 8.2 Hz,
2H), 7.92 (d, J ) 8.2 Hz, 2H), 8.00 (m, 6H), 8.09 (d, J ) 8.2
Hz, 2H); 13C NMR (CDCl3) δ 63.8, 120.8, 124.5, 127.0, 127.2,
127.3, 127.5, 127.5, 127.9, 128.5, 128.6, 129.1, 129.9, 132.7,
133.9, 135.7, 138.6, 139.5, 155.9, 158.0, 167.8.
C
24H20N2O2: C, 78.24; H, 5.47. Found: C, 78.03; H, 5.31.
3,3′-Bis(h yd r oxym eth yl)-6,6′-d im eth yl-2,2′-bip yr id in e
1
(2b): 76% yield; H NMR (CDCl3) δ 2.60 (s, 6H), 4.40 (s, 4H),
6.13 (b, 2H), 7.25 (d, J ) 7.8 Hz, 2H), 7.79 (d, J ) 7.8 Hz, 2H);
13C NMR (CDCl3) δ 23.8, 62.9, 123.4, 133.8, 140.1, 155.8, 156.3.
Anal. Calcd for C14H16N2O2: C, 68.83; H, 6.60. Found: C,
68.59; H, 6.81.
Cyclic d iester ((Rn a p,Spyr )-6b): 66% yield; [R]20 +0.4 (c
D
1.2, CHCl3); 1H NMR (CDCl3) δ 2.61 (s, 6H), 4.70 (d, J ) 11.9
Hz, 2H), 5.12 (d, J ) 11.9 Hz, 2H), 7.10 (d, J ) 8.6 Hz, 2H),
7.27 (t, J ) 7.5 Hz, 2H), 7.30 (d, J ) 8.1 Hz, 2H), 7.50 (t, J )
7.5 Hz, 2H), 7.77 (d, J ) 8.6 Hz, 2H), 7.88 (d, J ) 8.1 Hz, 2H),
(21) Mukkala, V.; Kankare, J . J . Helv. Chim. Acta 1992, 75, 1578.
(22) Rebek J r., J .; Trend, J . E.; Wattley, R. V.; Chakravorti, S. J .
Am. Chem. Soc. 1979, 101, 4333.
J . Org. Chem, Vol. 68, No. 16, 2003 6333

Shimada et al.
7.91 (d, J ) 8.2 Hz, 2H), 7.97 (d, J ) 8.6 Hz, 2H); 13C NMR
(CDCl3) δ 24.5, 63.8, 123.8, 124.6, 126.2, 127.1, 127.4, 127.6,
128.0, 128.5, 130.2, 132.8, 134.0, 135.6, 139.1, 155.3, 159.6,
168.1.
NMR (CDCl3) δ 30.2, 37.5, 65.1, 117.5, 125.2, 126.7, 127.2,
127.3, 127.4, 127.5, 127.8, 128.0, 132.8, 134.3, 138.5, 139.1,
155.9, 166.6, 168.1. Anal. Calcd for C42H38N2O4: C, 79.47; H,
6.03. Found: C, 79.64; H, 6.11.
Cyclic d iest er ((Rn a p ,Sp yr )-6c): 59% yield; [R]20 -27.7
Cyclic Diester N,N′-Dioxid e ((Rn a p,Spyr )-8a ). To a solu-
tion of (Rnap,Spyr)-6a (393 mg, 0.583 mmol) in dichloromethane
(5.8 mL) was added m-chloroperbenzoic acid (502 mg, 2.04
mmol) at 0 °C. The reaction mixture was stirred at room
temperature for 64 h, before water was added. It was extracted
with chloroform three times. The combined organic layer was
washed with saturated aqueous NaHCO3 and aqueous sodium
chloride and dried over anhydrous sodium sulfate. The solvent
was evaporated under reduced pressure, and the residue was
chromatographed on silica gel (ethyl acetate/hexane/chloro-
form ) 2/1/1) to give (Rnap,Spyr)-8a (261 mg, 63% yield) and a
mixture of substrate and the monoxide (132 mg). (Rnap,Spyr)-
D
(c 0.50, CHCl3); 1H NMR (CDCl3) δ 4.76 (d, J ) 12.1 Hz, 2H),
5.16 (d, J ) 12.1 Hz, 2H), 7.12 (d, J ) 8.5 Hz, 2H), 7.27 (t,
J ) 8.1 Hz, 2H), 7.48 (dd, J ) 7.7, 4.8 Hz, 2H), 7.51 (t, J ) 7.5
Hz, 2H), 7.79 (d, J ) 8.6 Hz, 2H), 7.92 (d, J ) 8.2 Hz, 2H),
7.98 (d, J ) 8.6 Hz, 2H), 8.02 (d, J ) 7.7 Hz, 2H), 8.76 (b, 2H);
13C NMR (CDCl3) δ 63.8, 123.9, 124.5, 127.2, 127.5, 127.6,
128.0, 128.6, 129.2, 130.0, 132.8, 134.1, 135.7, 139.0, 150.5,
155.8, 168.0.
Cyclic d iest er ((Rn a p ,Sp yr )-6d ): 52% yield; [R]20 +1.7
D
(c 2.25, CHCl3); 1H NMR (CDCl3) δ 1.35 (s, 18H), 4.78 (d, J )
12.0 Hz, 2H), 5.09 (d, J ) 12.0 Hz, 2H), 7.11 (d, J ) 8.7 Hz,
2H), 7.25 (t, J ) 7.6 Hz, 2H), 7.44 (d, J ) 8.4 Hz, 2H), 7.47 (t,
J ) 7.6 Hz, 2H), 7.80 (d, J ) 8.6 Hz, 2H), 7.87 (d, J ) 8.4 Hz,
2H), 7.89 (d, J ) 8.4 Hz, 2H), 7.95 (d, J ) 8.6 Hz, 2H); 13C
NMR (CDCl3) δ 30.0, 37.6, 64.0, 118.9, 124.6, 125.5, 127.0,
127.4, 127.6, 128.0, 128.5, 130.2, 132.8, 134.0, 135.8, 138.6,
155.4, 168.1, 169.7.
8a : [R]20 +190.9 (c 0.50, CHCl3); 1H NMR (CDCl3) δ 4.74 (d,
D
J ) 12.0 Hz, 2H), 5.21 (d, J ) 12.0 Hz, 2H), 7.05 (d, J ) 8.6
Hz, 2H), 7.26 (t, J ) 7.4 Hz, 2H), 7.41 (m, 6H), 7.52 (t, J ) 7.1
Hz, 2H), 7.62 (d, J ) 8.9 Hz, 2H), 7.64 (d, J ) 8.9 Hz, 2H),
7.84 (m, 6H), 7.93 (d, J ) 8.2 Hz, 2H), 8.01 (d, J ) 8.7 Hz,
2H); 13C NMR (CDCl3) δ 63.3, 124.6, 126.7, 127.2, 127.5, 127.6,
128.0, 128.0, 128.6, 129.2, 129.5, 129.7, 131.8, 132.8, 133.4,
134.2, 136.0, 142.4, 149.3, 167.4.
Cyclic Diester ((Rn a p,Rpyr )-7a ). To a solution of (R)-2,2′-
bis(chlorocarbonyl)-1,1′-binaphthalene (R)-5 (185 mg, 0.489
mmol) in chloroform (3.3 mL) under nitrogen atmosphere was
added dropwise a solution of 4a (120 mg, 0.326 mmol) and
triethylamine (0.18 mL, 1.3 mmol) in chloroform (3.3 mL) at
0 °C. The reaction mixture was stirred at room temperature
for 24 h, and the solvent was removed. Toluene (6.6 mL) was
added, and the mixture was refluxed for 48 h. It was diluted
with chloroform and washed with water, 0.1 N hydrochloric
acid, saturated aqueous NaHCO3, and aqueous sodium chlo-
ride. The organic layer was dried over anhydrous sodium
sulfate and evaporated under reduced pressure, and the
residue was chromatographed on silica gel (benzene/ethyl
acetate ) 20/1) and purified by GPC to give (Rnap,Rpyr)-7a (171
Cyclic Diester N,N′-Dioxid e ((Rn a p,Spyr )-8b). The above-
mentioned procedure was performed with a smaller amount
of m-chloroperbenzoic acid (2.5 equiv) and shorter reaction
time (8 h), because (Rnap,Spyr)-6b had higher reactivity. Cyclic
diester N,N′-dioxide (Rnap,Spyr)-8b was obtained in 93% yield:
1
[R]20 +73.5 (c 0.5, CHCl3); H NMR (CDCl3) δ 2.56 (s, 6H),
D
4.53 (d, J ) 12.0 Hz, 2H), 5.15 (d, J ) 12.0 Hz, 2H), 7.05 (d,
J ) 8.6 Hz, 2H), 7.26 (td, J ) 7.6, 1.1 Hz, 2H), 7.46 (d, J ) 8.3
Hz, 2H), 7.52 (td, J ) 7.6, 1.1 Hz, 2H), 7.52 (d, J ) 8.3 Hz,
2H), 7.77 (d, J ) 8.6 Hz, 2H), 7.92 (d, J ) 8.2 Hz, 2H), 7.97 (d,
J ) 8.6 Hz, 2H); 13C NMR (CDCl3) δ 17.9, 63.3, 124.5, 126.9,
127.2, 127.2, 127.5, 127.6, 128.0, 128.7, 129.5, 132.4, 132.8,
134.1, 135.7, 141.6, 149.9, 167.5.
mg, 75% yield): [R]20 +617 (c 0.25, CHCl3); 1H NMR (CDCl3)
D
δ 4.83 (d, J ) 12.0 Hz, 2H), 5.86 (d, J ) 12.0 Hz, 2H), 6.88 (d,
J ) 8.4 Hz, 2H), 7.18 (t, J ) 7.6 Hz, 2H), 7.36 (m, 12H), 7.65
(d, J ) 8.0 Hz, 2H), 7.78 (d, J ) 8.7 Hz, 2H), 7.87 (d, J ) 8.2
Hz, 2H), 8.05 (d, J ) 7.6 Hz, 4H); 13C NMR (CDCl3) δ 64.7,
119.2, 125.4, 126.8, 127.0, 127.4, 127.5, 127.6, 127.9, 128.0,
128.8, 129.1, 132.8, 134.4, 138.5, 138.9, 139.7, 156.3, 156.9,
166.7. Anal. Calcd for C46H30N2O4: C, 81.88; H, 4.48. Found:
C, 81.99; H, 4.71.
Cyclic Diester N,N′-Dioxid e ((Rn a p,Spyr )-8c). The title
compound was prepared according to the procedure described
for (Rnap,Spyr)-8b: 87% yield; [R]20 +46.5 (c 0.50, CHCl3/Me-
D
OH ) 1/1); 1H NMR (CDCl3) δ 4.58 (d, J ) 12.1 Hz, 2H), 5.17
(d, J ) 12.1 Hz, 2H), 7.04 (d, J ) 8.5 Hz, 2H), 7.27 (td, J )
7.6, 1.1 Hz, 2H), 7.47 (dd, J ) 8.1, 6.5 Hz, 2H), 7.52 (td, J )
7.6, 1.1 Hz, 2H), 7.61 (d, J ) 7.7 Hz, 2H), 7.79 (d, J ) 8.6 Hz,
2H), 7.93 (d, J ) 8.1 Hz, 2H), 7.99 (d, J ) 8.6 Hz, 2H), 8.34
(dd, J ) 6.5, 1.1 Hz, 2H); 13C NMR (CDCl3) δ 63.0, 124.5, 126.7,
127.2, 127.3, 127.5, 127.7, 128.0, 128.7, 129.2, 132.8, 134.2,
135.3, 136.0, 139.7, 141.3, 167.4.
Cyclic d iest er ((Rn a p ,Rp yr )-7b ): 83% yield; [R]20 +404
D
1
(c 0.50, CHCl3); H NMR (CDCl3) δ 2.59 (s, 6H), 4.63 (d, J )
11.9 Hz, 2H), 5.58 (d, J ) 11.9 Hz, 2H), 6.86 (d, J ) 8.6 Hz,
2H), 7.02 (d, J ) 7.9 Hz, 2H), 7.14 (t, J ) 7.5 Hz, 2H), 7.19 (d,
J ) 7.9 Hz, 2H), 7.43 (t, J ) 7.5 Hz, 2H), 7.54 (d, J ) 8.7 Hz,
2H), 7.78 (d, J ) 8.7 Hz, 2H), 7.85 (d, J ) 8.2 Hz, 2H); 13C
NMR (CDCl3) δ 24.1, 64.3, 121.9, 125.3, 126.7, 127.0, 127.3,
127.5, 127.5, 127.8, 127.9, 132.7, 134.3, 138.5, 139.2, 156.3,
157.5, 166.6. Anal. Calcd for C36H26N2O4: C, 78.50; H, 4.76.
Found: C, 78.53; H, 4.64.
Cyclic Diester N,N′-Dioxid e ((Rn a p,Spyr )-8d ). The title
compound was prepared according to the procedure described
for (Rnap,Spyr)-8a : 32% yield; [R]20 +76.9 (c 1.0, CHCl3); 1H
D
NMR (CDCl3) δ 1.47 (s, 18H), 4.58 (d, J ) 12.1 Hz, 2H), 5.17
(d, J ) 12.1 Hz, 2H), 7.04 (d, J ) 8.6 Hz, 2H), 7.27 (t, J ) 7.6
Hz, 2H), 7.48 (s, 4H), 7.50 (t, J ) 7.6 Hz, 2H), 7.79 (d, J ) 8.6
Hz, 2H), 7.93 (d, J ) 8.2 Hz, 2H), 7.99 (d, J ) 8.6 Hz, 2H); 13
C
Cyclic d iest er ((Rn a p ,Rp yr )-7c): 87% yield; [R]20 +315
NMR (CDCl3) δ 26.7, 36.4, 63.5, 124.1, 124.7, 125.9, 127.2,
127.6, 127.6, 128.0, 128.6, 129.5, 132.2, 132.9, 134.2, 136.1,
143.8, 158.0, 167.6.
D
1
(c 1.0, CHCl3); H NMR (CDCl3) δ 4.70 (d, J ) 12.2 Hz, 2H),
5.69 (d, J ) 12.2 Hz, 2H), 6.86 (d, J ) 8.8 Hz, 2H), 7.17 (td,
J ) 7.8, 1.5 Hz, 2H), 7.22 (dd, J ) 7.4, 4.9 Hz, 2H), 7.37 (dd,
J ) 7.8, 2.0 Hz, 2H), 7.46 (td, J ) 7.6, 1.5 Hz, 2H), 7.54 (d,
J ) 8.8 Hz, 2H), 7.80 (d, J ) 8.8 Hz, 2H), 7.87 (d, J ) 7.9 Hz,
2H), 8.63 (dd, J ) 4.9, 1.5 Hz, 2H); 13C NMR (CDCl3) δ 64.6,
122.7, 125.3, 126.8, 127.4, 127.6, 127.6, 127.8, 130.4, 132.8,
134.4, 138.6, 138.9, 148.5, 156.9, 166.6. Anal. Calcd for
C34H22N2O4: C, 78.15; H, 4.24. Found: C, 78.40; H, 4.46.
Cyclic Diester N,N′-Dioxid e ((Rn a p,Rpyr )-9a ). The proce-
dure described above for compound (Rnap,Spyr)-8a was followed
starting from (Rnap,Rpyr)-7a (1.10 g, 1.56 mmol), m-chloroper-
benzoic acid (1.2 g, 4.8 mmol), and dichloromethane (16 mL).
The mixture was purified as described for (Rnap,Spyr)-8a to give
(Rnap,Rpyr)-9a (491 mg, 43% yield) and a mixture of substrate
and the monoxide (537 mg). The mixture was oxidized accord-
ing to the same procedure to give (Rnap,Rpyr)-9a (316 mg, 28%
yield). The combined (Rnap,Rpyr)-9a was 806 mg (71% yield).
Cyclic d iest er ((Rn a p ,Rp yr )-7d ): 59% yield; [R]20 +418
D
(c 0.50, CHCl3); 1H NMR (CDCl3) δ 1.45 (s, 18H), 4.63 (d, J )
11.4 Hz, 2H), 5.80 (d, J ) 11.4 Hz, 2H), 6.85 (d, J ) 8.6 Hz,
2H), 7.15 (t, J ) 7.6 Hz, 2H), 7.20 (d, J ) 8.1 Hz, 2H), 7.26 (d,
J ) 8.1 Hz, 2H), 7.44 (t, J ) 7.6 Hz, 2H), 7.47 (d, J ) 8.7 Hz,
2H), 7.77 (d, J ) 8.7 Hz, 2H), 7.85 (d, J ) 8.2 Hz, 2H); 13C
(Rnap,Rpyr)-9a : [R]20 +875 (c 0.50 CHCl3); 1H NMR (CDCl3) δ
D
4.99 (d, J ) 12.0 Hz, 2H), 5.27 (d, J ) 12.0 Hz, 2H), 6.90 (t,
J ) 7.8 Hz, 4H), 7.22 (t, J ) 7.3 Hz, 2H), 7.42 (d, J ) 7.8 Hz,
2H), 7.50 (m, 8H), 7.71 (d, J ) 8.8 Hz, 2H), 7.91 (m, 8H); 13C
6334 J . Org. Chem., Vol. 68, No. 16, 2003

Axially Chiral 2,2′-Bipyridine N,N′-Dioxides
NMR (CDCl3) δ 63.9, 125.4, 126.6, 126.8, 127.1, 127.5, 127.7,
127.9, 128.0, 128.3, 129.5, 129.8, 132.5, 132.9, 134.6, 135.5,
138.9, 143.0, 149.4, 166.4. Anal. Calcd for C46H30N2O6: C,
78.17; H, 4.28. Found: C, 78.15; H, 4.20.
(S)-3,3′-Bis(h yd r oxym et h yl)-6,6′-d im et h yl-2,2′-b ip yr i-
,Spyr)-
d in e N,N′-Dioxid e ((S)-1b). To a suspension of (Rnap
8b (212 mg, 0.363 mmol) in methanol (7.6 mL) was added 6 N
aqueous sodium hydroxide (0.5 mL). After the mixture was
stirred at room temperature for 37 h, sodium salt was removed
using ion-exchange resin (DOWEX 50WX8-400). The methanol
was evaporated under reduced pressure from the resulting
mixture. After the mixture was acidified with concentrated
hydrochloric acid, the mixture was extracted with chloroform
three times. The combined organic layer was dried over
anhydrous sodium sulfate and then evaporated under reduced
pressure to give recovery of (R)-1,1′-binaphthalene 2,2′-dicar-
boxylic acid (113 mg, 91% yield). The aqueous layer was
evaporated to give (S)-3,3′-bis(hydroxymethyl)-6,6′-dimethyl-
2,2′-bipyridine N,N′-dioxide ((S)-1b) (92.5 mg, 84% yield):
Cyclic Diester N,N′-Dioxid e ((Rn a p ,Rpyr )-9b). The title
compound was prepared according to the procedure described
1
for (Rnap,Spyr)-8b: 98% yield; [R]20 +780 (c 0.35, CHCl3); H
D
NMR (CDCl3) δ 2.57 (s, 6H), 4.85 (d, J ) 12 Hz, 2H), 5.14 (d,
J ) 12 Hz, 2H), 6.67 (d, J ) 7.9 Hz, 2H), 6.85 (d, J ) 8.7 Hz,
2H), 7.18 (t, J ) 7.6 Hz, 2H), 7.23 (d, J ) 7.9 Hz, 2H), 7.48 (d,
J ) 7.6 Hz, 2H), 7.61 (d, J ) 8.6 Hz, 2H), 7.86 (d, J ) 8.6 Hz,
2H), 7.89 (d, J ) 8.2 Hz, 2H); 13C NMR (CDCl3) δ 18.0, 63.7,
125.3, 125.7, 126.2, 126.9, 127.4, 127.6, 127.7, 127.8, 127.9,
132.7, 134.1, 134.5, 138.7, 142.2, 149.2, 166.4. Anal. Calcd for
C
36H26N2O6: C, 74.22; H, 4.50. Found: C, 74.29; H, 4.55.
[R]20 -88.8 (c 1.49, EtOH); the enantiomeric excess is >99%
Cyclic Diester N,N′-Dioxid e ((Rn a p,Rpyr )-9c). The title
D
ee, which was determined by HPLC analysis with a chiral
column (Daicel Chiralcel OD-H, hexane/ethanol ) 1/1, 0.30
mL/min), tR (R)-(+), 15.7 min; (S)-(-), 21.1 min; 1H NMR (CD3-
OD) δ 2.54 (s, 6H), 4.20 (d, J ) 13.8 Hz, 2H), 4.32 (d, J ) 13.8
compound was prepared according to the procedure described
1
for (Rnap,Spyr)-8b: 100% yield; [R]20 +810 (c 1.6, CHCl3); H
D
NMR (CDCl3) δ 4.95 (d, J ) 12.5 Hz, 2H), 5.24 (d, J ) 12.5
Hz, 2H), 6.87 (d, J ) 8.5 Hz, 2H), 6.88 (d, J ) 7.6 Hz, 2H),
7.20 (t, J ) 7.7 Hz, 2H), 7.26 (t, J ) 7.1 Hz, 2H), 7.50 (t, J )
7.5 Hz, 2H), 7.63 (d, J ) 8.7 Hz, 2H), 7.86 (d, J ) 8.7 Hz, 2H),
7.90 (d, J ) 8.4 Hz, 2H), 8.31 (d, J ) 8.4 Hz, 2H); 13C NMR
(CDCl3) δ 63.8, 125.2, 125.8, 127.0, 127.1, 127.4, 127.5, 127.9,
127.9, 132.7, 134.5, 137.1, 138.7, 139.5, 141.8, 166.4. Anal.
Calcd for C34H22N2O6: C, 73.64; H, 4.00. Found: C, 73.61; H,
4.28.
Hz, 2H), 7.66 (d, J ) 8.2 Hz, 2H), 7.69 (d, J ) 8.2 Hz, 2H); 13
C
NMR (CD3OD) δ 17.7, 60.9, 128.4, 128.6, 140.4, 141.3, 149.7.
Anal. Calcd for C14H16N2O4: C, 60.86; H, 5.84. Found: C,
60.57; H, 5.77.
(R)-3,3′-Bis(h yd r oxym eth yl)-6,6′-d im eth yl-2,2′-bip yr i-
d in e N,N′-d ioxid e ((R)-1b): 88% yield; [R]20 +91.8 (c 1.49,
D
EtOH). Recovery of (R)-1,1′-binaphthalene 2,2′-dicarboxylic
Cyclic Diester N,N′-Dioxid e ((Rn a p,Rpyr )-9d ). The title
acid: 100% yield.
compound was prepared according to the procedure described
(S)-3,3′-Bis(h yd r oxym eth yl)-2,2′-bip yr id in e N,N′-Diox-
id e ((S)-1c). The procedure described above for compound (S)-
1b was followed starting from (Rnap,Spyr)-8c (166 mg, 0.318
mmol) and methanol (6.4 mL), and 6 N aqueous sodium
hydroxide (0.4 mL) was addded. The mixture was purified as
described for (S)-1b to give (S)-1c (86.5 mg, 100% yield) and
recovery of (R)-1,1′-binaphthalene 2,2′-dicarboxylic acid (108
1
for (Rnap,Spyr)-8a : 41% yield; [R]20 +94.0 (c 0.73, CHCl3); H
D
NMR (CDCl3) δ 1.58 (s, 18H), 4.83 (d, J ) 12.1 Hz, 2H), 5.13
(d, J ) 12.1 Hz, 2H), 6.78 (d, J ) 8.2 Hz, 2H), 6.85 (d, J ) 8.4
Hz, 2H), 7.19 (t, J ) 7.5 Hz, 2H), 7.28 (d, J ) 8.4 Hz, 2H),
7.49 (t, J ) 7.5 Hz, 2H), 7.58 (d, J ) 8.6 Hz, 2H), 7.86 (d, J )
8.6 Hz, 2H), 7.89 (d, J ) 8.2 Hz, 2H); 13C NMR (CDCl3) δ 27.2,
36.6, 63.9, 122.9, 125.4, 126.6, 127.0, 127.4, 127.7, 127.7, 127.8,
127.9, 132.8, 133.8, 134.5, 138.6, 144.5, 158.1, 166.4. Anal.
Calcd for C42H38N2O6: C, 75.66; H, 5.74. Found: C, 75.25; H,
5.70.
mg, 100% yield). (S)-1c: [R]20 -184 (c 0.33, MeOH); the
D
enantiomeric excess is >99% ee, which was determined by
HPLC analysis with a chiral column (Daicel Chiralcel OD-H,
ethanol, 0.20 mL/min), tR (S)-(-), 38.4 min; (R)-(+), 41.7 min;
1H NMR (D2O) δ 4.22 (d, J ) 14.5 Hz, 2H), 4.31 (d, J ) 14.5
Hz, 2H), 7.66 (dd, J ) 8.0, 6.5 Hz, 2H), 7.79 (d, J ) 8.0 Hz,
2H), 8.31 (d, J ) 6.5 Hz, 2H); 13C NMR (D2O) δ 60.2, 129.1,
131.3, 139.4, 139.5, 142.1. Anal. Calcd for C12H12N2O4: C,
58.06; H, 4.87. Found: C, 57.90; H, 4.77.
(S)-3,3′-Bis(h yd r oxym et h yl)-6,6′-d ip h en yl-2,2′-b ip yr i-
d in e N,N′-Dioxid e ((S)-1a ). To a suspension of (Rnap,Spyr)-
8a (265 mg, 0.375 mmol) in methanol (12 mL) was added 6 N
aqueous sodium hydroxide (3.1 mL). After the mixture was
stirred at room temperature for 31 h, methanol was removed
to give a white precipitate. It was filtered, and the filter cake
was washed with 15% aqueous sodium hydroxide to give 127
mg (85% yield) of (R)-3,3′-bis(hydroxymethyl)-6,6′-diphenyl-
2,2′-bipyridine N,N′-dioxide ((S)-1a ). The aqueous layer was
acidified with concentrated hydrochloric acid and extracted
with chloroform three times. The combined organic layer was
dried over anhydrous sodium sulfate and evaporated under
reduced pressure to give (R)-1,1′-binaphthalene 2,2′-dicarbox-
(R)-3,3′-Bis(h yd r oxym eth yl)-2,2′-bip yr id in e N,N′-d iox-
id e ((R)-1c): 100% yield; [R]20D +184 (c 0.27, MeOH). Recovery
of (R)-1,1′-binaphthalene 2,2′-dicarboxylic acid: 92% yield.
(S)-3,3′-Bis(h yd r oxym et h yl)-6,6′-d i-ter t-b u t yl-2,2′-b i-
p yr id in e N,N′-Dioxid e ((S)-1d ). To a solution of (Rnap,Spyr)-
8d (60.1 mg, 0.090 mmol) in methanol (6 mL) was added 6 N
aqueous sodium hydroxide (3 mL), and the mixture was stirred
at room temperature for 48 h. After the removal of methanol,
the aqueous layer was extracted with chloroform three times.
The combined organic layer was washed with aqueous sodium
chloride, dried over anhydrous sodium sulfate, and evaporated
to give (R)-3,3′-bis(hydroxymethyl)-6,6′-di-tert-butyl-2,2′-bipyr-
idine N,N′-dioxide ((S)-8d ) (30.8 mg, 95% yield). The aqueous
layer was acidified with concentrated hydrochloric acid and
extracted with chloroform three times. The combined organic
layer was washed with aqueous sodium chloride, dried over
anhydrous sodium sulfate, and evaporated under reduced
pressure to give recovery of (R)-1,1′-binaphthalene 2,2′-dicar-
boxylic acid (32.0 mg, 100% yield): [R]20D -537 (c 0.30, CHCl3).
The enantiomeric excess is >99% ee, which was determined
by HPLC analysis with a chiral column (Daicel Chiralpak AD,
hexane/ethanol ) 1/1, 0.50 mL/min), tR (S)-(-), 7.3 min; (R)-
(+), 8.9 min; 1H NMR (CDCl3) δ 1.54 (s, 18H), 4.08 (d, J )
11.9 Hz, 2H), 4.31 (d, J ) 11.9 Hz, 2H), 5.06 (b, 2H), 7.55 (s,
4H); 13C NMR (CDCl3) δ 27.3, 36.6, 63.1, 124.7, 129.2, 137.9,
144.1, 158.9. Anal. Calcd for C20H28N2O4: C, 66.64; H, 7.83.
Found: C, 66.38; H, 7.66.
ylic acid (129 mg, 100% yield). (S)-1a : [R]20 +67.1 (c 0.25,
D
CHCl3); the enantiomeric excess is >99% ee, which was
determined by HPLC analysis with a chiral column (Daicel
Chiralcel OD-H, hexane/2-propanol ) 1/1, 0.30 mL/min), tR (S)-
1
(+), 26.7 min; (R)-(-), 66.7 min; H NMR (CDCl3) δ 4.32 (d,
J ) 11.4 Hz, 2H), 4.43 (t, J ) 11.4 Hz, 2H), 4.85 (d, J ) 8.8
Hz, 2H), 7.48 (m, 6H), 7.65 (d, J ) 7.9 Hz, 2H), 7.67 (d, J )
7.8 Hz, 2H), 7.80 (d, J ) 7.9 Hz, 4H); 13C NMR (CDCl3) δ 60.1,
127.4, 127.7, 128.0, 129.2, 129.6, 131.6, 139.8, 140.5, 148.5.
Anal. Calcd for C24H20N2O4: C, 71.99; H, 5.03. Found: C,
71.72; H, 5.14. (R)-1,1′-Binaphthalene 2,2′-dicarboxylic acid:
1H NMR (CDCl3) δ 6.90 (d, J ) 8.6 Hz, 2H), 7.15 (t, J ) 7.5
Hz, 2H), 7.48 (t, J ) 7.5 Hz, 2H), 7.91 (d, J ) 8.2 Hz, 2H),
7.96 (d, J ) 8.8 Hz, 2H), 8.11 (d, J ) 8.8 Hz, 2H); 13C NMR
(CDCl3) δ 126.0, 126.3, 126.6, 127.3, 127.8, 128.2, 129.5, 132.8,
135.2, 141.2, 171.6.
(R)-3,3′-Bis(h yd r oxym eth yl)-6,6′-d ip h en yl-2,2′-bip yr i-
d in e N,N′-Dioxid e ((R)-1a ). 98% yield: [R]20 -69.2 (c 0.25,
D
CHCl3), and recovery of (R)-1,1′-binaphthalene 2,2′-dicarbox-
ylic acid: 100% yield.
J . Org. Chem, Vol. 68, No. 16, 2003 6335

Shimada et al.
TABLE 4. Cr ysta llogr a p h ic Da ta for (Rn a p,Spyr )-6a a n d
(Rn a p,Rpyr )-7a a
roacetic acid (10 µL, 0.13 mmol) in toluene-d8 (0.3 mL)),
because (Rnap,Spyr)-6c had poor solubility.
Ca ta lytic En a n tioselective Allyla tion of 4-Meth oxy-
ben za ld eh yd e w ith Allyl(tr ich lor o)sila n e. To a solution
of (R)-1a (0.4 mg, 0.001 mmol, 0.1 mol %), 4-methoxybenzal-
dehyde (10a ) (136 mg, 1.00 mmol), and diisopropylethylamine
(0.522 mL, 3.00 mmol) in acetonitrile (1 mL) was added
dropwise allyl(trichloro)silane (0.173 mL, 1.20 mmol) at -45
°C. The reaction mixture was stirred at -45 °C for 2.5 h, before
1 mL of 3 N sodium hydroxide was added. The reaction
mixture was stirred at room temperature for an additional 10
min, and it was extracted with diethyl ether three times. The
combined organic layer was washed with aqueous sodium
chloride, dried over anhydrous sodium sulfate, and evaporated
under reduced pressure, and the residue was purified by flash
column chromatography (ethyl acetate/hexane ) 1/5) to give
(S)-1-(4-methoxyphenyl)-3-buten-1-ol ((S)-11a ) (172 mg, 96%
(Rnap,Spyr)-6a
(Rnap,Rpyr)-7a
formula
fw
space group
cell dimensions
C
53H38N2O4
766.89
P212121(#19)
C58H42N2O4
830.98
P212121(#19)
Å
Å
Å
Å3
Z
34.2(1)
8.9674(1)
20.8342(2)
23.2481(3)
4343.41(7)
4
11.82(3)
10.60(2)
4280.2(2)
4
1.19
platelet
d
calcd, g‚cm-3
1.27
block
crystal shape
crystal size, mm
radiation
0.40 × 0.30 × 0.10
0.40 × 0.20 × 0.10
Mo KR
Mo KR
(λ ) 0.710 75 Å)
0.75
(λ ) 0.710 75 Å)
0.79
cm-1
yield): [R]20 -37.8 (c 1.9, C6H6). The enantiomeric excess of
D
max 2θ, deg
no. of unique data
no. of data used
R indices
-55.0
4320
3709 (I > 0.01σ(I))
R1 ) 0.089
wR2 ) 0.220
1.27
-55.0
5463
5116 (I > 0.20σ(I))
R ) 0.072
Rw ) 0.044
1.13
this sample was determined to be 94% ee by GLC analysis
with a chiral stationary phase column (CP-Chiralsil-Dex CB,
column temperature 125 °C): tR (R)-(+), 41.2 min; (S)-(-) (lit.23
43.5 min for (S)-11a of 88% ee); [R]24D -35.6 (c 1.07, C6H6); 1H
NMR (CDCl3) δ 1.96 (s, 1H), 2.50 (t, J ) 7.1 Hz, 2H), 3.81 (s,
3H), 4.69 (t, J ) 6.3 Hz, 1H), 5.13 (d, J ) 11.2 Hz, 1H), 5.16
(d, J ) 17.1 Hz, 1H), 5.81 (ddt, J ) 17.1, 11.2, 7.1 Hz, 1H),
6.88 (d, J ) 8.3 Hz, 2H), 7.28 (d, J ) 8.2 Hz, 2H); 13C NMR
(CDCl3) δ 43.6, 55.2, 72.9, 113.7, 118.0, 127.0, 134.6, 136.0,
158.9.
GOF
max shift/err
0.03
0.00
(R)-3,3′-Bis(h yd r oxym et h yl)-6,6′-d i-ter t-b u t yl-2,2′-b i-
p yr id in e N,N′-d ioxid e ((R)-1d ): 86% yield; [R]20 +545
D
(S)-1-(3,4-Dim et h oxyp h en yl)-3-bu t en -1-ol ((S)-11b ):24
[R]20D -32.7 (c 1.0, C6H6); 98% ee by GLC analysis: tR (R)-(+),
71.5 min; (S)-(-), 76.2 min, (CP-Chiralsil-Dex CB, column
temperature 125 °C) (lit.24 for (S)-11b of 65% ee: [R]20D -10.1);
1H NMR (CDCl3) δ 2.03 (d, J ) 3.1 Hz, 1H), 2.51 (t, J ) 7.9
Hz, 2H), 3.87 (s, 3H), 3.90 (s, 3H), 4.69 (t, J ) 7.2 Hz, 1H),
5.14 (d, J ) 10.3 Hz, 1H), 5.17 (d, J ) 17.8 Hz, 1H), 5.81 (ddt,
J ) 17.8, 10.3, 7.2 Hz, 1H), 6.84 (d, J ) 8.2 Hz, 1H), 6.88 (d,
J ) 8.8 Hz, 1H), 6.93 (s, 1H); 13C NMR (CDCl3) δ 43.8, 55.8,
55.9, 73.2, 108.9, 110.9, 118.0, 118.3, 134.5, 136.5, 148.4, 149.0.
(S)-1-(4-Bu toxyph en yl)-3-bu ten -1-ol ((S)-11c): [R]20D -23.2
(c 2.6, Et2O); 94% ee by HPLC analysis: tR (R)-(+), 23.8 min;
(S)-(-), 26.0 min (Daicel Chiralcel OD-H, hexane/2-propanol
(c 0.40, CHCl3). Recovery of (R)-1,1′-binaphthalene 2,2′-dicar-
boxylic acid: 91% yield.
X-r a y St r u ct u r e Det er m in a t ion of (Rn a p ,Sp yr )-6a a n d
(Rn a p,Rpyr )-7a . A suitable crystal of (Rnap,Spyr)-6a was obtained
by recrystalization from toluene, (Rnap,Rpyr)-7a from benzene.
Crystal data are summarized in Table 4.
Deter m in a tion of th e Ra te Con sta n t (k) of Th er m a l
Ep im er iza tion of Kin etic P r od u cts (Rn a p,Spyr )-6a -d . The
following treatment was carried out in order to remove the
small amount of proton of (Rnap,Spyr)-6a -d . To a solution of
(Rnap,Spyr)-6a -d (0.14 mmol) in CHCl3 (3.5 mL) was added
potassium carbonate 3.8 mg (0.028 mmol). The suspension was
stirred vigorously at room temperature for 12 h and passed
through Celite pad for removal of the salt, and the solvent was
evaporated.
The treated (Rnap,Spyr)-6a (7.4 µmol) was weighed into an
NMR tube. Toluene-d8 (0.5 mL) was added to it, followed by
sealing quickly under air atmosphere. The content of a NMR
tube was heated with oil bath at constant temperature
between each accumulation. The reaction temperature was
determined by the average of temperature collected at 30 s
for 5 min. NMR spectra were collected at appropriate intervals
until nine points. From the NMR spectra, the integral ratio of
(Rnap,Spyr)-6a to (Rnap,Rpyr)-7a could be obtained. Thus, the ratio
of [(Rnap,Spyr)-6a ]/[(Rnap,Spyr)-6a ]0 was equal to (Rnap,Spyr)-6a /
((Rnap,Spyr)-6a +(Rnap,Rpyr)-7a ) (integral ratio in NMR charts).
The observed rate constant was determined by plotting
[(Rnap,Spyr)-6a ]/[(Rnap,Spyr)-6a ]0 versus time, the slope of the
curve is the observed rate constant (R2 g 0.99).
1
) 98/2, 0.50 mL/min); H NMR (CDCl3) δ 0.97 (t, J ) 7.5 Hz,
3H), 1.48 (tq, J ) 7.7, 7.5 Hz, 2H), 1.75 (tt, J ) 7.7, 6.5 Hz,
2H), 2.12 (b, 1H), 2.47 (t, J ) 6.7 Hz, 2H), 3.94 (t, J ) 6.5 Hz,
2H), 4.65 (t, J ) 6.2 Hz, 1H), 5.10 (d, J ) 10.3 Hz, 1H), 5.13
(d, J ) 17.2 Hz, 1H), 5.78 (ddt, J ) 17.2, 10.3, 6.2 Hz, 1H),
6.86 (d, J ) 8.6 Hz, 2H), 7.24 (d, J ) 8.6 Hz, 2H); 13C NMR
(CDCl3) δ 13.8, 19.2, 31.3, 43.6, 67.6, 73.0, 114.3, 118.0, 127.0,
134.6, 135.8, 158.6. Anal. Calcd for C14H20O2: C, 76.33; H, 9.15.
Found: C, 76.49; H, 9.31.
(S)-1-(4-ter t-Bu tylp h en yl)-3-bu ten -1-ol ((S)-11d ):25 [R]20
D
-24.1 (c 1.0, Et2O); 89% ee by GLC analysis: tR (R)-(+), 49.8
min; (S)-(-), 53.0 min, (CP-Chirasil-Dex CB, column temper-
1
ature 125 °C); H NMR (CDCl3) δ 1.33 (s, 9H), 2.17 (b, 1H),
2.51 (m, 2H), 4.68 (t, J ) 6.5 Hz, 1H), 5.13 (d, J ) 11.4 Hz,
1H), 5.16 (d, J ) 17.3 Hz, 1H), 5.82 (ddt, J ) 17.3, 11.4, 6.9
Hz, 1H), 7.29 (d, J ) 8.2 Hz, 2H), 7.38 (d, J ) 8.5 Hz, 2H); 13
C
NMR (CDCl3) δ 31.3, 34.4, 43.6, 73.1, 118.1, 125.2, 125.5, 134.7,
The above-mentioned procedure was exceptionally per-
formed with less amount of (Rnap,Spyr)-6c (2.9 µmol), because
(Rnap,Spyr)-6c had poor solubility.
140.9, 150.4.
(S)-1-(4-Meth ylp h en yl)-3-bu ten -1-ol ((S)-11e):26 [R]20
D
-43.4 (c 1.1, C6H6); 89% ee by GLC analysis: tR (R)-(+), 56.4
Deter m in a tion of th e Ra te Con sta n t (kH+) of P r oton -
P r om oted Ep im er iza tion of Kin etic P r od u cts (Rn a p,Spyr )-
6a -d . Kinetic product (Rnap,Spyr)-6a (7.4 µmol) was weighed
into an NMR tube. Toluene-d8 (0.5 mL), trifluoroacetic acid
(7.4 µmol, 17 µL of the solution of trifluoroacetic acid (10 µL,
0.13 mmol) in toluene-d8 (0.3 mL)) was added to it. The NMR
tube was kept at 33 °C and spinning at 10-16 Hz. NMR
spectra were collected at appropriate intervals until nine
points.
min; (S)-(-), 63.5 min, (CP-Chiralsil-Dex CB, column temper-
ature 105 °C) (lit.26 for (S)-11e of 82% ee: [R]25 -37.3 (c 2.0,
D
1
C6H6)); H NMR (CDCl3) δ 2.51 (s, 3H), 2.65 (t, J ) 6.8 Hz,
2H), 4.81 (t, J ) 6.4 Hz, 1H), 5.27 (d, J ) 8.4 Hz, 1H), 5.29 (d,
(23) Denmark, S. E.; Fu, J . J . Am. Chem. Soc. 2001, 123, 9488.
(24) Chalecki, Z.; Guibe-J ampel, E.; Plenkiewicz, J . Synth. Commun.
1997, 27, 1217.
(25) Iseki, K.; Kuroki, K.; Kobayashi, Y. J apan Application No. J P
1997-09124675 A2 13.
(26) Mukaiyama, T.; Minowa, N.; Oriyama, T.; Narasaka, K. Chem.
Lett. 1986, 1, 97.
The above-mentioned procedure was performed with a
smaller amount of (Rnap,Spyr)-6c (2.9 µmol), toluene-d8 (0.5 mL),
trifluoroacetic acid (7.4 µmol, 17 µL of the solution of trifluo-
6336 J . Org. Chem., Vol. 68, No. 16, 2003

Axially Chiral 2,2′-Bipyridine N,N′-Dioxides
J ) 16.0 Hz, 1H), 5.95 (ddt, J ) 16.0, 8.4, 6.4 Hz, 1H), 7.31 (d,
J ) 8.0 Hz, 2H), 7.38 (d, J ) 8.0 Hz, 2H); 13C NMR (CDCl3) δ
21.1, 43.8, 73.2, 118.3, 125.8, 129.1, 134.6, 137.2, 140.9.
(S)-1-P h en yl-1,5-h exa d ien -3-ol ((S)-11j):8 [R]20 +10.9
D
(c 1.0, Et2O); 60% ee by HPLC analysis: tR (R)-(-), 14.5 min;
(S)-(+), 21.4 min, (Daicel Chiralcel OD-H, hexane/2-propanol
) 9/1, 0.50 mL/min) (lit.8 for (R)-11j of 80% ee: [R]D -11.3
(Et2O)); 1H NMR (CDCl3) δ 1.90 (b, 1H), 2.42 (m, 2H), 4.36 (b,
1H), 5.16 (d, J ) 10.2 Hz, 1H), 5.18 (d, J ) 17.3 Hz, 1H), 5.85
(ddt, J ) 17.3, 10.2, 7.2 Hz, 1H), 6.23 (dd, J ) 16.0, 6.4 Hz,
1H), 6.60 (d, J ) 16.0 Hz, 1H), 7.23 (t, J ) 7.3 Hz, 1H), 7.31
(t, J ) 7.5 Hz, 2H), 7.37 (d, J ) 7.9 Hz, 2H); 13C NMR (CDCl3)
δ 41.9, 71.7, 118.5, 126.4, 127.6, 128.5, 130.3, 131.5, 134.0,
136.6.
(S)-1-P h en yl-3-bu ten -1-ol ((S)-11f):23 [R]20 -48.9 (c 1.0,
D
C6H6); 84% ee by HPLC analysis: tR (R)-(+), 15.2 min; (S)-(-),
16.5 min, (Daicel Chiralcel OD-H, hexane/2-propanol ) 19/1,
0.50 mL/min) (lit.23 for (S)-11f of 87% ee: [R]24D -48.1 (c 1.05,
1
C6H6)); H NMR (CDCl3) δ 2.08 (b, 1H), 2.48 (m, 2H), 4.63 (t,
J ) 6.5 Hz, 1H), 5.13 (d, J ) 10.2 Hz, 1H), 5.16 (d, J ) 16.8
Hz, 1H), 5.75 (m, 1H), 7.29 (m, 5H); 13C NMR (CDCl3) δ 43.8,
73.3, 118.3, 125.8, 127.5, 128.4, 134.4, 143.8.
(S)-1-(1-Na p h th yl)-3-bu ten -1-ol ((S)-11g):26 [R]20 -84.1
(1S,2R)-2-Meth yl-1-p h en yl-3-bu ten -1-ol ((1S,2R)-12):8
D
[R]20 -21.1 (c 2.2, CHCl3); 77% ee by HPLC analysis: tR
(c 1.0, C6H6); 81% ee by HPLC analysis: tR (S)-(-), 16.5 min;
(R)-(+), 27.5 min, (Daicel Chiralcel OD-H, hexane/2-propanol
D
(1S,2R)-(-), 14.4 min; (1R,2S)-(+), 16.5 min, (Daicel Chiralcel
) 9/1, 0.50 mL/min) (lit.26 for (S)-11g of 80% ee: [R]24 -77.5
OD-H, hexane/2-propanol ) 95/5, 0.50 mL/min) (lit.8 for
D
1
1
(c 2.9, C6H6)); H NMR (CDCl3) δ 2.19 (b, 1H), 2.70 (m, 2H),
(1R,2S)-12 of 84% ee: [R]D +22.6 (CHCl3)); H NMR (CDCl3)
5.18 (d, J ) 10.1 Hz, 1H), 5.22 (d, J ) 17.2 Hz, 1H), 5.53 (b,
1H), 5.93 (ddt, J ) 17.2, 10.1, 7.1 Hz, 1H), 7.50 (m, 3H), 7.66
(d, J ) 7.3 Hz, 1H), 7.78 (d, J ) 8.2 Hz, 1H), 7.88 (d, J ) 7.8
Hz, 1H), 8.07 (d, J ) 8.3 Hz, 1H); 13C NMR (CDCl3) δ 42.9,
69.9, 118.4, 122.8, 122.9, 125.4, 125.5, 126.0, 128.0, 128.9,
130.2, 133.8, 134.7, 139.4.
δ 1.00 (d, J ) 6.9 Hz, 3H), 2.03 (b, 1H), 2.57 (m, 1H), 4.59 (d,
J ) 8.9 Hz, 1H), 5.03 (m, 2H), 5.80 (m, 1H), 7.30 (m, 5H); 13
C
NMR (CDCl3) δ 14.2, 44.7, 77.3, 115.5, 126.6, 127.4, 128.1,
140.3, 142.6.
(1S,2S)-2-Met h yl-1-p h en yl-3-b u t en -1-ol ((1S,2S)-12):8
[R]20 -88.1 (c 2.3, CHCl3); 73% ee by HPLC analysis: tR
D
(S)-1-(2-Meth oxyp h en yl)-3-bu ten -1-ol ((S)-11h ):26 [R]20
D
(1R,2R)-(+), 15.5 min; (1S,2S)-(-), 16.5 min, (Daicel Chiralcel
-68.4 (c 1.0, C6H6); 76% ee by HPLC analysis: tR (S)-(-), 15.6
min; (R)-(+), 16.7 min, (Daicel Chiralcel OD-H, hexane/2-
OD-H, hexane/2-propanol ) 95/5, 0.50 mL/min) (lit.8 for
1
(1R,2R)-12 of 86% ee: [R]D +94.6 (CHCl3)); H NMR (CDCl3)
propanol ) 9/1, 0.50 mL/min) (lit.26 for (S)-11h of 80% ee:
δ 0.87 (d, J ) 6.9 Hz, 3H), 2.17 (b, 1H), 2.48 (m, 1H), 4.35 (d,
J ) 8.0 Hz, 1H), 5.17 (d, J ) 10.3 Hz, 1H), 5.20 (d, J ) 17.5
Hz, 1H), 5.80 (ddd, J ) 17.5, 10.3, 8.3 Hz, 1H), 7.30 (m, 5H);
13C NMR (CDCl3) δ 16.5, 46.2, 77.7, 116.8, 126.8, 127.6, 128.2,
140.6, 142.4.
1
[R]23 -65.8 (c 3.56, C6H6)); H NMR (CDCl3) δ 2.56 (m, 3H),
D
3.85 (s, 3H), 4.96 (dd, J ) 8.1, 5.0 Hz, 1H), 5.10 (d, J ) 10.1
Hz, 1H), 5.13 (d, J ) 17.6 Hz, 1H), 5.85 (ddt, J ) 17.6, 10.1,
6.8 Hz, 1H), 6.88 (d, J ) 8.2 Hz, 1H), 6.96 (t, J ) 7.5 Hz, 1H),
7.25 (t, J ) 8.0 Hz, 1H), 7.34 (d, J ) 7.6 Hz, 1H); 13C NMR
(CDCl3) δ 41.8, 55.3, 69.7, 110.4, 117.6, 120.7, 126.8, 128.3,
131.7, 135.2, 156.4.
Ack n ow led gm en t. This work was supported by a
Grant-in-Aid for Scientific Research, the Ministry of
Education, J apan. We thank Professor Keiji Maruoka,
Dr. Hazumi Nomura, and Dr. Akira Saito for assistance
in solving the single-crystal X-ray structure.
(S)-1-(4-Tr iflu or om eth ylp h en yl)-3-bu ten -1-ol ((S)-11i):
23 [R]20D -18.1 (c 1.9, C6H6); 56% ee by HPLC analysis: tR (S)-
(-), 48.0 min; (R)-(+), 51.9 min, (Daicel Chiralcel OJ , hexane/
2-propanol ) 100/1, 0.40 mL/min) (lit.23 for (S)-11i of 80% ee:
1
[R]24 -25.5 (c 1.50, C6H6)); H NMR (CDCl3) δ 2.22 (b, 1H),
D
2.50 (m, 2H), 4.80 (dd, J ) 7.8, 4.8 Hz, 1H), 5.18 (m, 2H), 5.79
(dddd, J ) 17.7, 9.7, 7.9, 6.5 Hz, 1H), 7.48 (d, J ) 8.1 Hz, 2H),
7.61 (d, J ) 8.1 Hz, 2H); 13C NMR (CDCl3) δ 43.9, 72.5, 119.2,
124.2 (q, J ) 271.0 Hz), 125.3 (q, J ) 3.7 Hz), 126.1, 129.6 (q,
J ) 32.3 Hz), 133.7, 147.8.
Su p p or tin g In for m a tion Ava ila ble: X-ray crystallo-
graphic data for (Rnap,Spyr)-6a and (Rnap,Rpyr)-7a . This material
is available free of charge via the Internet at http://pubs.acs.org.
J O0300800
J . Org. Chem, Vol. 68, No. 16, 2003 6337