A novel axially chiral 2,2′-bipyridine N,N′-dioxide. Its preparation and use for asymmetric allylation of aldehydes with allyl(trichloro)silane as a highly efficient catalyst

Article abstract of DOI:10.1021/ol026376u

(Matrix presented) New axially chiral 2,2′-bipyridine N,N′-dioxides were obtained by a new method that does not involve any procedures for the separation of enantiomers. One of the dioxides, (R)-3,3′-bis(hydroxymethyl)-6,6′-diphenyl-2,2′-bipyridine N,N′-dioxide, exhibited extremely high catalytic activity for the asymmetric allylation of aldehydes with allyl(trichloro)silane. The allylation of aromatic aldehydes proceeded in the presence of 0.01 or 0.1 mol % of the dioxide catalyst to give the corresponding homoallyl alcohols of up to 98% ee.

Full text of DOI:10.1021/ol026376u

ORGANIC
LETTERS
2002
Vol. 4, No. 16
2799-2801
A Novel Axially Chiral 2,2′-Bipyridine
N,N′-Dioxide. Its Preparation and Use for
Asymmetric Allylation of Aldehydes with
Allyl(trichloro)silane as a Highly
Efficient Catalyst
Toyoshi Shimada, Asato Kina, Syushiro Ikeda, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity,
Sakyo, Kyoto 606-8502, Japan
thayashi@kuchem.kyoto-u.ac.jp
Received June 17, 2002
ABSTRACT
New axially chiral 2,2′-bipyridine N,N′-dioxides were obtained by a new method that does not involve any procedures for the separation of
enantiomers. One of the dioxides, (R)-3,3′-bis(hydroxymethyl)-6,6′-diphenyl-2,2′-bipyridine N,N′-dioxide, exhibited extremely high catalytic activity
for the asymmetric allylation of aldehydes with allyl(trichloro)silane. The allylation of aromatic aldehydes proceeded in the presence of 0.01
or 0.1 mol % of the dioxide catalyst to give the corresponding homoallyl alcohols of up to 98% ee.
Among the useful methods for allylation of carbonyl
compounds is the use of hypervalent allylsiliconates as the
allylating reagents,1 the reaction of which with aldehydes
proceeds by way of six-membered cyclic transition states.2
Kobayashi3 and Denmark4 found that the hypervalent sili-
conates can be conveniently generated by addition of DMF
or HMPA to allylic trichlorosilanes to give homoallylic
alcohols in high yield on reaction with aldehydes. On the
basis of these findings, Denmark reported, in 1994, the first
example of asymmetric allylation by use of chiral phos-
phoramides as chiral Lewis base ligands.4 After this report,
a variety of chiral Lewis bases have been designed and used
for the asymmetric allylation with allylic trichlorosilanes.5-9
One big problem in the Lewis base-catalyzed asymmetric
allylation is that a large amount (5-10 mol %) of the catalyst
is required for a reasonable reaction rate, as has been
observed also in most of the Lewis acid-catalyzed asym-
(5) For a review on catalytic asymmetric allylation: Yanagisawa, A. In
ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yama-
moto, H., Eds.; Springer-Verlag: Heidelberg, Germany, 1999; Chapter 27.
(6) (a) Denmark, S. E.; Fu, J. J. Am. Chem. Soc. 2000, 122, 12021. (b)
Denmark, S. E.; Fu, J. J. Am. Chem. Soc. 2001, 123, 9488.
(7) (a) Iseki, K.; Kuroki, Y.; Takahashi, M.; Kobayashi, Y. Tetrahedron
Lett. 1996, 37, 5149. (b) Iseki, K.; Kuroki, Y.; Takahashi, M.; Kishimoto,
S.; Kobayashi, Y. Tetrahedron 1997, 53, 3513. (c) Iseki, K.; Mizuno, S.;
Kuroki, Y.; Kobayashi, Y. Tetrahedron Lett. 1998, 39, 2767. (d) Iseki, K.;
Mizuno, S.; Kuroki, Y.; Kobayashi, Y. Tetrahedron 1999, 55, 977.
(8) (a) Nakajima, M.; Sasaki, Y.; Shiro, M.; Hashimoto, S. Tetra-
hedron: Asymmetry 1997, 8, 341. (b) Nakajima, M.; Saito, M.; Shiro, M.;
Hashimoto, S. J. Am. Chem. Soc. 1998, 120, 6419.
(1) (a) Cerveau, G.; Chuit, C.; Corriu, R. J. P.; Reye, C. J. Organomet.
Chem. 1987, 328, C17. (b) Hosomi, A.; Kohra, S.; Tominaga, Y. J. Chem.
Soc., Chem. Commun. 1987, 1517. (c) Kira, M.; Sato, K.; Sakurai, H. J.
Am. Chem. Soc. 1988, 110, 4599.
(2) Hayashi, T.; Matsumoto, Y.; Kiyoi, T.; Ito, Y.; Kohra, S.; Tominaga,
Y.; Hosomi, A. Tetrahedron Lett. 1988, 29, 5667.
(3) (a) Kobayashi, S.; Nishio, K. Tetrahedron Lett. 1993, 34, 3453. (b)
Kobayashi, S.; Nishio, K. Synthesis 1994, 457.
(4) Denmark, S. E.; Coe, D. M.; Pratt, N. E.; Griedel, B. D. J. Org.
Chem. 1994, 59, 6161.
(9) (a) Angell, R. M.; Barrett, A. G. M.; Braddock, D. C.; Swallow, S.;
Vickery, B. D. Chem. Commun. 1997, 919. (b) Chataigner, I.; Piarulli, U.;
Gennari, C. Tetrahedron Lett. 1999, 40, 3633. (c) Hellwig, J.; Belser, T.;
Mu¨ller, J. F. K. Tetrahedron Lett. 2001, 42, 5417.
10.1021/ol026376u CCC: $22.00 © 2002 American Chemical Society
Published on Web 07/04/2002

metric reactions.10 The axially chiral biquinoline N,N′-dioxide
(S)-1 reported by Nakajima8 attracted our attention because
of its highly skewed chiral environment capable of bringing
about high enantioselectivity in the asymmetric allylation of
aldehydes, and we have looked for a new type of axially
chiral bipyridine N,N′-dioxides whose catalytic activity for
the asymmetric allylation is higher than others and a new
general method for their synthesis where the optical resolu-
tion is not involved. Here we report our recent result that a
new 2,2′-bipyridine N,N′-dioxide (R)-2a prepared without
optical resolution has high catalytic activity as well as high
enantioselectivity for the asymmetric allylation.11
ence of triethylamine to give a high yield of the cyclic diester.
On heating the diester in refluxing toluene, thermodynami-
cally more stable diastereoisomer 5a was obtained as a single
isomer,13 whose axial chirality of bipyridine moiety is (R).14
Oxidation of the bipyridine in 5a with m-chloroperbenzoic
acid followed by alkaline hydrolysis gave enantiomerically
pure (R)-3,3′-bis(hydroxymethyl)-6,6′-diphenyl-2,2′-bipyri-
dine N,N′-dioxide (2a), whose axial chirality is now fixed
by the formation of N,N′-dioxide. In a similar manner, (R)-
2,2′-bipyridine N,N′-dioxides 2b, 2c, and 2d, which are
substituted with methyl, hydrogen, and tert-butyl, respec-
tively, at the 6 and 6′ positions, were prepared starting from
the corresponding phenanthroline derivatives 3.
The 2,2′-bipyridine N,N′-dioxide (R)-2a was found to
possess high catalytic activity as well as high enantioselec-
tivity for the asymmetric allylation of aldehydes with allyl-
(trichloro)silane (Scheme 2 and Table 1). Thus, the reaction
Scheme 2
For the preparation of enantiomerically pure 2,2′-bipyridine
N,N′-dioxide 2a, whose chirality is based on the biaryl axial
chirality, we developed a new method of introducing and
fixing the axial chirality by oxidation of the cyclic diester
5a, which consists of (R)-1,1′-binaphthalene-2,2′-dicarboxylic
acid and 3,3′-bis(hydroxymethyl)-6,6′-diphenyl-2,2′-bipyri-
dine (4a) (Scheme 1). Thus, bipyridine-diol 4a, which is
Scheme 1a
of 4-methoxybenzaldehyde (7a) with allyl(trichloro)silane
(1.2 equiv) in the presence of 0.1 mol % of (R)-2a and
diisopropylethylamine (3 equiv) in acetonitrile at -45 °C
was completed within 2.5 h to give 96% isolated yield of
homoallyl alcohol 8a, which is an (S) isomer of 94% ee
(entry 2). The amount of the catalyst can be reduced to 0.01
mol % without loss of the enantioselectivity, though the
reaction is somewhat slower (entry 3). The high catalytic
activity of (R)-2a observed here makes a remarkable contrast
to the much lower catalytic activity of other chiral Lewis
Table 1. Asymmetric Allylation of 4-Methoxybenzaldehyde
(7a) with Allyl(trichloro)silane Catalyzed by (R)-Bipyridine
Dioxides 2a
catalyst 2
temp
(°C)
time
(h)
yieldb
(%)
% eec
(config)d
entry
(mol %)
solvent
1
2
3
4
5
6
7
8
9
2a (1)
CH3CN
CH3CN
CH3CN
CH2Cl2
CH2Cl2
CH3CN
CH3CN
CH3CN
CH3CN
-45
-45
-45
-78
-45
-45
-45
-45
-45
0.25
2.5
12
2.5
2.5
2.5
2.5
2.5
2.5
96
96
68
90
91
22
20
0
94 (S)
94 (S)
94 (S)
78 (S)
76 (S)
85 (S)
75 (S)
2a (0.1)
2a (0.01)
2a (0.5)
2a (0.1)
2b (0.1)
2c (0.1)
2d (0.1)
2e (0.1)
a Reaction conditions: (a) KMnO4, NaIO4; (b) CH2N2; (c) (i)
SOCl2, (ii) MeOH, Et3N; (d) LiAlH4, THF; (e) (R)-2,2′-bis(chloro-
carbonyl)-1,1′-binaphthalene, Et3N, CHCl3; (f) PhMe, reflux; (g)
mCPBA, CH2Cl2; (h) 6 N NaOH, MeOH; (i) NaH, MeI.
readily accessible from 2,9-diphenylphenanthroline (3a)12 by
oxidation with potassium permanganate and sodium periodate
followed by esterification of the dicarboxylic acid and
reduction with lithium aluminum hydride, was coupled with
(R)-2,2′-bis(chlorocarbonyl)-1,1′-binaphthalene in the pres-
95
92 (S)
a The allylation was carried out with allyl(trichloro)silane (1.2 equiv)
and diisopropylethylamine (3 equiv) in 1.0 M (aldehyde) solution. b Isolated
yields. c Determined by GLC analysis with CP-Chiralsil-Dex. d Determined
by the optical rotation of alcohol 8a.
2800
Org. Lett., Vol. 4, No. 16, 2002

base catalysts used so far in the asymmetric allylation of
aldehydes, where 5-10 mol % of the catalyst is usually
required for a reasonable reaction rate.5-9 The allylation also
proceeded smoothly in dichloromethane with the low amount
loading of (R)-2a,15 which is reported to be the solvent of
choice with most of the Lewis base catalysts, though the
enantioselectivity was lower than in acetonitrile (entries 4
and 5). The high catalytic activity of (R)-2a is ascribed
mainly to the phenyl substituents at the 6 and 6′ positions.
The allylation was much slower with the bipyridine dioxides
(R)-2b and (R)-2c where the phenyl group in (R)-2a was
replaced by methyl and hydrogen, respectively (entries 6 and
7). No allylation took place with (R)-2d, which is the
bipyridine dioxide substituted with tert-butyl groups at the
6 and 6′ positions (entry 8). The π-π stacking between the
phenyl group on (R)-2a and the aromatic ring in aldehyde
7a in the transition state probably enhances the catalytic
activity as well as the enantioselectivity. The hydroxymethyl
groups at 3 and 3′ positions do not play an important role in
catalyzing the reaction, which was demonstrated by es-
sentially the same catalytic activity and enantioselectivity
observed with the methyl ether (R)-2e (entry 9).
The catalytic activity of bipyridine dioxides (R)-2a was
also very high for other aldehydes. The allylation of aromatic
aldehydes 7b-e substituted with electron-donating and
-withdrawing groups proceeded in high yields in the presence
of 0.1 mol % of the catalyst (Table 2). 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-dimethoxybenzaldehyde (7b) (entry 2).
Table 2. Asymmetric Allylation of Aldehydes 7 with
Allyl(trichloro)silane Catalyzed by 0.1 mol % of (R)-2aa
aldehyde 7
yieldb
% eec of 8
[R]20 of 8
D
entry
Ar in ArCHO
(%) of 8
(config)
(c in C6H6)
1
2
3
4
5
4-MeOC6H4 (7a )
3,4-(MeO)2C6H3 (7b) 95 (8b)
4-t-BuC6H4 (7c)
Ph (7d )
4-CF3C6H4 (7e)
96 (8a )
94 (S)
98 (S)
89 (S)
84 (S)
56 (S)
-32.7 (1.0)
-37.8 (1.9)
-24.1 (1.0)d
-48.9 (1.0)
-18.1 (1.9)
93 (8c)
95 (8d )
83 (8e)
a The allylation was carried out with (R)-2a (0.1 mol %), allyl(trichloro)-
silane (1.2 equiv), and diisopropylethylamine (3 equiv) in 1.0 M acetonitrile
solution at -45 °C for 2.5 h. b Isolated yields. c Determined by GLC analysis
with CP-Chiralsil-Dex for 8a, 8b, 8c, and 8e, and by HPLC analysis with
Chiralcel OD-H (hexane/2-propanol ) 95/5) for 8d. d Specific rotation in
Et2O.
To summarize, new axially chiral 2,2′-bipyridine N,N′-
dioxides (R)-2 were obtained by a new method that does
not involve any procedures for the separation of enantiomers.
One of the dioxides, 2a, exhibited extremely high catalytic
activity for the asymmetric allylation of aldehydes with allyl-
(trichloro)silane giving homoallyl alcohols. Such a low
catalyst loading (0.01-0.1 mol %) is unprecedented for the
Lewis base-catalyzed asymmetric allylation.4-9,16 Further
studies are in progress to rationalize the high catalytic activity
caused by the phenyl groups at the 6 and 6′ positions as
well as the solvent effects of acetonitrile on the enantio-
selectivity.
Acknowledgment. This work was supported in part by
a Grant-in-Aid for Scientific Research, the Ministry of
Education, Japan. We thank Professor Keiji Maruoka and
Mr. Hazumi Nomura for assistance in solving the single-
crystal X-ray structure.
(10) For books containing Lewis acid-catalyzed asymmetric reactions:
(a) Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley: New
York, 2000. (b) ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer: Heidelberg, Germany, 1999. (c)
Lewis Acids in Organic Synthesis; Yamamoto, H., Ed.; Wiley: New York,
2001.
(11) Very recently, new chiral bipyridine N,N′-dioxides have been
prepared and used for Lewis base-catalyzed asymmetric addition to carbonyl
compounds: (a) Malkov, A. V.; Orsini, M.; Pernazza, D.; Muir, K. W.;
Langer, V.; Meghani, P.; Kocovsky, P. Org. Lett. 2002, 4, 1047. (b)
Denmark, S. E.; Fan, Y. J. Am. Chem. Soc. 2002, 124, 4233.
(12) Dietrich-Buchecker, C. O.; Marnot, P. A.; Sauvage, J. P. Tetrahedron
Lett. 1982, 23, 5291.
Supporting Information Available: Full experimental
and spectroscopic details for the compounds reported and
X-ray crystallographic data for 5a (CIF). This material is
available free of charge via the Internet at http://pubs.acs.org.
OL026376U
(13) The diester formation reaction at a low temperature gave the other
diastereoisomer as a kinetic product with high selectivity (over 95%
selectivity), which is isomerized into the thermodynamic isomer by heating.
These phenomena will be described in detail elsewhere.
(14) The absolute configuration was determined by X-ray structure
analysis of the cyclic diester 5a (see Supporting Information).
(15) The allylation with 0.1 mol % of (R)-2a at -45 °C did not proceed
in toluene, diethyl ether, or THF.
(16) A few examples of this level of low catalyst loading have been
reported in the Lewis acid-catalyzed Hetero-Diels-Alder reactions: (a) Yao,
S.; Johannsen, M.; Audrain, H.; Hazell, R. G.; Jørgensen, K. A. J. Am.
Chem. Soc. 1998, 120, 8599, where 0.05 mol % of catalyst was used. (b)
Doyle, M. P.; Phillips, I. M.; Hu, W. J. Am. Chem. Soc. 2001, 123, 5366,
where 0.01 mol % of catalyst was used. (c) Long, J.; Hu, J.; Shen, X.; Ji,
B.; Ding, K. J. Am. Chem. Soc. 2002, 124, 10, where 0.005 mol % of catalyst
was used.
Org. Lett., Vol. 4, No. 16, 2002
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