Diastereoselective allylation of optically active imines with metallic samarium

Article abstract of DOI:10.1055/s-1998-1818

Barbier-type allylation of optically active imines such as N-benzylidenevalinol methyl ether was performed with metallic samarium, a catalytic amount of iodine, and allyl bromide. This reaction proceeded in a highly diastereoselective manner in THF at roo

Full text of DOI:10.1055/s-1998-1818

August 1998
SYNLETT
835
Diastereoselective Allylation of Optically Active Imines with Metallic Samarium
a
a
a
b
b
Nobuyuki Negoro, Reiko Yanada,* Masanori Okaniwa, Kazuo Yanada, Tetsuro Fujita
a
Faculty of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
b
Faculty of Pharmaceutical Sciences, Setsunan University, Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan
Received 4 May 1998
Abstract: Barbier-type allylation of optically active imines such as N-
benzylidenevalinol methyl ether was performed with metallic samarium,
a catalytic amount of iodine, and allyl bromide. This reaction proceeded
in a highly diastereoselective manner in THF at room temperature.
Samarium reagents have quite unique and useful properties such as long
ion radius, high coordination number, strong Lewis acidity, and high
oxophilicity. So the chemistry of samarium reagents to oxygen
functional groups, especially carbonyl groups, has been extensively
developed. Recently, several examples where high stereoselectivity was
achieved by chelation between the Sm(III) cation and oxygen functional
1
groups were reported. The chemistry of metallic samarium (Sm) is of
current interest in organic synthesis. Though samarium iodide (SmI ) is
2
a good synthetic tool (a mild, neutral and ether-soluble one-electron
2
reductant), its sensitivity to air makes it rather difficult to handle. We
have been studying the direct use of Sm to improve on this shortcoming
3
of SmI . The mildness and operational simplicity of this new protocol
2
encouraged us to further investigate the scope and utility with a series of
representative chiral imines. We report here the first diastereoselective
Barbier-type allylation of optically active imines with Sm and a
catalytic amount of iodine.
Three types of imines, N-benzylideneamino acid alkyl ester (1a), N-
benzylidene amino alcohol (1b), and N-benzylidene amino alcohol alkyl
4
ethers (1c-1k), have been designed for optically active substrates. The
former two have been used for Barbier-type allylation of imine to induce
chiral amines. No example has been reported on such reaction of N-
5
benzylidene aminoalcohol alkyl ether.
The general allylation procedure is as follows. A mixture of imine (0.30
6
mmol), Sm (0.63 mmol), iodine (0.03 mmol), and allyl bromide (0.60
mmol) was stirred in THF (2 ml) at room temperature under nitrogen for
30 min. The color changes of the mixture during the reaction served as
indicator of the progress of the reaction. After a short induction period,
the color of the solution turned to black- purple and then dark blue-
green. After the reaction was quenched with 1N-hydrochloric acid and
the resulting mixture was made basic with 10% NaOH aq., the product
was extracted with diethyl ether and was purified by preparative thin-
layer chromatography.
phenylglycinol gave only one diastereomer 3h in 77% yield and the
other diastereomer could not be detected by H-NMR (Entry 8). The
substituent, such as phenyl, at the β-position of the amino group did not
exert any influence upon the diastereoselectivity (Entries 6 and 7).
1
Table 2 shows that the substituent in the aldehyde side of imine affects
the allylation of (S)-valinol methyl ether type imines (1i-1l). Imine 1i
which has a 4-cyanophenyl group gave a complex mixture (Entry 1).
The reaction of 1j which has a 4-methoxyphenyl group proceeded
smoothly to give allylation products in 93% yield (Entry 2). These
results suggest that an electron-donating group helps the reaction. Imine
Table 1 summarizes the results of the allylation of imines. Among the
imines (1a-1d), methyl ether type 1c was the best substrate to give
allylation products in good yield (85%) and in high diastereoselectivity
(2c:3c= 96:4) (Entry 3). The absolute configurations of 2c (S, S) and 3c
(R, S) were determined by comparison with the authentic samples
1k which has
a
2-methoxyphenyl group showed high
diastereoselectivity (99:1) (Entry 3). This implies that the 2-methoxy
group on phenyl also coordinates to the Sm(III) cation in the
intermediate and constructs a stronger stereostructure. Imine 1l which
has a 1-naphthyl group gave the product in 62% yield with some by-
products (Entry 4).
7
prepared by O-methylation of known products 2b (S, S) and 3b (R, S).
Benzyl ether type 1d gave allylation products in 79% yield and in high
diastereoselectivity (2d:3d= 97:3) (Entry 4). Ester type imine 1a gave a
complex mixture (Entry 1). Alcohol type imine 1b gave allylation
products in 47% yield (2b:3b= 62:38) (Entry 2). The chiral allylation
product was readily converted into optically active homoallic amine
(Scheme 1). For example, 2c was converted into (S)-4c by
Figure 1 shows a plausible reaction mechanism. At the first stage, Sm
and allyl bromide would produce an allyl Sm complex in the presence of
8
iodine. The Sm(III) species was probably deposited in the reaction
demethylation with boron tribromide (BBr ) followed by oxidative
3
mixture during a short induction period. Because the Sm(III) species is a
strong Lewis acid, it would be coordinated by the intramolecular
nitrogen and oxygen atoms of the imine in the reactive intermediate
complex. In the case of imine 1c derived from (S)-valinol methyl ether,
7b
cleavage of the C-N bond (85 % yield). More bulkiness (phenyl,
isopropyl, ethyl, and methyl) at the α position from the amino group in
methyl ether type imines increased diastereoselectivity of allylation
(Table 1, Entries 8, 3, 5, and 6). Imine 1h derived from (R)-

836
LETTERS
SYNLETT
Chem. Jpn. 1995, 53, 987. (g) Kawatsura, M.; Dekura, F.;
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Kawatsura, M.; Kishi, E.; Kito, M.; Sakai, T.; Shirahama, H.;
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(2) (a) Kagan, H. B.; Namy, J. L. Tetrahedron 1986, 42, 6573.
(b) Kagan, H. B. Nouv. J. Chim. 1990, 14, 453. (c) Molander, G.
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(3) (a) Ogawa, A.; Takami, N.; Sekiguchi, M.; Ryu, I.; Kambe, N.;
Sonoda, N. J. Am. Chem. Soc., 1992, 114, 8729. (b) Ogawa, A.;
Nanke, T.; Takami, N.; Sumino, Y.; Ryu, I.; Sonoda, N. Chem.
Lett., 1994, 379. (c) Murakami, M.; Hayashi, M.; Ito, Y. Synlett,
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Yanada, K.; Fujita, T. Tetrahedron Lett. 1997, 38, 3271.
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and references cited therein.
(5) Examples of Grignard-type allylation to optically active imines
(N-benzylideneamino alcohol alkyl ether type): (a) Suzuki, Y.;
Takahashi, H. Chem. Pharm. Bull. 1983, 31, 2895. (b) Ukaji, Y.;
Watai, T.; Sumi, T.; Fujisawa, T. Chem. Lett. 1991, 1555.
(c) Hashimoto, Y.; Takaoki, K.; Sudo, A.; Ogasawara, T.; Saigo,
K. Chem. Lett. 1995, 235. (d) Alvaro, G.; Martelli, G.; Savoia, D.
J. Chem. Soc., Perkin Trans. 1. 1998, 775.
the bulky isopropyl group is oriented re face and obstructs the approach
of the allyl samarium species from the re face. The allyl samarium
species then approaches from the less hindered side si face to give the
(S, S) isomer 2c selectively.
In conclusion, the first diastereoselective Barbier-type allylation of
optically active imines was performed with Sm and a catalytic amount
of iodine. The induction of other substituents instead of the allyl group
is now being investigated.
(6) Addition of a catalytic amount of iodine was the best condition for
the allylation of 1c. No reaction occurred without iodine. One mol
eq. iodine to 1c gave 2c and 3c (95:5) in 24% yield accompanied
with the starting material 1c (30 %).
References and Notes
(7) (a) Bocoum, A.; Savoia, D.; Umani- Ronchi, A. J. Chem. Soc.,
Chem. Commun. 1993, 1542. (b) Basile, T.; Bocoum, A.; Savoia,
D.; Umani-Ronchi, A. J. Org. Chem. 1994, 59, 7766. (c) Alvaro,
G.; Pacioni, P.; Savoia, D. Chem. Eur. J. 1997, 3, 726.
(1) (a) Molander, G. A.; Kenny, C. Tetrahedron Lett., 1987, 28, 4367.
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Matsuda, F.; Shirahama, H. J. Org. Chem., 1994, 59, 5532.
(d) Kawatsura, M.; Matsuda, F.; Shirahama, H. J. Org. Chem.,
1994, 59, 6900. (e) Kawatsura, M.; Hosaka, K.; Matsuda, F.;
Shirahama, H. Synlett 1995, 729. (f) Matsuda, F. J. Synth. Org.
(8) We can not deny the mechanism in which the imine is reduced at
the first stage. But we think the formation of allyl Sm complex is
plausible because there is no imine dimer or amine, which is the
product from imine radical, under this experimental conditions.