Enantioselective addition of diethylzinc to aldehydes catalyzed by a new chiral β-amino alcohol derived from D-mannitol

Article abstract of DOI:10.1016/S0957-4166(98)00143-8

A new chiral β-dialkylamino alcohol 1 prepared from D-mannitol has been used as a highly effective chiral catalyst for the enantioselective addition of diethylzinc to unhindered aliphatic aldehydes to afford the product alcohols in up to 94% ee.

Full text of DOI:10.1016/S0957-4166(98)00143-8

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 1489–1492
Enantioselective addition of diethylzinc to aldehydes catalyzed by
†
a new chiral β-amino alcohol derived from D-mannitol
∗
Byung Tae Cho and Yu Sung Chun
Department of Chemistry, Hallym University, Chunchon 200-702, South Korea
Received 3 March 1998; accepted 4 April 1998
Abstract
A new chiral β-dialkylamino alcohol 1 prepared from D-mannitol has been used as a highly effective chiral
catalyst for the enantioselective addition of diethylzinc to unhindered aliphatic aldehydes to afford the product
alcohols in up to 94% ee. © 1998 Elsevier Science Ltd. All rights reserved.
Enantioselective carbon–carbon bond formation is one of the most interesting challenges in organic
synthesis. In recent years the catalytic enantioselective addition of diethylzinc to aldehydes has attracted
much attention because of its potential in the preparation of optically active secondary alcohols.1
Previously most of the studies have focused on the use of β-amino alcohols as chiral catalysts derived
from natural products, such as camphor, α-amino acids and norephedrine.1 Also, several kinds of
synthetic chiral amino alcohol derivatives have proved to be effective chiral catalysts and may afford
high asymmetric induction in such reactions.1 Recently, we reported the enantioselective addition of
,2
,2
3
diethylzinc to aldehydes catalyzed by chiral β- or γ-dialkylamino alcohols derived from α-D-xylose,
4
5
α-D-glucose and L-tartaric acid. On the other hand, it has been realized that most of the catalysts
reported so far are highly effective for aromatic and relatively hindered aliphatic aldehydes, leading to the
corresponding optically active secondary alcohols with high enantioselectivity. For unhindered aliphatic
aldehydes, only limited success has been achieved.3 In the course of developing new chiral catalysts
for the addition reaction from inexpensive chiral pools, we found that 3-deoxy-3-N,N-di-n-octylamino-
e,6
1,2;5,6-di-O-isopropylidene-D-altritol 1 obtained from D-mannitol served as a highly effective chiral
catalyst for the ethylation to both aromatic and unhindered aliphatic aldehydes. In this communication,
we report the preliminary results for the reaction.
7
The β-amino alcohol 1 was prepared by refluxing 3-amino-3-deoxy-1,2;5,6-di-O-isopropylidene-D-
8
altritol 2 with 2 equiv. of n-octyl iodide in the presence of excess potassium carbonate in acetonitrile
(Scheme 1).
∗
†
Corresponding author. E-mail: btcho@sun.hallym.ac.kr
Catalytic enantioselective reactions. Part 14.
0957-4166/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00143-8

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B. T. Cho, Y. S. Chun / Tetrahedron: Asymmetry 9 (1998) 1489–1492
Scheme 1.
The enantioselective reaction was carried out by the addition of 2 equiv. of diethylzinc to aldehydes
in the presence of 0.1 equiv. of the catalyst in toluene at 0°C. As shown in Table 1, all the reactions
proceeded smoothly to give the corresponding product alcohols in good yields. In particular, the catalyst
1
is highly effective for the enantioselective addition to relatively unhindered aliphatic aldehydes, such as
butanal, hexanal, heptanal, undecanal and 3-phenylpropanal, to provide the corresponding alcohols with
enantiomeric excesses of a range between 82 and 94% ee (entries 1–4). To the best of our knowledge,
the values of % ee are one of the best results reported for such aldehydes. Also, the catalyst was found
to be useful for the ethylation of aromatic aldehydes to afford good enantioselectivity (88–92% ee). In
this reaction, it is observed that the steric effect of the O-substituent on the benzene ring on asymmetric
induction is not significant (entries 9 and 10).
The following procedure is representative. Under a nitrogen atmosphere, a toluene solution (2 ml) of
diethylzinc (2 mmol) was added to 1 (48.6 mg, 0.1 mmol) in toluene (1 ml) and stirred at 0°C for 30 min.
After undecanal (170 mg, 1 mmol) was added to this, the mixture was stirred at the same temperature for
12 h and then diluted with ether (10 ml). The excess diethylzinc was destroyed by addition of 1 N HCl
(
10 ml) and then extracted with ether (3×10 ml). The ether extract was dried over anhydrous MgSO and
4
concentrated under reduced pressure. The alcohol product was purified by flash column chromatography
on silica gel (230–400 mesh) using ethyl acetate:hexane (1:9) as eluent to give 3-tridecanol (R 0.43, 184
f
mg, 92% yield). Enantiomeric excess was measured by capillary GC analysis of trifluoromethyl acetate
of the product alcohol using a Chiraldex B-PH capillary column (AStec Inc.). GC analysis showed a
composition of 97 (R) and 3 (S) (i.e., 94% ee, R).
In conclusion, we found that a new chiral β-amino alcohol 1 derived from D-mannitol serves as an
effective catalyst for enantioselective addition of diethylzinc to aldehydes. Especially, it is noteworthy
that this catalyst is highly effective for relatively unhindered aliphatic aldehydes to give high enantio-
selectivity with a range of 81–94% ee. Further applications using this catalyst are now under investiga-
tion.
Acknowledgements
This study was generously supported by the Basic Science Research Institute Program (BSRI 97-
3412), Ministry of Education, Republic of Korea.
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2
0
−1
7. 1: Colorless viscous oil; [α]
D
+41.4 (c 1.13, CHCl
056, 857; H NMR (400 MHz, CDCl ) δ 0.88 (t, 6H, J=7.0 Hz), 1.26–1.48 (m, 24H), 1.34 (s, 3H), 1.36 (s, 3H), 1.40
s, 6H), 2.56–2.63 (m, 2H), 2.71–2.80 (m, 3H), 3.30 (br s, 1H), 3.48 (t, 1H, J=6.0 Hz), 3.73 (t, 1H, J=7.8 Hz), 3.84–3.89
3
); IR (neat, cm ) ν 3482, 2985, 2859, 1466, 1378, 1255, 1214, 1160,
1
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(
(
3
1
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m, 1H), 4.09–4.14 (m, 3H), 4.53–4.59 (m, 1H); C NMR (100 MHz, CDCl
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: C, 69.23; H, 11.41; N, 2.88. Found: C, 69.11; H, 11.59; N,2.64.
3
) δ 109.22, 108.41, 76.23, 75.89, 70.93,
6
28 5
C H55NO

1492
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8
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