LETTER
Design and Synthesis of 1,4-Amino Alcohol Ligands
1669
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Table 2 Diethylzinc Addition to Aromatic Aldehydes Using the
Ligands 9c and 9da
Et2Zn
O
OH
10 mol% ligands
R
H
R
hexane, –15 °C
Entry
R
Ligand
Yield (%)b ee (%)c
1
2
2-MeOC6H4
3-MeOC6H4
4-MeOC6H4
2-ClC6H4
9c
9d
90
88
95
95
3
4
9c
9d
93
92
95
96
5
6
9c
9d
89
90
96
96
7
8
9c
9d
65
60
90
94
9
10
4-ClC6H4
9c
9d
77
80
96
96
11
12
1-naphthyl
9c
9d
94
93
96
97
a Reaction conditions: Et2Zn (220 mol%), ligand (10 mol%), hexane,
–15 °C, 48 h.
b Isolated yield after flash chromatography.
c Determined by HPLC analysis on Chiral Daicel OD-H column or by
GC analysis on Chiral cyclodextrin capillary column, and the absolute
configuration of the major enantiomer was assigned as R by compar-
ison with the literature data.
In conclusion, we have developed a new type of cis-cyclo-
propane-based 1,4-amino alcohol ligands, which were
synthesized in three steps from the cheap intermediate of
pyrethroid insecticide and promoted the enantioselective
diethylzinc addition to aromatic aldehydes under mild
conditions to afford the corresponding secondary alcohols
in high yield with excellent enantioselectivity. These re-
sults showed that a cyclopropane-based ligand is promis-
ing in asymmetric catalysis. Research on the synthesis of
other chiral cyclopropane-based ligands and their applica-
tion in other types of asymmetric reactions is being car-
ried out in this laboratory and will be reported in due
course.
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Acknowledgment
Financial support from the National Natural Science Foundation of
China (Grant No. 20472111) is gratefully acknowledged.
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For the chiral ligand including achiral cyclopropane moiety,
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2004, 126, 718.
(9) cis-Cyclopropane Aminoester 7a–d; Typical Procedure
To a solution of secondary amine (60 mmol) in MeOH (50
mL) was added 5 N HCl–MeOH (4 mL, 20 mmol), followed
by 6 (3.12 g, 20 mmol) and NaBH3CN (1 g, 16 mmol). The
resulting solution was stirred at r.t. for 16 h, then
References and Notes
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Asymmetry 1999, 10, 3969.
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Asymmetric Catalysis in Organic Synthesis; Wiley: New
York, 1994, Chap. 5.
Synlett 2006, No. 11, 1667–1670 © Thieme Stuttgart · New York