LETTER
Organocatalysis
2661
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Table 2 Lappacontine-Catalyzed Asymmetric Hydroxylation of
b-Keto Estersa
O
O
cat. (10 mol%)
t-BuOOH (1.5 equiv)
O
O
R1
R1
OR2
OR2
CHCl3, 15 °C, 72 h
n
n
OH
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1a–m
2a–m
Entry 1
n
1
1
1
1
1
1
1
1
1
1
1
1
1
2
1
R1
R2
Yield (%)b ee (%)c
1
2
1a
5-Cl
Me 92 (68)
Et 88
65 (>99)
65
67
59
78
68
75
85
73
74
67
–
1b
1c
1d
1e
1f
5-Cl
3
5-Cl
i-Pr 85
Bn 82
Me 95
4
5-Cl
5
6-Br
6
6-Br
Et
85
7
1g
1h
1i
5-Cl-6-Br
4-MeO
4-MeO
4-MeO
4-MeO
5,6-MeO
H
Me 90
Me 78
8
9
Et
75
10
11
12
13
14
15
1j
i-Pr 72
Bn 53
Me Nr
Me 94
Me 17d
1k
1l
1m
1n
1o
68
–
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H
without benzene ring Bn <5
–
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a Unless noted, reactions were run with 1 mmol b-keto ester, 5 mmol
oxidant, 16 mL solvent, 15 °C, 72 h.
b Isolated yields after column chromatography; yield after a single re-
crystallization is reported in parentheses.
c The ee values were determined by HPLC; the ee value after a single
recrystallization is reported in parentheses.
d Based on the recovered starting material.
In summary, we have developed the diterpenoid alkaloid
lappaconitine as a new chiral base organocatalyst for the
first time. Using lappacontine as the organocatalyst and
tert-butyl hydroperoxide as the oxidant in chloroform, the
a-hydroxylation of b-keto esters proceeds in high yield,
and the products are recovered with up to 85% ee. The ee
value was improved to >99% after a single recrystalliza-
tion. Further investigations on the application of lappac-
onitine and other alkaloids are under way.
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Supporting Information for this article is available online at
References and Notes
(1) For the reviews, see: (a) Dalko, P. I.; Moisan, L. Angew.
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Synlett 2009, No. 16, 2659–2662 © Thieme Stuttgart · New York