complexes in the enantioselective allylic oxidation of ole-
fins,11 cyclopropanation reactions,12 and propargylation of
imines.13 We observed that the diphenyl groups at the C-5
of the oxazoline rings played a crucial role in enhancing the
enantioselectivity. To further explore the efficiency of the
catalyst, we thought to extend the use of chiral pyridine 2,6-
bis(5′,5′diphenyloxazoline)- Cu(II) complexes in enanti-
oselective F-C reaction of indole with 2-enoylpyridines. The
Cu(II) complex of ligand 1a catalyzed the Friedel-Crafts
reaction of indole and benzylidene-2-acetylpyridine to give
the product in 89% yield and 16% ee (Scheme 1) after 24 h.
Table 1. Friedel-Crafts Alkylation of Indole with
Benzylidene-2-Acetylpyridine N-Oxide Catalyzed by Various
Catalysts
catalyst
(mol %)
yield
(%)a
ee
entry
1
T (°C)
time
(%)b
Scheme 1
. Enantioselective Friedel-Crafts Reaction of Indole
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
1a
1a
1b
1c
1d
1e
1f
1g
1h
1i
10
10
10
10
10
10
10
10
10
10
10
10
10
5
rt
0
0
0
0
0
0
0
0
15 min
15 min
15 min
15 min
15 min
15 min
15 min
15 min
12 h
15 min
8 h
48 h
15 min
15 min
5 h
90
96
95
89
86
98
65
87
84
97
93
92
97
96
94
89
88
96
94
17
94
5
6
1
1
65
59
25
99
99
96
82
Catalyzed by pybox-diph-Cu(II) Complex
0
0
0
1j
1k
1a
1a
1a
1a
-20
-20
-20
-20
2
1
12 h
a Isolated yield. b Determined by chiral HPLC using a Chiralpak AD-H
column (see the Supporting Information).
(1b and 1d) gave slightly lower enantioselectivity (94% ee)
(Table 1, entries 3 and 5). Lack of asymmetric induction
with the ligand 1h indicated that the pyridine nitrogen was
important for chelation with Cu(II). In order to find out the
role of the gem-diphenyl groups of the ligands on enanti-
oselectivity, we studied the reaction with ligands 1i-k. The
poor enantioselectivity with these ligands indicated that the
The poor enantioselectivity and reactivity could be due to
an inappropriate coordination between substrate and catalyst.
Pedro has reported that 2-enoylpyridine 1-oxides provide
better coordination than the 2-enoylpyridines with Cu(II)
metal.14 In this paper, we wish to report the use of
2-enoylpyridine 1-oxides in enantioselective F-C reaction.
The initial study was carried out by using indole and
benzylidene-2-acetylpyridine N-oxide as the substrates in the
presence of chiral Cu(II) complex of ligand 1a (10 mol %)
in chloroform at 0 °C. To our delight, the F-C reaction was
efficient with excellent enantioselectivity (96%) (Scheme 1).
Various pybox-diph ligands with different substituents at
chiral center (1a-g) were used in the above reaction, and
the results are summarized in Table 1. It was observed that
the ligand 1a having an isopropyl group at the chiral center
(C-4) of oxazoline rings was optimum (Table 1, entry 2).
However, bulkier substituents such as t-Bu and s-Bu groups
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