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Chemistry Letters Vol.38, No.7 (2009)
NO Cations as Highly Efficient Catalysts for Carbon–Carbon Bond Forming Reactions
Yasuhiro Yamashita and Shu¯ Kobayashiꢀ
Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033
The HFRE Division, ERATO, JST
(Received March 30, 2009; CL-090314; E-mail: shu kobayashi@chem.s.u-tokyo.ac.jp)
NO cations were found to be a highly effective catalysts in
Table 1. [3 þ 2] cycloadditions of nitrones 1 with tert-butyl vi-
a
nyl ether (2a) in the presence of a catalytic amount of NOPF6
several carbon–carbon bond forming reactions. For example,
[3 þ 2] cycloadditions of nitrones or azomethine imines with
vinyl ethers proceeded in the presence of 0.1–1 mol % of the
NO cation to afford the desired adducts in high yields.
Entry
1d Ph
R1
x/mol % Conditions Y/%b Drc
0.1
0.5
1
1 h, 1.0 M
1 h, 0.5 M
90
96
92
84
95
79
77
94
96
96
89
<3
38
78/22
82/18
86/14
84/16
83/17
85/15
76/24
84/16
84/16
56/44
84/16
—
2
4-MeC6H4
3e 4-MeOC6H4
21 h, 0.25 M
3 h, 0.17 M
1 h, 0.17 M
6 h, 0.17 M
1 h, 0.25 M
3 h, 0.25 M
1 h, 0.25 M
1 h, 0.25 M
1 h, 0.25 M
1 d, 0.25 M
13 h, 0.25 M
4
4-ClC6H4
1
1
1
1
The nitrosonium (NO) cation is an inorganic but nonmetallic
and is neither Brønsted acidic nor basic.1 While the NO cation is
well known in inorganic chemistry as an effective coordinating
ligand as well as an effective electron-withdrawing group, the
application of NO cations to organic synthesis as catalysts has
been quite limited despite its highly active nature.2 In recent
organic synthesis, the use of metal compounds is sometimes
avoided because of harmful waste generated after the reaction.
Although nonmetal activators, such as organocatalysts, have
been developed, their catalytic activity in some cases is not so
high. In our investigation of molybdenum or tungsten Lewis acid
chemistry,3 we were interested in the enhancement of Lewis
acidity of the metal complexes using NO cations as a coordina-
tive ligand.4 During this study, we also found that the NO cation
itself could work as a catalyst.5 Here we report the NO cation
catalyzed, highly efficient, carbon–carbon bond forming reac-
tions including [3 þ 2] cycloaddition reactions.
5e 4-FC6H4
6
7
8
9
4-MeO2CC6H4
1-Naphthyl
2-Furyl
Cinnamyl
0.5
1
0.5
1
10 Cyclohexyl
11f Ph
12g Ph
13h Ph
1
5
66/34
aThe reaction was carried out in CH2Cl2 at 0 ꢁC using nitrones
(R2 = Ph) and 2a in the presence of NOPF6 (x mol %) unless oth-
erwise noted. bIsolated yield. cDr = trans/cis. dMS 3A was used.
eAt ꢂ30 ꢁC. fR2 = 4-ClC6H4. gR2 = 4-MeOC6H4. hR2 = Bn.
reaction (Entry 9), an aliphatic nitrone also reacted in good yield
(Entry 10). We also examined the effect of the nitrones bearing
substituted aromatic or aliphatic groups on the nitrogen atom.
The electron-withdrawing group, p-chlorophenyl, gave similar
results (Entry 11), although a significant decrease in reactivity
was observed in the reaction of a nitrone with an electron-donat-
ing substituent, p-methoxyphenyl, on the nitrogen atom
(Entry 12). A nitrone with a benzyl group reacted but in low
yield and selectivity (Entry 13).
Next we turned our attention to development of other reac-
tions using NO cations as the catalyst. Azomethine imines pre-
pared from aldehydes and 3-pyrazolidinone have been shown
to be good 1,3-dipoles in [3 þ 2] cycloaddition reactions;8 how-
ever, to the best of our knowledge, no successful example of the
reaction using electron-rich olefins such as simple vinyl ethers
has been reported (Scheme 2) despite some reactions using al-
kynes or ꢀ,ꢁ-unsaturated carbonyl compounds as substrates.
First, a [3 þ 2] cycloaddition reaction of an azomethine imine
prepared from benzaldehyde with a vinyl ether was examined.
The reaction with tert-butyl vinyl ether proceeded well in the
[3 þ 2] cycloaddition of nitrones is an important method for
synthesis of isooxazolidine derivatives, which can be converted
to 1,3-amino alcohols by simple reductive cleavage of the N–O
bond (Scheme 1). It has been reported that several activators,
such as metal catalysts, promote this cycloaddition,6 however ef-
ficiency of this reaction is not necessarily satisfactory compared
with that of other reactions. We investigated the reaction of ni-
trones derived from benzaldehyde and N-phenylhydroxylamine
with tert-butyl vinyl ether in the presence of a catalytic amount
of NOPF6, and the desired cycloadduct was obtained in high
yield (Table 1, Entry 1).7 Nitrones prepared from aromatic alde-
hydes bearing electron-donating groups reacted with the vinyl
ether to afford the cycloadducts in high yields in the presence
of 0.5–1 mol % of NOPF6. The diastereoselectivities were almost
the same as those of the reactions using the nitrone derived from
benzaldehyde (Entries 2 and 3). Nitrones bearing electron-with-
drawing groups also gave good results without any side reaction
(Entries 4–6). Nitrones containing other aromatic rings, 1-naph-
thyl and 2-furyl groups, also reacted to afford the desired cyclic
adducts in good yields (Entries 7 and 8). Not only aromatic but
also ꢀ,ꢁ-unsaturated substituents were accommodated by this
O
N
O
NOPF6
+
N
N
N
OR3
O
R2
O
R2
OR3
NO+X–
N
N
R4
OR3
H
R4
+
OR3
2
5
R1
H
4
R1
1
2
3
Scheme 2. [3 þ 2] cycloaddition reaction of azomethine imine
4 with vinyl ether 2.
Scheme 1. [3 þ 2] cycloaddition of nitrones with vinyl ethers.
Copyright Ó 2009 The Chemical Society of Japan
Yamashita, Yasuhiro
