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E. Tayama et al. / Tetrahedron Letters 55 (2014) 3041–3044
electron-rich aromatics by electrophilic aromatic substitution. We
focused on the electrophilic character of 1-Cu+ and decided to ap-
ply our method to its reaction with electron-rich alkenes Eq. 3.
Herein, we report the cyclopropanation of alkenes 2 bearing an
and 2f (Table 2). The catalyst loading could be reduced to
0.1 mol % (entries 1–3). In the presence of Cu(acac)2 and BF3ÁOEt2
alone, the reaction did not proceed (entries 4, 5). Cu(I) salts, such
as (MeCN)4CuPF6, catalyzed the reaction without the addition of
electron-donating group (EDG), such as 1,3-dienamide, with
diazoester 1 in the presence of the Cu(II)–acid catalyst.
a-aryl
BF3ÁOEt2, and the product 3af was obtained in moderate yield (en-
13
try 6). Cu(I) triflate benzene complex [CuOTf(C6H6)0.5
]
worked
First, we examined the reactions of 1a (1.0 equiv) with a slight
excess of various alkenes 2 (1.1–1.5 equiv) (Table 1). The procedure
is straightforward and does not require the slow addition of 1a. A
solution of 1–2 mol % Cu(OTf)2 (Cat. A) or Cu(acac)2–BF3ÁOEt2 (Cat.
B) in dichloromethane was added to a solution of 1a and 2 in
dichloromethane at room temperature in 1 min under an argon
atmosphere. The reaction with allylbenzene (2a), a simple alkene,
did not show adduction because the dimerization of 1a predomi-
nated (entry 1).8 When the alkene moiety was activated by an
EDG such as butoxy (2b), the corresponding cyclopropanation
product 3ab was obtained in 46% yield (entry 2).9 The amino ana-
logues, enamides 2c and 2d, also provided products10 3ac and 3ad
in reasonable yields (entries 3–6). To further improve the synthetic
utility of this reaction, we attempted to use 1,3-dienyl derivatives
as substrates, which would afford synthetically valuable alkenyl
cyclopropane derivatives. The reactions of (E)-1,3-butadienylsilyl
ether 2e11 proceeded at positions 3 and 4, and b-cyclopropylenol
silyl ether 3ae was obtained in good yields with high diastereose-
lectivities (entries 7, 8). The use of the amino analogue, (E)-1,3-but-
adienamide 2f,12 also afforded b-cyclopropylenamide 3af with
similar yield, regio-, and diastereoselectivities (entries 9, 10).
Next, we tested various catalysts to clarify the catalytic activity
of Cu(OTf)2 and Cu(acac)2–BF3ÁOEt2 in the cyclopropanation of 1a
well to give 3af in 92% yield (entry 7). It is worth noting that the
use of rhodium(II) acetate dimer [Rh2(OAc)4], which is a standard
catalyst in a-diazocarbonyl reactions, resulted in modest yield (en-
try 8, 51%). The Cu(II)–acid catalyst was found to work as an alter-
native to previous catalysts, such as Rh, Ru, and Cu(I) complexes, in
the reaction of 1a and 2f. To expand the substrate scope of our
method, 2g and 2h were subjected to the reaction conditions.
The corresponding product, N-diphenylmethyl derivative 3ag was
obtained in similar yields (entries 9, 10); however, the reaction
of the N-methyl derivative 3ah showed low yields (entries 11,
12). The acid-catalyzed decomposition of 2h or 3ah might occur
as
a result of instability. The yield was improved using
CuOTf(C6H6)0.5 (entry 13). Although an explanation for this is not
entirely clear, it is likely that the Lewis acids interact with
Cu(acac)2, making copper more electrophilic, which might allow
generation of the Cu-stabilized carbocation 1-Cu+ depicted in
Scheme 1.14
To understand the scope and limitations of our proposed reac-
tion, we investigated the reactions of 2f with various analogs of
1 (Table 3). The reactions using
a-(substituted-aryl)diazoesters
1b–1g with 2f proceeded in reasonable yields through both cata-
lysts A and B (entries 1–12). However, the use of diazoesters with-
out an
3 (entries 13–16). The Cu-stabilized carbocation 1-Cu+ could not be
generated without an -aryl substituent.
Thus, an equimolar mixture of -phenyl diazoester 1a and a-(p-
a-aryl substituent, such as 1h and 1i, did not give the adduct
a
Table 1
a
Cu(II)–acid catalyzed cyclopropanation of various types of alkene 2 with 1aa,b
methoxyphenyl)diazoester 1e was subjected to the Cu(II)–acid cat-
alyzed cyclopropanation of 2f (Scheme 2). Interestingly enough,
product analysis revealed that the reaction with 1e proceeded
preferably to afford 3ef in 70% yield along with 3af in 12% yield.
Table 2
Cyclopropanation of 1,3-dienamides 2 with 1a under various conditionsa
Entry
R
Cat.
3c (%)
Drd
1
2
3
4
5
6
CH2Ph (2a)
On-Bu (2b)
NHCbz (2c)
NHCbz (2c)
NMeCbz (2d)
NMeCbz (2d)
A
A
A
B
A
B
0 (3aa)
—
46 (3ab)
93 (3ac)
82 (3ac)
53 (3ad)
60 (3ad)
>95:5
>90:10e
>90:10e
>95:5
>95:5
(2e)
(2e)
(2f)
7
8
9
A
B
A
81 (3ae)
86 (3ae)
89 (3af)
90:10
90:10
90:10
Entry
2
Catalyst (mol %)
3b (%)
Drc
1
2
3
4
5
6
7
8
9
10
11
12
13
f
f
f
f
f
f
f
f
g
g
h
h
h
Cu(OTf)2 (1)
85 (3af)
88 (3af)
77 (3af)
0 (3af)
90:10
90:10
90:10
—
—
95:5
90:10
90:10
85:15
90:10
90:10
90:10
90:10
Cu(acac)2–BF3ÁOEt2 (0.5–0.5)
Cu(acac)2–BF3ÁOEt2 (0.1–0.1)
Cu(acac)2 (1)
BF3ÁOEt2 (1)
0 (3af)
Cu(MeCN)4PF6 (2)
CuOTf(C6H6)0.5 (2)
Rh2(OAc)4 (2)
67 (3af)
92 (3af)
51 (3af)
83 (3ag)d
86 (3ag)d
45 (3ah)d
10 (3ah)d
75 (3ah)d
(2f)
10
B
89 (3af)
90:10
Cu(OTf)2 (2)
Cu(acac)2–BF3ÁOEt2 (1–1)
a
In entries 1–6, 1.5 equiv of 2 were used. For entries 7–10, 1.1 equiv of 2 were
used.
Cu(OTf)2 (2)
Cu(acac)2–BF3ÁOEt2 (1–1)
CuOTf(C6H6)0.5 (2)
b
The relative stereochemistries of 3ab, 3ae, and 3af were determined by com-
paring the 1H NMR chemical shifts with authentic samples. For details: see the
Supplementary data. The relative stereochemistries of 3ac and 3ad were tentatively
determined by analogy.
a
b
c
1.0 equiv of 1a and 1.1 equiv of 2 were used.
Isolated yield.
c
Determined by 1H NMR analysis of the isolated product.
Isolated yield.
Determined by 1H NMR analysis of the isolated product.
The exact ratio could not be determined because of the formation of rotamers.
d
d
The relative stereochemistries of 3ag and 3ah were tentatively determined by
e
analogy with 3af.