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Chemistry Letters Vol.38, No.7 (2009)
Ene Reaction Using the Iminium Salt Generated by the Oxidation
of Aminoketene Silyl Aetal
Makoto Shimizu,ꢀ Hiroyuki Itou, Takuya Iwao, and Yuki Umeda
Department of Chemistry for Materials, Graduate School of Engineering, Mie University, Tsu 514-8507
(Received May 15, 2009; CL-090484; E-mail: mshimizu@chem.mie-u.ac.jp)
Ene reaction of various olefins proceeded with the iminium
salt generated by the oxidation of aminoketene silyl acetal to
give addition products in good yields.
Table 1. Imino ene reaction of 2-phenylpropene with an imini-
um salt under various conditionsa
DDQ (1.0 equiv)
OEt
OTMS
NBn2
CO2Et
NEt3 (4.0 equiv)
5-20 min
LA (2.0 equiv)
Bn2N
+
Ph
Ph
Solvent, Temp.
3a (x equiv)
1
4a
18-20 h
Whereas carbonyl ene reactions offer useful methodologies
for C–C bond forming reactions in a stereocontrolled manner,
their imino versions have not been widely exploited.1 This is
in part due to the lack of powerful activation methods for the
imino moieties in ene reactions, since the imino ene reaction in-
volves larger energies for activation than their carbonyl counter-
parts.1a,2 We have been interested in activation methods for
imino moieties by transforming into iminium species. Intriguing
reactivity of the iminium salts generated by the oxidation of alu-
minum enolate derivatives has enabled the use of ꢀ-imino esters
as acceptors of two nucleophiles (eq 1).3 Generation of iminium
species by the oxidation of the intermediary enolates was ex-
tended to the use of aminoketene silyl acetal, readily isolable
enolate derivatives as starting materials, and this methodology
offers a simple approach to a variety of ꢀ-amino esters in a short
sequence (eq 2).4 When these iminium salts are used as eno-
philes, this methodology offers a rapid preparation of homoallyl-
ic amines. This paper describes a facile imino ene reaction using
the iminium salt 2 generated by the oxidation of aminoketene
silyl acetal 1 (eq 3).
Entry Olefin/equiv Solvent Lewis acid Temp/ꢁC 4a/%b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
2.0
1.5
1.2
1.0
4.0
4.0
4.0
4.0
MeCN
DMF
EtCN
MeCN BF3 Et2O
THF
CH2Cl2 BF3 Et2O
PhMe BF3 Et2O
EtCN BF3 Et2O
EtCN BF3 Et2O
EtCN BF3 Et2O
EtCN BF3 Et2O
EtCN BF3 Et2O
EtCN BF3 Et2O
EtCN BF3 Et2O
EtCN BF3 Et2O
EtCN BF3 Et2O
none
none
TiCl4
ꢂ45–rt
ꢂ60–rt
ꢂ78–rt
ꢂ45–rt
ꢂ78–rt
ꢂ78–rt
ꢂ78–rt
ꢂ78–rt
ꢂ78–rt
ꢂ78–rt
ꢂ78–rt
ꢂ78–rt
ꢂ78–rt
ꢂ78–rt
ꢂ78–rt
ꢂ78–rt
10
45
8
.
26
50
60
17
63
70
67
70
65
36
62
36
27
.
BF3 Et2O
.
.
.
.
.
.
.
c
.
d
.
e
f
.
.
aCarried out according to the typical procedure (Ref. 5).
bIsolated yield. Without NEt3 treatment. di-Pr2NEt was used
c
in place of NEt3. ei-Pr2NH was used in place of NEt3. fPyridine
was used in place of NEt3.
Et2AlCl , EtAlCl2
(PhCOO)2
+
Et
R
PMP
PMP
Et
R
PMP
N
N
N
Nu-
ð1Þ
ð2Þ
ð3Þ
CO2Et
-
R
CO2Et EtCN, -20 oC to rt
CO2Et
of the olefin (Entries 9 and 11). When the reaction was carried
out without NEt3 treatment, a much decreased amount of the ad-
duct was obtained (Entry 13). Diisopropylethylamine could be
used with almost equal efficiency as base, whereas diisopropyl-
amine and pyridine were not effective (Entries 14–16). Under
the optimum conditions a variety of olefins were subjected to
the imino ene reaction, and Table 2 summarizes the results.
As shown in Table 2, methylidenecyclopentane and its
cyclohexane and cyclooctane analogues gave the adduct in good
yields, in which methylidenecyclohexane needed 4 equivalents
of the olefin for completion of the addition (Entries 1–3).
Cyclopropyl derivatives also served as good enes to give the
adducts in moderate to good yields (Entries 4–6). We also at-
tempted to use tri- and tetra-substituted olefins such as 2-meth-
yl-2-butene and 2,3-dimethyl-2-butene as enes. However, no ad-
duct arising from the ene reaction was observed.
Nu
PhCO2
+
NBn2
NBn2
CO2Et
OEt
OTMS
DDQ
RMgX
Bn2N
ArO-
R
CO2Et
R2
+
NBn2
R2
R1
NBn2
CO2Et
OEt
OTMS
R1
DDQ
3
Bn2N
ArO-
CO2Et
4
1
2
The initial examination was carried out to find optimum imi-
no ene reaction conditions using 2-phenylpropene (3a) as nucle-
ophile, and Table 1 summarizes the results.
In the absence of an added Lewis acid the reaction gave the
adduct in low to moderate yields, whereas TiCl4 was not an ef-
fective promoter (Entries 1–3). When the reaction was carried
A possible reaction mechanism is depicted in Scheme 1.
First, oxidation of the amino ketene silyl acetal 1 with DDQ
gives the iminium salt 2, which in turn is attacked by olefin to
give the initial adduct 5. This adduct is further deprotonated
by the dibenzylamino moiety to give the second iminium salt
6. This species is finally neutralized with the added base to give
.
out in the presence of BF3 Et2O in THF, CH2Cl2, or EtCN, mod-
erate to good yields of the adducts were obtained (Entries 5, 6,
and 8). The best result was realized using 1.2 or 2.0 equivalents
Copyright Ó 2009 The Chemical Society of Japan