Triflic imide catalyzed [3+2] cycloaddition of aldimines with α,α-dimethylallylsilane

Article abstract of DOI:10.3987/COM-08-S(F)17

Tf₂NH-catalyzed [3+2] cycloaddition of N-aryl imines with α,α-dimethylallylsilane to give substituted pyrrolidines is described. We have found the mode of cycloaddition depends upon α-substituents of allylsilanes.

Full text of DOI:10.3987/COM-08-S(F)17

HETEROCYCLES, Vol. 77, No. 1, 2009
187
HETEROCYCLES, Vol. 77, No. 1, 2009, pp. 187 - 192. © The Japan Institute of Heterocyclic Chemistry
Received, 13th May, 2008, Accepted, 27th June, 2008, Published online, 30th June, 2008.
DOI: 10.3987/COM-08-S(F)17
TRIFLIC IMIDE CATALYZED [3+2] CYCLOADDITION OF
ALDIMINES WITH α,α-DIMETHYLALLYLSILANE
Naoya Shindoh,1 Hidetoshi Tokuyama,2 Yoshiji Takemoto,1,* and Kiyosei
Takasu1,*
1Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida,
Sakyo-ku, Kyoto 606-8501, Japan
E-mail: kay-t@pharm.kyoto-u.ac.jp
2Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama,
Sendai 980-8578, Japan
Abstract – Tf2NH-catalyzed [3+2] cycloaddition of N-aryl imines with
α,α-dimethylallylsilane to give substituted pyrrolidines is described. We have
found the mode of cycloaddition depends upon α-substituents of allylsilanes.
Triflic imide (Tf2NH), which is recognized as a super Brønsted acid,1 catalyzes several classes of C-C
bond formation reactions.2 We have shown Tf2NH efficiently activates imines in hetero Diels-Alder
reaction of imines with 2-siloxydienes.3,4 Moreover, we have recently reported Tf2NH-catalyzed cascade
hetero Diels-Alder and hydrogen transfer reaction.5 Namely, treatment of N-aryl imine (1) with allylsilane
(2) in the presence of a catalytic amount of Tf2NH afforded substituted quinoline (4) in a single operation
along with amine (5). Notably, in the cascade reaction Tf2NH activates two mechanistically distinct
reactions, such as hetero Diels-Alder reaction of 1 with 2 and hydrogen transfer between produced
tetrahydroquinoline (3) and imine (1) (Scheme 1). During the course of our study, we observed that
reaction of 1 with α,α-dimethylallylsilane in the presence of Tf2NH furnished, unexpectedly, not
hetero Diels-Alder
reaction
hydrogen transfer
Si
Si
Si
Tf2NH (cat.)
Tf2NH (cat.)
X
X
+
X
Ar
N
H
R
N
R
N
R
1
N
H
R
1
2
4
3
5
Scheme 1. Cascade hetero Diels-Alder and hydrogen transfer reaction catalyzed by Tf2NH
This paper is dedicated to Professor Emeritus Keiichiro Fukumoto on the occasion of his 75th birthday.

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HETEROCYCLES, Vol. 77, No. 1, 2009
quinolines but substituted pyrrolidines. In this communication, we wish to describe the Tf2NH catalyzed
[3+2] cycloaddition of imines with α,α-dimethylallylsilane.
α,α-Dimethylallylsilane (8) bearing tert-butyldimethylsilyl (TBS) moiety was prepared by Wittig
reaction of α-silylisobutyraldehyde (7), which was synthesized from acetaldehyde tert-butylimine (6) in 3
steps,6 in 83% yield (Scheme 2). Imines (1a-1h) were prepared from the corresponding aldehydes and
anilines according to a reported procedure.7
nBuLi
Tieze et al.
Ph3P+CH3 Br-
ref. 6
TBS
O
TBS
N
tBu
THF, 0 oC to rt
83%
H
83% for 3 steps
7
8
6
Scheme 2. Preparation of α,α-dimethylallylsilane
First of all, reaction of 1a (3 equiv) with 8 (1 equiv) was attempted for the purpose of preparation of
quinoline (9) under the reported conditions.5 As the result, neither 9 nor tetrahydroquinoline was observed,
but formation of substituted pyrrolidine (10a), which corresponds to a [3+2] cycloadduct, was obtained
in 77% yield (Scheme 3). When a mixture of 1a and 8 (molar ratio = 1 :1.2) was treated with a catalytic
amount of Tf2NH (10 mol%) in toluene at 60 oC for 24 h, 10a was obtained in 84% yield as a 3 :2 mixture
of diastereomers (Table 1, entry 1). In 1,2-dichloroethane, which has been reported to be an appropriate
solvent for the Tf2NH-catalyzed hetero Diels-Alder reaction,5 [3+2] cycloaddition also promoted to
1
furnish 10a in 76% yield (entry 2). H NMR spectra of each diastereomer of 10a,8 in which two sets of
doublet peaks derived from p-trifluoromethylaniline moiety were observed, ruled out production of [4+2]
cycloadducts, such as tetrahydroquinoline or quinoline (9). Careful recrystalization of a diastereomeric
mixture of 10a from MeOH gave single crystals of cis-10a, which corresponds to the major diastereomer.
The structure of cis-10a was confirmed unambiguously by an X-ray analysis (Figure 1).9 As shown in
Table 1, benzylidene and heteroarylidene imines except for 2-pyridylidene imine (1e) underwent [3+2]
cycloaddition to give substituted pyrrolidines (10) in 44―94% yield. All products were obtained as a
diastereomeric mixture (cis : trans = 1 : 1 ― 3 : 2). In the reaction of 1b, homoallylamine (11b) was
obtained in 27% yield along with 10b (entry 3). Since almost no formation of 11b was observed at the
early stage of the reaction, not Hosomi-Sakurai type allylation to 1b10 but decomposition of 10b via
β-silyl carbocation intermediate would cause formation of 11b. Actually, treatment of isolated 10b with
Tf2NH (10 mol%) in refluxing toluene afforded 11b exclusively. Reaction of α,β-unsaturated imine (1h)
was unsuccessful only to give a mixture of unidentified compounds (entry 10). We have assessed the
multicomponent variant starting from three materials: an allylsilane, an aldehyde and an aniline (Scheme

HETEROCYCLES, Vol. 77, No. 1, 2009
189
4). Treatment of a mixture of 8, p-tolylaldehyde (12) and p-trifluoromethylaniline (13) (molar ratio = 1.2 :
1 : 1) with 10 mol% of Tf2NH in toluene furnished the desired pyrrolidine (10a) in 78% yield as a 3 : 2
mixture of diastereomers.
TBS
TBS
X
TBS
Tf2NH (10 mol%)
X
X
N
+
toluene, 60 °C, 24 h
N
R
R
N
R
77% based on 8
1a (3 equiv.)
8 (1 equiv.)
10a
9a
(dr = 3 : 2)
Scheme 3. [3+2] Cycloaddition of 1a (X = CF3, R = p-tolyl) with 8 in the presence of Tf2NH
Table 1. Tf2NH-catalyzed [3+2] cycloaddition of 1 with 8a
entry imine (R, X)
%yield of 10b
dr (cis : trans)c
1
1a (p-MeC6H4, CF3)
84
3 : 2
2d
3e
4
1a
76
1 : 1
1b (o-NO2C6H4, CF3)
1c (2-furyl, CF3)
1d (2-thienyl, CF3)
1d
61
3 : 2
44
3 : 2
5
6f
60
3 : 2
70
3 : 2
7
1e (2-pyridyl, CF3)
1f (p-MeC6H4, NO2)
1g (p-MeC6H4, Br)
1h ((E)-CH=CH-Ph, CF3)
0
―
8
94
47
1 : 1
9
3 : 2
10
complex mixture
―
aStandard conditions: 1 (1.0 equiv.), 8 (1.2equiv.), Tf2NH (10
mol%), in toluene, at 60 oC, for 24 h. bYields were calculated
based on 1. cDiastereomeric ratio was determined by 1H NMR.
dReaction was carried out in 1,2-dichloroethane.
eHomoallylamine (11b) was obtained in 27% yield. f20 Mol% of
Tf2NH was used.
F3C
NH
R
11b (R = o-NO2C6H4)
Figure 1. Crystal structure of cis-10a (ORTEP drawing)

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HETEROCYCLES, Vol. 77, No. 1, 2009
Tf2NH (10 mol%)
60 °C, 24 h
78%
F3C
OHC
10a (cis : trans = 3 : 2)
+
+
8
NH2
12 (1.0 equiv.)
(1.2 equiv.)
13 (1.0 equiv.)
Scheme 4. Multicomponent reaction catalyzed by Tf2NH
In sharp contrast to our previous results,5 the mode of cycloaddition depends upon α-substitution of the
allylsilane. A plausible mechanism for reactions of imines with allylsilanes is outlined in Figure 2. With
α-nonsubstituted allylsilane (2), [4+2] cycloaddition took place to give tetrahydroquinolines 3 through a
stepwise manner. Namely, SE2’ reaction of 2 to imine (1) in the presence of Tf2NH would afford β-silyl
cation intermediate (14), and then intramolecular addition of the aromatic carbon of 14 would promote to
furnish [4+2] cycloadduct (3) (mode a). If intramolecular addition of the nitrogen atom of 14 takes place,
azetidine (15) would be produced (mode b). In contrast, in the reaction with α,α-disubstituted allylsilane
(8), intermediate (14) would transform into more stable β-silyl cation (16) or siliranium cation (17) by
1,2-silyl shift or silacyclopronation, respectively.11 Then, intramolecular addition of the nitrogen atom of
16 or 17 would afford [3+2] cycloadduct (10) (mode c).
R'
R'
Si
X
N
H
Ar
3 (R' = H)
[4 + 2]
cycloaddition
a
R'
R'
Si
R'
Si
Si
R'
a
R'
R'
c
X
b
X
N
b
R
N
H
R
N
H
R
[2 + 2]
cycloaddition
X
Tf2N
15
14
c
1,2-silyl shift
Si
R'
R'
R'
R'
R'
R'
Si
Si
X
X
X
N
[3 + 2]
cycloaddition
N
H
R
N
H
R
R
10 (R' = Me)
16 (R' = Me)
17
Figure 2. A plausible mechanism for [3 + 2] cycloaddition and substituent effects

HETEROCYCLES, Vol. 77, No. 1, 2009
191
Although several studies on cycloaddition reactions of imines with allylsilanes have been reported,12—15
studies to control modes of the cyloadditions are quite limited. Akiyama and his co-workers described
[3+2] cycloaddition of N-sulfonyl imines with triisipropylsilylpropene in the presence of a stoichiometric
amount of BF3-OEt2,13d whereas N-acyl and N-aryl imines took place [2+2]14 and [4+2] cycloadditions,15
respectively. They concluded N-substituent of imines would be a control factor in the selective formation
of [2+2], [3+2], or [4+2] cycloadducts. Our abovementioned study indicates α-substitution of
allylsilane is one of factors to control the mode of cycloaddition of N-aryl imines with allylsilanes.
In conclusion, reaction of imines with α,α-dimethylallylsilane in the presence of Tf2NH provides
substituted pyrrolidines by [3+2] cycloaddition. We found the mode of cycloaddition depends upon
α-substituents of allylsilanes. It is noteworthy that, to the best of our knowledge, it is the first example to
achieve the catalytic [3+2] cycloaddition of imines with allylsilanes.
ACKNOWLEDGEMENTS
This work was financially supported by a Grant-in-Aid for Scientific Research and Targeted Proteins
Research Program from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
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HETEROCYCLES, Vol. 77, No. 1, 2009
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