(Polyfluoro)silane-mediated generation of azomethine ylides from imines and their cycloaddition leading to N-heterocycles

Article abstract of DOI:10.1016/S0040-4039(03)00011-X

The novel generation and cycloaddition of azomethine ylides from an α-(trimethylsilyl)imine using (polyfluoro)silanes is described. The method was successfully applied to an efficient one-pot process. Namely, an azaallyl anion, generated by abstraction of the hydrogen α to an imino nitrogen, was treated with a di- or trifluorosilane to give an azomethine ylide intermediate below room temperature. The generated 1,3-dipole was smoothly trapped with dipolarophiles to afford nitrogen-containing five-membered heterocycles in good yields.

Full text of DOI:10.1016/S0040-4039(03)00011-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 1603–1606
(Polyfluoro)silane-mediated generation of azomethine ylides from
imines and their cycloaddition leading to N-heterocycles
Mitsuo Komatsu,* Hirofumi Okada, Seiji Yokoi and Satoshi Minakata
Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
Received 20 November 2002; revised 24 December 2002; accepted 25 December 2002
Abstract—The novel generation and cycloaddition of azomethine ylides from an a-(trimethylsilyl)imine using (polyfluoro)silanes
is described. The method was successfully applied to an efficient one-pot process. Namely, an azaallyl anion, generated by
abstraction of the hydrogen a to an imino nitrogen, was treated with a di- or trifluorosilane to give an azomethine ylide
intermediate below room temperature. The generated 1,3-dipole was smoothly trapped with dipolarophiles to afford nitrogen-con-
taining five-membered heterocycles in good yields. © 2003 Elsevier Science Ltd. All rights reserved.
1,3-Dipolar cycloaddition reactions constitute a power-
ful route to the construction of a variety of five-mem-
bered heterocycles.1 Of the various 1,3-dipoles available
for this reaction, an azomethine ylide is one of the most
important, in that it can be used in the synthesis of
N-heterocycles. As a result, a number of investigators
have reported on methods for generating azomethine
ylides.2 There are some examples of methods in which
the characteristics of silicon are utilized in the genera-
tion of dipoles from a-silylimine derivatives. These
methods enable the generation of less-stabilized azome-
thine ylides by taking advantage of the fact that car-
bon–silicon bonds are readily cleaved by nucleophiles
including fluoride ion. Thus, the desilylation of a-silyl-
iminium salts,3a–h the treatment of a-silylimine deriva-
tives with an acyl halide,3i–k trimethylsilyl triflate3l,3m or
acids,3n,3o the water-induced desilylation of a-
silylimines,3p–s and desilylation of ketene acetal3t,3u have
been developed to date. Among these, the unique
protodesilylation of (2-azaallyl)silanes leading to the
formation of N-unsubstituted azomethine ylides was
reported by Pearson and coworkers.3o On the other
hand, in our earlier papers, we reported that azome-
thine ylides can be generated from N-(silyl-
methyl)imines4a,b,e or N-(silylmethyl)amides4c through
an intramolecular silatropic rearrangement and from
a-silylimidates4d using F3SiPh or F2SiMePh as a quater-
nization–desilylation reagent. With these facts in mind,
we report on a novel and unique strategy for the
catalytic generation of azomethine ylides from imines
based on the fluorosilane-mediated generation of an
azomethine ylide from an a-silylimine.5
The generation of an azomethine ylide mediated by
(polyfluoro)silanes from an a-silylimine and its cycload-
dition were first examined as listed in Table 1. When
N-(a-trimethylsilylbenzyl)benzylideneamine (1)6 was
treated with 2 equiv. of N-phenylmaleimide (NPMI) in
the presence of dimethylphenylfluorosilane (1.2 equiv.)
in benzene at room temperature for 24 h, the expected
reaction did not proceed and the starting imine was
recovered (run 1). Although the use of a difluorosilane
(F2SiPhMe) led to the desired reaction, affording
cycloadducts in moderate yields as a mixture of
stereoisomers (run 2), a trifluorosilane (F3SiPh) was
found to be a superior reagent for the present purpose
(run 3). It is noteworthy that cycloaddition was
achieved even in the presence of a catalytic amount of
F3SiPh (run 4). Although these results indicate that
trifluorosilane is a good mediator for generation of the
azomethine ylide (especially, in the step of an a-
silylimine), further investigation is necessary to improve
the reaction efficiency under catalytic conditions.
In an attempt to overcome the problem concerning the
catalytic reaction, we propose an alternative method for
generating
azomethine
ylides
mediated
by
(polyfluoro)silanes as outlined in Scheme 1, which is
mechanistically rationalized as follows. The abstraction
of the hydrogen a to the imino nitrogen of the starting
imine is accomplished by LDA, followed by the addi-
tion of (polyfluoro)silanes, to give a-fluorosilylimines.
Keywords: azomethine ylide; 1,3-dipolar cycloaddition; fluorosilane;
a-silylimine; pyrrolidine.
* Corresponding
author.
Fax:
(+81)6-6879-7402;
e-mail:
komatsu@chem.eng.osaka-u.ac.jp
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(03)00011-X

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M. Komatsu et al. / Tetrahedron Letters 44 (2003) 1603–1606
Table 1. Generation of N-silylated azomethine ylides and
their cycloaddition with N-phenylmaleimide (NPMI) from
an a-silylimine using fluorosilanesa
atoms) on the silyl group, and their conversion to
azomethine ylides mediated by (polyfluoro)silane
(Table 2). An azaallyl anion, generated from N-ben-
zylidene-N-benzylamine (2) and LDA, was reacted
with 2 equiv. of difluorosilane (F2SiMePh), followed
by treatment with NPMI (3 equiv.) to afford the cor-
responding cycloadducts in high yield as a mixture of
stereoisomers. Monitoring of the reaction by 1H
NMR (in d8-THF) at −78°C to room temperature
confirmed the nearly quantitative formation of the a-
fluorosilylated imine. The NMR study indicated that
only 1 equiv. of F2SiMePh was required to produce
the a-fluorosilylimine. When F2SiMePh (1.1 equiv.)
was employed in the reaction (1 equiv. for formation
of the imine and 0.1 for the generation of the ylide),
the catalytic cycloaddition proceeded in good yield. A
trifluorosilane (F3SiPh) was found to be a more
efficient mediator in the present reaction, giving the
desired products in high yield. When dimethyl
fumarate was used as a dipolarophile in the presence
of 1.2 equiv. of F3SiPh under the same conditions,
the corresponding cycloadducts were obtained in
good yields. Although the use of a stoichiometric
amount of F2SiMePh gave good results in the case of
dimethyl maleate, catalytic cycloaddition was also
realized. The use of N-benzylidene-N-methylamine as
a dipolarophile was successful in the cycloaddition
and imidazolidines were obtained in good yields. It is
noteworthy that the present method was found to be
applicable to the generation of less-stabilized azome-
thine ylides which do not bear ylide-stabilizing sub-
stituents on each carbon. In particular, the
cycloaddition of N-neopentylidene-N-benzylamine as
the starting imine proceeded efficiently and involved
the catalytic generation of a less-stabilized azomethine
ylide.
Run Fluorosilane Time (h)
(equiv.)
Yield (%)
(3,5-cisb:
3,5-trans)
1
2
FSiMe2Ph
(1.2)
F2SiMePh
(1.2)
24
24
0
–
47c
(70:30)
3
4
F3SiPh (1.2) 24
F3SiPh (0.2) 48
98
(74:26)
(73:27)
41d
a Reaction conditions: 1 (1 mmol), NPMI (2 mmol), fluorosilane
(0.2–1.2 mmol), in PhH (4 mL) at rt, 24–48 h.
b Endo:exo=ca. 40:60.
c Recovery of 1: 45%.
d Recovery of 1: 53%.
In summary, this represents the first description of
the catalytic generation of azomethine ylides from
imines
including
less-stabilized
ylides
using
(polyfluoro)silanes under extremely mild conditions.
The 1,3-dipoles were successfully trapped with dipo-
larophiles to afford five-membered heterocycles in
good yields. The present reaction proceeds in a one-
pot system: the (polyfluoro)silanes play multiple func-
tions as a reagent for (1) the silylation of the starting
imines, (2) quaternization of the a-(fluorosilyl)imines
generated in situ, (3) desilylation of the species
formed in (2), and (4) a catalyst for the generation of
azomethine ylides. We are currently investigating the
mechanism of this reaction including the stereochem-
istry, in more detail, as well as applications to the
synthesis of other N-heterocycles.
Scheme 1.
The free (polyfluoro)silane at this stage acts as a
mediator for the generation of azomethine ylides from
a-(fluorosilyl)imines. The ylides react smoothly with
dipolarophiles to afford the initial cycloadducts, the
NꢀSi bond of which is cleaved by water during the
workup process.
Acknowledgements
On the basis of the concept, we investigated the in
situ formation of a-fluorosilylated imines, which
might be more readily desilylated by F− because of
their electron-withdrawing substituents (fluorine
This work was supported, in part, by a Grant-in-Aid
for Scientific Research from the Ministry of Educa-
tion, Science, Sports and Culture of Japan.

M. Komatsu et al. / Tetrahedron Letters 44 (2003) 1603–1606
1605
Table 2. Generation of N-silylated azomethine ylides from imines using fluorosilanes and their cycloaddition with
dipolarophilesa
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