Aminosilylation of arynes with aminosilanes: Synthesis of 2-silylaniline derivatives

Article abstract of DOI:10.1039/b505615b

The nitrogen-silicon σ-bond of aminosilanes added across the triple bond of arynes to give varied 2-silylaniline derivatives straightforwardly. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b505615b

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Aminosilylation of arynes with aminosilanes: synthesis of 2-silylaniline
derivatives{
Hiroto Yoshida,* Takashi Minabe, Joji Ohshita and Atsutaka Kunai*
Received (in Cambridge, UK) 21st April 2005, Accepted 12th May 2005
First published as an Advance Article on the web 9th June 2005
DOI: 10.1039/b505615b
Table 1 Aminosilylation of benzynea
The nitrogen–silicon s-bond of aminosilanes added across the
triple bond of arynes to give varied 2-silylaniline derivatives
straightforwardly.
Much attention has been focused on the addition reactions of an
element–element s-bond across the carbon–carbon triple bond of
arynes as potent synthetic approaches to diverse polysubstituted
Yield
arenes, which are otherwise difficult to prepare.1 In particular, the
reactions using metallic reagents would be much more attractive
from the synthetic standpoint, because the resulting carbon–metal
bond can be applied to further carbon–carbon bond formation
and/or introduction of a functional group. In this context, we have
recently developed the addition of a carbon–tin,2 silicon–silicon3 or
tin–tin4 s-bond to arynes using a palladium catalyst. Furthermore,
we have also disclosed a different type of the addition, in which the
nucleophilic attack of stannyl sulfides (sulfur–tin s-bond)5 or ureas
(nitrogen–carbonyl s-bond)6 to arynes is a key step, and
demonstrated that the use of element–element s-bond compounds
bearing appropriate nucleophilic and electrophilic sites is essential
for the reactions to proceed smoothly. Herein we report on the
addition of a nitrogen–silicon s-bond of aminosilanes to arynes
(aminosilylation), which provides a variety of 2-silylaniline
derivatives in one step (eqn. 1).
Entry R92N
SiR03
2
Time/h (%)
3
1
2
3
4
5
6
7
8
a
Et2N
Me2N
Bu2N
SiMe2Ph
SiMe2Ph
SiMe2Ph
2a 1.5
2b
2c
2d 10
2e
2f
65
54
42
33
49
43
52
40
3aa
3ab
3ac
3ad
3ae
3af
3ag
3ah
5
5
(MeOCH2CH2)2N SiMe2Ph
Et2N
Et2N
Et2N
Et2N
SiMe2Bn
SiEt3
SiMe2(vinyl)
5
6
3
4
2g
SiMe2[(CH2)2CH2Cl] 2h
The reaction was carried out in THF (1 mL) at 0 uC using 1a
(0.30 mmol), (0.20 mmol), KF (0.60 mmol) and 18-crown-6
(0.60 mmol). Isolated yield based on the aminosilane.
2
b
introduction of a 1-azepinyl (3ai), piperidino (3aj), 2-isoquinolinyl
(3ak) or morpholino (3al) moiety into the aromatic skeleton
(Scheme 1).
The aminosilylation of substituted arynes was next investigated.
As depicted in Scheme 2, 4,5-dimethylbenzyne (from 1b) or 2,3-
naphthalyne (from 1c) underwent the addition of 2a efficiently,
giving 3ba or 3ca in 64% or 45% yield, whereas the yields of the
ð1Þ
We first examined the reaction of in situ-generated benzyne
(from 1a and KF–18-crown-6)7 with (diethylamino)dimethylphe-
nylsilane (2a) in THF at 0 uC, and observed that benzyne was
inserted into the nitrogen–silicon bond of 2a to afford N,N-diethyl-
2-(dimethylphenylsilyl)aniline (3aa) in 65% yield (Table 1, entry 1).
Aminosilanes containing a dimethylamino (2b), dibutylamino (2c)
or bis(2-methoxyethyl)amino (2d) moiety also reacted with
benzyne (entries 2–4), and (diethylamino)benzyldimethylsilane
(2e) or (diethylamino)triethylsilane (2f) furnished the correspond-
ing products (3ae or 3af) in moderate yields (entries 5 and 6). It
should be noted that the vinyl (2g) or 3-chloropropyl (2h) group on
the silicon atom did not interfere with the course of the
aminosilylation, leading to the formation of products (3ag or
3ah) with these reactive functional groups remaining intact (entries
7 and 8). Furthermore, cyclic amine-derived aminosilanes could
participate in the reaction as well, which resulted in the
{ Electronic supplementary information (ESI) available: Experimental
procedures and characterization of the products. See http://www.rsc.org/
suppdata/cc/b5/b505615b/
*yhiroto@hiroshima-u.ac.jp (Hiroto Yoshida)
akunai@hiroshima-u.ac.jp (Atsutaka Kunai)
Scheme 1 Aminosilylation with cyclic amine-derived aminosilanes.
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Scheme 3 A reaction pathway of the aminosilylation.
undergoes an intramolecular nucleophilic substitution at the silyl
moiety to provide the product. The exclusive formation of 3ga–3ia
in the reaction using 3-substituted arynes can be rationally
explained by unfavorable steric repulsion between the substituent
in the arynes and an incoming aminosilane, which prevents the
nitrogen atom approaching the ortho position of the arynes. Owing
to the strong electron-withdrawing effect of the fluoro substituent,
the developing negative charge at the meta position (vs. para)
would be stabilized to a greater extent in the transition state by the
addition of an aminosilane to 4-fluorobenzyne, which leads to the
predominant formation of 3ka.11 In contrast, steric and electronic
effects around the triple bond would be negligible in the reaction of
4-methylbenzyne, and equal addition of an aminosilane to both
ends of the triple bond occurs.12,13
Finally, utility of the aminosilylation has been demonstrated by
application to aminosilanes bearing two reaction sites (2m or 2n).
Thus, benzyne was inserted into each of the nitrogen–silicon bonds
to afford bis(2-aminophenyl)silane 3am or N,N9-bis(2-silylphenyl)-
piperazine 3an in 35% or 25% yield, respectively (Scheme 4).
In conclusion, we have disclosed that arynes are readily inserted
into the nitrogen–silicon s-bond of aminosilanes to produce
diverse 2-silylaniline derivatives, which are hardly accessible by
conventional methods. Further studies on addition reactions of
element–element s-bonds to arynes are in progress.
Scheme 2 Aminosilylation of substituted arynes.
reaction using a cyclopentene- or cyclohexene-condensed aryne
(from 1d or 1e, respectively) were somewhat low. Besides 4,5-
disubstituted arynes, sterically congested 3,6-dimethoxybenzyne
(from 1f) or 3-substituted arynes (from 1g–1i) also reacted with 2a
to offer the corresponding products (3fa–3ia). The regioselectivities
of the reaction with these 3-substituted arynes were perfect, and
thus, the diethylamino group was introduced into the m-position
of the substituent. In sharp contrast, 4-methylbenzyne (from 1j)
gave almost equal amounts of regioisomeric products (3ja and
39aj), which implies that the present reaction indeed proceeds
through an aryne intermediate. Although the steric surroundings
of 4-fluorobenzyne (from 1k) should be analogous to those of
4-methylbenzyne, its reaction with 2a provided 3ka preferentially.8
The nucleophilic attack of a nitrogen atom of an aminosilane to
an aryne would be an initiation step of the aminosilylation as
described in Scheme 3.9,10 The resulting zwitterion (4) subsequently
Scheme 4 Aminosilylation with aminosilanes bearing two reaction sites.
Chem. Commun., 2005, 3454–3456 | 3455
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5 H. Yoshida, T. Terayama, J. Ohshita and A. Kunai, Chem. Commun.,
2004, 1980.
6 H. Yoshida, E. Shirakawa, Y. Honda and T. Hiyama, Angew. Chem.,
Int. Ed., 2002, 41, 3247.
We thank Central Glass Co. Ltd. for a generous gift of
trifluoromethanesulfonic anhydride.
Hiroto Yoshida,* Takashi Minabe, Joji Ohshita and Atsutaka Kunai*
Department of Applied Chemistry, Graduate School of Engineering,
Hiroshima University, Higashi-Hiroshima 739-8527, Japan.
E-mail: yhiroto@hiroshima-u.ac.jp; akunai@hiroshima-u.ac.jp;
Fax: +81-82-424-5494; Tel: +81-82-424-7724
7 Y. Himeshima, T. Sonoda and H. Kobayashi, Chem. Lett., 1983, 1211.
8 The reactions with longer reaction times occasionally resulted in lower
yields. At present, the relationship between the yields and the reaction
times is unclear, since the aminosilylation products did not decompose
under the reaction conditions even with the prolonged reaction times.
9 For reviews on the nucleophilic couplings with arynes, see: S. V. Kessar,
in Comprehensive Organic Synthesis, ed. B. M. Trost and I. Flemming,
Pergamon Press, Oxford, 1991, vol. 4, pp. 483–515; H. Pellissier and
M. Santelli, Tetrahedron, 2003, 59, 701.
10 For reported examples of the nucleophilic couplings of amines with
arynes, see: Z. Liu and R. C. Larock, Org. Lett., 2003, 5, 4673; Z. Liu
and R. C. Larock, Org. Lett., 2004, 6, 3739.
11 Alternatively, the observed regioselectivity can also be explained by
polarization of the triple bond of 4-fluorobenzyne induced by the fluoro
substituent.
Notes and references
1 Se–Se and Te–Te s-bond: N. Petragnani and V. G. Toscano, Chem.
Ber., 1970, 103, 1652; S–S s-bond: J. Nakayama, T. Tajiri and
M. Hoshino, Bull. Chem. Soc. Jpn., 1986, 59, 2907; C–Si s-bond:
Y. Sato, Y. Kobayashi, M. Sugiura and H. Shirai, J. Org. Chem., 1978,
43, 199; Sn–Cl s-bond: C.-L. Tseng, S.-H. Tung and K.-M. Chang,
Chem. Abstr., 1964, 61, 7035; B–O s-bond: C.-L. Tseng, K.-M. Chang
and S.-H. Tung, Chem. Abstr., 1964, 61, 16084.
12 Similar regioselectivities were observed in the three-component coupling
of arynes, isocyanides and aldehydes: H. Yoshida, H. Fukushima,
J. Ohshita and A. Kunai, Angew. Chem., Int. Ed., 2004, 43, 3935.
13 As a referee commented, the charge density of an aryne in the ground
state should be dependent on the substituent, and affect the reactivity of
the aryne. However, the yields of the reactions using substituted arynes
varied widely from high to low irrespective of the electron-donating
or -withdrawing character of the substituents.
2 H. Yoshida, Y. Honda, E. Shirakawa and T. Hiyama, Chem. Commun.,
2001, 1880.
3 H. Yoshida, J. Ikadai, M. Shudo, J. Ohshita and A. Kunai, J. Am.
Chem. Soc., 2003, 125, 6638; H. Yoshida, J. Ikadai, M. Shudo,
J. Ohshita and A. Kunai, Organometallics, 2005, 24, 156; J. Ikadai,
H. Yoshida, J. Ohshita and A. Kunai, Chem. Lett., 2005, 34, 56.
4 H. Yoshida, K. Tanino, J. Ohshita and A. Kunai, Angew. Chem., Int.
Ed., 2004, 43, 5052.
3456 | Chem. Commun., 2005, 3454–3456
This journal is ß The Royal Society of Chemistry 2005