Phosphazene base-promoted functionalization of aryltrimethylsilanes

Article abstract of DOI:10.1039/b611090h

The activation of Ar-Si bonds in aryltrimethylsilane was investigated using a catalytic amount of t-Bu-P4 base and selective functionalizations of aryltrimethylsilanes in the absence of strong electron withdrawing groups on the aromatic rings were accomplished. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b611090h

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Phosphazene base-promoted functionalization of aryltrimethylsilanes{
Koichi Suzawa,a Masahiro Ueno,a Andrew E. H. Wheatleyb and Yoshinori Kondo*a
Received (in Cambridge, UK) 1st August 2006, Accepted 18th September 2006
First published as an Advance Article on the web 4th October 2006
DOI: 10.1039/b611090h
1-Trimethylsilylnaphthalene (1) was chosen as a substrate for
the optimization of suitable conditions and the reactions of 1 with
aldehydes in the presence of various strong organic bases were
examined. The reaction of 1 with pivaldehyde in the presence of
20 mol% t-Bu-P4 base proceeded smoothly at room temperature
to give the alcohol 2a in 91% yield (Table 1, entry 1). Other
phosphazene bases with weaker basicities, such as t-Bu-P2 base
and BEMP showed no catalytic activity (Table 1, entries 2, 3). As
one of the conventional strong organic bases, DBU was employed
in conjunction with pivaldehyde and was found to be inactive. CsF
was then examined as a fluoride anion donor, but no carbon–
silicon bond cleavage was observed. The reactions with other
aldehydes were examined, that with benzaldehyde was found to
proceed somewhat slowly at room temperature. However, if the
reaction temperature was elevated to 80 uC then the product 2b
was obtained in 61% yield. Other aryl aldehydes with electro-
donating groups were also employed as electrophiles and the
reactions proceeded smoothly at room temperature. Interestingly
electron-rich arylaldehydes seemed to react faster than benzalde-
hyde (Table 1, entries 7–8).
The activation of Ar–Si bonds in aryltrimethylsilane was
investigated using a catalytic amount of t-Bu-P4 base and
selective functionalizations of aryltrimethylsilanes in the
absence of strong electron withdrawing groups on the aromatic
rings were accomplished.
Aryltrimethylsilanes have been used as important synthons and
various desilylative functionalizations have been investigated to
date.1 Among these, anion mediated generation of aryl anions is
one of the most important methods for selective bond formation.2
However, anion promoted activation has been limited to
aryltrimethylsilanes with strong electron withdrawing groups on
the aromatic rings, due to the instability of the generated aryl
anions. Phosphazene bases3 developed by Schwesinger and
proazaphosphatranes4 developed by Verkade are known to be
strong non-metallic organic superbases (Fig. 1). Among them,
t-Bu-P4 base shows extremely high basicity and has been used in
various selective deprotonative transformations.5 While the strong
affinity of t-Bu-P4 base for protons is regarded as synthetically
useful, the ability of t-Bu-P4 base to activate organometallic
compounds is largely undocumented.6 In a recent paper, we
reported that t-Bu-P4 base could be used as an excellent catalyst to
activate organosilicon compounds and demonstrated the possibi-
lity of catalytic activation of phenyltrimethylsilane.7 In order to
disclose the scope and limitation of this novel selective conversions
of phenyltrimethylsilanes catalyzed by t-Bu-P4 base, we have now
surveyed the functionalizations of various aryltrimethylsilanes in
the presence of catalytic phosphazene base.
Table 1
Yield
Entry Base
R
Temp./uC Time/h Product (%)
1
2
3
4
5
6
7
8
t-Bu-P4 t-Bu
t-Bu-P2 t-Bu
BEMP t-Bu
rt
rt
rt
rt
rt
80
1
24
24
24
24
6
2a
2a
2a
2a
2a
2b
2c
2d
91
0
0
0
0
61
78
68
DBU
CsF
t-Bu
t-Bu
t-Bu-P4 Ph
t-Bu-P4 4-MeOC6H4 rt
t-Bu-P4 2-MeOC6H4 rt
1
1
The reactions of other aryltrimethylsilanes were subsequently
examined. 2-Trimethylsilylnaphthalene reacted with pivalaldehyde
in the presence of t-Bu-P4 base at room temperature to give the
alcohol 4a in 68% yield (Table 2, entry 1). 4-Fluorophenyltrime-
thylsilane 3b and 4-bromophenyltrimethylsilane 3c gave the
corresponding alcohols 4b and 4c in 64% and 73% yields,
respectively (Table 2, entries 2, 3). Similarly, 4-trifluoromethyl-
phenyltrimethylsilane (3d) and 2-trifluoromethylphenyltrimethylsi-
lane (3e) reacted smoothly to give the alcohols 4d and 4e in 69%
and 73% yields, respectively (Table 2, entries 4, 5).
4-Methoxycarbonylphenyltrimethylsilane 3f reacted to give the
alcohol 4f in 46% yield (Table 2, entry 6). The reactions of
Fig. 1 Phosphazene bases and DBU.
aGraduate School of Pharmaceutical Sciences, Tohoku University,
Aramaki Aza Aoba 6-3, Aoba-ku, Sendai 980-8578, Japan.
E-mail: ykondo@mail.pharm.tohoku.ac.jp; Fax: +81 22 795 6804;
Tel: +81 22 795 6804
bDepartment Chemistry, University of Cambridge, Lensfield Road,
Cambridge, UK CB2 1EH. E-mail: aehw2@cam.ac.uk;
Fax: +44 1223 336362; Tel: +44 1223 763122
{ Electronic supplementary information (ESI) available: Experimental
procedures and spectral data for synthesized compounds. See DOI:
10.1039/b611090h
4850 | Chem. Commun., 2006, 4850–4852
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Table 2
Scheme 2
Entry
Ar
Time/h
Product
Yield (%)
1
2
3
4
5
6
7
8
9
2-Naphthyl (3a)
4-FC6H4 (3b)
4-BrC6H4(3c)
4-CF3C6H4(3d)
2-CF3C6H4(3e)
4-MeOOCC6H4(3f)
2-Pyridyl(3g)
3
1
1
2
1
1
1
1
1
4a
4b
4c
4d
4e
4f
4g
4h
4i
68
64
73
69
73
46
67
80
81
3-Pyridyl(3h)
2-Thienyl(3i)
heteroaryltrimethylsilanes were then examined. 2-Pyridyltrimethyl-
silane 3g and 3-pyridyltrimethylsilane 3h reacted smoothly to give
the alcohols 4g and 4h in 67% and 80% (Table 2, entries 7, 8).
2-Thienyltrimethylsilane 3i also reacted to give the alcohol 4i in
81% yield (Table 2, entry 9).
2-Trimethylsilylated benzamide was now reacted with benzalde-
hyde to give the 1,2-adduct which was treated with AcOH–toluene
to give the phthalide 6 in 76% yield (Scheme 1). Phthalides have
been used as precursors for the synthesis of anthraquinones,
though in the previous report of this, excess CsF was used for the
same carbodesilylation of 5 and the yield of 6 was reported to be
48%.8
Scheme 3
The mechanism of the catalytic reaction is speculated as shown
in Scheme 3. The directed interaction of t-Bu-P4 base and the
trimethylsilyl group activates the carbon–silicon bond to form a
highly reactive phosphazenium species (b) which reacts with
carbonyl compounds to give a 1,2-adduct (c) that undergoes
silylation of the oxy anion to release t-Bu-P4 base.
In summary, it is found that arylsilanes can be carbodesilylated
by the use of t-Bu-P4 base as a promoter and the selective
functionalizations of arylsilanes possessing no strong electron-
withdrawing group can be acomplished. t-Bu-P4 base is already
commercially available as a dry hexane solution and can be used as
a catalyst without drying. Further investigations on the scope and
limitation of the t-Bu-P4 base-promoted reaction of arylsilanes and
the mechanistic studies on this carbon–silicon activation are
underway.
Scheme 1
Additionally, the vinylsilane 7 was reacted with pivaldehyde in
the presence of t-Bu-P4 base and the allyl alcohol 8a was obtained
in 56% yield (Table 3, entry 1). Arylaldehydes were also used as
electrophiles to give the allyl alcohols 8b, 8c (Table 3, entries 2, 3).
As for the mechanism of the carbon–silicon bond activation, the
participation of phosphazenium hydroxide formed by the presence
of a trace amount of water cannot be avoided and we examined
the reactivity of phosphazenium hydroxide toward the activation.
When adding the same equivalent of water to t-Bu-P4 base, the
catalytic activity was found to be completely lost (Scheme 2).
This work was partly supported by the Grant-in Aid for
Scientific Research (No. 16659002, No. 16033208, No. 16390002)
from the Ministry of Education, Science, Sports and Culture,
Japan and grants from the Sumitomo Foundation and Yamada
Science Foundation and also by a Visiting Fellowship from The
Japan Society for the Promotion of Science.
Notes and references
Table 3
1 (a) E. W. Colvin, Silicon in Organic Synthesis, Butterworths, London,
1981; (b) W. P. Weber, Silicon Reagents for Organic Synthesis, Springer-
Verlag, Berlin, 1983.
2 (a) F. Effenberger and W. Spiegler, Chem. Ber., 1985, 118, 3872–3899; (b)
F. Effenberger and W. Spiegler, Chem. Ber., 1985, 118, 3900–3914; (c)
G. Seconi, M. Taddei, C. Eaborn and J. G. Stamper, J. Chem. Soc.,
Perkin Trans. 2, 1982, 643–646; (d) A. S. Pilcher and P. DeSchong, J. Org.
Chem., 1996, 61, 6901–6905.
3 (a) R. Schwesinger and H. Schlemper, Angew. Chem., Int. Ed. Engl.,
1987, 26, 1167–1169; (b) R. Schwesinger, H. Schlemper, C. Hasenfratz,
J. Willaredt, T. Dambacher, T. Breuer, C. Ottaway, M. Fletschinger,
J. Boele, H. Fritz, D. Putzas, H. W. Rotter, F. G. Bordwell, A. V. Satish,
G.-Z. Ji, E.-M. Peters, K. Peters, H. G. von Schnering and L. Walz,
Liebigs Ann., 1996, 1055–1081.
Entry
R
Time/h
Product
Yield (%)
1
2
3
t-Bu
2-MeOC6H4
4-MeOC6H4
2
1
2
8a
8b
8c
56
58
52
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4 J. G. Verkade and P. B. Kisanga, Tetrahedron, 2003, 59, 7819–7858.
5 (a) G. A. Kraus, N. Zhang, J. G. Verkade, M. Nagarajan and P. B.
Kisanga, Org. Lett., 2000, 2, 2409–2410; (b) T. Pietzonka and D. Seebach,
Chem. Ber., 1991, 124, 1837–1843; (c) T. Pietzonka and D. Seebach,
Angew. Chem., Int. Ed. Engl., 1993, 32, 716–717; (d) I. Leito, T. Rodima,
I. A. Koppel, R. Schwesinger and V. M. Vlasov, J. Org. Chem., 1997, 62,
8479–8483; (e) H. Schlaad, H. Kukula, J. Rudloff and I. Below,
Macromolecules, 2001, 34, 4302–4304; (f) T. Imahori and Y. Kondo,
J. Am. Chem. Soc., 2003, 125, 8082–8083; (g) T. Imahori, C. Hori and
Y. Kondo, Adv. Synth. Catal., 2004, 346, 1090–1092; (h) K. Kobayashi,
M. Ueno and Y. Kondo, Chem. Commun., 2006, 3128–3130.
6 M. Ueno, A. E. H. Wheatley and Y. Kondo, Chem. Commun., 2006,
3549–3550.
7 M. Ueno, C. Hori, K. Suzawa, M. Ebisawa and Y. Kondo, Eur. J. Org.
Chem., 2005, 1965–1968.
8 (a) R. J. Mills, N. J. Taylor and V. Snieckus, J. Org. Chem., 1989, 54,
4372–4385; (b) R. J. Mill and V. Snieckus, J. Org. Chem., 1989, 54,
4386–4390.
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