One-pot chemoselective functionalization of arylsilanes via cascade metal-metal exchange reactions

Article abstract of DOI:10.1039/b203320h

A cascade-transmetallation sequence allows a one-pot conversion of arylsilanes into functionalized arylcoppers; they react with various types of electrophiles (allylic halides, acid chlorides, bromoalkynes); bimetallic zinc-copper-reagents can be prepared by this method either directly or in a sequential fashion.

Full text of DOI:10.1039/b203320h

One-pot chemoselective functionalization of arylsilanes via cascade
metal–metal exchange reactions
Eike Hupe, M. Isabel Calaza and Paul Knochel*
Department Chemie, Ludwig-Maximilians-Universität München Butenandtstr, 5-13, Haus F, D-81377
München, Germany. E-mail: Paul.Knochel@cup.uni-muenchen.de; Fax: (+49)-89-2180-7680;
Tel: (+49)-89-2180-7681
Received (in Cambridge, UK) 4th April 2002, Accepted 13th May 2002
First published as an Advance Article on the web 28th May 2002
A cascade-transmetallation sequence allows a one-pot con-
version of arylsilanes into functionalized arylcoppers; they
react with various types of electrophiles (allylic halides, acid
chlorides, bromoalkynes); bimetallic zinc–copper-reagents
can be prepared by this method either directly or in a
sequential fashion.
Cascade reactions allow the preparation of complex molecules
via highly reactive intermediates.1 Herein, we wish to report a
one-pot reaction involving up to three successive transmetalla-
tion reactions which allows the conversion of arylsilanes into a
range of organic products with excellent chemoselectivity.
Arylsilanes are readily prepared but undergo the formation of
new carbon–carbon bonds only sluggishly.2 This is due to the
covalent character of the carbon–silicon bond and to the
absence of low-lying vacant orbitals available to participate in
bond formations. For these reasons, arylsilanes of type ArSiMe3
are poor substrates for direct transmetallation to the correspond-
ing zinc species Ar2Zn. However, the propensity of arylsilanes
to undergo ipso-substitutions3 allows smooth transmetallation
from silicon to boron by treatment with BCl3, leading to
ArBCl2.4 Previously, we have shown that various organobor-
Scheme 1
anes, including arylboranes, undergo a fast boron–zinc ex-
change.5 Herein, we report that the use of i-Pr2Zn6 allows a fast
and quantitative boron–zinc exchange of various arylsilanes
(2-bromomethyl)acrylate and 1-bromo-2-trimethylsilylethyne8
under very mild conditions (25 °C, 2 h). Thus, the treatment of
furnished the expected products 10a–c (Scheme 2).
phenylboron dichloride with i-Pr2Zn (3.0 equiv.) furnished
Finally, bis-silylated aromatics were double-functionalized
Ph2Zn after the removal of the excess of i-Pr2Zn and the
by this approach. Thus, the reaction of the bis-silane 11 with
solvents under vacuum. After a further transmetallation with
BCl3, followed by the addition of i-Pr2Zn (6.0 equiv., 25 °C, 2
CuCN·2LiCl,7 the resulting phenylcopper derivative reacted
h) and then CuCN·2LiCl (2.0 equiv., 230 °C, 10 min) provided
with an excess of propionyl chloride (25 °C, 3 h) providing
via the intermediate zinc-copper compound 12 the reaction
propiophenone in 84% yield. By using this method, para- and
products 13 in 75% yield (reaction with allyl bromide) and 14 in
meta bis-trimethylsilyl aromatics 1a,b were reacted with
electrophiles with high chemoselectivity in a one-pot procedure
leading to products of type 5–7 (Scheme 1).
Thus, the reaction of 1a,b with BCl3 (3.0 equiv., 25 °C, 10 h)
furnished the corresponding para- and meta mixed bimetallics
2a,b. They could be reacted with ICl (1.0 equiv., 25 °C, 16 h)
leading to the para- and meta-iodoarylboranes 3a,b. Similarly,
the reaction of 2a,b with bromine (1.0 equiv., 25 °C, 16 h)
provided the para- and meta-bromoarylboranes 4a,b. The
reaction of 2–4 with i-Pr2Zn (3.0 equiv., 25 °C, 2 h) followed by
the addition of CuCN·2LiCl (230 °C, 10 min) and an
electrophile furnished products 5–7 in good overall yields
(45–73 %)(Fig. 1). Allylation reactions did lead to products 5a,
6d, 7c, and 7d under very mild conditions. The use of propargyl
bromide as electrophile furnished arylated allenes (5c, 5d, 6b
and 7b) in 46–73% yield. The reaction with propionyl chloride
led to the expected ketones (5b, 6a, 7a, 5e and 6c) in 45–72%
yield (Fig. 1).
Interestingly, our typical reaction sequence left the benzylic
silane function of the mixed benzylic-aromatic disilane 8
unaffected,4 furnishing the functionalized benzylic silanes 10a–
c in 58–76% yield (Scheme 2), the first step being the formation
of the mixed Si,B-bimetallic species 9. After transmetallation of
9 to the zinc species (i-Pr2Zn, 3.0 equiv., 25 °C, 2 h) and further
to the copper intermediate (addition of CuCN·2LiCl), the
addition of electrophiles like propionyl chloride, ethyl
Fig. 1 Products of type 5–7 obtained by the one-pot procedure described in
Scheme 1. Yields of analytically pure products.
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CHEM. COMMUN., 2002, 1390–1391
This journal is © The Royal Society of Chemistry 2002

Chemetall GmbH (Frankfurt), BASF AG and Degussa AG
(Hanau) for generous gifts of chemicals.
Notes and references
1 L. F. Tietze, Chem. Rev., 1996, 96, 115.
2 W. P. Weber, Silicon Reagents for Organic Synthesis, Springer-Verlag,
Berlin, 1983E. W. Colvin, Best Synthetic Methods, Silicon Reagents in
Organic Synthesis, Academic Press, London, 1988.
3 M. Herrlich, N. Hampel and H. Mayr, Org. Lett., 2001, 3, 1629.
4 D. Kaufmann, Chem. Ber., 1987, 120, 853; D. Kaufmann, Chem. Ber.,
1987, 120, 901; U. Gross and D. Kaufmann, Chem. Ber., 1987, 120, 991;
C. Malan and C. Morin, Synlett, 1996, 167.
Scheme 2
5 F. Langer, L. Schwink, A. Devasagayaraj, P. Y. Chavant and P. Knochel,
J. Org. Chem., 1996, 61, 8229; M. Rottländer, N. Palmer and P. Knochel,
Synlett, 1996, 573; E. Hupe, M. I. Calaza and P. Knochel, Tetrahedron
Lett., 2001, 42, 8829.
6 A. Boudier, C. Darcel, F. Flachsmann, L. Micouin, M. Oestreich and P.
Knochel, Chem. Eur. J., 2000, 6, 2748; E. Hupe and P. Knochel, Org.
Lett., 2001, 3, 127.
68% yield (reaction with 1-bromo-2-trimethylsilylethyne)8
(Scheme 3).
In summary, we have developed a new one-pot procedure
allowing the conversion of various arylsilanes into several
classes of polyfunctional compounds. Both carbon–silicon
bonds react chemoselectively. Bimetallic zinc–copper reagents
like 12 can be prepared by this method. Extension to more
complex arylsilanes is currently underway.9
We thank the DFG (Leibniz-Program) for financial support.
E. H. thanks the Fonds der Chemischen Industrie for a Kekulé-
fellowship. M. I. C. thanks the European Community for a
Marie Curie fellowship (HPMF-CT-2000-01024). We thank
7 P. Knochel, M. C. P. Yeh, S. C. Berk and J. Talbert, J. Org. Chem., 1988,
53, 2390.
8 M. C. P. Yeh and P. Knochel, Tetrahedron Lett., 1989, 30, 4799.
9 Typical procedure: preparation of 1-(4-iodophenyl)propan-1-one (5b): to
1,4-bis(trimethylsilyl)benzene (1.0 mmol, 222 mg) in CH2Cl2 (1.5 mL) at
0 °C was added BCl3 (3.0 equiv., 3.0 mmol, 3 mL, 1 M in CH2Cl2). The
reaction mixture was stirred at room temperature for 10 h. After pumping
off the volatiles (0.1 mm Hg, 25 °C, 30 min), CH2Cl2 (2 mL) was added
and the reaction mixture was cooled to 0 °C. After addition of ICl (1.0
equiv., 1.0 mmol, 162 mg) the reaction mixture was stirred for 16 h at 25
°C. After pumping off the volatiles (0.1 mm Hg, 25 °C, 30 min), i-Pr2Zn
(3.0 equiv., 3.0 mmol, 0.5 mL, 6.0 M in Et2O) was added carefully and
the mixture was stirred for 2 h at 25 °C. The volatiles were pumped off
(0.1 mm Hg, 25 °C, 0.5 h), the residue was diluted with THF (2 mL) and
cooled to –30 °C. A freshly prepared solution of CuCN·2LiCl (1.0 equiv.,
1.0 mmol, 1.0 mL, 1 M in THF) was slowly added over 10 min and the
mixture was stirred for 10 min at 230 °C. Propionyl chloride (3.0 equiv.,
3.0 mmol, 278 mg) in THF (1 mL) was added slowly (10 min). The
mixture was allowed to warm up to room temperature and stirred at this
temperature for 3 h. The reaction mixture was then poured into a saturated
aqueous NH4Cl solution (150 mL) containing NH3 (aq) (2 mL, 30% in
H2O). After extraction with Et2O (3 3 100 mL) the combined organic
phases were dried over MgSO4. The solvent was removed and the crude
product purified by column chromatography (SiO2) affording 5b as a
colourless oil (54%, 0.54 mmol, 140 mg).
Scheme 3
CHEM. COMMUN., 2002, 1390–1391
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