Synthesis of biaryls by intramolecular radical aryl migration from silicon to carbon

Article abstract of DOI:10.1021/ol005661f

(equation presented) A new method for the preparation of biaryls via intramolecular 1,5 aryl migration reaction from silicon in silyl ethers to aryl radicals is presented. Various readily available diphenylsilyl ethers can be used as substrates in this reaction. Functionalized aryl groups can also be transferred. The analogous 1,4 aryl migration reaction is less efficient.

Full text of DOI:10.1021/ol005661f

ORGANIC
LETTERS
2000
Vol. 2, No. 7
985-988
Synthesis of Biaryls by Intramolecular
Radical Aryl Migration from Silicon to
Carbon
Armido Studer,* Martin Bossart, and Tomaso Vasella
Laboratorium fu¨r Organische Chemie, Eidgeno¨ssische Technische Hochschule,
ETH Zentrum, UniVersita¨tstrasse 16, CH-8092 Zu¨rich
studer@org.chem.ethz.ch
Received February 14, 2000
ABSTRACT
A new method for the preparation of biaryls via intramolecular 1,5 aryl migration reaction from silicon in silyl ethers to aryl radicals is
presented. Various readily available diphenylsilyl ethers can be used as substrates in this reaction. Functionalized aryl groups can also be
transferred. The analogous 1,4 aryl migration reaction is less efficient.
Biaryls are an important class of compounds which occur
in many natural products.1 Moreover, biaryls have found
widespread application as ligands in catalytic asymmetric
synthesis.2 They are also found as components in new organic
materials, such as electroluminescent conjugated polymers,3
semiconductors, and liquid crystals.4
from oxygen in phenyl ethers to aryl radicals have been
disclosed.7 Amides8 as well as diazenes9 have been used as
linkers in aryl migration reactions. In these systems, the aryl
moiety is transferred from nitrogen to aryl radicals. Biaryls
have also been prepared via intramolecular aryl migration
from carbon to aryl radicals.10
Most often, biaryls are prepared by transition metal-
catalyzed cross-coupling reactions.5 Radical chemistry has
also successfully been used to construct the biaryl unity.
Motherwell has shown that biaryls can be prepared under
mild conditions by intramolecular radical aryl migration
reactions from sulfur in sulfones and sulfonamides to aryl
radicals.6 Similar transformations where aryl migration occurs
Recently, we presented the phenyl migration reaction from
silicon to secondary C-centered radicals as a new method
for the stereoselective C(sp2)-C(sp3) bond formation (Scheme
1).11 In this Letter we disclose our first results on the
application of this method for the preparation of biaryls.12
As in our previous studies, we decided to use the silyl
(7) Rosa, A. M.; Lobo, A. M.; Branco, P. S.; Prabhakar, S. Tetrahedron
1997, 53, 285. See also: Crich, D.; Hwang, J.-T. J. Org. Chem. 1998, 63,
2765.
(8) Hey, D. H.; Moynehan, T. M. J. Chem. Soc. 1959, 1563. Grimshaw,
J.; Trocha-Grimshaw, J. J. Chem. Soc., Perkin Trans. 1 1979, 799.
Grimshaw, J.; Haslett, R. J. J. Chem. Soc., Perkin Trans. 1 1980, 657.
Grimshaw, J.; Hamilton, R.; Trocha-Grimshaw, J. J. Chem. Soc., Perkin
Trans. 1 1982, 229.
(1) Bringmann, G.; Breuning, M.; Tasler, S. Synthesis 1999, 525 and
references therein.
(2) Pu, L. Chem. ReV. 1998, 98, 2405.
(3) Kraft, A.; Grimsdale, A. C.; Holmes, A. B. Angew. Chem., Int. Ed.
1998, 37, 402.
(4) Roncali, J. Chem. ReV. 1992, 92, 711.
(5) Stanforth, S. P. Tetrahedron 1998, 54, 263.
(6) Motherwell, W. B.; Pennell, A. M. K. J. Chem. Soc., Chem. Commun.
1991, 877. Da Mata, M. L. E. N.; Motherwell, W. B.; Ujjainwalla, F.
Tetrahedron Lett. 1997, 38, 137. Da Mata, M. L. E. N.; Motherwell, W.
B.; Ujjainwalla, F. Tetrahedron Lett. 1997, 38, 141.
(9) Benati, L.; Spagnolo, P.; Tundo, A.; Zanardi, G. J. Chem. Soc., Chem.
Commun. 1979, 141.
(10) Giraud, L.; Lacoˆte, E.; Renaud, P. HelV. Chim. Acta 1997, 80, 2148.
Alcaide, B.; Rodr´ıguez-Vicente, A. Tetrahedron Lett. 1998, 39, 6589.
10.1021/ol005661f CCC: $19.00 © 2000 American Chemical Society
Published on Web 03/14/2000

Scheme 1. Stereoselective Radical Phenyl Migration from
Scheme 2. Radical Phenyl Migration from Silicon to Aryl
Silicon to Carbon
Radicals
ether functionality to link the attacking aryl radical with the
migrating aryl group. Silicon tethers have often been used
to transform an intermolecular reaction to an intramolecular
process, a concept often called the Stork13 temporary silicon
connection.14 However, in the aryl migration reactions from
Si to aryl radicals discussed herein, the tether is cleaved
during the reaction as will be discussed in the mechanistic
section of the paper. Differently substituted diphenylsilyl
ethers 1-7 were readily prepared from the corresponding
chlorosilanes and benzyl alcohols using standard condi-
tions.15-17 Phenyl migrations were performed by slow
addition (syringe pump, 7 h) of Bu3SnH and AIBN to a
solution of the silyl ether in benzene (0.05 M). After
complete addition, stirring was continued for 30 min and
the reaction mixture was then allowed to cool to room
temperature. Desilylation using methyllithium18 afforded after
chromatography (SiO2) the desired biphenyl derivatives 8
or 9 in moderate to good yields (Scheme 2, Table 1) along
silicon (SHi)17,19 and subsequent ring opening of the inter-
mediate cyclic silyl ether with MeLi (see Scheme 3).
Scheme 3. Mechanism
Table 1. Optimization of the Phenyl Migration from Silicon to
Aryl Radicals by Varying the Silyl Ether
entry
silyl ether
8 (%)
10 (%)
1
2
3
4
5
6
1
2
3
4
5
6
55
52
28
39
84
56
52
71
As expected from our previous studies on the SHi reaction
at silicon,17,19 no biphenyl 8 was formed in the reaction of
stannylated silyl ether 3 and the SHi-derived alcohol 10 was
isolated in 84% yield (Table 1, entry 3). Phenyl migration
to the aryl radical generated from 3 is too slow to compete
with the SHi reaction. For germylated or silylated silyl ethers,
the SHi reaction with primary alkyl radicals is about 100-
1000 times slower than the corresponding reaction with
stannylated silyl ethers.17 Similar kinetics may also be
expected for the SHi reaction at silicon with aryl radicals;
with silylated benzyl alcohol 10 (for 1-3). The side product
10 derives from intramolecular homolytic substitution at
(11) Studer, A.; Bossart, M.; Steen, H. Tetrahedron Lett. 1998, 39, 8829.
Amrein, S.; Bossart, M.; Vasella, T.; Studer, A. Submitted for publication.
For stereoselective radical aryl migrations from sulfur to C-centered radicals,
see: Studer, A.; Bossart, M. Chem. Commun. 1998, 2127.
(12) To the best of our knowledge, radical aryl migrations from silicon
to aryl radicals are unknown. For early reports on the aryl migration from
Si to primary C-centered radicals, see: Wilt, J. W.; Dockus, C. F. J. Am.
Chem. Soc. 1970, 92, 5813. Wilt, J. W.; Chwang, W. K. J. Am. Chem. Soc.
1974, 96, 6194. Wilt, J. W.; Chwang, W. K.; Dockus, C. F.; Tomiuk, N.
M. J. Am. Chem. Soc. 1978, 100, 5534. Sakurai, H.; Hosomi, A. J. Am.
Chem. Soc. 1970, 92, 7507.
(16) Tamao, K.; Kawachi, A.; Ito, Y. J. Am. Chem. Soc. 1992, 114, 3989.
Murakami, M.; Suginome, M.; Fujimoto, K.; Nakamura, H.; Andersson, P.
G.; Ito, Y. J. Am. Chem. Soc. 1993, 115, 6487. Kawachi, A.; Doi, N.; Tamao,
K. J. Am. Chem. Soc. 1997, 119, 233.
(13) Stork, G.; Suh, H. S.; Kim, G. J. Am. Chem. Soc. 1991, 113, 7054.
(14) For reviews, see: Bols, M.; Skrydstrup, T. Chem. ReV. 1995, 95,
1253. Fensterbank, L.; Malacria, M.; Sieburth, S. McN. Synthesis 1997,
813.
(17) Studer, A.; Steen, H. Chem. Eur. J. 1999, 5, 759.
(18) In the desilylation, an excess of MeLi was used in order to transform
the tributyltin bromide formed as a byproduct in the aryl migration to
methyltributylstannane, which is easily removed by chromatography. See
also: Crich, D.; Sun, S. J. Org. Chem. 1996, 61, 7200. Renaud, P.; Lacoˆte,
E.; Quaranta, L. Tetrahedron Lett. 1998, 39, 2123.
16
(15) 1 from ClSiPh2SiMe3 and 1-(2-bromophenyl)ethanol (NEt3,
DMAP, THF, 92%); 2 in analogy from ClSiPh2GeMe317 (71%); 3 in analogy
from ClSiPh2SnMe316 (60%); 4 in analogy from ClSiPh2-t-Bu (74%); 5 in
analogy from ClSiPh2Me (84%); 6 from ClSiPh3 and imidazole in DMF
(37%); 8 from benzyl alcohol and ClSiPh3 in pyridine/toluene (1:1, 64%).
(19) Studer, A. Angew. Chem., Int. Ed. 1998, 37, 462.
986
Org. Lett., Vol. 2, No. 7, 2000

thus, the SHi reaction should be supressed for silylated as
well as for germylated silyl ethers, and the desired phenyl
migration should be the major reaction pathway. Indeed, the
phenyl migration product 8 is the main product in the reaction
of 1 (55%) and the SHi-derived alcohol 10 was isolated in
only 28% yield (entry 1). Similar results were obtained for
the germylated silyl ether 2, where biphenyl 8 was isolated
in 52% yield along with 39% of the side product 10 (entry
2).
Table 2. 1,5-Migration of Functionalized Aryl Groups
To completely supress the SHi reaction, the heavier group
14 substituent (R2 in Scheme 2) was replaced by an alkyl or
a phenyl group. For all these diphenylsilyl ethers (4-6),
phenyl migration worked well, and biphenyl 8 was isolated
in good yields (52-71%, entries 4-6). An additional
advantage of 4-6 over their silylated or germylated conge-
ners besides suppression of the undesired SHi reaction is the
fact that they are derived from commercially available
chlorosilanes. To illustrate that issue, we prepared biphenyl
9 from commercially available 2-bromobenzyl alcohol and
triphenylchlorosilane in two steps via silylation (pyridine/
toluene, f 7, 64%, unoptimized) and subsequent phenyl
transfer reaction (52%). As a side product, benzyl alcohol,
derived from direct reduction of the initially formed aryl
radical (dehalogenation) and subsequent removal of the
triphenylsilyl group, was formed in 17%.
a The corresponding SHi product was formed as a side product. b Various
inseparable products were formed. c Various inseparable products were
formed. In addition, 46% of 18 were recovered.
For the phenyl migration, we suggest the following
mechanism (Scheme 3). Depending on the substituent X, aryl
radical 11 either undergoes SHi reaction at silicon to form
cyclic silyl ether 13 or it reacts with one of the two phenyl
groups to form radical 12, which then rearomatizes to form
silyl radical 14. Radical 14 can either abstract a halogen atom
from the starting bromide20 or it can react with benzene in
a homolytic aromatic substitution.21 Desilylation (MeLi) then
affords biphenyl 8. In the other reaction pathway, ring
opening of 13 with MeLi eventually leads to alcohol 10.
We also tried to run the phenyl migration reaction using
catalytic amounts of tin hydride. Reaction of 6 with 18%
Bu3SnH and 4% AIBN under otherwise identical conditions
(benzene, 0.05 M, syringe pump, 7 h) afforded after
desilylation alcohol 8 in only 21% along with 72% of 1-(2-
bromophenyl)ethanol derived from unreacted starting mate-
rial. Thus, halogen abstraction of silyl radical 14 does not
seem to be the major reaction pathway.
similar to those for the corresponding disilyl ethers 15 and
16 (entries 3 and 4). The best result was obtained for the
transfer of the p-methoxyphenyl group (f 22 (77%), entry
5).
We then studied the 1,5 phenyl migration to vinyl radicals.
The aryl migration reactions were conducted under the
above-mentioned conditions. Unfortunately, neither for 23
nor for 24 (Figure 1) did phenyl migration occurr. To our
Figure 1.
We next tested whether it is possible to transfer function-
alized aryl groups from silicon to aryl radicals. To this end,
silyl ethers 15-19 were prepared from the corresponding
chlorosilanes.22
For the p-fluoro derivative 15, the aryl migration product
20 was formed in 49% (Table 2, entry 1). Reaction with
thienyl derivative 16 afforded an inseparable product mixture.
Compound 21 could not be clearly identified (entry 2). With
tert-butylated silyl ethers 17 and 18, the results obtained were
surprise, no reduction product (dehalogenation) was formed
in the reaction of 23 and the starting bromide was recovered.
For 24 only 28% of the dehalogenation product was observed
1
along with unreacted bromide as determined by H NMR
spectroscopy. We also tried to reduce bromide 24 under
radical dehalogenation conditions (addition of tin hydride
in one portion at higher concentration). However, even under
these conditions only 45-50% of the dehalogenation product
was formed (1H NMR) and no phenyl migration was
observed.
(20) Chatgilialoglu, C.; Ingold, K. U.; Scaiano, J. C. J. Am. Chem. Soc.
1982, 104, 5123.
(21) Chatgilialoglu, C.; Ingold, K. U.; Scaiano, J. C. J. Am. Chem. Soc.
1983, 105, 3292.
(22) The chlorosilanes were prepared according to known procedures
(see ref 16) starting from the corresponding di(aryl)dichlorosilanes, see
Supporting Information.
Finally, we investigated the 1,4 phenyl migration from
silicon to aryl radicals. Silyl ethers 25-27 were prepared
16
from o-bromophenol using ClSiPh2SiMe3 or ClSiPh2Me
and NEt3/DMAP in THF (for 25, 27) or ClSiPh3 and NEt3/
Org. Lett., Vol. 2, No. 7, 2000
987

recovered in 71% yield. It turned out that even upon adding
Bu3SnH in one portion to the bromide, no reaction occurred.
Since silyl ether 26 was carefully purified by chromatography
followed by recrystallization, we do not believe that phenol
impurities are the reason for the failure of the radical reaction.
Neither with tris(trimethylsilyl)silane25 nor with tin chloride
in t-BuOH in the presence of cyanoborohydride26 was any
reaction observed. Even SmI2 in THF (HMPA) did not lead
to any aryl migration. It seems that the triphenylsilyl group
completely blocks the bromide. We also obtained an X-ray
structure of 26. Surprisingly, in the solid state the bromide
is not protected by the silyl group and reaction with tin
radicals seems to be feasible. Also for 27 bearing the smaller
methyl substituent, no radical reaction was observed. Al-
though the X-ray structure of 26 did not offer the final
answer, we believe that in solution the bulky silyl group
protects the bromide toward any attack.
Scheme 4. 1,4 Phenyl Migration from Silicon to Aryl
Radicals
DMAP in CH2Cl2 (26) (Scheme 4). The aryl migrations were
performed under our standard aryl transfer conditions.
Interestingly, transformation of 25 afforded silylated phenol
29 as the major product in 50% yield along with the desired
biphenyl derivative 28 (38%). Phenol 29 is formed via initial
SHi reaction at silicon (see 30). This is the first time in our
studies on the homolytic substitution at silicon17,19 that a
trimethylsilyl group migration was observed. Obviously, the
transition state of the 4-exo attack at the silicon next to the
oxygen atom is too strained and 5-endo attack at the silicon
atom on the periphery occurs in addition to ipso attack (minor
pathway). Trimethylsilyl group migrations to heteroatom-
centered radicals are well-known;23 however, similar migra-
tions to C-centered radicals have not been observed so far.24
Interestingly, no products derived from ortho attack at the
phenyl group were observed.6
In conclusion, we present a new method for the preparation
of biaryls by intramolecular aryl migration from silicon to
aryl radicals. The starting materials are readily prepared from
commercially available silicon protecting groups and experi-
ments are very easy to conduct.
Acknowledgment. We thank Prof. Dr. Dieter Seebach
for generous financial support and Prof. Dr. Volker Gramlich
for performing the X-ray analysis. We also thank the Roche
Research Foundation and the Swiss Science National Foun-
dation (2100-055280.98/1) for funding our work. The work
described herein is part of the planned dissertation of M.B.
Supporting Information Available: Full experimental
details, spectroscopic and analytical data for all new com-
pounds, and X-ray structural data for 26 (CCDC-141621).
This material is available free of charge via the Internet at
http://pubs.acs.org.
To suppress the SHi reaction, the trimethylsilyl group in
25 was replaced by a phenyl group (26). However, neither
phenyl migration nor dehalogenation was observed in the
reaction of 26. After desilylation, o-bromophenol was
OL005661F
(23) Schiesser, C. H.; Wild, L. M. Tetrahedron 1996, 52, 13265.
(24) For a 1,2 silyl migration to C-centered radicals, see: Sugimoto, I.;
Shuto, S.; Matsuda, A. Synlett 1999, 1766 and references therein.
(25) Chatgilialoglu, C. Acc. Chem. Res. 1992, 25, 188.
(26) Stork, G.; Sher, P. M. J. Am. Chem. Soc. 1986, 108, 303.
988
Org. Lett., Vol. 2, No. 7, 2000