Arylsilanes: Application to gold-catalyzed oxyarylation of alkenes

Article abstract of DOI:10.1021/ol1019162

Arylsilanes are efficient reagents for the gold-catalyzed oxyarylation of alkenes (21 examples, up to 85% isolated yield). Using commercially available Ph₃PAuCl and readily prepared, benign arylsilanes, these two- and three-component reactions

Full text of DOI:10.1021/ol1019162

ORGANIC
LETTERS
2010
Vol. 12, No. 21
4724-4727
Arylsilanes: Application to
Gold-Catalyzed Oxyarylation of Alkenes
Liam T. Ball, Michael Green, Guy C. Lloyd-Jones,* and Christopher A. Russell*
School of Chemistry, UniVersity of Bristol, Cantock’s Close, Bristol,
United Kingdom BS8 1TS
guy.lloyd-jones@bristol.ac.uk; chris.russell@bristol.ac.uk
Received August 14, 2010
ABSTRACT
Arylsilanes are efficient reagents for the gold-catalyzed oxyarylation of alkenes (21 examples, up to 85% isolated yield). Using commercially
available Ph3PAuCl and readily prepared, benign arylsilanes, these two- and three-component reactions proceed smoothly in air. The oxidant,
Selectfluor, not only facilitates entry to the Au(I/III) manifold but also provides a fluoride anion for silane activation, thereby avoiding the need
for addition of a stoichiometric base.
While the isolobal relationship between gold and palladium
Au(I/III) and Pd(0/II) has been remarked upon,1 the full
potential for development of gold-catalyzed “palladium-like”2
cross-coupling has not been realized, and there exist only a
few reports3 of gold-mediated Sonogashira4 and Suzuki1b,5
couplings. The difficulty in achieving these very powerful
transformations stems from the fact that the two-electron
redox cyclesanalogous to the Au(I/III) cycle central to most
cross-coupling reactions6sis not facile.1d,7 However, the
Au(I/III) manifold can be accessed through use of an
exogenous oxidant, such as tert-butylhydroperoxide, PhI(O-
Ac)2, or Selectfluor:8 this approach has been the subject of
significant recent interest, with a number of oxidative
transformations, including dimerization,1a,9,10 arylation,11 and
C-O12 and C-N13 bond formation, having been reported.
(4) Examples of gold-catalyzed Sonogashira coupling: (a) Li, P.; Wang,
L.; Wang, M.; You, F. Eur. J. Org. Chem. 2008, 5946. (b) Gonza´lez-
Arellano, C.; Abad, A.; Corma, A.; Garcia, H.; Iglesias, M.; Sa´nchez, F.
Angew. Chem., Int. Ed. 2007, 46, 1536. (c) Gonza´lez-Arellano, C.; Corma,
A.; Iglesias, M.; Sa´nchez, F. Eur. J. Inorg. Chem. 2008, 1107. Echavarren1d
has recently demonstrated that trace palladium contaminants in gold
complexes can induce what appear to be “gold-catalyzed” Sonogashira
couplings.
(5) Examples of gold-catalyzed Suzuki coupling: (a) Lin, J. C. Y.; Tang,
S. S.; Vasam, C. S.; You, W. C.; Ho, T. W.; Huang, C. H.; Sun, B. J.;
Huang, C. Y.; Lee, C. S.; Hwang, W. S.; Chang, A. H. H.; Lin, I. J. B.
Inorg. Chem. 2008, 47, 2543. (b) Corma, A.; Gutie´rrez-Puebla, E.; Iglesias,
M.; Monge, A.; Pe´rez-Ferreras, S.; Sa´nchez, F. AdV. Synth. Catal. 2006,
348, 1899.
(1) (a) Carretin, S.; Guzman, J.; Corma, A. Angew. Chem., Int. Ed. 2005,
44, 2242. (b) Gonza´lez-Arellano, C.; Corma, A.; Iglesias, M.; Sa´nchez, F.
J. Catal. 2006, 238, 497. (c) Hashmi, A. S. K.; Schwarz, L.; Choi, J.-H.;
Frost, T. M. Angew. Chem., Int. Ed. 2000, 39, 2285. (d) Lauterbach, T.;
Livendahl, M.; Rosello´n, A.; Espinet, P.; Echavarren, A. M. Org. Lett. 2010,
12, 3006. (e) Carretin, S.; Corma, A.; Iglesias, M.; Sa´nchez, F. Appl. Catal.,
A 2005, 291, 247.
(6) Christmann, U.; Vilar, R. Angew. Chem., Int. Ed. 2005, 44, 366.
(7) For a computational comparison of reductive elimination from
Cu(III), Ag(III), and Au(III) species, see: Nakanishi, W.; Yamanaka, M.;
Nakamura, E. J. Am. Chem. Soc. 2005, 127, 1446.
(2) See, for example: (a) Handbook of Organopalladium Chemistry for
Organic Synthesis; Negishi, E., Ed.; Wiley: New York, 2004; Vol. 1 and
2. (b) Tsuji, J. Palladium Reagents and Catalysis: New PerspectiVes for
the 21st Century; Wiley: Chichester, 2004.
(8) The mechanism of oxidative fluorinationsi.e., electrophilic attack
by “F+” vs two single-electron transfer eventsscontinues to be debated.
See (and references therein): Kirsch, P. Modern Fluoroorganic Chemistry:
Synthesis, ReactiVity, Applications; Wiley: Weinheim, 2005; Chapter 2, p
76.
(3) For a review, see: Garcia, P.; Malacria, M.; Aubert, C.; Gandon,
V.; Fensterbank, L. ChemCatChem 2010, 2, 493.
10.1021/ol1019162  2010 American Chemical Society
Published on Web 09/29/2010

Herein we demonstrate the use of arylsilanes in gold-
catalyzed oxidative oxyarylation of olefins (Scheme 1).
handling, stability, and low toxicitysupon gold catalysis,
without the need to employ “more than stoichiometric
amounts of expensive additives”2b to achieve their activation.
The reaction between 1-octene, methanol, and trimeth-
yl(phenyl)silane in the presence of Selectfluor was used
to assay the viability of our proposed methodology and,
subsequently, to identify the most efficient gold precatalyst
(Table 1) and optimal conditions:21 it was encouraging
Scheme 1. Gold-Catalyzed Oxidative Oxyarylation of Alkenes
with Arylsilanes in the Presence of Selectfluor
Table 1. Screening of Precatalyst for Oxyarylation of Alkenes:a
Summary of Reaction Optimizationb
Within the remit of gold chemistry, such reactions are
unusual in that they proceed in generally good to excellent
yield, despite being three-component systems and requiring
activation of an alkenyl, as opposed to the more common
alkynyl or allenyl, substrate.
entry
precatalyst
1, yield %c d
,
Recently, the groups of Zhang14 and Toste15 independently
reported the gold-catalyzed amino- and oxyarylation of
terminal olefins with arylboronic acids in the presence of
Selectfluor as the stoichiometric oxidant. The proposed
mechanisms involve oxidative fluorination of Au(I) to furnish
a Au(III) species with concomitant generation of a fluoride
anion, the latter activating the arylboronic acid and thereby
facilitating transmetalation through formation of a B-F bond.
The use of organosilanes (the Hiyama16 reaction) and
organosiloxanes (the Tamao-Ito17 reaction) as the nucleo-
philic partner in palladium-catalyzed cross-coupling is well
established and typically requires a stoichiometric base as
an activator.18 We envisaged that the fluoride formed in situ
by oxidation of Au(I) would be similarly capable of
activating a silane and thus that an arylsilane could be used
in place of the boronic acid for alkene oxyarylation;
formation of a strong Si-F bond19,20 would provide the
thermodynamic driving force. This supposition was further
supported by the observation12a that silyloxyethers are not
stable under the conditions of Selectfluor-mediated oxidation
of Au(I). Our planned methodology would thus confer the
benefits inherent in silanessnamely, ease of preparation and
1
2
3
4
5
6
7
8
Ph3PAuCl
t-Bu3PAuCl
Cy3PAuCl
(o-Tol)3PAuCl
AuCl
99
27
80
79
98
83
22
6
70
86e
13f
96g
Me2SAuCl
AuCl3
HAuCl4·3H2O
XPhosAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PauCl
9
10
11
12
a Reaction conditions: 1-octene (0.1 mmol), trimethyl(phenyl)silane (0.2
mmol), Selectfluor (0.2 mmol), and precatalyst (10 mol %, added in 2 equal
portions at t ) 0 and t ) 2 h) were stirred in anhydrous MeCN (0.9 mL)
and anhydrous MeOH (0.1 mL) in a 7 mL vial under air at 70 °C. b For
full details of reaction optimization, see Supporting Information. c Yields
determined by GC-FID referenced to an internal standard (mesitylene).
d Yields are averages of at least two repetitions. e PhSi(OMe)3 used in place
of PhSiMe3. f PhSiMe2OH used in place of PhSiMe3. g 5 mol % Ph3PAuCl
used, added in a single portion at t ) 0. XPhos is 2-dicyclohexylphosphino-
2′,4′,6′-tri-iso-propylbiphenyl.
to find that, using commercially available Ph3PAuCl (10
mol %, added in two portions) under an atmosphere of
air, the expected methoxyphenylated product 1 was
obtained in excellent yield (entry 1). This result was not
surpassed with other precatalysts, although Cy3PAuCl, (o-
Tol)3PAuCl, AuCl,22 and Me2SAuCl (entries 3-6) also
exhibited significant activity. It was interesting to note
that simple Au(III) salts were able to catalyze the reaction
(entries 7 and 8) and that use of tri-tert-butylphosphine
and XPhos (2-dicyclohexylphosphino-2′,4′,6′-tri-iso-
propylbiphenyl)sbulky phosphines which are outstanding
(9) See, for example: Gonza´lez-Arellano, C.; Corma, A.; Iglesias, M.;
Sa´nchez, F. Chem. Commun. 2005, 1990.
(10) (a) Kar, A.; Mangu, N.; Kaiser, H. M.; Beller, M.; Tse, M. K. Chem.
Commun. 2008, 386. (b) Wegner, H. A.; Ahles, S.; Neuburger, M.
Chem.sEur. J. 2008, 14, 11310. (c) Cui, L.; Zhang, G.; Zhang, L. Bioorg.
Med. Chem. Lett. 2009, 19, 3884. (d) Hopkinson, M. N.; Tessier, A.;
Salisbury, A.; Giuffredi, G. T.; Combettes, L. E.; Gee, A. D.; Gouverneur,
V. Chem.sEur. J. 2010, 16, 4739.
(11) Zhang, G.; Peng, Y.; Cui, L.; Zhang, L. Angew. Chem., Int. Ed.
2009, 48, 3112.
(12) (a) Peng, Y.; Cui, L.; Zhang, G.; Zhang, L. J. Am. Chem. Soc.
2009, 131, 5062. (b) Whitman, C. A.; Mauleo´n, P.; Shapiro, N. D.; Sherry,
B. D.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 5838.
(13) Iglesias, A.; Muniz, K. Chem.sEur. J. 2010, 15, 10563.
(14) Zhang, G.; Cui, L.; Wang, Y.; Zhang, L. J. Am. Chem. Soc. 2010,
132, 1474.
(20) This hypothesis was corroborated by subsequent observation of
Me3SiF in the 19F NMR spectrum of a crude reaction mixture (δF-157.5
(decet, 3JHF ) 7.6 Hz)). Myers, E. L.; Butts, C. P.; Aggarwal, V. K. Chem.
Commun. 2006, 4434.
(15) (a) Melhado, A. D.; Brenzovich, W. E., Jr.; Lackner, A. D.; Toste,
F. D. J. Am. Chem. Soc. 2010, 132, 8885. (b) Brenzovich, W. E., Jr.; Benitez,
D.; Lackner, A. D.; Shunatona, H. P.; Tkatchouk, E.; Goddard, W. A., III;
Toste, F. D. Angew. Chem., Int. Ed. 2010, 49, 5519.
(21) The formation of biphenylsfrom oxidative homocoupling of the
arylsilaneswas observed during the optimization process; this is comparable
to Zhang’s findings when trifluoroborate salts were assayed in oxy- and
aminoarylation,14 as well as Corma’s reports that arylboronic acids are
efficiently homocoupled by Au(III) complexes.1b These observations are
the subject of ongoing investigations.
(16) Hatanaka, Y.; Hiyama, T. J. Org. Chem. 1988, 53, 918.
(17) Tamao, K.; Kobayashi, K.; Ito, Y. Tetrahedron Lett. 1989, 30, 6051.
(18) Denmark, S. E.; Sweiss, R. F. Acc. Chem. Res. 2002, 35, 835.
-1
(19) The Me3Si-F bond has a dissociation energy of 807 kJ mol
:
(22) We thank one of the reviewers for suggesting the use of AuCl as
a precatalyst. While AuCl is effective as a catalyst, the reaction generates
a higher proportion of biphenyl21 as compared to Ph3PAuCl.
Colvin, E. W. Silicon in Organic Synthesis; Butterworths: London, 1981;
Chapter 2, p 4
.
Org. Lett., Vol. 12, No. 21, 2010
4725

three components (Table 2). Olefins 2 bearing both func-
tionalized (2a, 2b, and 2d) and simple alkyl (2c) substituents
proved suitable substrates for oxyarylation, reacting with a
range of primary alcohols to afford the expected ethers in
good to excellent yield. Use of secondary alcohols, however,
resulted in lower yields and/or recovery of starting material
2, suggesting sensitivity to the steric nature of the alcohol;
with tert-butanol (entry 4), the expected product 3d was not
isolated.27 In addition to alcohols, both acetic acid and water
proved competent O-nucleophiles, furnishing acetates 3g and
3n and alcohols 3o, 3r, and 3s in respectable yield. Variation
of the arylsilane indicated that both electron-deficient and
electron-rich arenes (compare, e.g., entry 1 with entries
8-12) could be employed in the key C-C bond forming
step, with the best results obtained using silane reagents
bearing an electron-withdrawing substituent. Again, use of
sterically demanding reagents resulted in reduced yields
(compare entries 8 and 9). Overall, the oxyarylation process
tolerated a diverse range of functionality; that bromidesa
versatilesynthetichandleforuseinfurthermanipulationsscould
be incorporated in both the arylsilane and the olefin further
illustrates the different reactivities of palladium and gold.
The combination of arylsilanes with a commercially available
precatalyst (5 mol % Ph3PAuCl) afforded the oxyarylation
products 3 in yields comparable to those obtained at the
higher loadings of more complex precatalyst (dppm(AuBr)2;
10 mol % in Au; dppm ) bis(diphenylphosphino)methane)
reported by Toste15a for arylboronic acids (Table 2).
Table 2. Oxyarylation of Terminal Alkenes: Investigation of
Scope and Comparison of Arylsilanesa and Arylboronic Acids
The two-component reaction also proceeded efficiently under
our optimized conditions: intramolecular alkoxycyclization of
4-penten-1-ol and subsequent arylation furnished 2-benzyltet-
rahydrofuran 4a in 70% isolated yield (Scheme 2). 2-Benzyl-
a Reaction conditions: olefin 2 (0.5 mmol), arylsilane (1.0 mmol),
Selectfluor (1.0 mmol), Ph3PAuCl (5 mol %), and R1OH (0.5 mL for liquids,
5.0 mmol for solids and water) were stirred in anhydrous MeCN (0.1 M
concentration of olefin) in a 7 mL vial under air at 70 °C. b Isolated yields;
values in parentheses are calculated by recovered 2. c Data for boronic acids
taken from ref 15a. d 27% conversion observed by 1H NMR of crude reaction
mixture. Np is neo-pentyl (Me3CCH2-).
Scheme 2
.
Two-Component Oxyarylation via Intramolecular
Alkoxycyclization
ligands in palladium6,23 and Au(I) chemistry24safforded 1
in only poor to moderate yield (entries 2 and 9). Also worthy
of note is that excellent yields were obtained when a siloxane
was used in place of the silane but that the analogous silanol
performed poorly (compare entries 1, 10, and 11). Having
identified Ph3PAuCl as the preferred precatalyst, a screen
of reaction conditions (Table S1, Supporting Information)
indicated that portionwise addition of reagents and use of
inert atmosphere was unnecessary, that the precatalyst
loading could be lowered to 5 mol % without significant
attenuation of yield, and that 2 equiv of both Selectfluor and
arylsilane was required for high conversion of the alkene.25
Having identified optimal conditions26 (Table 1, entry 12),
we probed the reaction scope with regards to each of the
a Data for boronic acids taken from ref 14. b Obtained as a 1:1.13 mixture
of diastereomers (determined by H NMR).
1
5-pentyltetrahydrofuran 4b was similarly prepared in good yield
from dec-1-en-5-ol.
(23) (a) Fu, G. C. Acc. Chem. Res. 2008, 41, 1555. (b) Huang, X.;
Anderson, K. W.; Zim, D.; Jiang, L.; Klapars, A.; Buchwald, S. L. J. Am.
Chem. Soc. 2003, 125, 6653. (c) Surry, D. S.; Buchwald, S. L. Angew.
Chem., Int. Ed. 2008, 47, 6338.
(25) While excess silane remained in the crude reaction mixture,
lowering the number of equivalents resulted in decreased yield of 1.
(26) Despite furnishing 1 in marginally lower yield than the conditions
outlined in Table 1, entry 1, the conditions in entry 12 were chosen as
optimal on the grounds of lower precatalyst loading.
(24) (a) Jime´nez-Nu´n˜ez, E.; Echavarren, A. M. Chem. ReV. 2008, 108,
3326. (b) Gorin, D. J.; Sherry, B. D.; Toste, F. D. Chem. ReV. 2008, 108,
3351.
4726
Org. Lett., Vol. 12, No. 21, 2010

fording the products of two- and three-component coupling
in generally good to excellent isolated yields. While the
substrate scopesas seen in this preliminary studysis cur-
rently limited to terminal olefins, the rapid increase in
molecular complexity that can be achieved may lend itself
to the synthesis of biologically relevant compounds. The dual
role of Selectfluor as both an oxidant and a source of fluoride
negates the need for an additional, stoichiometric activator.29
In addition, the ability to use a commercially available
catalyst under air and the ease of preparation and benign
nature of arylsilanes/siloxanes make this methodology a
potentially important addition to the repertoire of gold-
catalyzed oxidative transformations.
Figure 1. Possible side products of oxyarylation, arising from
dimerization 5a, protodeauration 5b, or reductive elimination
5c of an alkylgold fluoride intermediate or protodesilylation 6a
or oxidation 6b of arylsilane reagents (not observed). Biaryl 6c,
from oxidative homocoupling of the silane reagent, was ob-
served.
Acknowledgment. We thank Umicore AG & Co. KG for
the generous donation of HAuCl4. L.T.B. thanks the Bristol
Chemical Synthesis Doctoral Training Centre, funded by
EPSRC (EP/G036764/1), AstraZeneca, GlaxoSmithKline,
Novartis, Pfizer, Syngenta, and the University of Bristol, for
the provision of Ph.D. studentship. G.C.L.J. is a Royal
Society Wolfson Research Merit Award Holder.
We carefully monitored the reaction for formation of
potential side products: during the course of our investiga-
tions we did not observe the products arising from dimer-
ization 5a, protodeauration 5b,28 or reductive elimination 5c
(Figure 1) of a putative alkylgold fluoride intermediate.14,15
The protio- 6a or phenolic 6b products arising from
protodesilylation or oxidation of the arylsilanes also were
not detected, although the homocoupled species 6c was
generated in 3-5% isolated yield (up to 7% by GC-FID)
based on silane.21
Supporting Information Available: Experimental pro-
cedures, characterization data. and NMR spectra. This
material is available free of charge via the Internet at
http://pubs.acs.org.
In conclusion, we have demonstrated that arylsilanes can
be employed in gold-catalyzed oxyarylation reactions, af-
OL1019162
(27) Integration of characteristic peaks15a in the H NMR spectrum of
1
the crude reaction mixture indicated that ca. 27% of tert-butyl ether 3d
had been formed.
(28) Cf. the formation of comparable species, either as the intended
product or as a side product, from vinylgold intermediates: refs 10b-d,
11, and 12a.
(29) Use of alternative oxidants (CuF2, AgF2, PhI(OAc)2, [Ph2I][OTf]),
with or without an external source of fluoride (TBAF, TBAT) under
conditions analogous to Table 1, entry 12, gave product 1 in 0-2.8% yield;
see Table S2, Supporting Information.
Org. Lett., Vol. 12, No. 21, 2010
4727