Gold(I)-catalyzed intermolecular addition of phenols and carboxylic acids to olefins

Article abstract of DOI:10.1021/ja050392f

Ph₃PAuOTf can catalyze efficient intermolecular addition of phenols and carboxylic acids to olefins under relatively mild conditions. Copyright

Full text of DOI:10.1021/ja050392f

Published on Web 04/22/2005
Gold(I)-Catalyzed Intermolecular Addition of Phenols and Carboxylic Acids to
Olefins
Cai-Guang Yang and Chuan He*
Department of Chemistry, The UniVersity of Chicago, 5735 South Ellis AVenue, Chicago, Illinois 60637
Received January 20, 2005; E-mail: chuanhe@uchicago.edu
Table 2. Intermolecular Addition of Phenols and Carboxylic Acids
Gold-catalyzed reactions have emerged as important synthetic
methods.1 Cationic gold(I) and gold(III) show exceptional activities
to activate alkynes toward addition by a variety of functional groups
both intra- and intermolecularly. This chemistry is also very valuable
in constructing complex molecules.1,2 Despite the successes with
alkynes, reactions involving nucleophilic addition to olefins cata-
lyzed by gold are very limited.3,4 Recently, an interesting gold-
(III)-mediated addition of â-diketone to alkenes was shown, but
the role of gold(III) was thought to mainly activate the nucleophile
and the alkene scope is limited to styrene and norbornylene.4 To
this date, there has not been a report of gold-catalyzed formation
of carbon-heteroatom bonds through activation of inert olefins.
Such reactions have been traditionally mediated by acids or
stoichiometic amounts of toxic reagents.5 Platinum,6 ruthenium,7
and palladium8 have been shown to catalyze some of these reactions,
but efficient intermolecular addition of various nucleophiles to
inactivated olefins under mild conditions has yet to be achieved.
In the case of palladium-catalyzed reactions, â-hydride elimination
often occurs to afford unsaturated products.8
to Olefinsh
We report here that simple olefins can be activated by
Ph3PAuOTf.9 Intermolecular additions of phenols and carboxylic
acids to alkenes can be catalyzed by this catalyst under relatively
mild conditions. A reaction between p-methoxyphenol (1 mmol)
and 4-allylanisole (4 mmol) was used to investigate activity of
different catalysts (eq 1). Triflic acid, ZnOTf2, AgOTf, and AuCl3/
3AgOTf all failed to give the desired product in good yields (Table
1). A combination of 2 mol % of Ph3PAuCl and AgOTf gave a
Table 1. Effect of Catalysts on an Intermolecular Addition
Reaction
entry
catalyst
yielda
a The isolated yields are reported. b NMR yield with an internal standard.
c With 5 mol % of the catalyst. d Isolated yield for 3h. e 5 mol %
Ph3PAuSbF6 was used. f Conversion is 55% based on the alkene. g 1:1 ratio
of acid and nobornylene were used. h Reactions were conducted with 1 mmol
of nucleophiles, 4 mmol of olefins, and 2 mol % (for phenols) or 5 mol %
(for carboxylic acids) of Ph3PAuCl/AgOTf in 2 mL of toluene at 85 °C.
1
2
3
4
5
6
15% HOTf
5% ZnOTf2
5% AgOTf
5% AuCl3/15% AgOTf
2% Ph3PAuCl/2% AgOTf
2% Ph3PAuOTf
0%
0%
trace
<5%
84%
78%
work well in this reaction. Good yields can be obtained for all cases
reported. Although excess amounts of olefins were used (4 equiv),
usually 2 equiv of olefins could be recovered after the reaction.
Carboxylic acids can also be added to alkenes to give esters under
the same reaction conditions (Table 2), but a higher catalyst loading
(5 mol %) is required for the completion of the reactions. A
sterically bulky acid was employed, which still afforded a reasonable
yield of the product (entry 15, Table 2).
a Yield based on the phenol and determined by crude 1H NMR using an
internal standard.
good yield of the Markovnikov product (entry 5, Table 1). If AgCl
precipitates were filtered after mixing the same equivalents of
Ph3PAuCl and AgOTf, the filtrate still exhibited the same catalytic
activity (entry 6, Table 1). Different solvents were screened, and
toluene was found to be the best solvent for this reaction.
Both electron-rich and electron-deficient phenols serve as good
substrates (Table 2). Different olefins including inactivated ones
We are exploring the scope of this gold(I)-based activity. Our
data indicate that an intramolecular cyclization of a γ-hydroxyl
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J. AM. CHEM. SOC. 2005, 127, 6966-6967
10.1021/ja050392f CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Intramolecular Addition of Alcohol to Olefin
Acknowledgment. This research was supported by the Uni-
versity of Chicago. We acknowledge the donors of the American
Chemical Society Petroleum Research Fund for support of this
research (PRF 38848-G3). This research is also supported by a
Research Innovation Award (RI1179) from Research Corporation.
Supporting Information Available: Experimental details. This
material is available free of charge via the Internet at http://pubs.acs.org.
Scheme 2. Terminal Olefin Migration Catalyzed by Au(I)
Scheme 3 Proposed Catalytic Mechanism
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(Scheme 1). The product yield is comparable to that reported
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in Table 2). To confirm the observation, we took 4-phenyl-1-butene
and heated it at 85 °C for 20 h in the presence of 1 mol % of
Ph3PAuOTf without any nucleophiles in toluene. Seventy-five
percent of the alkene was converted to 4-phenyl-2-butene in a 2.2:
1/E:Z ratio (Scheme 2). Further migration to the conjugated system
was not observed; the same phenomenon was also discovered with
a ruthenium-based system.10
The reaction mechanism is proposed in Scheme 3. We believe
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proton-transfer step affords the final product and regenerates gold-
(I) catalyst. The gold catalyst also promotes migration of double
bonds, which gives rise to formation of small amounts of side
products for some substrates (Scheme 3). The mechanism of the
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In summary, we report here the gold(I)-catalyzed intermolecular
addition of phenols and carboxylic acids to olefins. The reaction is
simple and runs under relatively mild conditions. To our knowledge,
this is the first example of a gold(I)-mediated activation of inert
alkenes toward nucleophilic addition. Experimental results support
a proposed mechanism with the gold(I) directly activating the olefin.
This study may open a new direction for alkene functionalization.
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