Efficient generation and increased reactivity in cationic gold via Bronsted acid or lewis acid assisted activation of an imidogold precatalyst

Article abstract of DOI:10.1021/ol501443m

Bronsted or Lewis acid assisted activation of an imidogold precatalyst (L-Au-Pht, Pht = phthalimide) offers a superior way to generate cationic gold compared with the commonly used silver-based system. It is also broadly applicable for most common gold-catalyzed reactions. For reactions that require milder conditions, milder acids can be used for optimized efficiency.

Full text of DOI:10.1021/ol501443m

Letter
pubs.acs.org/OrgLett
Open Access on 06/23/2015
Efficient Generation and Increased Reactivity in Cationic Gold via
Brønsted Acid or Lewis Acid Assisted Activation of an Imidogold
Precatalyst
Junbin Han,† Naoto Shimizu,‡ Zhichao Lu,† Hideki Amii,‡ Gerald B. Hammond,*,† and Bo Xu*,†
†Department of Chemistry, University of Louisville, Louisville, Kentucky 40292, United States
‡Department of Chemistry and Chemical Biology, Graduate School of Engineering, Gunma University, Gunma 376-8515, Japan
S
* Supporting Information
ABSTRACT: Brønsted or Lewis acid assisted activation of an
imidogold precatalyst (L-Au-Pht, Pht = phthalimide) offers a
superior way to generate cationic gold compared with the commonly
used silver-based system. It is also broadly applicable for most
common gold-catalyzed reactions. For reactions that require milder
conditions, milder acids can be used for optimized efficiency.
ationic gold catalysis is an important addition to the field of
There are alternative ways to generate cationic gold.10 Teles
and others11 reported the protonolysis of Ph3PAu−CH3 in the
hydration and amination of alkynes with good turnover numbers
(Scheme 1a). Nolan and co-workers reported a Brønsted acid
C
organic synthesis.1 Silver-mediated halogen abstraction is
the most preferred method to generate cationic gold from a gold
catalyst precursor (e.g., L−Au−Cl) because of the mild
conditions needed and the relative availability of silver activators
(AgX, X= OTf−, SbF6 , NTf2 , etc.). However, the use of silver
activators is not problem free. First, some of the preferred silver
activators are either relatively expensive (e.g., AgNTf2),2
commercially unavailable, or troublesome to prepare (e.g.,
Ag[B(C6F5)4]).3 Second, the presence of silver may cause side
reactions.4 Indeed, recent reports have revealed that the silver
mediated halogen abstraction is not as simple a process as initially
thought (Figure 1). Possibly because of the high affinity of silver
−
−
Scheme 1. Selected Silver-Free Cationic Gold Generation
activation of NHC−Au−OH that generated cationic [NHC-
Au]+ or [Au−O−Au]+ species (Scheme 1b).12 Bertrand and co-
workers generated cationic gold taking advantage of the high
affinity of silica toward chloride (Scheme 1c).13 Recently, Lafolle
and Gandon reported the use of Cu(OTf)2 to activate L−AuCl.14
The aforementioned nonsilver activation methods have
limitations though. First, gold precatalysts like L−Au−CH3
and L−Au−OH have only been synthesized successfully for a
limited set of ligands.11a,15 This limitation is a constraint in gold
catalysis because different gold-catalyzed reactions usually
require different ligands for optimal efficiency.16 Second, for
each of the activation methods reported, only a limited set of
gold-catalyzed reactions has been tested.10a Third, the relative
reactivity of the nonsilver based system viz a viz the equivalent
silver-based system has not been aptly compared. Fourth, L−
Figure 1. Various Au−Ag intermediates.
toward gold and halogen, various Au−Ag intermediates (A,5 B,6
C7) are formed during the halogen abstraction step (Figure 1).
The presence of silver could also have an additional deleterious
effect: the formation of a dinuclear gold−silver resting state (i.e.,
intermediate D in Figure 1).8 Although silver activators do not
always negatively affect the system, using preformed L−Au+X−
complexes with weakly coordinating anions often can avoid the
problems described in Figure 1.9
Received: May 19, 2014
Published: June 23, 2014
© 2014 American Chemical Society
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Au−CH3/acid system has been reported to be very unstable in
some solvents.17
Table 1. Relative Rate of Intermolecular Hydroamination
In our continuing effort to improve the efficiency of gold
catalysis,18 we found that a gold phthalimide complex (L−Au−
Pht) can be easily synthesized from L−Au−Cl and potassium
phthalimide for a diversity of ligands (Scheme 2).19 L−Au−Pht
Scheme 2. Synthesis of L-Au-Pht
in itself is not an active gold catalyst due to strong an Au−N
bond. But due to the affinity of Pht toward Brønsted acid and
Lewis acid, we can generate cationic gold using L−Au−Pht/acid
combination. The reactivity of the L−Au−Pht/acid system
could be fine-tuned by readily available Brønsted acids/Lewis
acids, each of which with a unique acid strength and counterion.
31P NMR is a good indicator of the electronic properties of
gold complexes, which may relate to catalytic reactivity.
Treatment of Ph3PAu−Pht with TfOH does generate a cationic
gold species system similar to the commonly used Ph3PAu−OTf
(Scheme 3).
be tolerated, then we can replace it with a milder acid, such as
Yb(OTf)3 (Table 1, entry 13, its aqueous solution is close to
neutral) or AgCTf3 (Table 1, entry 18).21
Scheme 3. Brønsted/Lewis Acid Activation of L-Au-Pht
To assess the generality of our approach, we screened other
common gold-catalyzed reactions and compared our results with
standard silver-based methods. We began by investigating the
most common type of gold-catalyzed reaction, namely the X−H
(X = O, N, C) addition to C−C unsaturated compounds
(Scheme 4). The addition of a basic alkyl amine to an alkene
(Scheme 4a) is a very demanding reaction in gold catalysis not
only because the basic amine binds strongly to cationic gold3 but
also because the basic amine may inhibit protodeauration by
quenching any acid present in the system.22 Hartwig and co-
workers have used cationic rhodium complexes (2.5% loading)
of a biaryldialkylphosphine (DavePhos) to catalyze this
reaction.15 A commonly used gold catalytic system such as
PPh3PAu/AgOTf gives very low conversion (5%) even at high
catalyst loading (Scheme 4a). Instead, our Ph3P−Au−Pht/
HCTf3 system gives very good yields under the same conditions
(Scheme 4a) using a much lower loading (0.5%), and a simple
Ph3P ligand. Our L−Au−Pht/acid system also showed good
reactivity in the intermolecular hydroamination of allene23
(Scheme 4b), whereas the silver-based system is less efficient.
Lafolle and Gandon reported the use of Cu(OTf)2 to activate L−
AuCl directly in the intramolecular C−H addition of alkene14
(Scheme 4c); our L−Au−Pht/HCTf3 also worked well in this
reaction.
We used the hydroamination of alkynes10b,11b as a model
system and found the reactivity of the L−Au−Pht/acid system
was superior to the traditional silver halide removal protocol
(Figure 2). We measured the initial reaction rate for each
Figure 2. Effects of acids on hydroamination of 1.
Next, we investigated the hydration of alkynes; Ph3PAuCl/
AgOTf was not efficient at relatively low temperature and catalyst
loading, but our Ph3P−Au−Pht/HCTf3 performed nicely
activator at a given concentration (Table 1). We found that weak
acids like benzoic acid did not promote this reaction and stronger
acids were more effective (HCTf3 > HNTf2 > TfOH).20 Most
24
(Scheme 4d). The IPr−Au−Cl/AgSbF6 system was slow at
lower temperature (60 °C), but IPr−Au−Pht/HCTf3 system
was capable of completing the reaction in less than 45 min
(Scheme 4b). A similar outcome took place in the cyclization of
homopropargylic diols (Scheme 4e).25 Ph3PAuCl/AgOTf was
able to complete the reaction in less than 0.5 h using a relatively
high loading (2%), but at low loading (0.1%) only trace amounts
of product were observed after 5h. In contrast, our Ph3P−Au−
Pht/HCTf3 furnished the product in high yield after only 1 h.
Lewis acids also worked well. The counterions of Brønsted acids
−
or Lewis acids played an important role (rate: CTf3− > NTf2
>
TfO− > BF4 ). We also evaluated other gold catalyst precursors
(Ph3PAuCl, Ph3PAu−Sac, Ph3PAu−OAc, Table 1, entries 8−10)
and found them less effective. The data in Table 1 also
demonstrate that we have many more options to choose from
compared to silver activators. For example, if a strong acid cannot
−
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Scheme 4. Addition of X−H (X = O, N, C) to Alkyne/Alkene
Scheme 5. Other Examples of Gold-Catalyzed Reactions
but needed only a 10-fold lower catalyst loading (0.5%). In our
study, the only reaction in which our silver-free method and the
conventional silver-based method worked equally well was in the
cycloisomerization of allenone (Scheme 5d).9,28 In in the
synthesis of α-pyrone (Scheme 5e), we obtained the pyrone
product in 99% yield using only a catalyst load of 0.1%, whereas
the same reaction cited in the literature29 needed a 5% loading.
The activation of L−Au−Pht by stronger acids usually gives
better reactivity, but in some reactions, the starting material or
the product may not withstand the strong acids. An added feature
of our approach is that it allows us to either reduce the amount of
acid activator or use a weaker acid instead. For example, the
addition of a carboxylic acid to an alkyne could produce a useful
intermediate, a functionalized vinyl acetate (Scheme 6a),30 but a
silver-based cationic gold generation protocol produces a
mixture of double-bond migration products and the hydrolysis
byproduct 2-octanone (Scheme 6a). The weak carboxylic acid is
able to activate the L−Au−Pht precatalyst. In this manner, we
obtained the single product exclusively. The same approach was
used successfully in the intramolecular version of the reaction
(Scheme 6b).
Although in most of the aforementioned reactions we used 2
equiv (vs gold catalyst) of acid activator, we can reduce the
amount of acid activator further (e.g., 0.9 equiv vs gold) and
foster milder conditions. For example, in the gold(I)-catalyzed
isomerization of allenyl carbinol ester,31 the resulting product
can be hydrolyzed by the trace water present in the presence of
acid. But we can overcome this problem by simply using less than
1 equiv of acid activator or by choosing a milder Lewis acid
(Scheme 6c).
Furthermore, our L−Au−Pht/HCTf3 system worked well in the
C−H addition to alkynes (Scheme 4f),26 whereas the silver-
based system only gave trace amounts of product under the same
conditions. We also revisited the hydroamination reaction using
a more electron-rich ligand (JohnPhos); the reaction was
completed in only 15−70 min (Scheme 4g).
Then we proceeded to examine a wider range of gold-catalyzed
reactions (Scheme 5). In the gold-catalyzed cycloisomerization
of 1,6-enyne, the silver-based system catalyzed a fast conversion
to product using a relatively high loading (2%), but at a lower
loading (0.2%) the reaction was sluggish (Scheme 5a). However,
our Ph3P−Au−Pht/HCTf3 system was very efficient even at
0.02% catalyst loading.
A similar result occurred during the cycloisomerization of
propargyl amide: the Ph3PAuCl/AgOTf system was very slow at
low catalyst loadings whereas our Ph3P−Au−Pht/HCTf3 system
was very fast. We also tested an oxygen-transfer reaction recently
reported by Zhang and co-workers (Scheme 5c);27 the authors
used L−Au−NTf2 (5% loading, L = Ph3P or BrettPhos, prepared
from L−Au−Cl and AgNTf2). Our system worked equally well
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Scheme 6. Reactions That Benefit from Milder Conditions
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In summary, the Brønsted acid or Lewis acid activation of
imido gold precatalyst (L−Au−Pht) is a superior way to
generate cationic gold, compared to a silver-based activator. Our
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number in a large variety of gold-catalyzed reactions.
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ASSOCIATED CONTENT
* Supporting Information
(17) Wang, D.; Cai, R.; Sharma, S.; Jirak, J.; Thummanapelli, S. K.;
Akhmedov, N. G.; Zhang, H.; Liu, X.; Petersen, J. L.; Shi, X. J. Am. Chem.
Soc. 2012, 134, 9012−9019.
■
S
Experimental procedure. This material is available free of charge
via the Internet at http://pubs.acs.org.
(18) Malhotra, D.; Mashuta, M. S.; Hammond, G. B.; Xu, B. Angew.
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AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: gb.hammond@louisville.edu.
*E-mail: bo.xu@louisville.edu.
Notes
(20) Kutt, A.; Rodima, T.; Saame, J.; Raamat, E.; Maemets, V.;
̈
̈
Kaljurand, I.; Koppel, I. A.; Garlyauskayte, R. Y.; Yagupolskii, Y. L.;
Yagupolskii, L. M.; Bernhardt, E.; Willner, H.; Leito, I. J. Org. Chem.
2010, 76, 391−395.
The authors declare no competing financial interest.
(21) AgCTf3 is available from Sigma-Aldrich (catalog no. L511854).
(22) (a) Khin, C.; Hashmi, A. S. K.; Rominger, F. Eur. J. Inorg. Chem.
2010, 2010, 1063−1069. (b) Hashmi, A. S. K.; Schuster, A. M.;
Rominger, F. Angew. Chem., Int. Ed. 2009, 48, 8247−8249.
(23) Wang, Z. J.; Benitez, D.; Tkatchouk, E.; Goddard Iii, W. A.; Toste,
F. D. J. Am. Chem. Soc. 2010, 132, 13064−13071.
ACKNOWLEDGMENTS
■
We are grateful to the National Science Foundation for financial
support (CHE-1111316) and to the National Institutes of Health
(R15 GM101604-01) for a graduate research assistantship to Mr.
Junbin Han. Professor Hideki Amii and Mr. Naoto Shimizu
acknowledge the support of the Ministry of Education, Culture,
Sports, Science and Technology of Japan (Grant-in-Aid for
Scientific Research).
(24) Marion, N.; Ramon, R. S.; Nolan, S. P. J. Am. Chem. Soc. 2009,
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