Cationic cyclizations and rearrangements promoted by a heterogeneous gold catalyst

Article abstract of DOI:10.1021/ol403542k

A heterogeneous gold catalyst with remarkable activity for promoting the electrophilic reactions of aryl vinyl ketones and aryl dienyl ketones is described. The catalyst is easy to prepare, is robust, and can be recycled. Low loadings are effective for different types of cationic reactions, including Nazarov cyclizations, lactonizations, and [1,2] shifts.

Full text of DOI:10.1021/ol403542k

Letter
pubs.acs.org/OrgLett
Cationic Cyclizations and Rearrangements Promoted by a
Heterogeneous Gold Catalyst
Tulaza Vaidya, Ryan Cheng, Peter N. Carlsen, Alison J. Frontier,* and Richard Eisenberg*
Department of Chemistry, University of Rochester, Rochester, New York 14627-0216, United States
S
* Supporting Information
ABSTRACT: A heterogeneous gold catalyst with remarkable
activity for promoting the electrophilic reactions of aryl vinyl
ketones and aryl dienyl ketones is described. The catalyst is easy to
prepare, is robust, and can be recycled. Low loadings are effective
for different types of cationic reactions, including Nazarov
cyclizations, lactonizations, and [1,2] shifts.
a
Table 1. Gold-Catalyzed Nazarov Cyclizations Aryl Enone 1
atalysis of pericyclic reactions using coinage metals (Cu,
CAg, Au) is a rapidly evolving field. In this context, catalysis
of the Nazarov electrocyclization of aryl and vinyl enones has
been studied with numerous Cu(II) complexes1 and with
Ag(I).2−4 Homogeneous Au(I) and Au(III) complexes have
been reported to promote both iso-Nazarov cyclizations5 and the
cyclization of more typical divinyl ketone substrates.6,7 When
considering effective catalysts for the Nazarov cyclization of less
reactive aryl enones,1c the Ir(III) complexes developed in our
group demonstrate unique reactivity, promoting Nazarov
cyclization and novel electrophilic chemistry of otherwise inert
aryl and heteroaryl enones.8,9 However, multistep reaction
sequences are necessary to prepare the dicationic and tricationic
Ir(III) complexes.
Several reports have detailed the in situ generation of a
catalytically active [Au] species from gold(III) chloride (AuCl3)
and silver(I) salts for catalysis of arene and alkene functionaliza-
tion reactions,10−15 as well as Nazarov cyclization.6,7 However,
the identity of the active catalyst in these reactions is unknown.16
We describe here a related gold catalyst that is generated in situ
from a combination of AuCl3 and silver(I) hexafluoroantimonate
(AgSbF6). This catalyst is convenient to prepare, heterogeneous,
recyclable, and comparable in activity to the Ir(III) complexes for
the catalysis of Nazarov cyclization and other electrophilic
chemistry of aryl vinyl ketones.
temp
(°C)
time
(h)
yield
b
entry
catalyst
(%)
1
2
3
4
5
6
7
8
AuCl3/AgSbF6 (1:3)
rt
rt
rt
rt
rt
rt
rt
rt
0.5
0.5
0.5
0.5
0.5
24
0.5
1
>99
>99
AuCl3/AgSbF6 (1:2)
d
AuCl3/AgSbF6 (1:1)
−
>99
AuCl3/AgSbF6 (1:2) recycled once
AuCl3/AgSbF6 (1:2) recycled twice
(AuCl)2dppe/AgSbF6
97
NR
>99
>99
AuCl3/Na[BArF ] (1:2)
4
AuCl3/AgSbF6 (1:2) + Proton-
e
sponge
c
d
9
AuCl3
60
60
24
24
−
c
d
10
AgSbF6
−
a
Reaction conditions: 1 mol % of AuCl3 was used; catalyst was
premixed for 0.5 h prior to reaction in dichloromethane or toluene;
reactions containing AgSbF6 were run under minimal light conditions.
Isolated yields. 15 mol % was used. Incomplete reactions
monitored by thin layer chromatography (<50% conversion). 100
b
c
d
e
mol % was used. NR = no reaction, dppe =1,2-bis(diphenylphosphino)-
ethane, [BArF ]− = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, Proton-
4
The catalyst was identified during a screen performed to
identify gold(III) complexes able to promote the Nazarov
cyclization of aryl enone 1, a polarized,17,18 but relatively
unreactive substrate (Table 1). The addition of AgSbF6 to AuCl3
was intended to abstract gold-bound chloride ions to generate an
unsaturated, cationic Au(III) species.10 The suspension obtained
upon addition of AgSbF6 (2−3 mol %) to AuCl3 (1 mol %) was
found to be highly active, promoting the cyclization of 1 at room
sponge =1,8-bis(dimethylamino)naphthalene.
temperature within 0.5 h with >99% yield (entries 1 and 2). In an
earlier study, cyclization of a similar substrate using Cu(ClO4)2
Received: December 6, 2013
Published: January 16, 2014
© 2014 American Chemical Society
800
dx.doi.org/10.1021/ol403542k | Org. Lett. 2014, 16, 800−803

Organic Letters
Letter
required heating at 45 °C for 8 h to achieve cyclization (80%
yield).17
Table 2. Cyclization of Aryl and Heteroaryl Enones with the
Heterogeneous Gold Catalyst [Au]
a
A 1:1 mixture of AuCl3 and AgSbF6 shows diminished activity
with incomplete conversion over 0.5 h (entry 3). The dark
precipitate generated from the 1:2 mixture can be recovered after
the reaction by filtration through Celite and reused in the
presence of Celite for catalysis with negligible loss in activity. The
filtrate is not catalytically active. Subsequent cyclizations were
performed with the recovered heterogeneous substance, giving
>99% after the first recycle (entry 4) and 97% after the second
recycle (entry 5).
Cyclization does not occur upon exposure to a combination
of (AuCl)2dppe (dppe = 1,2-bis(diphenylphosphino)ethane)
with AgSbF6 (Au/Ag = 1:1) (entry 6). However, a CH2Cl2
mixture of AuCl3/Na[BArF ] ([BArF ]− = tetrakis[3,5-bis-
4
4
(trifluoromethyl)phenyl]borate) in a 1:2 ratio (entry 7) has
the same catalytic activity as the optimal catalyst formed from
AuCl3/AgSbF6 (1:2), indicating that silver does not play a significant
role in the catalysis. A CH2Cl2 mixture of AuCl3/AgSbF6 (1:2) with
Proton-sponge (100 mol %; Proton-sponge =1,8-bis(dimethyl-
amino)naphthalene) gives a quantitative yield of cyclized product
but requires a slightly longer reaction time (entry 8). Thus, trace
amounts of H+ may aid in the catalysis, but the effect is not great.
Finally, neither AuCl3 (15 mol %) nor AgSbF6 (15 mol %) used
alone exhibits high activity (entries 9 and 10), giving incomplete
conversions after 24 h at 60 °C.
To determine the reaction scope and look for new reactivity
patterns, the aryl vinyl and aryl dienyl ketones shown in Table 2
were exposed to the electrophilic heterogeneous gold catalyst
(Au(III) loading = 1 mol %). We observed rapid and quantitative
cyclizations of aryl dienone 3 as well as dienones having aromatic
β-substituents such as PMP (p-methoxyphenyl) 5 and TMP
(2,4,6-trimethoxyphenyl) 7 (entries 2 and 3, respectively). While
aryl enone 9 provides Nazarov cyclopentenone 10 (entry 4), aryl
γ-cyclobutyl enone 11 affords electrocyclized product 12 and
unexpected naphthalenol 13 (entry 5). Similarly, the aryl γ-
cyclopropyl enone 14 provides both electrocyclized product 15
and tricycle 16 (entry 6).
The gold catalyst is effective for electrocyclizations of
unprotected pyrroles 17, 19, and 21, promoting efficient
cyclization using 1 mol % of the gold complex under mild
conditions (entries 7−9). In comparison, cyclization of 19 using
Sc(OTf)3 (5 mol %) and LiClO4 (1 equiv) requires heating at 80
°C for 8.5 h.18
The electrophilic nature of the heterogeneous gold catalyst
([Au]) is evident in its ability to promote [1,2] rearrangement
chemistry, which was previously only possible using a tricationic
Ir(III) complex.9 For example, rearrangement of 23 produced
tetrasubstituted enone 24 (entry 10), and furyl enone 25
rearranges and cyclizes to afford 26 in 50% yield (entry 11).19
These results also suggest that product 13 is produced from 11
via a [1,2]-alkyl shift/Friedel−Crafts annulation,9 followed by
aromatization upon air oxidation.
Exposure of aryl enone 27a to the [Au] catalyst for 5 h at room
temperature exclusively generates tricyclic lactone 29a, via a
novel Nazarov cyclization/lactonization cascade (Table 3, entry
1).20 Aryl vinyl enone 14 undergoes a related, but less efficient,
cyclization/lactonization (Table 2, entry 6). Similarly, cyclization
of precursors 27b−d produces lactones 29a−c, respectively, but
requires heating in a mixture of dichloromethane/toluene and a
longer reaction time (entries 2−4).
a
Reaction conditions: AuCl3 (1 mol %)/AgSbF6 (2 mol %), premixed
prior to reaction, CH2Cl2 or toluene, rt unless otherwise indicated,
minimal light conditions. Reactions monitored using thin layer
chromatography. Isolated yields. Reactions at 80 °C. Reaction at 60
°C. 10 mol % catalyst. PMP = para-methoxyphenyl, TMS =
trimethylsilyl, TMP = 2,4,6-trimethoxyphenyl.
b
c
d
e
f
Probing the reaction further, when enone 27c is added to a
solution containing the heterogeneous gold catalyst in the
presence of Proton-sponge, no reaction is observed (entry 5). On
the other hand, enone 27c cyclizes to give 28b, but not lactone
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Organic Letters
Letter
a
Table 3. Nazarov/Lactonization Cascade Reactions of Aryl Vinyl Enones with Heterogeneous Gold Catalyst
b
c
no.
dienone
R1
R2
Br
R3
time (h)
temp (°C)
solvent
CH2Cl2
additive
none
product
29a
yield (%)
1
2
3
4
5
6
7
27a
27b
27c
27d
27c
27c
27c
TIPS
TIPS
Me
TBS
TMS
TBS
TMS
TBS
TBS
TBS
5
rt
79
82
83
88
NR
80
92
Br
20
24
24
24
24
24
60
60
60
60
60
60
CH2Cl2/PhMe (1:1)
CH2Cl2/PhMe (1:1)
CH2Cl2/PhMe (1:1)
CH2Cl2/PhMe (1:1)
CH2Cl2/PhMe (1:1)
CH2Cl2/PhMe (1:1)
none
29a
OMe
H
none
29b
Me
none
29c
d
Me
OMe
OMe
OMe
Proton-sponge
3 Å mol sieves
−
28b
Me
e
Me
HOTf (1 equiv)
27e (R3H)
a
Reaction conditions (unless otherwise specified): 1 mol % of AuCl3 was used; catalyst was premixed prior to reaction; reactions were protected
b
c
d
e
from light. Reactions monitored using thin layer chromatography. Isolated yields. 100 mol %. Reaction was conducted without the AuCl3/
AgSbF6 catalyst. TBS = tert-butyldimethylsilyl, TIPS = triisopropylsilyl, TMS = trimethylsilyl, Proton-sponge = 1,8-bis(dimethylamino)naphthalene.
NR = no reaction, HOTf = triflic acid.
29b, when molecular sieves are added to the reaction (entry 6).
Furthermore, treating 27c with HOTf effects protodesilylation
without cyclization (entry 7). From these experiments, it can be
deduced that protic acid must effect protodesilylation of 27
before cyclization can occur and that water is necessary for the
lactonization (conversion of 28 to 29).
To test this hypothesis, 28b was methylated at the α position
to lock the ester and olefin groups of cyclopentanone 30 in the cis
conformation (Scheme 2). Indeed, the lactonization of 30 occurs
at room temperature to give 31 in near-quantitative yield.
Scheme 2. Room Temperature Conversion of Nazarov
Product to Lactone
Aryl enone 27a can be cyclized with stoichiometric amounts of
AlCl3, allowing isolation of intermediate 28a (Scheme 1).8 21
b,
Subsequently, heating cyclopentanone 28a with [Au] at 60 °C
furnishes tricycle 29a in 80% yield. However, heating 28a to
60 °C in wet 1,2-dichloroethane for 16 h did not produce lactone
29a. This finding, along with the result in Table 3, entry 6,
indicates that both water and [Au] are required for lactone
formation. The isolation of product 16 (Table 2, entry 6) is
additional evidence that [Au] promotes lactone formation,
although the mechanism for formation of 16 is not yet clear to us.
A tentative mechanism for the multistep transformation of the
Nazarov cyclization/lactonization cascade is presented in
Scheme 3. The serendipitous discovery of the cascade is due to
the adventitious presence of water and acid in the reaction
medium. Thus, the sequence begins with protodesilylation,
promoted by trace amounts of acid in the reaction mixture. The
Nazarov cyclization step only occurs upon exposure to the gold
catalyst: protic acid alone does not promote cyclization, and
cyclization was also efficient when water was excluded from the
reaction using molecular sieves. Lactone formation, however,
requires the presence of both the [Au] catalyst and water.
Scheme 1. Stepwise Nazarov Electrocyclization/
Lactonization
Scheme 3. Proposed Mechanism for the Nazarov Cyclization/
Lactonization Cascade
There is a significant rate difference between the one-step
cyclization/lactonization and the stepwise version (Scheme 1).
We propose that the one-pot sequence occurs via the kinetically
favored 28a (cis),22 which is rapidly converted to 29a. However,
in the stepwise reaction sequence, elevated temperature and
extended reaction times are required for the isomerization of 28a
(trans) to 28a (cis) which has the geometry necessary for lactone
formation.
In conclusion, we report an electrophilic heterogeneous gold
catalyst that promotes cationic reactions of relatively unreactive
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Organic Letters
Letter
(15) Sun, X.; Sun, W.; Fan, R.; Wu, J. Adv. Synth. Catal. 2007, 349,
2151.
(16) For reviews on organic reactions catalyzed by gold, see:
polarized dienones. The reactivity of the gold catalyst is
comparable to the unusually reactive Ir(III) tricationic complex,6
but the gold catalyst is easily prepared and can be recycled, and
only 1 mol % of AuCl3 is used as the catalyst precursor. Aryl and
heteroaryl enones with diverse functionalities are readily
cyclized, and other cationic reaction chemistry is also observed,
including [1,2]-rearrangements and an unexpected lactonization.
(a) Boorman, T. C.; Larrosa, I. Chem. Soc. Rev. 2011, 40, 1910.
(b) Furstner, A. Chem. Soc. Rev. 2009, 38, 3208. (c) Arcadi, A. Chem. Rev.
̈
2008, 108, 3266. (d) Hashmi, A. S. K.; Rudolph, M. Chem. Soc. Rev.
2008, 37, 1766. (e) Skouta, R.; Li, C.-J. Tetrahedron 2008, 64, 4917.
(f) Li, Z.; Brouwer, C.; He, C. Chem. Rev. 2008, 108, 3239. (g) Hashmi,
A. S. K. Chem. Rev. 2007, 107, 3180.
ASSOCIATED CONTENT
* Supporting Information
(17) He, W.; Herrick, I. R.; Atesin, T. A.; Caruana, P. A.; Kellenberger,
C. A.; Frontier, A. J. J. Am. Chem. Soc. 2008, 130, 1003.
(18) Malona, J. A.; Colbourne, J. M.; Frontier, A. J. Org. Lett. 2006, 8,
5661.
(19) These reactions can also be promoted by tricationic Ir(III), with
similar efficiency (see ref 9).
■
S
Experimental details, preparation, and characterization of new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
(20) In order to reveal the product identity, silyl ether 29a was
deprotected with TBAF (tetrabutylammonium fluoride) to obtain the
phenol product.
AUTHOR INFORMATION
Corresponding Authors
■
(21) Marcus, A. P.; Lee, A. S.; Davis, R. L; Tantillo, D. J.; Sarpong, R.
Angew. Chem., Int. Ed. 2008, 47, 6379.
(22) Janka, M.; He, W.; Frontier, A. J.; Flaschenriem, C.; Eisenberg, R.
Tetrahedron 2005, 61, 6193.
*E-mail: frontier@chem.rochester.edu.
*E-mail: eisenberg@chem.rochester.edu.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Science Foundation (Grants CHE-
0556225 and CHE-0849892) and the NIH (NIGMS Grant R01
GM079364) for funding this work. We are grateful to Dr. Alice
Bergmann (SUNY Buffalo) and Dr. Furong Sun (UIUC) for
HRMS analysis.
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