AuI-catalyzed intramolecular cyclization of 2-alkenylphenyl carbonyl compounds: Exploring the oxophilic Lewis acidity of AuI species

Article abstract of DOI:10.1002/ejoc.201100113

A Au^I-catalyzed intramolecular cyclization reaction of 2-alkenylphenyl carbonyl compounds to afford a variety of indene, indenol, and indanone ring systems was developed. In this process, Au^I serves to activate the carbonyl group of β-keto esters, aldehydes, and ketones, preferentially exhibiting oxophilicity in the presence of C-C multiple bonds. Furthermore, β-keto esters could participate as the electrophilic partner in reactions with carbon nucleophile such as alkenes. Copyright

Full text of DOI:10.1002/ejoc.201100113

FULL PAPER
DOI: 10.1002/ejoc.201100113
AuI-Catalyzed Intramolecular Cyclization of 2-Alkenylphenyl Carbonyl
Compounds: Exploring the Oxophilic Lewis Acidity of AuI Species
Arun R. Jagdale[a] and So Won Youn*[a]
Keywords: Gold / Cyclization / Carbonyl compounds / Alkenes / Fused-ring systems
A AuI-catalyzed intramolecular cyclization reaction of 2-alk-
enylphenyl carbonyl compounds to afford a variety of in-
dene, indenol, and indanone ring systems was developed. In
this process, AuI serves to activate the carbonyl group of β-
keto esters, aldehydes, and ketones, preferentially exhibiting
oxophilicity in the presence of C–C multiple bonds. Further-
more, β-keto esters could participate as the electrophilic part-
ner in reactions with carbon nucleophile such as alkenes.
attack.[1c–1e,2] Meanwhile, it has also been reported that
AuIII can exhibit oxophilic character towards the carbonyl
group, thereby rendering an electrophilic nature to the latter
functionality.[3–5] In stark contrast, synthetic applications
that exploits the oxophilicity of AuI remains scarce, espe-
cially in substrates bearing C=C bonds where the latter
functionality is known to be more susceptible towards acti-
vation by AuI catalysts.[6] As a pioneering example, Liu and
co-workers reported a AuI-catalyzed deoxygenative Naza-
rov cyclization of 2,4-dien-1-als in the preparation of cyclo-
pentene derivatives, demonstrating the oxophilicity exhib-
ited by AuI catalysts towards the aldehyde function-
ality.[6b,6c] Herein, we report an unprecedented AuI-cata-
Introduction
Transition-metal-catalyzed carbon–carbon bond formation
reactions between 1,3-dicarbonyl compounds and alk-
enes have been of significant synthetic interest in recent
years.[1] In general, such transformations operate through
the nucleophilic character of the 1,3-dicarbonyl function-
ality, forging a carbon–carbon bond with the alkene com-
ponent through π-philic transition-metal activations
(Scheme 1, path a). AuIII and AuI are both well documented
soft π-philic Lewis acids that show a high degree of electro-
philicity towards carbon–carbon multiple bonds, generating
an activated species that is susceptible towards nucleophilic
Scheme 1. Transition-metal-catalyzed reactions between β-keto carbonyl compounds and olefins.
[a] Department of Chemistry and Research Institute for Natural
lyzed intramolecular cyclization reaction of 2-alkenylphenyl
Sciences, Hanyang University,
carbonyl compounds (Scheme 1, path b). In particular, for
the first time, oxophilic activation of alkenyl β-keto esters
has been demonstrated, thereby rendering the latter func-
tionality susceptible to nucleophilic attack by the pendent
Seongdong-Gu, Seoul 133-791, South Korea
Fax: +82-2-2299-0762
E-mail: sowony73@hanyang.ac.kr
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100113.
3904
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 3904–3910

Exploring the Oxophilic Lewis Acidity of AuI Specie
alkenyl moiety. This protocol enabled convenient entry to a Table 1. Catalyst screening for the intramolecular cyclization of 1a.
variety of indenes,[7] indenols,[8] and indanones,[9] which are
privileged structural motifs found in a diverse array of com-
pounds possessing important physical and biological prop-
erties.[10]
Results and Discussion
Prompted by recent reports of Au-catalyzed addition of
1,3-dicarbonyl compounds to alkenes,[1c–1e,2] we initially an-
ticipated a Au-catalyzed intramolecular cyclization of alk-
enyl β-keto esters 1a to afford tetralone A and/or its oxidat-
Entry
Catalyst (mol-%)
Yield [%][a]
ively aromatized derivative naphthol B (Table 1).[11] Much
to our surprise, treatment of 1a with Ph3PAuCl/AgOTf (1:1,
5 mol-%) in ClCH2CH2Cl (0.025 m) at 100 °C led to, exclu-
sively, the formation of indene 2a in 70% yield (Table 1,
Entry 1). We speculated this unexpected outcome originates
from initial nucleophilic attack at the ketone moiety by the
stilbene olefin, followed by subsequent dehydration. Ex-
pected products A and B, or C,[1h,1i] resulting from intramo-
lecular nucleophilic addition of the β-keto ester to the al-
kene functionality through either C or O attack, respec-
tively, could neither be isolated nor detected. Inspired by
this serendipitous discovery, we set out to examine the reac-
tion of 1a in the presence of other Lewis acidic metal salts
1
2
3
4
5
6
7
8
Ph3PAuCl (5)/AgOTf (5)
AuCl (5)/AgOTf (5)
AuCl3 (5)/AgOTf (10)
PtCl2 (5)/AgOTf (10)
RuCl3 (5)/AgOTf (10)
AgOTf (5)
70
50
45
40
45
45
45
10
Cu(OTf)2 (5)
In(OTf)3 (5)
Sc(OTf)3 (5)
9
0
10[b]
11[b]
12[b]
13[b]
14[b]
15[c]
16[d]
17[e]
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
Ph3PAuCl (5)/AgOTf (5)
Ph3PAuCl (5)/AgBF4 (5)
Ph3PAuCl (5)/AgSbF6 (5)
Ph3PAuCl (5)/AgOTs (5)
Ph3PAuCl (5)/Ag(O2CCF3) (5)
Ph3PAuCl (5)/AgOTf (5)
Ph3PAuCl (5)/AgOTf (5)
Ph3PAuCl (5)/AgOTf (5)
Ph3PAuCl (3 or 4)/AgOTf (3 or 4)
Ph3PAuCl (5)
70 (66)
0
0
0
0
50–60
40
0–trace
45–60
(Table 1; for details, see the Supporting Information). AuIII
,
PtII, RuIII, AgI, and CuII triflate salts gave product 2a in
moderate yields, whereas other metal triflates were ineffec-
tive (Table 1, Entries 1–9). Considering the well-known π-
philic Lewis acidity of AuI that activates the alkene moiety
towards nucleophilic attack by 1,3-dicarbonyls, and recog-
nizing that AuIII is more oxophilic than AuI,[1c–1e,2–5] our
findings are particularly noteworthy. The combination of
AuCl and AgOTf also promoted the reaction in the absence
of a phosphane ligand, albeit in lower yield (Table 1, En-
try 2). Among a variety of Ag salts examined, AgOTf
proved to be uniquely effective and essential as a cocatalyst
(Table 1, Entries 10–14). On the other hand, a selection of
Lewis and Brønsted acids examined did not promote the
reaction at all (Table 1, Entries 20–34).[12] It is noteworthy
that the reaction did not take place in the absence of cat-
ionic AuI catalyst (Table 1, Entry 19). Control experiments
employing protic acid that could conceivably be generated
in situ to thereby catalyze the reaction did not give any
products (Table 1, Entry 31), ruling out the possibility of
protic acid catalysis. ClCH2CH2Cl proved to be the solvent
of choice (Table 1, Entries 16 and 17), and the reaction yield
showed little dependence on concentration (Table 1, En-
0
0
0
0
0
0
0
0
0
0
0
0
PdCl2 (5)
Pd(OAc)2 (5)
PdCl2(MeCN)2 (5)
AuCl (5)
AuCl3 (5)
PtCl2 (5)
RuCl3 (5)
AlCl3 (5)
ZnCl2 (5)
FeCl3 (5)
BF3·Et2O (5)
TfOH(5)
trace
trace
0
pTsOH (5)
AcOH (5)
CF3CO2H (5)
0
1
[a] Yield determined by H NMR spectroscopy using trichloroeth-
ylene as an internal standard. Value in parentheses indicates iso-
lated yield. [b] For 4 h. [c] In 0.05 or 0.017 m ClCH2CH2Cl. [d] At
80 °C. [e] Using THF, DMF, DMSO, MeCN, or toluene as the sol-
vent at 80 °C for 48 h.
try 15). Finally, reducing either the reaction temperature or strates bearing electron-deficient aryl groups (Table 2, En-
catalyst loading led to a lower yield of 2a (Table 1, En- tries 7 and 8) as well as a sterically hindered alkyl group
tries 16 and 18).
(Table 2, Entry 14) underwent the cyclization reaction suc-
With the optimized reaction conditions in hand, we set cessfully, whereas a terminal alkene afforded a much in-
out to explore the substrate scope of this process. As shown ferior yield of product (Table 2, Entry 16). Interestingly, re-
in Table 2, the reaction showed little dependence on the na- actions of substrates bearing a 4-methoxyphenyl-substi-
ture of the ester group (Table 2, Entries 1–4), and both aryl tuted alkene (R4 = 4-MeOC6H4) afforded the correspond-
(Table 2, Entries 1–11) and alkyl (Table 2, Entries 13–15) ing tetralones 2fЈ and 2lЈ in high yields (exist in tautomeric
substituted styrenes were well tolerated. Furthermore, sub- forms; Table 2, Entries 6 and 12), where the structure of the
Eur. J. Org. Chem. 2011, 3904–3910
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3905

A. R. Jagdale, S. W. Youn
FULL PAPER
latter compound was unambiguously validated through X- be investigated; however, a working hypothesis involving
ray analysis of its O-acetylated derivative (for details, see electrophilic activation of the alkene moiety could be con-
the Supporting Information).[13] The exact reason for the ceived where a species resonance-stabilized by an electron-
unexpected formation of tetralones 2fЈ and 2lЈ remains to releasing OMe group renders the β carbon (carbon bonded
Table 2. AuI-catalyzed intramolecular cyclization of alkenyl β-keto esters 1.[a]
[a] Reaction conditions: 1 (1 equiv.), Ph3PAuCl (5 mol-%), and AgOTf (5 mol-%) in ClCH2CH2Cl (0.025 m) at 100 °C for 1–6 h, unless
otherwise noted. [b] Isolated yield. [c] Performed with Ph3PAuCl/AgOTf (10 mol-%). [d] Performed with AuCl/P(C6F5)3/AgOTf (5 mol-
%) at 70 °C for 10 h. [e] No reaction occurred using either Ph3PAuCl/AgOTf (5 mol-%) at 100 °C or AuCl/P(C6F5)3/AgOTf (5 mol-%) at
60–80 °C for 9–24 h, and starting materials were recovered in 60–90% yield.
3906
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 3904–3910

Exploring the Oxophilic Lewis Acidity of AuI Specie
Table 3. AuI-catalyzed intramolecular cyclization of 2-alkenylbenzaldehydes 3 and 2-alkenylaryl ketones 5 & 7.[a]
[a] Reaction conditions: 3, 5, or 7 (1 equiv.), AuCl (5 mol-%), P(C6F5)3 (5 mol-%), and AgOTf (5 mol-%) in ClCH2CH2Cl (0.025 m) at
25–100 °C for 0.5–8 h. [b] Isolated yield. [c] Performed with Ph3PAuCl/AgOTf (5 mol-%). [d] No reaction occurred using either Ph3PAuCl/
AgOTf (5 mol-%) at 100 °C for 24 h or AuCl/P(C6F5)3/AgOTf (5 mol-%) at 60 °C for 14 h, and starting materials were recovered in 90–
95% yield.
Eur. J. Org. Chem. 2011, 3904–3910
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3907

A. R. Jagdale, S. W. Youn
FULL PAPER
to R4) more electrophilic to nucleophilic attack by the prox-
Scheme 2 outlines a plausible mechanism for the cycliza-
imal 1,3-dicarbonyl. Substituent effects of R1 and R2 were tion reaction described herein.[19] Activation of the carbonyl
also examined, and in general, reaction yields were higher group through its coordination with the Lewis acidic AuI
for substrates bearing electron-neutral or electron-with- center (D) precedes intramolecular nucleophilic attack by
drawing substituents than for substrates bearing electron- the pendant alkene moiety, thereby generating a newly
donating substituents (Table 2, Entries 9–11).[14] With the formed carbon–carbon bond (E). Subsequent proton trans-
exception of 2p (Table 2, Entry 16), only E isomers were fer regenerates the AuI catalyst and produces indenol prod-
obtained stereoselectively. The structure of all indene prod- uct 4, which undergoes further dehydration for substrates
ucts were supported by 1H NMR and NOESY spec- where R1 ϶ H. Alternatively, a mechanistic explanation
troscopy experiments of compound 2a,[15] and X-ray crys- that invokes a Nazarov-type cyclization of activated species
tallographic analysis of product 2k.[13] Lastly, this cycliza- D could also be conceived.[6b,6c,17]
tion reaction failed to take place with β-keto esters bearing
an enoate (R4 = CO2Et) or 1,3-diketones (R3 = Me, Ph)
(Table 2, Entries 17–19), findings supported by the prefer-
ential AuI activation of the dicarbonyl moiety and propen-
sity of diketones to exist in their less-reactive enol tauto-
meric forms,[16] respectively.
Encouraged by the AuI-mediated cyclizations of alkenyl
β-keto esters, we turned our attention to alkenyl benzalde-
hyde and aryl ketone substrates. We speculated a similar
reaction pathway may take place leading to a variety of
indenols and indenes. The results of our findings are shown
in Table 3. Compared to the β-keto ester substrates, simple
monocarbonyl substrates generally required longer reaction
times. To circumvent this decreased reactivity, an electron-
deficient ligand was employed to enhance the electrophilic-
ity of the AuI catalyst.
Scheme 2. Proposed mechanism for the AuI-catalyzed intramolecu-
lar cyclization of 2-alkenylphenyl carbonyl compounds.
Conclusions
Much to our delight, although the Ph3PAuCl/AgOTf-me-
diated reaction required a longer reaction time at a higher
temperature (100 °C, 21 h, 72%), the combination of AuCl,
AgOTf, and P(C6F5)3 rapidly converted 3a into 4a at a
lower temperature with an improved chemical yield (60 °C,
4 h, 85%; Table 3, Entry 1). The same catalyst blend also
permitted the reaction to take place at room temperature
with comparable yield, albeit a longer reaction time was
required (25 °C, 24 h, 75%). The efficiency of this transfor-
mation is remarkable, considering that the related AuI-cata-
lyzed reaction of cis-2,4-dien-1-als resulted in a complex re-
action mixture in the absence of the external nucleophile.[6b]
Furthermore, cycloisomerization of cis-2,4-dien-1-als with
other Lewis acids in the absence of a nucleophile only af-
forded cyclopentenones.[17] Under the optimized reaction
conditions, 2-alkenylbenzaldehydes 3 and 2-alkenylaryl
methyl ketones 5 proceeded smoothly to form the corre-
sponding indenols 4 (Table 3, Entries 1–2, 4–9, and 11) and
indenes 6 (Table 3, Entries 12–19), respectively. Aryl butyl
ketone 7 also proved to be an effective substrate for this
transformation (Table 3, Entry 20), whereas diaryl ketone 9
(R3 = Ph) was unsuccessful (Table 3, Entry 21). Similar to
the reactions with alkenyl β-keto esters 1 described earlier,
substrates 3 and 5 bearing either aryl- or alkyl-substituted
styrenes (R4 = aryl or alkyl) were once again well tolerated.
2-Alkenylbenzaldehydes bearing electron-rich aromatic sub-
stituents (R4 = 4-Me-C6H4, 4-MeO-C6H4) were found to
undergo extensive isomerization of the initially formed in-
denols 4 into indanones 4Ј, an observation also reported by
other research groups (Table 3, Entries 2, 3, and
10).[10d,10f,18]
We have developed a AuI-catalyzed intramolecular cycli-
zation reaction of 2-alkenylphenyl carbonyl compounds to
afford a variety of indenes, indenols, and indanones. In this
process, AuI served to activate the carbonyl group of β-keto
esters as well as aldehydes and ketones, preferentially exhib-
iting oxophilicity in the presence of C–C multiple bonds. In
parallel, β-keto esters could participate as the electrophilic
component in reactions with carbon nucleophiles, for exam-
ple, alkenes. On both accounts, the unique reactivities of
both the AuI catalyst and the alkenyl β-keto esters allow
them to partake in a process that is counterintuitive.[1c–1e,2]
Further investigations to broaden the substrate scope and
application of this enabling technology to construct cyclic
motifs through AuI catalysis are currently underway in our
laboratory.
Experimental Section
General Procedure for the AuI-Catalyzed Intramolecular Cyclization
of Alkenyl β-Keto Esters 1: To a solution of 2-alkenyl β-keto esters
1 in ClCH2CH2Cl (0.025 m) in a pressure tube was added Ph3PAuCl
(5–10 mol-%) and AgOTf (5–10 mol-%). The resulting mixture was
stirred at 100 °C for the reported time. After the reaction was com-
plete, the reaction mixture was poured into sat. NH4Cl, and then
the product was extracted with CH2Cl2 (3ϫ), dried with MgSO4,
and concentrated in vacuo. The residue was purified by column
chromatography on silica gel to afford corresponding product 2.
General Procedure for the AuI-Catalyzed Intramolecular Cyclization
of 2-Alkenylbenzaldehydes 3 and 2-Alkenylaryl Ketones 5 & 7: To a
solution of 2-alkenylbenzaldehydes 3 or 2-alkenylaryl ketones 5 and
3908
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 3904–3910

Exploring the Oxophilic Lewis Acidity of AuI Specie
Qiu, F. Li, Y. Zhang, J. Wang, Angew. Chem. 2010, 122, 2072–
2076; Angew. Chem. Int. Ed. 2010, 49, 2028–2032.
7 in ClCH2CH2Cl (0.025 m) in a pressure tube was added AuCl
(5 mol-%), P(C6F5)3 (5 mol-%) (or 5 mol-% Ph3PAuCl), and AgOTf
(5 mol-%). The resulting mixture was stirred at the reported tem-
perature for the reported time. After the reaction was complete, the
reaction mixture was poured into sat. NH4Cl, and then the product
was extracted with CH2Cl2 (3ϫ), dried with MgSO4, and concen-
trated in vacuo. The residue was purified by column chromatog-
raphy on silica gel to afford corresponding product 4, 6, or 8.
Oxophilic AuIII vs. π-philic AuI: a) A. W. Sromek, M. Rubina,
V. Gevorgyan, J. Am. Chem. Soc. 2005, 127, 10500–10501; b)
A. S. Dudnik, A. W. Sromek, M. Rubina, J. T. Kim, A. V. Ke-
lЈin, V. Gevorgyan, J. Am. Chem. Soc. 2008, 130, 1440–1452.
Y. Yamamoto, J. Org. Chem. 2007, 72, 7817–7831.
[4]
[5]
[6]
For examples of oxophilic AuI, see: a) T. Dombray, A. Blanc,
J.-M. Weibel, P. Pale, Org. Lett. 2010, 12, 5362–5365; b) C.-C.
Lin, T.-M. Teng, A. Odedra, R.-S. Liu, J. Am. Chem. Soc. 2007,
129, 3798–3799; c) C.-C. Lin, T.-M. Teng, C.-C. Tsai, H.-Y.
Liao, R.-S. Liu, J. Am. Chem. Soc. 2008, 130, 16417–16423.
Biologically active compounds: a) I.-M. Karaguni, K.-H. Glu-
senkamp, A. Langerak, C. Geisen, V. Ullrich, G. Winde, T.
Möröy, O. Müller, Bioorg. Med. Chem. Lett. 2002, 12, 709–713;
b) O. Müller, E. Gourzoulidou, M. Carpintero, I.-M. Kara-
guni, A. Langerak, C. Herrmann, T. Möröy, L. Klein-Hitpaβ,
H. Waldmann, Angew. Chem. 2004, 116, 456–460; Angew.
Chem. Int. Ed. 2004, 43, 450–454. Functional materials: c) J.
Barberá, O. A. Raitin, M. B. Ros, T. Torroba, Angew. Chem.
1998, 110, 308–312; Angew. Chem. Int. Ed. 1998, 37, 296–299;
d) A. Cappelli, S. Galeazzi, G. Giuliani, M. Anzini, A. Donati,
L. Zetta, R. Mendichi, M. Aggravi, G. Giorgi, E. Paccagnini,
S. Vomero, Macromolecules 2007, 40, 3005–3014. Ligands: e)
D. Zargarian, Coord. Chem. Rev. 2002, 233, 157–176; f) M. J.
Calhorda, V. Felix, L. F. Veiros, Coord. Chem. Rev. 2002, 230,
49–64.
Supporting Information (see footnote on the first page of this arti-
cle): Full experimental details and characterization data.
[7]
Acknowledgments
This work was supported by the Mid-Career Researcher Program
(No. R01-2009–008–3940) and Basic Science Research Program
(Nos. 2010–0017149 and 2010–0007737) through the National Re-
search Foundation of Korea (NRF) grant funded by the Ministry
of Education, Science and Technology (MEST). A.R.J. is grateful
for 2009 NRF Post-doctoral Fellowship Program for Foreign Re-
searchers (No. K20802001473-10B120004500). We gratefully
acknowledge Professor Juyoung Yoon (Department of Chemistry
and Nano Science, Ewha Womans University) for his generous sup-
port. We also thank Dr. Ji-Eun Lee (Central Instrument Facility,
Gyeongsang National University) for X-ray crystallographic analy-
sis and Mr. Byung Seok Kim for assistance with spectroscopic data
collection and analysis.
[8]
a) Kurakay Co. Ltd. Jpn. Kokai Tokkyo Koho JP 81, 113, 740
(C1. C07C69/017), 1981 [Chem. Abstr. 1982, 96, 68724b]; b)
Kurakay Co., Ltd. Jpn. Kokai Tokkyo Koho JP 82 04,945 (C1.
C07C69/013), 1982 [Chem. Abstr. 1982, 96, 199935u]; c) D. L. J.
Clive, M. Yu, M. Sannigrah, J. Org. Chem. 2004, 69, 4116–
4125.
[1] Intramolecular addition of 1,3-dicarbonyl compounds to al-
kenes by C-attack. Pd catalysis: a) T. Pei, R. A. Widenhoefer,
J. Am. Chem. Soc. 2001, 123, 11290–11291; b) T. Pei, X. Wang,
R. A. Widenhoefer, J. Am. Chem. Soc. 2003, 125, 648–649; AuI
catalysis: c) C.-Y. Zhou, C.-M. Che, J. Am. Chem. Soc. 2007,
129, 5828–5829. Intermolecular addition of 1,3-dicarbonyl
compounds to alkenes by C-attack. AuIII catalysis: d) X. Yao,
C.-J. Li, J. Am. Chem. Soc. 2004, 126, 6884–6885; e) R.-V.
Nguyen, X.-Q. Yao, D. S. Bohle, C.-J. Li, Org. Lett. 2005, 7,
673–675; CuII catalysis: f) Y. Li, Z. Yu, S. Wu, J. Org. Chem.
2008, 73, 5647–5650; PdII & PtII catalysis: g) M. E. Cucciolito,
A. DЈAmora, A. Vitagliano, Organometallics 2010, 29, 5878–
5884. Intramolecular addition of 1,3-dicarbonyl compounds to
alkenes by O-attack. Pd catalysis: h) R. M. Trend, Y. K. Ram-
tohul, E. M. Ferreira, B. M. Stoltz, Angew. Chem. 2003, 115,
2998–3001; Angew. Chem. Int. Ed. 2003, 42, 2892–2895; i)
R. M. Trend, Y. K. Ramtohul, B. M. Stoltz, J. Am. Chem. Soc.
2005, 127, 17778–17788; j) X. Han, R. A. Widenhoefer, J. Org.
Chem. 2004, 69, 1738–1740.
[2] For selected reviews on gold catalysis, see: a) A. S. K. Hashmi,
Chem. Rev. 2007, 107, 3180–3211; b) R. Skouta, C.-J. Li, Tetra-
hedron 2008, 64, 4917–4938; c) Z. Li, C. Brouwer, C. He, Chem.
Rev. 2008, 108, 3239–3265; d) A. Arcadi, Chem. Rev. 2008, 108,
3266–3325; e) D. J. Gorin, B. D. Sherry, F. D. Toste, Chem. Rev.
2008, 108, 3351–3378; f) F. Dénès, A. Pérez-Luna, F. Chemla,
Chem. Rev. 2010, 110, 2366–2447.
[3] For examples of the activation of 1,3-dicarbonyl compounds
toward either heteroaromatic or heteroatom (e.g., N, O, S, P)
nucleophilic attack by AuIII catalyst, see: a) A. Arcadi, M. Al-
fonsi, G. Bianchi, G. DЈAnniballe, F. Marinelli, Adv. Synth.
Catal. 2006, 348, 331–338; b) A. Arcadi, G. Bianchi, S. Di Giu-
seppe, F. Marinelli, Green Chem. 2003, 5, 64–67 and references
cited therein. For selected examples of the activation of the
carbonyl or imine group toward electrophilic addition by AuIII
catalysis, see: c) S. W. Youn, J. Org. Chem. 2006, 71, 2521–2523;
d) A. S. K. Hashmi, L. Schwarz, P. Rubenbauer, M. C. Blanco,
Adv. Synth. Catal. 2006, 348, 705–708; e) R. Balamurugan, V.
Gudla, Org. Lett. 2009, 11, 3116–3119; f) F. Mo, J. M. Yan, D.
[9]
a) H. Sugimoto, Pure Appl. Chem. 1999, 71, 2031–2038; b) J.
Guillon, P. Dallemagne, J.-M. Leger, J. Sopkova, P. R. Bovy, C.
Jarry, S. Rault, Bioorg. Med. Chem. 2002, 10, 1043–1050.
For the transition-metal-mediated syntheses of indenols or in-
denes through sequential coupling and cyclization between o-
halobenzoyl compounds or its equivalents and alkynes, see: in-
denols: a) L. S. Liebeskind, J. R. Gasdaska, J. S. McCallum, J.
Org. Chem. 1989, 54, 669–677; b) J. Vicente, J.-A. Abad, J. Gil-
Rubio, Organometallics 1996, 15, 3509–3519; c) L. G. Quan, V.
Gevorgyan, Y. Yamamoto, J. Am. Chem. Soc. 1999, 121, 3545–
3546; d) V. Gevorgyan, L. G. Quan, Y. Yamamoto, Tetrahedron
Lett. 1999, 40, 4089–4092; e) D. K. Rayabarapu, C.-H. Yang,
C.-H. Cheng, J. Org. Chem. 2003, 68, 6726–6731; f) K.-J.
Chang, D. K. Rayabarapu, C.-H. Cheng, J. Org. Chem. 2004,
69, 4781–4787; g) T. Matsuda, M. Makino, M. Murakami,
Chem. Lett. 2005, 34, 1294–1295; h) R. Shintani, K. Okamoto,
T. Hayashi, Chem. Lett. 2005, 34, 1416–1417; i) M. Yang, X.
Zhang, X. Lu, Org. Lett. 2007, 9, 5131–5133; indenes: j) M.
Miyamoto, Y. Harada, M. Tobisu, N. Chatani, Org. Lett. 2008,
10, 2975–2978; k) K. Tsuchikama, M. Kasagawa, K. Endo, T.
Shibata, Synlett 2010, 97–100.
[10]
[11]
[12]
[13]
For an example of the cyclization of alkenyl β-keto esters 1 by
using selenium electrophiles in the presence of the Lewis acid
FeCl3 for the synthesis of naphthols, see: S. A. Shahzad, C.
Vivant, T. Wirth, Org. Lett. 2010, 12, 1364–1367.
For selected examples showing the higher reactivity of Au cata-
lysts than those of Lewis and/or Brønsted acids, see: Y.-H.
Wang, L.-L. Zhu, Y.-X. Zhang, Z. Chen, Chem. Commun.
2010, 46, 577–579, and ref.[3b,3c,3e]
CCDC-799118 (for 2k) and -799119 (for acetylated 2lЈ) contain
the supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge Crys-
tallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
1
[14]
In the case of highly electron-rich substrates 1, 3, and 5 (R =
R2 = OMe for 1 and 3; R1 = OMe, R2 = H for 1 and 5),
serious decomposition occurred under all conditions examined,
Eur. J. Org. Chem. 2011, 3904–3910
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3909

A. R. Jagdale, S. W. Youn
FULL PAPER
although substrates with similar electron density (R1, R2 = –
OCH2O–) worked smoothly. At this point we cannot provide
an unambiguous explanation for these inconsistent results.
[15] a) N. D. Cá, F. Campanini, B. Gabriele, G. Salerno, C. Mas-
sera, M. Costa, Adv. Synth. Catal. 2009, 351, 2423–2432; b)
C. S. Bryan, M. Lautens, Org. Lett. 2010, 12, 2754–2757.
[16] All β-keto esters 1 exist as a mixture of keto and enol forms in
a ratio of ca. 7:3 (by 1H NMR spectroscopy), favoring the keto
form. A similar observation was reported in ref.[11] In contrast,
1,3-diketones exist only in the enol form; this accounts for the
failure of the Au-catalyzed nucleophilic addition of alkene
groups to 1,3-diketone moieties.
[17] Lewis acid catalyzed cycloisomerization of 2,4-dien-1-als: a)
C.-Y. Lo, C.-C. Lin, H.-M. Cheng, R.-S. Liu, Org. Lett. 2006,
8, 3153–3156; b) A. K. Miller, M. R. Banghart, C. M. Beaudry,
J. M. Suh, D. Trauner, Tetrahedron 2003, 59, 8919–8930.
[18] For examples of isomerization of indenols into indanones, see:
a) W. M. Clark, A. M. Tickner-Eldridge, G. K. Huang, L. N.
Pridgen, M. A. Olsen, R. J. Mills, I. Lantos, N. H. Baine, J.
Am. Chem. Soc. 1998, 120, 4550–4551; b) D. R. Boyd, N. D.
Sharma, N. I. Bowers, I. N. Brannigan, M. R. Groocock, J. F.
Malone, G. McConville, C. C. R. Allen, Adv. Synth. Catal.
2005, 347, 1081–1089; c) E. M. Coyanis, J.-L. Panayides, M. A.
Fernandes, C. B. de Koning, W. A. L. van Otterlo, J. Or-
ganomet. Chem. 2006, 691, 5222–5239; d) G. B. Womack, J. G.
Angeles, V. E. Fanelli, B. Indradas, R. L. Snowden, P. Sonnay,
J. Org. Chem. 2009, 74, 5738–5741.
Examples of mechanistically related similar reactions. Ir-cata-
lyzed cyclization of ortho-alkenylated acetophenone, see:
ref.[10k]; Pd-mediated cyclization of α-arylketone bearing a pen-
dant alkene group, see: X. Han, R. A. Widenhoefer, Organome-
tallics 2007, 26, 4061–4065.
[19]
Received: January 26, 2011
Published Online: March 22, 2011
3910
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 3904–3910