Gold-Catalyzed Electrophilic Addition to Arylalkynes. A Facile Method for the Regioselective Synthesis of Substituted Naphthalenes

Article abstract of DOI:10.1021/ol900863d

An interesting gold-catalyzed electrophilic addition to arylalkyne to synthesize substituted naphthalenes has been presented. Different metal hexafluoroantimonates have also been found to effect the transformation. Counter anion and oxo- and alkynophilicities of catalytic gold species might play an important role in this annulation reaction.

Full text of DOI:10.1021/ol900863d

ORGANIC
LETTERS
2009
Vol. 11, No. 14
3116-3119
Gold-Catalyzed Electrophilic Addition to
Arylalkynes. A Facile Method for the
Regioselective Synthesis of Substituted
Naphthalenes
Rengarajan Balamurugan* and Vanajakshi Gudla
School of Chemistry, UniVersity of Hyderabad, GachiBowli, Hyderabad, India 500046
rbsc@uohyd.ernet.in
Received April 20, 2009
ABSTRACT
An interesting gold-catalyzed electrophilic addition to arylalkyne to synthesize substituted naphthalenes has been presented. Different metal
hexafluoroantimonates have also been found to effect the transformation. Counter anion and oxo- and alkynophilicities of catalytic gold
species might play an important role in this annulation reaction.
Use of homogeneous gold catalysts for organic transforma-
tions has shown tremendous potential in this decade.1 Several
Scheme 1
.
Gold-Catalyzed Annulation of Arylacetaldehydes
with Arylalkynes
reactions are now viable under mild conditions with great
efficiencies using gold catalysts. In most of the reported gold-
catalyzed reactions gold acts as a soft carbophilic Lewis acid
to activate carbon-carbon multiple bonds. The activated
species is then employed in the nucleophilic attack with
carbon or heteroatom nucleophiles. In this paper, we report
an electrophilic addition to arylalkynes catalyzed by gold.
Electrophilic addition to an alkyne catalyzed by gold is rather
an interesting case considering the Lewis acidity of gold
toward an alkynic bond. Catalytic amounts of AuCl3/AgSbF6
were sufficient for the annulation of arylacetaldehydes with
arylalkynes to generate substituted naphthalenes in a regi-
oselective manner (Scheme 1).
Substituted naphthalenes are part of many biologically
important compounds.2 Eventually, different strategies were
developed to generate substituted naphthalene derivatives in
a regioselective manner.3 Recently, Gevorgyan et al.4 and
Yamamoto et al.5 have reported the synthesis of naphthalene
derivatives involving gold-catalyzed nucleophilic attack on
the triple bond. However, the present reaction involving
(1) For selected reviews, see: (a) Hoffmann-Ro¨der, A.; Krause, N. Org.
Biomol. Chem. 2005, 3, 387. (b) Hashmi, A. S. K.; Hutchings, G. J. Angew.
Chem., Int. Ed. 2006, 45, 7896. (c) Gorin, D. J.; Toste, F. D. Nature 2007,
446, 395. (d) Marion, N.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46,
2750. (e) Li, Z.; Brouwer, C.; He, C. Chem. ReV. 2008, 108, 3239. (f) Arcadi,
A. Chem. ReV. 2008, 108, 3266. (g) Jime´nez-Nu´n˜ez, E.; Echavarren, A. M.
Chem. ReV. 2008, 108, 3326. (h) Gorin, D. J.; Sherry, B. D.; Toste, F. D.
Chem. ReV. 2008, 108, 3351. (i) Shen, H. C. Tetrahedron 2008, 64, 3885.
(j) Skouta, R.; Li, C.-J. Tetrahedron 2008, 64, 4917. (k) Muzart, J.
Tetrahedron 2008, 64, 5815. (l) Widenhoefer, R. A. Chem.sEur. J. 2008,
14, 5382.
(2) (a) Corornelli, C.; Pagani, H.; Bardone, M. R.; Lancini, G. C. J.
Antibiot. 1974, 27, 161. (b) Silva, O.; Gomes, E. T. J. Nat. Prod. 2003, 66,
447. (c) Dai, J.; Liu, Y.; Zhou, Y.-D.; Nagle, D. G. J. Nat. Prod. 2007, 70,
1824. (d) Brasholz, M.; So¨rgel, S.; Azap, C.; Reissig, H.-U. Eur. J. Org.
Chem. 2007, 3801. (e) Krohn, K.; Kounam, S. F.; Cludius-Brandt, S.;
Draeger, S.; Schulz, B. Eur. J. Org. Chem. 2008, 3615. (f) Lowell, A. N.;
Fennie, M. W.; Kozlowski, M. C. J. Org. Chem. 2008, 73, 1911.
10.1021/ol900863d CCC: $40.75
Published on Web 06/17/2009
 2009 American Chemical Society

AuCl3/AgSbF6 is believed to involve an electrophilic attack
on the triple bond.
We carried out several experiments to ascertain the nature
of gold species responsible for the transformation and to find
out the optimum reaction conditions (Table 1). For this
might helped the annulation to occur.6 However, the AuCl3/
AgOTf combination was not as effective as AuCl3/AgSbF6
(entry 10). While there was no product formation with
(Ph3P)AuCl, cationic (Ph3P)AuCl/AgSbF6-catalyzed reaction
yielded only 3% of the product (entries 11 and 12).
The [Au+] species in (Ph3P)AuCl and (Ph3P)AuCl/AgSbF6
is considered to be π-philic, whereas the [Au3+] in AuCl3 is
oxophilic.7 In a similar reported TiCl4-assisted annulation,3c
TiCl4 was needed in stoichimetric amounts, and moreover,
no reaction was observed when 2 equiv of aldehyde with
respect to TiCl4 were used. The authors claimed that the
TiCl4-bis(carbonyl) complex formed with 2 equiv of the
aldehyde did not give room for the coordination of Ti to
alkyne. Hence, with the catalytic amounts of gold in the
present reaction, it gives the impression that the alkynophi-
licity of gold might play a role for the reaction to take place
by bringing the alkyne close to the carbonyl function. The
above observations reveal that a gold species which is both
oxo- and alkynophilic is essential. This postulation was
supported by carrying out two distinct experiments with
lesser amounts of AgSbF6 added to AuCl3, which is expected
to proportionately lower the cationic character of [Au3+]
compared to that when 3 equiv of AgSbF6 with respect to
the amount of AuCl3 was used. Keeping the catalyst loading
of AuCl3 at 2 mol %, when the amount of AgSbF6 was varied
to 4 mol % and 2 mol % the reactions resulted in lower
yields in proportion to the amount of AgSbF6 used (entries
13 and 14). In order to draw more support, we carried out
the reaction with CuCl2/AgSbF6 as copper also has the ability
to complex with alkynes. Fascinatingly, it gave the naph-
thalene derivative with a yield comparable to that of the
AuCl3/AgSbF6-catalyzed reaction (entry 16). However, the
reaction required more time. The reactions employing CuCl/
AgSbF6 and Cu(OTf)2 were not that effective (entries 17 and
18).
Table 1. Screening of Different Catalysts and Conditions in the
Annulation of Phenylacetaldehyde and Phenylacetylene
time yieldg
entry
catalyst
solvent and condition (h)
(%)
a
1
2
3
4
5
6
7
8
9
AuCl3
CH2Cl2/4 Å MS, reflux 12 3
AuCl3a/AgSbF6
AgSbF6
CH2Cl2, rt
CH2Cl2/4 Å MS, reflux 12
4
41
5
b
b
AuCl3a/AgSbF6
AuCl3a/AgSbF6
AuCl3a/AgSbF6
AuCl3a/AgSbF6
AuCl3a/AgSbF6
AuCl3a/AgSbF6
CH2Cl2/4 Å MS, rt
CH2Cl2/4 Å MS, reflux
CH2Cl2/4 Å MS, reflux
DCE, rt
4
5
5
51
69
51h
b
b
b
b
b
b
24 40
DCE, reflux
DCE/4 Å MS, reflux
CH2Cl2/4 Å MS, rt
4
5
59
64
10 AuCl3a/AgOTfb
11 (Ph3P)AuCla
20 16
CH2Cl2/4 Å MS, reflux 14
0
12 (Ph3P)AuCla/AgSbF6 CH2Cl2/4 Å MS, reflux 12
3
a
13 AuCl3a/AgSbF6
CH2Cl2/4 Å MS, reflux
CH2Cl2/4 Å MS, reflux
5
5
25
7
c
a
14 AuCl3a/AgSbF6
15 NaAuCl4.2H2Oa
CH2Cl2/4 Å MS, reflux 12 14
CH2Cl2/4 Å MS, reflux 22 67
CH2Cl2/4 Å MS, reflux 14 21
16 CuCl2a/AgSbF6
c
17 CuCla/AgSbF6
a
a
18 Cu(OTf)2
CH2Cl2/4 Å MS, reflux 16
7
19 FeCl3a/AgSbF6
CH2Cl2/4 Å MS, reflux 20 32
CH2Cl2/4 Å MS, reflux 16 62
b
20 TiCl4a/AgSbF6
d
b
21 HCl/AgSbF6
22 Sn(OTf)2
23 Sn(OTf)2
CH2Cl2/4 Å MS, reflux
CH2Cl2/4 Å MS, rt
CH2Cl2/4 Å MS, rt
5
24
e
20 trace
20 61
f
a 2 mol %. b 6 mol %. c 4 mol %. d 8 mol %. e 5 mol %. f 100 mol %.
g Isolated yield. h Reaction carried with premixed catalysts.
We then went to the extent of attempting the reaction with
catalytic amounts (2 mol %) of FeCl3 and TiCl4 in combina-
tion with AgSbF6. To our delight, the reaction worked well
with catalytic TiCl4/AgSbF6 as well. This finding hints that
the counteranion SbF6- could also play a certain role in the
purpose, simple substrates, phenylacetaldehyde and pheny-
lacetylene, were used. Our first attempt using 2 mol % of
AuCl3 in anhydrous CH2Cl2 was not encouraging as only
less than 3% yield of 1-phenylnaphthalene was obtained. The
yield did not improve even in the presence of 4 Å molecular
sieves, which improved the yields in other attempts (vide
supra) after 12 h of reflux (entry 1). To our delight, reaction
using a mixture of AuCl3 (2 mol %) and AgSbF6 (6 mol %)
in CH2Cl2 gave 41% of 1-phenylnaphthalene in 4 h at room
temperature (entry 2). The yield improved considerably when
the reaction was refluxed in the presence of 4 Å molecular
sieves (entries 4 and 5). Notably, only 5% of the product
was obtained when AgSbF6 (6 mol %) alone was used as
the catalyst (entry 3). It indicates that the cationic character
of gold which is achieved by the addition of AgSbF6 to AuCl3
(4) (a) Dudnik, A. S.; Schwier, T.; Gevorgyan, V. Org. Lett. 2008, 10,
1465. (b) Dudnik, A. S.; Schwier, T.; Gevorgyan, V. Tetrahedron 2009,
65, 1859.
(5) (a) Asao, A.; Takahashi, K.; Lee, S.; Kasahara, T.; Yamamoto, Y.
J. Am. Chem. Soc. 2002, 124, 12650. (b) Asao, A.; Nogami, T.; Lee, S.;
Yamamoto, Y. J. Am. Chem. Soc. 2003, 125, 10921.
(6) One of the reviewers of this manuscript evoked the possibility that
Bronsted acid HSbF6, which could form under the reaction conditions, could
have catalyzed the reaction. We examined the reaction using HSbF6 (formed
by passing HCl gas through a solution of AgSbF6 in CH2Cl2, see the
Supporting Information for complete details). However, the yield of the
product was roughly 1/3 of that of obtained employing AuCl3/AgSbF6.
Further, he had revealed that their attempts to generate cationic [Au3+] were
unsuccessful as gold precipitated quickly. In our attempts we did not see
any precipitation of gold. We believe that, in the presence of excess
aldehyde, the [Au3+] species is stabilized by the coordination to aldehyde
molecules. This draws support from one of our observations that when
phenylacetylene and phenylacetaldehyde were added after 15 min to
premixed AuCl3 and AgSbF6, the yield of the naphthalene derivative dropped
to 51%.
(3) For a review, see: (a) de Koning, C. B.; Rousseau, A. L.; van Otterlo,
W. A. L. Tetrahedron 2003, 59, 7. For the latest syntheses, see: (b)
Viswanathan, G. S.; Wang, M.; Li, C.-J. Angew. Chem., Int. Ed. 2002, 41,
2138. (c) Kabalka, G. W.; Ju, Y.; Wu, Z. J. Org. Chem. 2003, 68, 7915.
(d) Barluenga, J.; Va´zquez-Villa, H.; Ballesteros, A.; Gonza´lez, J. M. Org.
Lett. 2003, 5, 4121. (e) Zhang, X.; Sarkar, S.; Larock, R. C. J. Org. Chem.
2006, 71, 236. (f) Wang, Y.; Xu, J.; Burton, D. J. J. Org. Chem. 2006, 71,
7780. (g) Duan, S.; Sinha-Mahapatra, D. K.; Herndon, J. W. Org. Lett.
2008, 10, 1541.
(7) Sromek, A. W.; Rubina, M.; Gevorgyan, V. J. Am. Chem. Soc. 2005,
127, 10500. (b) Dudnik, A. S.; Gevorgyan, V. Angew. Chem., Int. Ed. 2007,
46, 5195. (c) Dudnik, A. S.; Sromek, A. W.; Rubina, M.; Kim, J. T.; Kel’in,
A. V.; Gevorgyan, V. J. Am. Chem. Soc. 2008, 130, 1440.
Org. Lett., Vol. 11, No. 14, 2009
3117

reaction. The counteranions such as Cl- and TfO- can
quench the intermediate vinyl cation shown in the mechanism
of the reaction (Scheme 2), thereby hindering the progress
Table 2. Scope of Gold-Catalyzed Annulation Reaction in the
Synthesis of Substituted Naphthalenes
1
2
time
(h)
yielda
(%)
entry
R1
R2
R3
R4
3
Scheme 2. Tentative Mechanism for the Catalytic Cycle
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
H
H
H
Ph
Ph
Ph
5
4
10
4
a
b
c
69
61
87
NR
NR
NR
67
H
H
H
H
OEt H
H
Br
Me
H
CH2OBn
CH2OBn CH2OBn 10
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
13
5
Ph
H
d
e
f
g
h
i
j
k
l
-CH2(CH2)2CH2-
-CH2(CH2)2CH2-
10
24b
20b
13
14
14c
13
12b
60
Br
Me
H
Ph
H
44d,f
77
10 -CH2(CH2)2CH2-
11 n-Bu
12 n-Bu
13 Ph
14
H
H
H
80
78
58
H
H
Me Br
Me
40e,f
58
15
H
a Isolated yield. b AuCl3 (4 mol %)/AgSbF6 (12 mol %). c AuCl3 (3
mol %)/AgSbF6 (9 mol %). d The corresponding debrominated product was
obtained in 7% yield. e The corresponding debrominated product was
obtained in 14% yield. f Yields were calculated based on the integrals in
the 1H NMR spectrum of the column-purified inseparable mixture. NR: no
reaction.
of the reaction. There have been reports of Cl- quenching
the vinyl carbocation generated in the reaction of alkyne
Based on the above observations, a catalytic cycle as
indicated in Scheme 1 could be proposed to explain the
mechanism of the reaction. Initially, the [Au3+] species
coordinates with the carbonyl oxygen.10 Electrophilic attack
of the carbonyl carbon on the arylalkyne takes place to form
a new C-C bond at the ꢀ carbon of the arylalkyne as the
resulting vinyl carbocation is stabilized by the aryl group.
involving TiCl4,8 whereas counteranion SbF6 will not
-
quench such vinyl cation. It has to be mentioned that
pentavalent antimony catalyzes aromatic electrophilic sub-
stitution.9 Hence, the possibility of SbF6- promoting aromatic
electrophilic substitution of the vinyl carbocation on the
phenyl ring could not be excluded. Further, in the presence
of oxophilic Lewis acid Sn(OTf)2, the reaction proceeded
only when it was used in stoichiometric amounts and not
when 5 mol % was used (entries 22 and 23).
We then examined different reaction conditions to explore
the optimum conditions for the formation of substituted
naphthalenes. Similar trends were observed when dry dichlo-
roethane was used as solvent, however, with slightly lesser
efficiencies (entries 7-9).
The applicability of the AuCl3/AgSbF6 catalytic system
in naphthalene synthesis was examined with different phe-
nylacetaldehydes/phenylmethyl ketones (Table 2). Diverse
alkynes including terminal, internal, aryl, and aliphatic
alkynes were tested in the annulation reaction. Arylalkynes
only gave the corresponding naphthalene derivatives and not
the aliphatic counterparts. The regioselectivity was excellent
as only the 1-arylnaphthalene derivatives were obtained. Both
substituted phenlylacetaldehydes and phenylmethyl ketones
could be employed. Yields were generally good except in a
few cases. Importantly, tetrahydrophenanthrene derivatives
could be obtained from 2-phenylcyclohexanone (entries
8-10). A similar reaction is not possible with ethyl pheny-
lacetate (entry 6). Bromo-substituted naphthalenes could also
be obtained in good yields using this methodology. However,
some amounts of corresponding debrominated products were
also obtained when phenylmethyl ketones were used which
required longer reaction times and more catalysts.
-
SbF6 -assisted aromatic electrophilic reaction takes place to
form the bicycle, which subsequently gives up two protons
in order to aromatize the rings to form the product. In this
event, the hydrated gold species is expelled which later gives
up a water molecule. This makes the gold species to go back
to its [Au3+] state, which subsequently involves in the next
catalytic cycle.
In conclusion, we have shown a simple protocol to
synthesize substituted naphthalene derivatives involving gold-
catalyzed electrophilic addition on a C-C triple bond
followed by benzannulation. Other transition-metal catalysts
such as CuCl2 and TiCl4 in combination with AgSbF6 were
also effective for the transformation. The oxo- and alkyno-
philicities of AuCl3/AgSbF6 in addition to the counteranion
-
SbF6 might have made the catalyst more effective. A
(8) Kabalka, G. W.; Wu, Z.; Ju, Y. Org. Lett. 2002, 4, 3415. (b)
Lemarchand, D.; M’Baye, N.; Braun, J. J. Organomet. Chem. 1972, 39,
C69.
(9) Matano, M. In Antimony and Bismuth in Organic Synthesis;
Yamamoto, H., Oshima, K., Eds.; Main Group Metals in Organic Synthesis;
Wiley-VCH: Weinheim, 2004; Chapter 14, pp 753-811.
(10) We tried to follow the reaction of phenylacetaldehyde and pheny-
lacetylene involving 2, 5, 10, and 25 mol % of the catalyst (AuCl3/3AgSbF6)
by NMR spectroscopy using CDCl3 as the solvent. We did not see the peaks
corresponding to the alkyne coordinated species in the 13C spectrum, and
the product peaks started to appear. It is important to note that with 100
mol % of the catalyst the reaction was complete in less than 5 min in an
NMR tube. For the same reaction using equimolar Sn(OTf)2 and TiCl43c it
has taken 20 and 3 h, respectively, to reach completion.
3118
Org. Lett., Vol. 11, No. 14, 2009

detailed study on the actual contribution of these effects is
being carried out. Further, application of this methodology
and exploration of other applications of this catalytic system
are under examination. Capitalizing the advantage of coun-
teranion SbF6- might facilitate the discovery of new reactions
that could take place catalytically.
edges the School of Chemistry, University of Hyderabad,
for initial financial assistance.
Supporting Information Available: Experimental details
and characterization data of the prepared compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. This work was funded by DST, India.
V.G. thanks the CSIR, India for a fellowship. R.B. acknowl-
OL900863D
Org. Lett., Vol. 11, No. 14, 2009
3119