Gold(I)-catalyzed benzannulation of 3-hydroxy-1,5-enynes: an efficient synthesis of substituted tetrahydronaphthalenes and related compounds

Article abstract of DOI:10.1016/j.tet.2007.10.084

We report a novel gold(I)-catalyzed benzannulation of 3-hydroxy-1,5-enynes to prepare tetrahydronaphthalenes. The reaction is catalyzed by 2.5 mol % Ph₃PAuCl and 2.5 mol % AgOTf in dichloromethane. We discovered that this process can be also catalyzed by 1 mol % Ph₃PAuCl and 1 mol % TfOH. To the best of our knowledge, this constitutes the first report of an active gold catalyst generated from Au(PPh₃)Cl and triflic acid. This mild process is compatible with a variety of functional groups and proves to be an effective method to synthesize various meta-substituted aromatic rings in good yields.

Full text of DOI:10.1016/j.tet.2007.10.084

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 797e808
www.elsevier.com/locate/tet
Gold(I)-catalyzed benzannulation of 3-hydroxy-1,5-enynes: an
efficient synthesis of substituted tetrahydronaphthalenes and
related compounds
*
´
Christiane M. Grise, Eric M. Rodrigue, Louis Barriault
Center for Catalysis and Innovation, Department of Chemistry, 10 Marie Curie, University of Ottawa, Ottawa, Canada K1N 6N5
Received 20 July 2007; accepted 3 October 2007
Available online 25 October 2007
Abstract
We report a novel gold(I)-catalyzed benzannulation of 3-hydroxy-1,5-enynes to prepare tetrahydronaphthalenes. The reaction is catalyzed by
2.5 mol % Ph3PAuCl and 2.5 mol % AgOTf in dichloromethane. We discovered that this process can be also catalyzed by 1 mol % Ph3PAuCl and
1 mol % TfOH. To the best of our knowledge, this constitutes the first report of an active gold catalyst generated from Au(PPh3)Cl and triflic
acid. This mild process is compatible with a variety of functional groups and proves to be an effective method to synthesize various meta-
substituted aromatic rings in good yields.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
a selective synthesis of substituted phenols using 2 mol %
AuCl3 in acetonitrile.3 Subsequently, Asao and co-workers
have developed a gold-catalyzed [4þ2]-benzannulation be-
tween enynals and carbonyl compounds.4 From this point,
the number of reports on gold-catalyzed benzannulation reac-
tions has increased dramatically. It was shown that the cyclo-
isomerization of aromatic enynes gave an access to substituted
phenanthrenes,5 naphthalenes,6 or styrenes.7 Toste and
co-workers provided a new approach to form substituted naph-
thalenes via a metal-catalyzed tandem [3,3]-sigmatropic
rearrangement/formal MyerseSaito cyclization.8 Liu and
co-workers disclosed the synthesis of various arenes using an in-
tramolecular [3þ2]-cycloaddition of arenyne-yne substrates.9
1,2,3,4-Tetrahydronaphthalenes and related derivatives are
found to be key fragments of medicinally important mole-
cules. Selected examples are shown in Figure 1. Methionine
aminopeptidase-2 reversible inhibitor 1, glucocorticoid recep-
tor agonist 2, a1A-adronoceptor selective agonist 3, serotonin
5-HT7 receptor agonist 4, and thromboxane receptor antago-
nist 5 are just a few of the biologically active compounds
that were identified.10 Numerous syntheses to obtain this im-
portant class of molecules have been developed. One of the
most common ways to access these molecules is hydrogena-
tion of naphthalenes.11 Alternatively, the cyclohexane ring
Substituted aromatic compounds have a fundamental im-
portance in organic chemistry. They are found in natural prod-
ucts, medicinally important molecules, as well as in materials.
Although there are many methods to functionalize aromatic
rings, one must also consider a benzannulation reaction as
an efficient approach to access these substituted aromatic com-
pounds. Various strategies have been developed for acyclic
precursors to be transformed into aromatic rings. Generally,
these methods have the advantages that the substituted aro-
matic compounds are accessed in few steps and with high re-
gioselectivity. Examples of benzannulation reactions include
the Dotz reaction of Fisher carbene complexes, acid-promoted
¨
benzannulation, anionic cyclization, [4þ2] cycloaddition, and
metal-catalyzed carbocyclization.1
Taking into account the peculiar reactivity of gold salts to
activate alkynes, allenes, and alkenes,2 one can imagine the
use of gold complexes to catalyze benzannulation and related
reactions. For instance, Hashmi and co-workers described
* Corresponding author. Tel.: þ1 613 562 5800; fax: þ1 613 562 5170.
E-mail address: lbarriau@uottawa.ca (L. Barriault).
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.10.084

798
C.M. Grise´ et al. / Tetrahedron 64 (2008) 797e808
yield (Eq. 2).14b Also, Malacria and co-workers established
that polycyclic compound 13 was the major product when
dienyne 11 was treated with PtCl2 (Eq. 3).14h
3-Hydroxy-1,5-enynes were also shown to rearrange via the
OH
H
N
O
OH
F3C
R3
R1
H
N
O
O
S
N
O
O
O
R2
´
oxy-Cope reaction in the presence of soft Lewis acid. Gore and
1
2
co-workers reported Ag(I)-mediated sigmatropic rearrange-
ment of 3-hydroxy-1,5-enynes to provide the desired enone
(Eq. 4).15 However, they disclosed that treatment of alcohol
16 with a stoichiometric amount of AgOTf in THFeH2O gave
a complex mixture of products (Scheme 2). The only product
that they were able to isolate in 15% yield and characterize
was tetrahydronaphthalene 17.15a Therefore, we decide to
explore a catalytic version of this unusual benzannulation.16
O O
R4 S NH
H
N
Ar
O
S
R7
R6
O
R5
NR'2
N
CO2H
Cl
NH
3
4
5
Figure 1. Examples of biologically active tetrahydronaphthalenes.
metal
can be generated via a FriedeleCrafts alkylation.12 Another
frequent approach is the use of [4þ2] cycloadditions to form
the aromatic ring of the tetrahydronaphthalenes.13 These ap-
proaches are limited due to the regioselectivity problems, the
restricted scope and/or low yields. Thus, gold-catalyzed benz-
annulation of hydroxy-enynes represents an attractive alterna-
tive for de novo synthesis of the tetrahydronaphthalene
framework.
solvent
OH
16
17
Scheme 2. Metal-mediated benzannulation.
2. Results and discussion
It has been demonstrated that 3-hydroxy-1,5-enynes un-
dergo cycloisomerization when they were treated with Cu,
Pt, or Au salts.14 Typically, the products generated were either
metathesis-type or polycyclic compounds. For example,
Gagosz has shown that enyne 6 rearranged to give bicyclic
compound 7 and cyclopentenol 8 (Eq. 1, Scheme 1).14c In
2006, Fehr and co-workers reported that ring expansion of hy-
droxy-enyne 9 to polycyclic compound 10 occurred in 85%
Propargylic alcohol 16 and related compounds were readily
prepared in 2e3 steps from commercially available cycloal-
kene oxide.16 Exposure of alcohol 16 as a cis and trans mix-
ture (1:1) to 1 mol % Au(PPh3)Cl and 1 mol % AgOTf in
dichloromethane at room temperature for 18 h gave 17 in
72% yield (Scheme 2).17 Other soft Lewis acids such as
AuCl, AuCl3, AgOTf, and PdCl2(PhCN)2 gave low conver-
sions and low yields.18 After an optimization of the reaction
conditions, we found that the combination of 2.5 mol %
Au(PPh3)Cl and AgOTf in dichloromethane (23 ꢀC, 18 h)
led to the desired product 17 in 84% yield. It is important to
note that the reduction of the catalyst loading to 0.1 mol %
Au(PPh3)Cl and AgOTf led to a significant loss in yield
(58%) along with longer reaction time (96 h).
C5H11
Ph
C5H11
(1)
(PPh3)AuBF4
DCM, -20 °C
+
HO
Ph
C5H11
HO
O
Ph
6
7 (63%)
8 (29%)
To gain more insight into the reaction mechanism, com-
pounds 18 and 19 were treated with a catalytic amount of
Au(PPh3)Cl and AgOTf (Scheme 3). In both cases, only tetra-
hydronaphthalene 17 was isolated in 73% and 65% yield, re-
spectively. Surprisingly, acetate 19 did not form any
products resulting from a gold-catalyzed propargylic acetate
rearrangement (carbene formation). Based on these results,
we proposed the following mechanism illustrated in Scheme 4.
The combination of the pre-catalysts Au(PPh3)Cl and
AgOTf produces a cationic gold species, which can coordinate
to the alkyne in a reversible manner. This enables the nucleo-
philic attack of the alkene onto the alkyne via a 5-exo-dig19 or
6-endo-dig6b,7,14b,20 mode to afford 21 and 22, respectively. In-
termediate 22 could be in equilibrium with 23. Examples of
polycyclic products arising from a 1,2-hydride shift of inter-
mediates analogous to 23 have been demonstrated recen-
tly.14a,c,f However, in the present case, the formation of such
polycyclic products is not possible due to the tertiary alcohol.
From intermediate 22, two possible pathways are considered.
O
HO
Cu(BF4)(CH3CN)4
Toluene, 70 °C
(2)
(3)
9
10 (85%)
OH
HO
H
OH
PtCl2
+
Toluene, 80 °C
H
13 (48%)
11
12 (7%)
R1
R2
R3
O
AgOTf
R1
(4)
R2
THF-H2O
HO
R3
14
15 (30-73%)
Scheme 1. Metal-catalyzed rearrangement of hydroxy-enynes.

C.M. Grise´ et al. / Tetrahedron 64 (2008) 797e808
799
Table 1
Au(I)-catalyzed cyclization of 3-hydroxy-1,5-enynes
10 mol% Au(PPh3)Cl
(1)
(2)
R1
R1
10 mol% AgOTf
DCM, r.t. (73%)
2.5% Au(PPh3)Cl,
2.5% AgOTf
O
18
X
X
17
CH2Cl2, 23 °C
18 h
R2
n
n
OH
16
R2
17
R1
R2
n
X
Yielda %
2.5 mol% Au(PPh )C
l
Entry
3
2.5 mol% AgOTf
DCM, r.t. (65%)
1
2
3
4
5
6
7
Me
H
H
0
1
1
1
1
1
1
CH2
CH2
CH2
CH2
CH2
CH2
CH2
17a, 28
17b, 10
17c, 84
17d, 77
17e, 86
17f, 73
17g, 66
O
H
O
Ph
H
19
17
Scheme 3. Benzannulation of enynes.
Me
Me
Me
Me
Me
Ph
4-NO2C6H4
4-NHAcC6H4
The first scenario (pathway a) could be a ring expansion of 22
to give the formal oxy-Cope product 24.14c At this point, 24
could undergo a transannular ene reaction to give 25, which
upon loss of water followed by aromatization would give 17.
Alternatively, intermediate 22 could undergo a subsequent de-
protonation, protonation, and aromatization sequence to afford
tetrahydronaphthalene 17 (pathway b). To determine which
pathway, A or B, is involved in the reaction mechanism, we
treated alcohol 2521 with 2.5 mol % Au(PPh3)Cl and AgOTf
in dichloromethane at room temperature. After stirring for
3 h, 25 was slowly converted to 17.22 One might propose
that pathway A could be involved in the reaction mechanism.
However, we did not detect any products in the crude reaction
mixture resulting from an oxy-Cope reaction when 18 and 19
were treated a catalytic amount of Au(I) and Ag(I) (Eqs.1 and
2, Scheme 3). The slow conversion of 25 to 17 combined by
the absence of any oxy-Cope products during the benzannula-
tion process suggests that the reaction would proceed through
pathway B. Having established the reaction mechanism and
found the optimal reaction conditions, the scope of the reac-
tion was then examined (Tables 1 and 2).
Me
8
Me
1
CH2
17h, 75b
N
9
OEt
Me
Me
Me
Me
Me
H
1
2
2
1
1
1
CH2
CH2
CH2
NTs
NTs
O
17i, 12c
17j, 51
17k, 65
17l, 49
17m,67
17n, 51
10
11
12
13
14
a
H
Ph
H
Ph
H
Isolated yield after column chromatography.
PTSA (1.5 equiv) was added and 10 mol % of Au(I) and Ag(I) were used.
Beside the desired product, only decomposition was only observed.
b
c
the reaction yield. A low yield of 28% was observed when the
reaction was performed on substrate having five-membered
ring (Table 1, entry 1). When R1 is a hydrogen, the desired
product 17b was obtained in 10% yield (Table 1, entry 2).
One might assume that the stability of the carbocation in 22
affects the process. Thus, the substituents R1 were chosen in
function of their ability to stabilize the carbocation. Although
enol ether 16i does satisfy this criterion, the benzannulation
gave the desired product 17i in only 12% yield (Table 1, entry
9). In contrast, substrates bearing a phenyl (Table 1, entry 3) or
a methyl (Table 1, entries 4e6) substituent on the alkene gave
the desired benzannulation product in good yields. Also, elec-
tron rich aromatic ring system such as furan 28, aryl 30, and
indole 32 proceeded in 57, 76, and 81% yield, respectively
(Table 2, entries 1e3). Satisfyingly, the reaction proceeded
in good yields with substrates having an internal alkyne (Table
1, entries 4e8 and 11). This generated meta-substituted aro-
matic rings, which are rather difficult to obtain via cross-coup-
ling reactions. However, benzannulation of the pyridine
derivative 16h did not occur under the typical reaction condi-
tions as only starting material was recovered. One might pro-
pose that the pyridine group could bind on the gold complex
thereby inhibiting the benzannulation. Addition of 1.5 equiv
of PTSA was proved to be necessary to obtain 17h (Table 1,
entry 8).
A cursory inspection of the results illustrated in the Table 1
revealed that the ring size and the substitution at R1 influence
OH
O
24
25
HO
23
Au(L)
Au(L)
path a
H2O
HO
HO
17
Au(L)
Au(L)
20
22
B:
H2O
path b
BH
Lastly, we investigated substitution on the cyclohexane
ring. Protected piperidines 16l and 16m were treated under
the benzannulation conditions to give the corresponding tetra-
hydroisoquinolines 17l and 17m in 49 and 67% yield, respec-
tively (Table 1, entries 12e13). The method can be extended
to a cyclic ether 17n (Table 1, entry 14) and methyl-substituted
BH
B:
HO
HO
HO
Au(L)
Au(L)
Au(L)
21
26
27
Scheme 4. Proposed mechanism for Au(I)-catalyzed benzannulation.

800
C.M. Grise´ et al. / Tetrahedron 64 (2008) 797e808
Table 2
Au(I)-catalyzed cyclization of 3-hydroxy-1,5-enynesa
Table 3
Investigation into the reactive species
Entry
Substrate
Product
Yieldb
57
%
Au(1), additive
solvent
O
O
OH
16
1
17
OH
28
29
Entry
Catalysta
Additive (equiv)
Conv.b (%)
X
OMe
1
2
3
4
5
6
a
Au(PPh3)Cl, AgOTf
Au(PPh3)Cl, AgOTf
TfOHc
DTBMP (1.05)
DTBMP (0.05)
d
0
31e50
0
Y
˚
4 A Mol. sieves
Au(PPh3)Cl, AgOTf
Au(PPh3)Cl, TfOH
AuCl, TfOH
>95
95
2
3
76
81
d
d
OH
31A X = OMe, Y = H (1.5)
31B X = H, Y = OMe (1)
29
30
Reactions were done with 2.5 mol % of each species in DCM at 23 ꢀC for
18 h.
b
N
N
Determined by 1H NMR.
TfOH of 5 mol % was used.
c
OH
32
conversion was observed when the reaction was carried out
in the presence of 5 mol % DTBMP (entry 2). Recently, Hart-
wig reported examples of reaction catalyzed by metal triflates,
which are the result from simple protic acid catalysis.23 In our
case, exposure of alcohol 16 to 5 mol % TfOH, PTSA, or
chloroacetic acid did not give any desired product 17. Only
starting material was recovered, thus it was possible to rule
out simple Brønsted acid catalyzed benzannulation or forma-
tion of a diene-yne intermediate.24
33
4
5
70
81
74
OH
34
35
Ph
OH
36
To explore the effect of water in the reaction, hydroxy-
enyne 16 was treated with the standard conditions but molecu-
lar sieves were added. The conversion was greater than 95%,
thus it is possible to exclude the role of water in the mechanism
other than a leaving group. In order to further investigate the
reactive species, hydroxy-enyne 16 was treated with
2.5 mol % of each Au(PPh3)Cl and TfOH. Surprisingly, tetra-
hydronaphthalene 17 was obtained in 95% conversion. In con-
trast, 2.5 mol % of each AuCl and TfOH only gave 29%
conversion to the desired tetrahydronaphthalene. It is important
to note that Au(PPh3)Cl alone did not catalyze the reaction
whereas AuCl alone gave a 22% conversion. To the best of
our knowledge, this is first report of an active catalyst gener-
ated from Au(PPh3)Cl and triflic acid. To study this novel cata-
lytic system, we investigated different sources of protic acid.
Weak organic acids (acetic acid, tartaric acid, trichloroace-
tic acid, trifluoroacetic acid, phenyl phosphonic acid, and min-
eral acids (HBr, HCl, H3PO4, and H2SO4) did not catalyze the
reaction. Nonetheless, PTSA and CSA in combination with
Au(PPh3)Cl did promote the benzannulation with good con-
version. However, the results were not reproducible. It was
later found that reactions performed with freshly recrystallized
PTSA or CSA did not produce the desired product. Only start-
ing material was recovered. One might propose that the com-
mercial acids were contaminated with a stronger acid, which
was responsible for the catalysis. This suggests an active cata-
lyst can only be generated when Au(PPh3)Cl is in the presence
of a very strong acid.
Ph
37
6
OH
38
39
a
The reaction conditions are 2.5 mol % of each AgOTf and Au(PPh3)Cl in
dichloromethane at 23 ꢀC for 18 h.
b
Isolated yield after column chromatography.
cyclohexane 38 (Table 2, entry 6). Thus, the gold-catalyzed
benzannulation can be utilized to generate many different tet-
rahydronaphthalene scaffolds.
As previously mentioned above, the reaction with pyridine
substrate 17h only proceeded in the presence of an excess of
acid. This result suggests that acid might play a role in the
other benzannulation reactions. One might assume that a trace
of triflic acid could be present in the typical reaction condi-
tions due to the presence of silver triflate. From a mechanistic
point of view, one might propose that elimination of water
could be assisted with acid (27/17, Scheme 4). Alternatively,
one might suggest that the elimination of water could occur
initially to generate
undergoes a gold-catalyzed benzannulation.
a diene-yne intermediate, which
To clarify the role of the protic acid, hydroxy-enyne 16 was
treated with 2.5 mol % each of Au(PPh3)Cl and AgOTf in the
presence of a hindered base such as 2,6-di-tert-butyl-4-methyl-
pyridine (DTBMP, 1.05 equiv) (Table 3, entry 1). After 18 h,
only starting material was recovered. However, a low
We also studied the use of Lewis acids as potential activa-
tors of Au(PPh3)Cl. Hydroxy-enyne 16 was submitted to

C.M. Grise´ et al. / Tetrahedron 64 (2008) 797e808
801
Table 5
Au(PPh3)Cl/TfOH-catalyzed benzannulationa
conditions consisting of 5 mol % Au(PPh3)Cl and 5 mol %
BF3eOEt2 or TMSOTf. In both cases, the benzannulation oc-
curred in 83% and 80% conversion, respectively. However, we
must take into consideration the possible presence of protic
acids in the reaction mixture. To avoid background reactions
created by the presence of protic acids, the reactions were per-
formed by pre-mixing the Lewis acid (5 mol %), Au(PPh3)Cl
(5 mol %), and DTBMP (20 mol %) followed by the addition
of substrate 16. Four Lewis acids were tested under these con-
ditions (BF3eOEt2, TMSOTf, MgBr2eOEt2, and SnCl4). In
all cases, we recovered only starting material. These results
show that Au(PPh3)Cl can only be activated by a strong protic
acid. Undoubtedly, triflic acid was the best acid to use in com-
bination with Au(PPh3)Cl since it gave the best conversion
(95%). We found that an increase of the triflic acid loading
while keeping constant Au(PPh3)Cl at 2.5 mol % was detri-
mental to the reaction. This resulted in low conversions to tet-
rahydronaphthalene 17. Thus, a 1:1 ratio of triflic acid to Au(I)
revealed to be optimal.
Next, we carried out the benzannulation reactions in vari-
ous solvents at room temperature for 18 h. Reactions ran in
toluene, methanol, THF, diethyl ether, acetonitrile, water,
and a dichloromethane/water combination showed very low
conversions. Changing the solvent for dichloroethane and
heating to reflux proved to be successful as a 100% conversion
was observed (Table 4, entry 1). Gratifyingly, we were able to
decrease the catalyst loading to 1 mol % without affecting the
conversion (entry 2). A quantitative conversion was observed
when the reaction was performed using 1 mol % of AuCl,
TfOH, and PPh3 (entry 3). Unexpectedly, treating substrate
16 with Au(PPh3)Cl in dichloroethane at 80 ꢀC did give the
desired product in 43% conversion (entry 4). In contrast,
only starting material was recovered when hydroxy-enyne 16
was treated with Au(PPh3)Cl in dichloroethane at room tem-
perature. Also, it was noticed that no desired product was ob-
served when the substrate was heated alone or in the presence
of triflic acid (entries 5 and 6).25 Having established the opti-
mal reaction conditions, we investigated the scope of this
Au(I)/TfOH-catalyzed benzannulation using selected hy-
droxy-enynes (Table 5).
Entry
Substrate
Product
Yieldb
%
1
50
68
67
56
62
51
64
OH
16
17
2
3
4
5
6
7
OH
16j
17j
TsN
TsN
OH
16l
17l
TsN
TsN
Ph
OH
16m
Ph
17m
O
O
OH
16n
17n
OEt
OH
16o
OEt
17o
O
O
OH
28
29
N
N
8
9
76
OH
32
33
Cyclization of six and seven-membered hydroxy-enynes
16, 16j, and 38 gave the corresponding aromatic compounds
17, 17j, and 39 in 50, 68, and 82% yield, respectively (entries
1e2 and 10). N-Tosyl-piperidine 16l and 16m and tetrahydro-
pyran 16n were easily transformed to the corresponding
82
82
OH
34
35
10
OH
38
Table 4
Optimization of the catalyst system
39
a
The reaction conditions are 1 mol % of each TfOH and Au(PPh3)Cl in
dichloroethane at 80 ꢀC for 18 h.
Entry
Catalysta
Loading (mol %)
Conv.b (%)
b
Isolated yield after column chromatography.
1
2
3
4
5
6
a
Au(PPh3)Cl, TfOH
Au(PPh3)Cl, TfOH
AuCl, TfOH, PPh3
Au(PPh3)Cl
2.5
1
100
100
100
43
0
1
tetrahydroisoquinolines 17l, 17m, and isochromane 17n in
good yields (entries 3e5). To our delight, the highly acid sen-
sitive ynol ether 16o was converted to the corresponding phe-
nol ether 17o in 51% yield (entry 10).26 Under these
conditions, electron rich aromatics 28 and 32 gave the desired
1
TfOH
None
1
d
0
Reactions were done in DCE at 80 ꢀC for 18 h.
Determined by GC.
b

802
C.M. Grise´ et al. / Tetrahedron 64 (2008) 797e808
process. In general, the tetrahydronaphthalenes were obtained
in higher yields. Application of this novel catalyst system to-
ward the development of new tandem reactions and further in-
vestigations into the nature of the catalyst are on going and
will be reported in due course.
4. Experimental
4.1. General
31
Figure 2. P NMR study at 23 ꢀC in CDCl3 (PPh3 used as a standard at
ꢃ6.0 ppm). (a) Au(PPh3)Cl; (b) Au(PPh3)Cl (2.5 mol %) and AgOTf
(2.5 mol %) after 16 h; (c) Au(PPh3)Cl (2.5 mol %), AgOTf (2.5 mol %), and
alcohol 16 (59% conversion); (d) Au(PPh3)Cl (5 mol %), TfOH (5 mol %),
and alcohol 16 (37% conversion).
All reactions were performed under argon atmosphere in
flame-dried glassware equipped with a magnetic stir bar and
a rubber septum, unless otherwise indicated. All solvents
were freshly distilled prior to use; diethyl ether and THF
over sodium and benzophenone; acetonitrile and DCM over
calcium hydride. Triflic acid was distilled over triflic anhy-
dride and kept under argon in the refrigerator. All other com-
mercial reagents were used without purification, unless
otherwise noted.
Reactions were monitored by thin layer chromatography
(TLC) analysis of aliquots using glass sheets pre-coated
(0.2 mm layer thickness) with silica gel 60 F254 (E. Merck).
Thin layer chromatography plates were viewed under UV light
and stained with phosphomolybdic acid or p-anisaldehyde
staining solution. Column chromatographies were carried out
with silica gel 60 (230e400 mesh, Merck). 1H and 13C
NMR spectra were recorded in deuterated solvents, on Bruker
Avance 300, 400, and 500 MHz spectrometers. IR spectra
were recorded with a Bomem Michaelson 100 FTIR spectro-
meter. HRMS were obtained on a Kratos Analytical Concept
instrument (University of Ottawa Mass Spectrum Centre).
Melting points were recorded on a Gallenkamp melting point
machine apparatus P 1106G.
tetrahydronaphthalenes 29 and 33 in 64 and 76% yield, respec-
tively (entries 6 and 7). Benzannulation of cyclic olefin 34 oc-
curred smoothly providing 35 in 82% yield (entry 8). With the
exception of substrates 16 and 16n, the yields were higher
when the benzannulation was catalyzed with Au(PPh3)Cl
and TfOH in comparison with Au(PPh3)Cl and AgOTf. Over-
all, we have shown that 1 mol % Au(PPh3)Cl and triflic acid
generated an effective catalyst system for benzannulation of
3-hydroxy-1,5-enyne. Since neither species catalyzed the benz-
annulation reaction on their own (at room temperature), an
active catalyst must be generated when these two species are
in contact. Teles and co-workers reported that a cationic
gold complex is generated by protonolysis of Au(PPh3)Me
and methanesulfonic acid.27 By analogy, one might suggest
that protonolysis of Au(PPh3)Cl by triflic acid might give
the cationic gold catalyst, Au(PPh3)OTf.
31P NMR studies were performed to gain insight into the re-
active species (Fig. 2). Different Au(I) complexes were de-
tected when Au(PPh3)Cl and AgOTf were mixed alone to
form Au(PPh3)OTf (spectrum b) or in the presence of substrate
16 (spectrum c). In the latter case, the complex generated could
be such as [Au(PPh3)eAr]þ (Ar¼tetrahydronaphthalene) since
the benzannulation occurred in the NMR tube. In contrast,
Au(I) cationic species were not identified when Au(PPh3)Cl
and TfOH were combined in the presence of the substrate 16
(spectrum d). In fact, the chemical shift of the single peak
(32.7 ppm) correspond to that of Au(PPh3)Cl (spectrum a).
Based on the NMR data, one might suggest that a more reac-
tive Au catalyst, in the case of Au(PPh3)Cl and TfOH, is gen-
erated and its concentration is below the limits of detection.
The spectroscopic data of following compounds have been
previously described:16 16aek, 17aek, 28e31, and 34e37.
4.1.1. 1-Ethynyl-2-isopropenyl-1-prop-2-ynyloxy-
cyclohexane (18)
To a solution of (ꢁ)-[1S,2S]-1-ethynyl-2-isopropenyl-cy-
clohexanol16 (2.55 g, 15.5 mmol) and propargyl bromide
(5.16 mL, 46.0 mmol) in THF/DMF (9:3 mL) was added so-
dium hydride 60% in oil (1.86 g, 46.0 mmol) slowly at room
temperature. The reaction was followed by TLC and quenched
with NH4Cl (satd aq) upon completion. The mixture was ex-
tracted with diethyl ether (3ꢂ) and the combined organic
layers were dried over MgSO4, filtered, and concentrated.
Flash chromatography (5% ethyl acetate in hexanes) afforded
18 (2.57 g, 81%) as a yellow oil. IR (neat, cmꢃ1) 3303 (s),
3073 (m), 2934 (s), 2858 (s), 1641 (m), 1448 (m), 1376 (m),
1143 (m), 1094 (s), 1063 (s), 892 (s); 1H NMR (CDCl3)
d 4.81 (d, J¼1.2 Hz, 2H), 4.24 (dd, JAB¼15.2 Hz, JAx¼2.5 Hz,
1H), 4.13 (dd, JAB¼15.2 Hz, JBx¼2.5 Hz, 1H), 2.48 (s, 1H),
2.34 (t, J¼2.5 Hz, 1H), 2.25e2.12 (m, 2H), 1.86 (qd,
J¼12.4, 3.7 Hz, 1H), 1.78 (s, 3H), 1.75e1.67 (m, 1H),
1.60e1.38 (m, 4H), 1.33e1.16 (m, 1H); 13C NMR (CDCl3)
d 146.6 (C), 113.5 (CH2), 84.2 (C), 80.9 (C), 75.9 (C), 74.9
(CH), 73.1 (CH), 54.3 (CH), 51.9 (CH2), 35.8 (CH2), 26.2
3. Conclusion
In summary, we disclosed a gold-catalyzed benzannulation
of 3-hydroxy-1,5-enynes. The reaction conditions were com-
patible with a variety of functional groups proving to be an ef-
fective method to generate substituted tetrahydronaphthalenes.
In the course of the study, we discovered that the combination
of 1 mol % Au(PPh3)Cl and TfOH in dichloroethane emerged
as a novel and effective catalyst for the benzannulation

C.M. Grise´ et al. / Tetrahedron 64 (2008) 797e808
803
(CH2), 25.7 (CH2), 22.1 (CH3), 20.6 (CH2); HRMS (EI) m/z
2.63 (dd, J¼11.9, 11.9 Hz, 1H), 2.58 (br, 1H), 2.42 (s, 3H),
2.39 (dd, J¼11.8, 3.7 Hz, 2H), 2.04e1.99 (m, 1H), 1.83 (dd,
J¼12.7, 4.4 Hz, 1H), 1.81 (s, 3H); 13C NMR (CDCl3,
100 MHz) d 143.6 (C), 141.3 (C), 134.0 (C), 129.8 (2ꢂCH),
127.5 (2ꢂCH), 116.6 (CH2), 83.5 (C), 76.3 (CH), 68.9 (C),
53.2 (CH), 47.2 (CH2), 44.0 (CH2), 39.0 (CH2), 22.1 (CH3),
21.6 (CH3); HRMS (EI) m/z calcd for C17H21NO3S (Mþ)
319.1242, found 319.1240; mp¼116.0e126.0 ꢀC.
calcd for C14H18O (Mþ) 202.1358, found 202.1348.
4.1.2. Acetic acid 1-ethynyl-2-isopropenyl-cyclohexyl ester
(19)
To a solution of (ꢁ)-[1S,2R]-1-ethynyl-2-isopropenyl-cyclo-
hexanol16 (0.600 g,3.66 mmol) in DCM (45.0 mL) was added
4-DMAP (223 mg,1.83 mmol) followed by triethylamine
(0.713 mL, 5.12 mmol) and acetic anhydride (0.420 mL,
4.39 mmol). The following solution was stirred at room tem-
perature for 3 h. The solution was quenched with water. The
mixture was extracted with DCM (3ꢂ). The combined organic
layers were dried over MgSO4, filtered, and concentrated in va-
cuo. Purification by flash chromatography (5% ethyl acetate in
hexanes) afforded ester 19 (465 mg, 62%) as a colorless oil. IR
(neat, cmꢃ1) 2934 (s), 2115 (m), 1733 (m), 1240 (m); 1H NMR
(CDCl3, 400 MHz) d 4.88 (s, 1H), 4.87 (s, 1H), 2.73e2.69 (m,
1H), 2.65 (s, 1H), 2.43e2.38 (dd, J¼12.5, 9.5 Hz, 1H), 1.98 (s,
4.1.4. 3-Isopropenyl-4-phenylethynyl-1-(toluene-4-
sulfonyl)-piperidin-4-ol (16m)
PdCl2(PPh3)2 (30.6 mg, 0.05 mmol) and CuI (8.3 mg,
0.05 mmol) were weighed in the glovebox under argon. A so-
lution of [3S,4S]-16l (0.280 g, 1.00 mmol) in acetonitrile
(13.4 mL) was transferred via cannula. Following the addition
of the iodobenzene (108 mg, 1.11 mmol), the resulting
solution was degassed with argon for 10 min. Then, freshly
distilled diisopropylethylamine (0.760 mL, 5.00 mmol) was
added and the mixture was stirred at room temperature.
Upon completion, the reaction mixture was concentrated and
loaded directly onto a silica gel column for purification
(10% ethyl acetate in hexanes) to give 16m (181 mg, 48%)
as a yellow solid.
3H), 1.85 (s, 3H), 1.78e1.61 (m, 6H), 1.27e1.21 (m, 1H); 13
C
NMR (CDCl3, 100 MHz) d 169.1 (C), 145.3 (C), 113.6 (CH2),
81.1 (C), 79.8 (C), 77.3 (CH), 52.7 (CH), 37.4 (CH2), 29.3
(CH2), 25.6 (CH2), 23.5 (CH2), 23.5 (CH3), 22.1 (CH3);
HRMS (EI) m/z calcd for C11H14 (MꢃC2H4Oþ2 ) 146.1096,
found 146.1107.
IR (neat, cmꢃ1) 3496 (br), 2932 (m), 2870 (m), 1595 (w),
1
1345 (s), 1210 (s); H NMR (CDCl3, 400 MHz) d 7.58 (d,
4.1.3. 4-Ethynyl-3-(prop-1-en-2-yl)-1-tosylpiperidin-4-ol
(16l)
J¼8.3 Hz, 2H), 7.29e7.26 (m, 2H), 7.24e7.23 (m, 5H),
4.99 (s, 1H), 4.67 (s, 1H), 3.59e3.56 (m, 1H), 3.53e3.49
(m, 1H), 2.57e2.49 (m, 3H), 2.36 (s, 3H), 2.20e2.06 (m,
3H), 1.96 (s, 3H); 13C NMR (CDCl3, 100 MHz) d 144.3 (C),
143.6 (C), 133.3 (C), 131.6 (2ꢂCH), 129.8 (CHꢂ2), 128.7
(CH), 128.4 (2ꢂCH), 127.7 (2ꢂCH), 122.2 (C), 113.8
(CH2), 91.5 (C), 84.3 (C), 65.1 (C), 50.8 (CH), 45.4 (CH2),
41.3 (CH2), 38.0 (CH2), 26.3 (CH3), 21.6 (CH3); HRMS
(EI) m/z calcd for C23H25NO3S (Mþ) 395.1555, found
395.1575; mp¼155.8e156.7 ꢀC.
To a solution of 3-isopropenyl-1-(toluene-4-sulfonyl)-pi-
peridin-4-one28 (0.910 g, 3.10 mmol) in THF (2 mL) at 0 ꢀC
was added dropwise ethynylmagnesium bromide (15.4 mL,
7.72 mmol). The solution was warmed to room temperature
and stirred for 3 h. The mixture was cooled to 0 ꢀC and
quenched with NH4Cl (satd aq). The mixture was extracted
with ether (3ꢂ). The combined organic layers were washed
with brine, dried over MgSO4, filtered, and concentrated.
Flash chromatography (10% ethyl acetate in hexane) afforded
compound 16l as a mixture of diastereoisomers as a beige
solid (0.497 g, 50%).
4.1.5. 3-(3-Methyl-but-2-enyloxy)-propan-1-ol (16nA)
1,3-Propanediol (0.110 g, 1.43 mmol) was dissolved in
DMF (2 mL) and the mixture was stirred at 0 ꢀC for 15 min.
At that point, NaH (30.0 mg, 1.24 mmol) was added and the
resulting solution was stirred for 15 min before 1-bromo-3-
methyl-but-2-ene (0.070 mL, 0.590 mmol) was added. The so-
lution was stirred until the reaction was complete by TLC. The
reaction was quenched with NH4Cl, extracted 3ꢂ with Et2O,
and the combined organic phases were washed with brine,
dried over MgSO4, and concentrated in vacuo. Purification
by flash column chromatography (30e60% ethyl acetate in
hexanes) gave 16nA (60.0 mg, 71%) as a colorless oil.
4.1.3.1. Major (ꢁ)-[3S,4S]. IR (neat, cmꢃ1) 3495 (br), 3279
(br), 2926 (w), 2867 (w), 1340 (m), 1168 (s); 1H NMR
(CDCl3, 400 MHz) d 7.62 (d, J¼8.0 Hz, 2H), 7.31 (d,
J¼8.0 Hz, 2H), 5.03 (s, 1H), 4.68 (s, 1H), 3.63e3.58 (m,
1H), 3.55e3.51 (ddd, J¼10.9, 2.0, 3.3 Hz, 1H), 2.59e2.38
(m, 4H), 2.44 (s, 1H), 2.42 (s, 3H), 2.41 (br s, 1H), 2.09 (dd,
J¼3.1, 3.1 Hz, 1H), 1.97 (s, 3H); 13C NMR (CDCl3,
100 MHz) d 144.2 (C), 143.7 (C), 133.2 (C), 129.8 (2ꢂCH),
127.6 (2ꢂCH), 113.8 (CH2), 86.2 (C), 72.6 (CH), 64.6 (C),
50.4 (CH), 45.2 (CH2), 41.1 (CH2), 37.9 (CH2), 26.3 (CH3),
21.6 (CH3); HRMS (EI) m/z calcd for C17H21NO3S (Mþ)
319.1242, found 319.1234; mp¼143.0e148.5 ꢀC.
1
IR (neat, cmꢃ1) 3402 (s), 2930 (s), 2867 (s), 1085 (s); H
NMR (CDCl3, 400 MHz) d 5.33e5.29 (m, 1H), 3.94 (d,
J¼6.9 Hz, 2H), 3.75 (t, J¼5.7 Hz, 2H), 3.59 (t, J¼5.8 Hz,
2H), 2.14 (br, 1H), 1.81 (dddd, J¼5.8, 5.8, 5.8, 5.8 Hz, 2H),
1.72 (s, 3H), 1.65 (s, 3H); 13C NMR (CDCl3, 100 MHz)
d 137.2 (C), 120.9 (CH), 69.4 (CH2), 67.6 (CH2), 62.3
(CH2), 32.1 (CH2), 25.8 (CH3), 18.0 (CH3); HRMS (EI) m/z
calcd for C8H16O2 (Mþ) 144.1150, found 144.1151.
4.1.3.2. Minor (ꢁ)-[3S,4R]. IR (neat, cmꢃ1) 3490 (br), 3274
1
(s), 2926 (m), 2866 (w), 1340 (s), 1167 (s); H NMR (CDCl3,
400 MHz) d 7.65 (d, J¼8.3 Hz, 2H), 7.31 (d, J¼8.0 Hz, 2H),
5.04 (t, J¼1.5 Hz, 1H), 4.95 (s, 1H), 3.86e3.80 (m, 1H),
3.78e3.74 (m, 1H), 2.71 (ddd, J¼12.5, 12.5, 2.6 Hz, 1H),

804
C.M. Grise´ et al. / Tetrahedron 64 (2008) 797e808
4.1.6. 3-(3-Methyl-but-2-enyloxy)-propionaldehyde (16nB)
DMSO (1.94 mL, 27.3 mmol) was slowly added to a solu-
tion of oxalyl chloride (1.19 mL, 13.7 mmol) in DCM (34 mL)
at ꢃ78 ꢀC. After stirring for 20 min, 16nA in DCM (16 mL)
was added and the mixture was stirred for another 90 min.
Triethylamine (7.90 mL, 56.9 mmol) was added and the solu-
tion was again stirred at 0 ꢀC for another hour before being
quenched with NH4Cl (satd aq). The mixture was extracted
with ether (3ꢂ). The combined organic layers were washed
with brine, dried over MgSO4, filtered, and concentrated.
Flash chromatography (30% ethyl acetate in hexane) gave
16nB (0.820 g, 51%) as a yellow oil.
washed with brine, dried over MgSO4, filtered, and concen-
trated. Flash chromatography (20% ethyl acetate in hexanes)
afforded compound 16n as a mixture of diastereoisomers as
colorless oils (0.822 g, 70%).
4.1.8.1. Major (ꢁ)-[3S,4S]. IR (neat, cmꢃ1) 3351 (br), 3231
(s), 2961 (m), 2864 (m), 1113 (s); 1H NMR (CDCl3,
400 MHz) d 5.04e5.03 (t, J¼1.4 Hz, 1H), 4.75 (s, 1H),
3.73e3.70 (m, 2H), 3.61e3.56 (m, 2H), 2.52e2.48 (dd,
J¼9.8, 6.1 Hz, 1H), 2.44 (s, 1H), 2.35 (br, 1H), 2.04e1.93
(m, 2H), 1.96 (dd, J¼1.4, 1.0 Hz, 3H); 13C NMR (CDCl3,
100 MHz) d 143.8 (C), 113.7 (CH2), 87.0 (C), 71.9 (CH),
66.2 (CH2), 64.7 (C), 62.7 (CH2), 51.1 (CH), 38.6 (CH2),
26.5 (CH3); HRMS (EI) m/z calcd for C10H13O2 (MꢃH)þ
165.0921, found 165.0919.
1
IR (neat, cmꢃ1) 2863 (s), 1725 (s), 1085 (m); H NMR
(CDCl3, 400 MHz) d 9.74 (s, 1H), 5.30e5.26 (m, 1H), 3.93
(d, J¼6.9 Hz, 2H), 3.71 (t, J¼6.1, 6.1 Hz, 2H), 2.62 (td, J¼
1.7, 6.2 Hz, 2H), 1.70 (s, 3H), 1.63 (s, 3H); 13C NMR (CDCl3,
100 MHz) d 201.3 (CH), 137.5 (C), 120.7 (CH), 67.6 (CH2),
63.6 (CH2), 44.0 (CH2), 25.8 (CH3), 18.0 (CH3); HRMS (EI)
m/z calcd for C7H11O2 (MꢃMe)þ 127.0754, found 127.0761.
4.1.8.2. Minor (ꢁ)-[3S,4R]. IR (neat, cmꢃ1) 3381 (br), 2962
(s), 2869 (m), 1640 (w), 1107 (s); 1H NMR (CDCl3,
400 MHz) d 5.03e5.02 (t, J¼1.6 Hz, 1H), 4.96 (s, 1H),
3.99e3.94 (m, 1H), 3.85 (dd, J¼11.5, 4.0 Hz, 1H), 3.75e3.69
(ddd, J¼7.6, 7.6, 2.3 Hz, 1H), 3.64e3.58 (dd, J¼11.5 Hz,
1H), 2.61 (br, 1H), 2.56 (s, 1H), 2.40e2.36 (dd, J¼11.5,
4.0 Hz, 1H), 1.99e1.94 (m, 1H), 1.87 (dd, J¼12.4, 4.6 Hz,
1H), 1.84 (s, 3H); 13C NMR (CDCl3, 100 MHz) d 141.3 (C),
115.9 (CH2), 84.5 (C), 75.6 (CH), 68.9 (C), 68.6 (CH2), 65.8
(CH2), 54.6 (CH), 40.6 (CH2), 22.5 (CH3); HRMS (EI) m/z
calcd for C10H13O2 (MꢃH)þ 165.0921, found 165.0919.
4.1.7. 3-Isopropenyl-tetrahydro-pyran-4-one (16nC)
To a suspension of molecular sieves (0.41 g) in DCM
(8.1 mL) was added 16nB (0.580 g, 4.23 mmol). The mixture
was cooled to ꢃ78 ꢀC and tin tetrachloride (0.410 mL,
0.423 mmol) was added dropwise. The solution was stirred
at ꢃ60 ꢀC for 1 h before it was quenched with NH4Cl. The so-
lution was allowed to stir overnight at room temperature. The
mixture was filtered through Celite and the resulting solution
was extracted with DCM 3ꢂ. The combined organic layers
were washed with brine, dried over MgSO4, filtered, and
concentrated.
4.1.9. 1-Ethoxyethynyl-2-isopropylcyclohexanol (16o)
A solution of ethoxyethynyl ether (40% in hexanes,
2.17 mmol, 380 mg) in THF was cooled to ꢃ78 ꢀC and
n-BuLi (1.86 M in hexanes, 1.08 mmol, 0.58 mL) was added.
After stirring for 40 min, a solution of (ꢁ)-2-isopropenylcy-
cloxenone (99.9 mg, 0.72 mmol) in THF (7 mL) was added
at ꢃ78 ꢀC. After stirring for 5 h, the reaction quenched with
NH4Cl (satd aq). The mixture was extracted with ether (3ꢂ).
The combined organic layers were washed with brine, dried
over MgSO4, filtered, and concentrated. Flash chromatography
(10% ethyl acetate in hexanes) afforded compound 16o as
a mixture of diastereoisomers as colorless oils (78.8 mg, 53%).
DMSO (0.430 mL, 6.13 mmol) was slowly added to a solu-
tion of oxalyl chloride (0.270 mL, 3.06 mmol) in DCM
(8.0 mL) at ꢃ78 ꢀC. After stirring for 20 min, the alcohol in
DCM (4.0 mL) was added and the mixture was stirred for an-
other 90 min. Triethylamine (1.78 mL, 12.8 mmol) was added
and the solution was again stirred at 0 ꢀC for another hour be-
fore being quenched with NH4Cl (satd aq). The mixture was
extracted with ether (3ꢂ). The combined organic layers
were washed with brine, dried over MgSO4, filtered, and con-
centrated. Flash chromatography (25% ethyl acetate in hex-
anes) gave 16nC (0.100 g, 27%) as a colorless liquid.
4.1.9.1. Major (ꢁ)-[1S,2S]. IR (neat, cmꢃ1) 3445 (br), 2931
(s), 2858 (m), 2258 (s), 1603 (m); 1H NMR (CDCl3,
400 MHz) d 4.93e4.86 (m, 1H), 4.87e4.86 (m, 1H), 4.06
(q, J¼7 Hz, 2H), 2.54 (s, 1H), 2.09 (dd, J¼10.7, 4.2 Hz,
1H), 2.00e1.96 (m, 1H), 1.85 (s, 3H), 1.75e1.58 (m, 5H),
1.45 (ddd, J¼12, 12, 4 Hz, 1H), 1.35 (t, J¼7 Hz, 3H), 1.22e
1.15 (m, 1H); 13C NMR (CDCl3, 100 MHz) d 145.1 (C),
114.3 (CH2), 94.7 (C), 74.1 (C), 69.9 (C), 56.3 (CH), 41.2
(CH2), 39.7 (CH2), 28.5 (CH2), 25.6 (CH2), 23.9 (CH2), 21.0
(CH3), 14.3 (CH3); HRMS (EI) m/z calcd for C13H20O2
(Mþ) 208.1463, found 208.1475.
1
IR (neat, cmꢃ1) 2968 (s), 2856 (s), 1718 (m); H NMR
(CDCl3, 400 MHz) d 4.99 (s, 1H), 4.85 (s, 1H), 4.10e4.06
(m, 2H), 3.87e3.79 (m, 2H), 3.13 (dd, J¼8.5, 6.0 Hz, 1H),
2.53e2.49 (m, 2H), 1.73 (s, 3H); 13C NMR (CDCl3,
100 MHz) d 206.1 (C), 139.9 (C), 114.8 (CH2), 71.4 (CH2),
68.3 (CH2), 58.8 (CH), 41.9 (CH2), 22.0 (CH3); HRMS (EI)
m/z calcd for C8H12O2 (Mþ) 140.0837, found 140.0840.
4.1.8. 4-Ethynyl-3-isopropenyl-tetrahydro-pyran-4-ol (16n)
To a solution of 16nC (0.100 g, 0.703 mmol) in THF
(7 mL) at 0 ꢀC was added dropwise ethynylmagnesium bro-
mide (3.50 mL, 1.76 mmol). The solution was warmed to
room temperature and stirred for 3 h. The mixture was cooled
to 0 ꢀC and quenched with NH4Cl (satd aq). The mixture was
extracted with ether (3ꢂ). The combined organic layers were
4.1.10. 2-Chloro-1-(1-methyl-1H-indol-2-yl)-cyclohexanol
(32A)
1-Methylindole (1.46 mL, 11.4 mmol) was dissolved in
THF (6.8 mL) and the resulting mixture was cooled to 0 ꢀC

C.M. Grise´ et al. / Tetrahedron 64 (2008) 797e808
805
before n-BuLi (7.63 mL, 15.2 mmol) was added. The ice bath
was then removed and the solution stirred for 2 h at room tem-
perature. The mixture was cooled to ꢃ78 ꢀC before 2-chloro-
cyclohexanone (1.10 mL, 9.50 mmol) dissolved in THF
(3.4 mL) was slowly cannulated. The reaction was then stirred
at room temperature until completed by TLC. The reaction
was quenched with the addition of NH4Cl, followed by the ad-
dition of water to dissolve the precipitate. The mixture was ex-
tracted with ether (3ꢂ). The combined organic layers were
washed with brine, dried over MgSO4, filtered, and concen-
trated. Flash chromatography (10% ethyl acetate in hexanes)
gave 32A (0.840 g, 33%) as a yellow oil.
120.3 (CH), 119.4 (CH), 109.3 (CH), 100.3 (CH), 84.8 (C),
76.1 (CH), 73.6 (C), 46.4 (CH), 40.6 (CH2), 31.1 (CH2),
30.1 (CH3), 26.0 (CH2), 25.6 (CH2); HRMS (EI) m/z calcd
for C17H19NO (Mþ) 253.1467, found 253.1474.
4.1.12. 1-Ethynyl-2-isopropenyl-5-methyl-cyclohexanol (38)
To a solution of (þ)-isopulegone29 (1.00 g, 6.57 mmol) in
THF (1 mL) was added dropwise ethynylmagnesium bromide
(1.17 mL, 0.582 mmol). The reaction was stirred until comple-
tion by TLC (3 h) before being quenched with NH4Cl (satd
aq). The mixture was extracted with diethyl ether (3ꢂ) and
the combined organic layers were washed with brine, dried
over MgSO4, filtered, and concentrated. Flash chromatography
(5% ethyl acetate in hexanes) gave 38 as a mixture of diaste-
reoisomers (0.940 g, 80%) as colorless oils.
IR (neat, cmꢃ1) 3530 (m), 2940 (s), 2861 (m), 1720 (m),
1
1467 (m); H NMR (CDCl3, 400 MHz) d 7.58 (d, J¼7.8 Hz,
1H), 7.32 (d, J¼8.2 Hz, 1H), 7.24e7.20 (m, 1H), 7.12e7.08
(m, 1H), 6.45 (s, 1H), 4.73 (dd, J¼6.9, 6.9 Hz, 1H), 4.00 (s,
3H), 2.66 (br, 1H), 2.47e2.44 (m, 1H), 2.19e2.16 (m, 2H),
1.87e1.76 (m, 2H), 1.64e1.57 (m, 2H), 1.46e1.40 (m, 1H);
13C NMR (CDCl3, 100 MHz) d 142.5 (C), 138.4 (C), 126.9
(C), 121.7 (CH), 120.6 (CH), 119.7 (CH), 109.1 (CH), 99.6
(CH), 73.7 (C), 66.7 (CH), 38.5 (CH2), 32.6 (CH2), 32.1
(CH3), 25.7 (CH2), 20.7 (CH2); HRMS (EI) m/z calcd for
C17H17N (Mþ) 263.1077, found 263.1084.
4.1.12.1. Major (ꢁ)-[1S,2S,5R]. IR (neat, cmꢃ1) 3549 (br),
1
3309 (s), 2951 (s), 1727 (m), 1638 (w), 1455 (s); H NMR
(CDCl3, 400 MHz) d 4.97 (t, J¼1.6 Hz, 1H), 4.81 (s, 1H),
2.37 (s, 1H), 2.15e2.08 (m, 3H), 1.94 (s, 3H), 1.76e1.63
(m, 3H), 1.46e1.41 (m, 1H), 1.32 (dd, J¼12.3, 13.7 Hz,
1H), 0.93e0.88 (m, 1H), 0.84 (d, J¼6.6 Hz, 3H); 13C NMR
(CDCl3, 100 MHz) d 147.9 (C), 112.4 (CH2), 88.6 (C), 71.2
(CH), 67.4 (C), 52.2 (CH), 48.0 (CH2), 34.5 (CH2), 26.8
(CH2), 26.6 (CH), 25.9 (CH3), 21.8 (CH3); HRMS (EI) m/z
calcd for C12H18O (Mþ) 178.1358, found 178.1345.
4.1.11. 1-Ethynyl-2-(1-methyl-1H-indol-2-yl)-cyclohexanol
(32)
To a solution of cyclohexanol 32A (46.0 mg, 0.178 mmol)
in THF (1 mL) was added dropwise ethynylmagnesium bro-
mide (1.17 mL, 0.582 mmol). The reaction was heated to re-
flux and stirred until completion by TLC (3 h), at which
point it was cooled to room temperature and quenched with
NH4Cl (satd aq). The mixture was extracted with diethyl ether
(3ꢂ) and the combined organic layers were washed with brine,
dried over MgSO4, filtered, and concentrated. Flash chroma-
tography (10% ethyl acetate in hexanes) gave 32 as a mixture
of diastereoisomers (27.3 mg, 61%) as yellow oils.
4.1.12.2. Minor (ꢁ)-[1R,2S,5R]. IR (neat, cmꢃ1) 3459 (br),
1
3307 (s), 2928 (s), 1633 (w), 1455 (s); H NMR (CDCl3,
400 MHz) d 4.95 (t, J¼0.7 Hz, 1H), 4.88 (s, 1H), 2.43 (s,
1H), 2.10e2.00 (m, 2H), 1.95e1.60 (m, 5H), 1.84 (s, 3H),
1.17 (dd, J¼12.3, 12.3 Hz, 1H), 0.92 (d, J¼5.2 Hz, 3H),
0.95e0.83 (m, 1H); 13C NMR (CDCl3, 100 MHz) d 145.4
(C), 115.2 (CH2), 86.3 (C), 74.2 (CH), 69.6 (C), 55.7 (CH),
48.7 (CH2), 34.4 (CH2), 30.3 (CH), 28.0 (CH2), 21.9 (CH3),
21.0 (CH3); HRMS (EI) m/z calcd for C12H18O (Mþ)
178.1358, found 178.1345.
4.1.11.1. Major (ꢁ)-[1S,2S]. IR (neat, cmꢃ1) 3527 (br), 3285
(s), 2938 (s), 2856 (m), 1465 (m); 1H NMR (CDCl3, 400 MHz)
d 7.67 (dt, J¼7.8, 0.8 Hz, 1H), 7.41e7.38 (m, 1H), 7.31e7.26
(m, 1H), 7.20e7.16 (m, 1H), 6.50 (s, 1H), 3.87 (s, 3H), 3.28e
3.24 (dd, J¼12.6, 3.7 Hz, 1H), 3.14 (s, 1H), 2.59 (s, 1H),
2.39e2.33 (m, 1H), 2.33 (s, 1H), 2.17e1.44 (m, 6H); 13C
NMR (CDCl3, 100 MHz) d 141.1 (C), 137.5 (C), 127.7 (C),
121.4 (CH), 120.2 (CH), 119.6 (CH), 109.5 (CH), 99.6
(CH), 88.2 (C), 71.7 (CH), 66.8 (C), 43.7 (CH), 38.8 (CH2),
30.6 (CH3), 27.9 (CH2), 25.8 (CH2), 20.3 (CH2); HRMS
(EI) m/z calcd for C17H19NO (Mþ) 253.1467, found 253.1465.
4.2. General procedures for gold(I)-catalyzed
benzannulation of 3-hydroxy-1,5-enynes
Procedure A: AgOTf (2.5 mol %) and Au(PPh3)Cl
(2.5 mol %) were weighed in the glovebox. Then, a solution
of the substrate in dichloromethane (0.1 M based on the alco-
hol) was cannulated. The resulting dark solution was stirred
for 15e18 h until completion by TLC. The reaction mixture
was filtered through Celite and evaporated in vacuo. Purifica-
tion by flash chromatography yielded the desired benzannula-
tion products.
Procedure B: Au(PPh3)Cl (1.0 mol %) was weighed in the
glovebox. Then, a solution of TfOH (1.0 mol %) (0.01 M in
ether) was added to the flame-dried flask. Subsequently, the
substrate in dichloroethane (0.1 M based on the alcohol) was
cannulated. The resulting dark solution was refluxed for 15e
18 h until completion by TLC. The reaction mixture was
cooled to room temperature and quenched with NaHCO3.
The mixture was extracted with DCM (3ꢂ) and the combined
4.1.11.2. Minor (ꢁ)-[1R,2S]. IR (neat, cmꢃ1) 3424 (m), 3285
1
(m), 2936 (s), 2859 (m), 1468 (m), 1317 (m), 1231 (w); H
NMR (CDCl3, 400 MHz) d 7.65 (d, J¼7.8 Hz, 1H), 7.36 (d,
J¼8.2 Hz, 1H), 7.24 (td, J¼1.2, 7.0, 7.0 Hz, 1H), 7.16e7.12
(m, 1H), 6.70 (s, 1H), 3.79 (s, 3H), 3.01 (dd, J¼3.3,
12.1 Hz, 1H), 2.65 (s, 1H), 2.44 (s, 1H), 2.26e2.22 (m, 1H),
2.10e1.73 (m, 6H), 1.50e1.38 (m, 1H); 13C NMR (CDCl3,
100 MHz) d 140.5 (C), 137.2 (C), 127.7 (C), 121.0 (CH),

806
C.M. Grise´ et al. / Tetrahedron 64 (2008) 797e808
organic layers were washed with brine, dried over MgSO4, fil-
tered, and concentrated in vacuo. Purification by flash chroma-
tography yielded the desired benzannulated products.
HRMS (EI) m/z calcd for C23H23NO2S (Mþ) 377.1450, found
377.1442; mp¼52.7e55.1 ꢀC.
4.2.5. 8-Methyl-isochromane (17n)
4.2.1. 5-Methyl-1,2,3,4-tetrahydro-naphthalene (17)
Procedure B: purification by flash chromatography (5%
ethyl acetate/hexanes) afforded tetrahydronaphthalene 17
(16.9 mg, 48%) as a yellow oil. Characterization is available
through the literature.16
Procedure A: purification by flash chromatography (10%
ethyl acetate/hexanes) afforded tetrahydronaphthalene 17n
(5.0 mg, 51%) as a beige solid.
Procedure B: purification by flash chromatography (10%
ethyl acetate/hexanes) afforded tetrahydronaphthalene 17n
(12.7 mg, 62%) as a beige solid.
IR (neat, cmꢃ1) 2927 (br), 2855 (m), 1725 (m), 1264 (s); 1H
NMR (CDCl3, 400 MHz) d 7.08 (dd, J¼7.5, 7.5 Hz, 1H),
6.98e6.95 (m, 2H), 4.71 (s, 2H), 3.93 (t, J¼5.6 Hz, 2H),
2.85 (t, J¼5.6 Hz, 2H), 2.13 (s, 3H); 13C NMR (CDCl3,
100 MHz) d 133.5 (C), 133.2 (C), 133.1 (C), 127.6 (CH),
126.6 (CH), 126.1 (CH), 66.5 (CH2), 64.9 (CH2), 28.7
(CH2), 17.8 (CH3); HRMS (EI) m/z calcd for C10H12O (Mþ)
148.0888, found 148.0883.
4.2.2. 1-Methyl-6,7,8,9-tetrahydro-5H-benzocycloheptene
(17j)
Procedure B: purification by flash chromatography (5%
ethyl acetate/hexanes) afforded benzannulated product 17j
(12.0 mg, 68%) as a yellow oil. Characterization is available
through the literature.16
4.2.3. 1,2,3,4-Tetrahydro-8-methyl-2-tosylisoquinoline (17l)
Procedure A: purification by flash chromatography (10%
ethyl acetate/hexanes) afforded benzannulated product 17l
(16.2 mg, 67%) as a white solid.
4.2.6. 7-Ethoxy-5-methyl-1,2,3,4-tetrahydronaphthalene
(17o)
Procedure B: purification by flash chromatography (10%
ethyl acetate/hexanes) afforded tetrahydronaphthalene 17o
(5.7 mg, 51%) as a colorless oil.
IR (neat, cmꢃ1) 2925 (br), 2857 (m), 1607 (m), 1477 (m); 1H
NMR (CDCl3, 400 MHz) d 6.55 (br s, 1H), 6.45 (br s, 1H), 3.97
(q, J¼7 Hz, 2H), 2.70 (dd, J¼5.6 Hz, 2H), 2.52 (dd, J¼5.6 Hz,
2H), 2.15 (s, 3H), 1.83e1.67 (m, 4H), 1.35 (t, J¼7 Hz, 3H);
13C NMR (CDCl3, 100 MHz) d 138.1 (C), 128.2 (C), 114.5
(CH), 112.3 (CH), 63.6 (CH2), 30.9 (CH2), 26.4 (CH2), 24.0
(CH2), 23.4 (CH2), 20.1 (CH3), 15.3 (CH3); HRMS (EI) m/z
calcd for C13H18O (Mþ) 190.1358, found 190.1353.
Procedure B: purification by flash chromatography (10%
ethyl acetate/hexanes) afforded benzannulated product 17l
(51.4 mg, 55%) as a white solid.
Mixture of atropisomers: IR (neat, cmꢃ1) 2922 (w), 2852
1
(w), 1597 (w), 1461 (w), 1335 (m), 1165 (s), 1094 (m); H
NMR (CDCl3, 400 MHz) d 7.72 (dd, J¼9.1, 8.4 Hz, 4H), 7.31
(dd, J¼5.8, 2.1 Hz, 4H), 7.06e6.87 (m, 6H), 4.18 (s, 2H),
4.13 (s, 2H), 3.31 (ddd, J¼7.1, 5.8, 1.2 Hz, 4H), 2.95e2.83
(m, 4H), 2.41 (s, 6H), 2.25 (s, 2.7H), 2.16 (s, 3.3H); 13C
NMR (CDCl3, 100 MHz) d 143.7 (C), 143.6 (C), 136.3 (C),
134.6 (C), 133.3 (2ꢂC), 133.0 (C), 132.9 (C), 130.1 (C),
129.7 (2ꢂCH), 129.7 (2ꢂCH), 129.3 (CH), 128.6 (C), 127.9
(CH), 127.8 (2ꢂCH), 127.7 (2ꢂCH), 127.2 (CH), 126.5 (CH),
126.4 (CH), 126.2 (CH), 47.4 (CH2), 45.8 (CH2), 43.8 (CH2),
43.3 (CH2), 29.4 (CH2), 28.9 (CH2), 21.5 (2ꢂCH3), 21.0
(CH3), 18.6 (CH3); HRMS (EI) m/z calcd for C17H19NO2S
(Mþ) 301.1137, found 301.1142; mp¼119.0e123.4 ꢀC.
4.2.7. 6,7,8,9-Tetrahydro-naphtho[1,2-b]furan (29)
Procedure B: purification by flash chromatography (5%
ethyl acetate/hexanes) afforded tetrahydronaphthalene 29
(15.5 mg, 64%) as an orange oil. Characterization is available
through the literature.16
4.2.4. 8-Methyl-6-phenyl-2-(toluene-4-sulfonyl)-1,2,3,4-
tetrahydro-isoquinoline (17m)
Procedure A: purification by flash chromatography (10%
ethyl acetate/hexanes) afforded tetrahydronaphthalene 17m
(18.2 mg, 67%) as a beige solid.
4.2.8. 11-Methyl-2,3,4,11-tetrahydro-1H-
benzo[a]carbazole (33)
Procedure A: purification by flash chromatography (10%
ethyl acetate/hexanes) afforded tetrahydronaphthalene 33
(12.2 mg, 81%) as a white solid.
Procedure B: purification by flash chromatography (10%
ethyl acetate/hexanes) afforded tetrahydronaphthalene 17m
(20.0 mg, 56%) as a beige solid.
Procedure B: purification by flash chromatography (10%
ethyl acetate/hexanes) afforded tetrahydronaphthalene 33
(21.6 mg, 76%) as a white solid.
IR (neat, cmꢃ1) 2910 (m), 2830 (w), 1605 (w), 1450 (w),
1
1340 (m), 1164 (s), 1098 (m); H NMR (CDCl3, 400 MHz)
IR (neat, cmꢃ1) 2919 (m), 2857 (w), 1467 (s), 1403 (s), 745
1
d 7.75e7.73 (m, 2H), 7.52e7.50 (m, 2H), 7.41e7.37 (m,
2H), 7.33e7.30 (m, 3H), 7.21 (s, 1H), 7.14 (s, 1H), 4.16 (s, 2H),
3.35 (dd, J¼5.8, 5.8 Hz, 2H), 2.98 (dd, J¼5.7, 5.7 Hz, 2H), 2.41
(s, 3H), 2.23 (s, 3H); 13C NMR (CDCl3, 100 MHz) d 143.7
(C), 140.7 (C), 139.5 (C), 135.1 (C), 133.5 (C), 133.4 (C),
129.8 (2ꢂCH), 129.3 (C), 128.7 (2ꢂCH), 127.7 (2ꢂCH),
127.3 (CH), 127.0 (2ꢂCH), 126.8 (CH), 125.2 (CH), 45.7
(CH2), 43.4 (CH2), 29.5 (CH2), 21.5 (CH3), 18.8 (CH3);
(s); H NMR (CDCl3, 300 MHz) d 8.04 (d, J¼7.7 Hz, 1H),
7.86 (d, J¼7.9 Hz, 1H), 7.48e7.36 (m, 2H), 7.22 (t,
J¼7.7 Hz, 1H), 6.98 (t, J¼8.0 Hz, 1H), 4.15 (s, 3H), 3.43 (t,
J¼5.6 Hz, 2H), 3.02 (t, J¼6.1 Hz, 2H), 1.99e1.85 (m, 4H);
13C NMR (CDCl3, 100 MHz) d 141.9 (C), 140.0 (C), 135.4
(C), 124.9 (CH), 123.1 (C), 121.4 (CH), 121.3 (C), 120.6
(C), 119.5 (CH), 118.8 (CH), 117.5 (CH), 108.6 (CH), 33.2
(CH3), 30.7 (CH2), 26.9 (CH2), 23.6 (CH2), 22.8 (CH2);

C.M. Grise´ et al. / Tetrahedron 64 (2008) 797e808
807
HRMS (EI) m/z calcd for C17H17N (Mþ) 235.1361, found
235.1361; mp¼149.3e150.2 ꢀC.
4. (a) Asao, N.; Aikawa, H. J. Org. Chem. 2005, 71, 5249; (b) Asao, N.;
Takahashi, K.; Sunyoung, L.; Kasahara, T.; Yamamoto, Y. J. Am. Chem.
Soc. 2002, 124, 12650.
5. (a) Furstner, A.; Mamane, V. J. Org. Chem. 2002, 67, 6264; (b) Mamane,
¨
¨
V.; Hannen, P.; Furstner, A. Chem.dEur. J. 2004, 10, 4556; (c) Kennedy,
4.2.9. 1,2,3,4,5,6,7,8-Octahydro-phenanthrene (35)
Procedure B: purification by flash chromatography (5%
ethyl acetate/hexanes) afforded tetrahydronaphthalene 35
(37.9 mg, 49%) as a yellow oil. Characterization is available
through the literature.16
J. W. J.; Furstner, A. Chem.dEur. J 2006, 12, 7398.
¨
6. (a) Shibata, T.; Ueno, Y.; Kanda, K. Synlett 2006, 411; (b) Dankwardt,
J. W. Tetrahedron Lett. 2001, 42, 5809.
7. Lin, M.-Y.; Das, A.; Liu, R.-S. J. Am. Chem. Soc. 2006, 128, 9340.
8. Zhao, J.; Hugues, C. O.; Toste, F. D. J. Am. Chem. Soc. 2006, 128, 7436.
9. Lian, J.-J.; Chen, P.-C.; Lin, Y.-P.; Ting, H.-C.; Liu, R.-S. J. Am. Chem.
Soc. 2006, 128, 11372.
4.2.10. 2,5-Dimethyl-1,2,3,4-tetrahydro-naphthalene (39)
Procedure A: purification by flash chromatography (5%
ethyl acetate/hexanes) afforded tetrahydronaphthalene 39
(72.6 mg, 74%) as a yellow oil.
10. (a) Sheppard, G. S.; Wang, J.; Kawai, M.; Fidanze, S. D.; BaMaung, N. Y.;
Erickson, S. A.; Barnes, D. M.; Tedrow, J. S.; Kolaczkowski, L.;
Vasudeva, A.; Park, D. C.; Wang, G. T.; Sanders, W. J.; Mantei, R. A.;
Palazzo, F.; Tucker-Garcia, L.; Lou, P.; Zhang, Q.; Park, C. H.; Kim,
K. H.; Petros, A.; Olejniczak, E.; Nettesheim, D.; Hajduk, P.; Henkin, J.; Les-
niewski, R.; Davidsen, S. K.; Bell, R. L. J. Med. Chem. 2006, 49, 3832; (b)
Barker, M.; Clakers, M.; Copley, R.; Demaine, D. A.; Humphreys,
D.; Inglis, G. G. A.; Johnson, M. J.; Jones, H. T.; Haase, M. V.;
House, D.; Loiseau, R.; Lesley, N.; Pacquet, F.; Skone, P. A.; Shana-
han, S. E.; Tape, D.; Vinader, V. M.; Washington, M.; Uings, I.; Upton,
R.; McLay, I. M.; Macdonald, S. J. F. J. Med. Chem. 2006, 49, 4216;
(c) Altenback, R. J.; Khilevich, A.; Kolasa, T.; Rohde, J. J.; Bhatia,
P. A.; Patel, M. V.; Searle, X. B.; Yang, F.; Bunnelle, W. H.; Tietje, K.; Bay-
burt, E. K.; Carroll, W. A.; Meyer, M. D.; Henry, R.; Buckner, S. A.; Kuk, J.;
Daza, A. V.; Milicic, I. V.; Cain, J. C.; Kang, C. H.; Ireland, L. M.; Carr, T. L.;
Miller, T. R.; Hancock, A. A.; Nakane, M.; Esbenshade, T. A.; Brune, M. E.;
O’Neill, A. B.; Gauvin, D. M.; Katwala, S. P.; Holladay, M. W.; Brioni, J. D.;
Sullivan, J. P. J. Med. Chem. 2004, 47, 3220; (d) Holmberg, P.; Sohn,
D.; Leideborg, R.; Caldirola, P.; Zlatoidsky, P.; Hanson, S.; Mohell, N.;
Rosqvist, S.; Nordvall, G.; Johansson, A. M.; Johansson, R. J. Med.
Chem. 2004, 47, 3927; (e) Cimetiere, B.; Dubuffet, T.; Landras, C.;
Descombes, J.-J.; Simonet, S.; Verbeuren, T. J.; Lavielle, G. Bioorg.
Med. Chem. Lett 1998, 8, 1381.
Procedure B: purification by flash chromatography (5%
ethyl acetate/hexanes) afforded tetrahydronaphthalene 39
(67.5 mg, 82%) as a yellow oil.
1
IR (neat, cmꢃ1) 2917 (s), 1587 (m), 1455 (s), 764 (s); H
NMR (CDCl3, 400 MHz) d 7.04e6.92 (m, 3H), 2.83e2.73
(m, 2H), 2.63e2.54 (m, 1H), 2.43 (dd, J¼16.3, 10.8 Hz,
1H), 2.22 (s, 3H), 1.98e1.92 (m, 1H), 1.84e1.80 (m, 1H),
1.45e1.35 (m, 1H), 1.05 (d, J¼6.6 Hz, 3H); 13C NMR
(CDCl3, 100 MHz) d 136.9 (C), 136.4 (C), 135.2 (C), 127.0
(CH), 126.9 (CH), 125.2 (CH), 38.8 (CH2), 31.7 (CH2), 28.8
(CH), 27.8 (CH2), 21.9 (CH3), 19.6 (CH3); HRMS (EI) m/z
calcd for C12H16 (Mþ) 160.1252, found 160.1277.
Acknowledgements
We thank the NSERC, Merck Frosst Canada, Merck and
Co., Boehringer Ingelheim, PREA, CFI, OIT, Center for
Catalysis Research and Innovation and the University of Ottawa
for generous funding. C.M.G. thanks NSERC for a post-gradu-
ate scholarship (CGS-D).
11. Selected examples: (a) Carreno, M. C.; Gonzalez-Lopez, M.; Latorre, A.;
Urbano, A. J. Org. Chem. 2006, 71, 4956; (b) Clayden, J.; Westlund, N.;
Frampton, C. S.; Helliwell, M. Org. Biomol. Chem. 2006, 4, 455.
12. Selected examples: (a) Kurteva, V. B.; Santos, A. G.; Afonso, C. A. M.
Org. Biomol.Chem. 2004, 2, 514; (b) Ma, S.; Zhang, J. Tetrahedron
2003, 49, 6273.
13. Selected examples: (a) Henderson, L. C.; Loughlin, W. A.; Jenkins, I. D.;
Healy, P. C.; Campitelli, M. R. J. Org. Chem. 2006, 71, 2384; (b) Sestelo,
J. P.; Real, M. d. M.; Sarandeses, L. A. J. Org. Chem. 2001, 66, 1395.
14. (a) PtCl2: Harrack, Y.; Blaszykowski, C.; Bernard, M.; Cariou, K.; Mainetti,
References and notes
1. Selected examples: Dotz benzannulation: (i) Rawat, M.; Prutyanov, V.;
¨
`
Wulff, W. D. J. Am. Chem. Soc. 2006, 128, 11044; (ii) Eastham, S. A.;
Ingham, S. P.; Hallett, M. R.; Herbert, J.; Quayle, P.; Raftery, J. Tetra-
hedron Lett. 2006, 47, 2299; (iii) Zhang, Y.; Candelaria, D.; Herndon,
J. W. Tetrahedron Lett. 2005, 46, 2211; Acid-promoted: (i) Nishii, Y.;
Yoshida, T.; Asano, H.; Wakasugi, K.; Morita, J.-i.; Aso, Y.; Yoshida,
E.; Motoyoshiya, J.; Aoyama, H.; Tanabe, Y. J. Org. Chem. 2005, 70,
2667; (ii) Kozik, B.; Wilamowski, J.; Gora, M.; Sepiol, J. Tetrahedron
Lett. 2006, 47, 3435; Anionic cyclization: (i) Austin, W. F.; Zhang, Y.;
Danheiser, R. L. Org. Lett. 2005, 7, 3905; (ii) Waddell, M. K.; Bekele,
E.; Mouries, V.; Dhimane, A.-L.; Fensterbank, L.; Malacria, M. J. Am.
Chem. Soc. 2004, 126, 8656; (b) Cu(BF4)(CH3CN)4 or PtCl2: Fehr, C.;
Farris, I.; Sommer, H. Org. Lett. 2006, 8, 1839; (c) Au salts: Gagosz, F.
Org. Lett. 2005, 7, 4129; (d) PtCl2 and Au salts: Mamane, V.; Gress, T.;
Krause, H.; Furstner, A. J. Am. Chem. Soc. 2004, 126, 8654; (e) Pt, Cu
¨
and Au salts: Fehr, C.; Galindo, J. Angew. Chem., Int. Ed. 2006, 45, 2901;
(f) Pt and Au-salts: Furstner, A.; Hannen, P. Chem.dEur. J. 2006, 12,
¨
3006; (g) Au-salts: Marion, N.; de Fremont, P.; Lemiere, G.; Stevens,
´
`
E. D.; Fensterbank, L.; Malacria, M.; Nolan, S. P. Chem. Commun. 2006,
´
`
2048; (h) Pt-salts: Mainetti, E.; Mouries, V.; Fensterbank, L.; Malacria,
T.; Lipton, M. A. J. Org. Chem. 2006, 71, 8372; Cycloaddition: Martı-
´
´
nez-Esperon, M. F.; Rodrıguez, D.; Castedo, L.; Saa, C. Tetrahedron
2006, 62, 3843; Metal-catalyzed: (i) Rubina, M.; Conley, M.; Genorgyan,
V. J. Am. Chem. Soc. 2006, 128, 5818; (ii) Xi, C.; Chen, C.; Lin, J.; Hong,
X. Org. Lett. 2005, 7, 347.
M.; Marco-Contelles, J. Angew. Chem., Int. Ed. 2002, 41, 2132; (i) Pt-salts:
Blaszykowski, C.; Harrak, Y.; Goncualves, M.-H.; Cloarec, J.-M.; Dhimane,
¨
A.-L.; Fensterbank, L.; Malacria, M. Org. Lett. 2004, 6, 3771.
´
15. (a) Bluthe, N.; Malacria, M.; Gore, J. Tetrahedron Lett. 1984, 25, 2873;
´
(b) Bluthe, N.; Malacria, M.; Gore, J. Tetrahedron 1986, 42, 1333.
2. Recent reviews on gold-catalyzed reactions: (a) Hashmi, S. A. K.;
Hutchings, G. J. Angew. Chem., Int. Ed. 2006, 45, 7896; (b) Zhang, L.;
Sun, J.; Kozmin, S. A. Adv. Synth. Catal. 2006, 348, 2271; (c) Widenhoe-
fer, R. A.; Han, X. Eur. J. Org. Chem. 2006, 4555; (d) Ma, S.; Yu, S.; Gu,
´
16. Grise, C. M.; Barriault, L. Org. Lett. 2006, 8, 5905.
17. The use of other Ag salt such as AgBF4 and AgSbF6 in combination with
Ph3PAuCl gave low yields.
Z. Angew. Chem., Int. Ed. 2006, 45, 200; (e) Furstner, A.; Davies, P. W.
18. Only starting material was recovered when alcohol 16 was treated with
2.5 mol % Au(PPh3)Cl.
¨
Angew. Chem., Int. Ed. 2007, 46, 3410; (f) Gorin, D. J.; Toste, F. D. Na-
ture 2007, 446, 395.
3. Hashmi, A. S. K.; Frost, T. M.; Bats, J. W. J. Am. Chem. Soc. 2000, 122,
11553.
19. Lopez, S.; Herrero-Gomez, E.; Perez-Galan, P.; Nieto-Oberhuber;
Echavarren, A. M. Angew. Chem., Int. Ed. 2006, 45, 6029 and references
herein.

808
C.M. Grise´ et al. / Tetrahedron 64 (2008) 797e808
20. Some examples of 6-endo cyclizations of enynes: (a) Zhang, L.; Kozmin,
S. A. J. Am. Chem. Soc. 2004, 126, 11806; (b) Sherry, B. D.; Toste, F. D.
J. Am. Chem. Soc. 2004, 126, 15978; (c) For theoretical analysis: Soriano,
E.; Marco-Contelles, J. J. Org. Chem. 2005, 70, 9345.
crude mixture. Compound 17 was exposed to TfOH (1 equiv) for 2.5 h
at 23 ꢀC, and no degradation products were observed.
25. In entry 5, no more starting material was present but no desired
product was detected by 1H NMR. In entry 6, only starting material
was recovered.
21. This product was obtained from 16 via a tandem oxy-Cope/ene reaction.
See: Warrington, J. M.; Barriault, L. Org. Lett. 2005, 7, 4589.
22. Conversion of 80%, determined by 1H NMR of the crude mixture.
23. Rosenfeld, D. C.; Shekhar, S.; Takemiya, A.; Utsunomiya, M.; Hartwig,
J. F. Org. Lett. 2006, 8, 4179.
26. No products from a gold-catalyzed MeyerseSchuster rearrangement were
observed. (a) Lopez, S. S.; Engel, D. A.; Dudley, G. B. Synlett 2007, 949;
(b) Engel, D. A.; Dudley, G. B. Org. Lett. 2006, 8, 4027.
27. Teles, J. H.; Brode, S.; Chabanas, M. Angew. Chem., Int. Ed. 1998, 37,
1415.
24. Exposure of 16 to 1 equiv of TfOH and PTSA, respectively, in DCM at
room temperature gave a myriad of compounds from which no tetrahydro-
naphthalene 17 or diene-yne products were observed by 1H NMR of the
28. Bahia, P. S.; Snaith, J. S. J. Org. Chem. 2004, 69, 3226.
29. Buschmann, H.; Scharf, H.-D. Synthesis 1988, 10, 827.