Gold-catalyzed cycloisomerization of 1,7-diyne benzoates to indeno[1,2-c]azepines and azabicyclo[4.2.0]octa-1(8),5-dines

Article abstract of DOI:10.1021/ja304964s

A synthetic method that relies on Au(I)-catalyzed cycloisomerization reactions of 1,7-diyne benzoates to prepare indeno[1,2-c]azepines and azabicyclo[4.2.0]octa-1(8),5-dines is described.

Full text of DOI:10.1021/ja304964s

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Communication
Gold-Catalyzed Cycloisomerization of 1,7-Diyne Benzoates to
Indeno[1,2-c]azepines and Azabicyclo[4.2.0]octa-1(8),5-dines
Weidong Rao, Ming Joo Koh, Prasath Kothandaraman, and Philip Wai Hong Chan
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/ja304964s • Publication Date (Web): 04 Jun 2012
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Gold-Catalyzed Cycloisomerization of 1,7-Diyne Benzoates to
Indeno[1,2-c]azepines and Azabicyclo[4.2.0]octa-1(8),5-dines
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Weidong Rao, Ming Joo Koh, Prasath Kothandaraman, and Philip Wai Hong Chan*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological
University, Singapore 637371, Singapore
Supporting Information Placeholder
details of this chemistry, which offers an expedient and che-
moselective approach to these two potentially useful classes of
nitrogen heterocycles in good to excellent yields and as single
ABSTRACT: A synthetic method that relies on Au(I)-
catalyzed cycloisomerization reactions of 1,7-diyne benzoates
to prepare indeno[1,2-c]azepines and azabicyclo[4.2.0]octa-
regio- and diastereomers. The N-heterocycles were additional-
1(8),5-dines is described. By taking advantage of the ortho-
ly obtained as a single enantiomer that demonstrated the nitro-
gonal modes of coordination between the π-bonds of the
mono- and disubstituted substrate with the metal catalyst, a
gen ring forming process occurred with efficient transfer of
chirality from the enantiopure starting material to the product.
divergence in product selectivity was observed.
Scheme 1. Gold-Catalyzed Reactions of 1,n-Diyne Esters
previous works:
[Au]+
ROCO
OCOR
ROCO
[Au]+
Gold-catalyzed cycloisomerizations of 1,n-diynes provide one
of the most powerful and versatile synthetic strategies for the
efficient and atom-economical assembly of complex mole-
cules.1-3 In recent years, this has hitherto included a handful of
impressive methods to synthetically useful cyclic compounds
from 1,n-diynes 1 containing a carboxylic ester moiety at one
of the propargylic positions (Scheme 1, eq 1).3 From a mecha-
nistic viewpoint, the reaction relies on the proclivity of the
acyloxy moiety of the gold-activated substrate I to undergo
1,3-migration. This is followed by further functionalization by
a remaining pendant group of the corresponding allenyl ester
intermediate II. A tandem process that allows for the selective
activation of either alkyne moiety of a 1,n-diyne ester and
access to a potentially wider scope of cycloisomerization
products, by contrast, has not been investigated. In this context
and as part of an ongoing program examining the utility of
gold catalysis in heterocyclic synthesis,4 we became interested
in the potential cycloisomerization chemistry of 1,7-diyne
benzoates 1 (Scheme 1, eq 2). We reasoned that when R4 = H
in this class of compounds, the gold catalyst might selectivity
coordinate at the sterically less hindered propargyl moiety of
the substrate (path a in Scheme 1, eq 2). In doing so, we dis-
covered that the resultant putative Au(I)-coordinated species
III generated in situ was susceptible to a concerted 5-endo-dig
followed by a 7-endo-dig cyclization process triggered by
nucleophilic attack by an appropriately placed aryl moiety and
provide the indeno[1,2-c]azepine ring system. To our know-
ledge, this mode of reactivity has not observed in 1,n-diyne
cycloisomerizations because of other more facile and general-
ly favored rearrangements.1-3 On the other hand, in substrates
where R4 ≠ H, we reasoned activation of the estereal alkyne
moiety of the 1,7-diyne benzoate might occur (path b in
Scheme 1, eq 2). Subsequent tandem 1,3-migration/Prins-type
[2+2] cycloaddition of the ensuing gold-activated intermediate
IV would then be expected to deliver azabicyclo[4.2.0]octa-
1(8),5-dine derivatives. This contrasts to a recent work that
showed allenyl esters derived from Au(I)-catalyzed 1,3-
migration of 1,6-diyne acetates to undergo a 5-endo-dig cycli-
zation process to give 3-pyrrolines.3b Herein, we disclose the
ref 3
R'
R'
products (1)
R'
R''
R''
R''
[Au]+
1
I
II
this work:
R2
R3
R2
R3
R4 = H
path a
BzO
R1
BzO
R1
R2
N
N
Ts
Ts
[Au]+
R3
[Au]+
2
III
(2)
BzO
R2
R3
BzO
R2
R1
N
R4
Ts
R4 = H
path b
R4
R3
[Au]+
1
BzO
R1
R1
N
Ts
N
Ts
R4
3
IV
We began by examining the gold-catalyzed cycloisomeriza-
tions of the enantiopure monosubstituted syn-1,7-diyne ben-
zoate 1a, prepared from L-phenylalanine following literature
procedures,5 to establish the reaction conditions (Table 1). The
(3S,4S) absolute configuration of the starting material was
determined by X-ray single crystal structure analysis of a
closely related adduct (vide infra).6 This study revealed that
treating 1a with 5 mol % of gold(I) catalyst A and 4Å molecu-
lar sieves (MS) in toluene at 80 °C for 24 h gave the best re-
sult, affording 2a in 70% yield as a single regio-, diastereo-
and enantiomer (entry 1).7 The (1S,10bS) absolute configura-
tion of the indeno[1,2-c]azepine product was ascertained by
X-ray crystallography.6 Lower product yields were obtained
when the reaction was conducted at room temperature or in the
absence of 4Å MS; in the case of the former, the substrate was
also recovered in 70% yield (entries 2 and 3). A similar out-
come was found when the reaction was repeated with Au(I)
complexes B-F in place of A or changing the solvent from
toluene to benzene or 1,2-dichloroethane (entries 4-5 and 8-
12).7 In contrast, the analogous reactions with gold(I) carbene
complexes G-I, Ph3PAuNTf2, gold(I) phosphite complex J and
gold(III) complex K as the catalyst gave a mixture of 2a
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and/or the δ-diketone byproduct 4a in low yields (entries 13-
of the substrate was found to have no influence on the course
17 and 20).7-9 No reaction was detected when PPhAuCl, AuCl
or PtCl2 was used as the catalyst, or when polar solvents such
as THF and CH3CN were used as the reaction medium (entries
6 and 7, 18 and 19, and 21).
of the reaction with 2d and 2m-n furnished in 60-75% yield. A
1,7-diyne benzoate with two terminal alkyne moieties was also
examined under the standard conditions at room temperature
and 80 °C but was found to give a mixture of decomposition
1
2
3
4
1
Table 1. Optimization of the Reaction Conditionsa
products that could not be identified by H NMR analysis of
5
the crude mixture. On the other hand, the indeno[1,2-
c]azepines 2o-t containing an alkyl or phenyl group on the
amino carbon center, were obtained in good yield from the
corresponding 1,7-diyne benzoates 1o-t. Likewise, substrates
containing a OTBS (1u) or SO2Me moiety (1v) were found to
be well-tolerated under the reaction conditions and gave the
corresponding N-heterocyclic products 2u and 2v in 65 and
57% yield, respectively. More notably, these cycloisomeriza-
tions also demonstrated that the ring-forming process occurs in
a highly selective manner. In contrast to recent reports show-
ing the propensity of Au-catalyzed 1,n-diyne ester cyclizations
to undergo an initial 1,3-migration step,3 other than a number
of unidentifiable decomposition products, no other cyclic
products that could be formed from such a pathway were de-
6
7
8
9
Ph
O
Ph
Ph
Ph
[Au]+
BzO
Bn
Ph
Bn
Ph
+
3
10b
BzO
Bn
4 Å MS, 80 ºC
24 h
O
4
N
1
N
N
Ts
Ts
Ts
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
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44
45
46
47
48
49
50
51
52
53
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57
58
59
60
1a
2a
4a
R1 R1
1R1
P
R
SbF6
SbF6
R3
R4
P
Au NCMe
Ar
N
N
Ar
AuNTf2
R2
R2
R4
R2
Au
R2
R2
L
R2
R3
A: R1 = tBu, R2 = R3 = R4 = H
G: Ar = 2,6-i-Pr2C6H3,
L = PhCN
H: Ar = 2,4,6-Me3C6H2
L = 2,4,6-(MeO)3C6H2CN
E: R1 = tBu, R2 = H
F: R1 = Cy, R2 = iPr
B: R1 = Cy, R2 = iPr, R3 = R4= H
C: R1 = tBu, R2 = iPr, R3 = R4= Me
D: R1 = Cy, R2 = iPr, R3 = OMe, R4= H
tBu
Ar
N
N Ar
1
O
N
Cl Au
Cl
SbF6
tected by H NMR analysis of the crude mixtures. Additional-
Au
NTf2
I: Ar = 2,6-i-Pr2C6H3
P Au-NCPh
t-Bu
O
O
3
ly, the [1,2-c]-tricyclic ring adducts were afforded as a single
diastereo- and enantiomer with the (1S,10bS) absolute confi-
gurations for 2h and 2t established by X-ray crystallography.6
J
K
Entry
Catalyst
Solvent
Yield (%)b
2a
70
23
59
65
42
4a
-
Table 2. Cycloisomerization of Monosubstituted 1,7-Diyne Ben-
zoates 1b-v Catalyzed by Aa
1
PhMe
A
A
A
A
A
A
A
B
C
D
E
F
2c
3d
4
PhMe
PhMe
C6H6
(CH2Cl)2
MeCN
THF
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
-
-
-
-
-
-
-
-
R2
X
X
R2
OBz
A (5 mol %)
3
5
6
7
8
10b
BzO
R1
4Å MS, PhMe
80 oC, 24 h
e
R1
N
4
-
1
N
Ts
e
Ts
1b-v
2b-v
-
39
52
43
42
37
22
-
X
Ph
Ph
Ph
9
10
11
12
13
14
15
16
17
18
19
20
21
-
-
-
+
BzO
BzO
Bn
BzO
Ph
Ph
N
N
Ts
N
Ts
Ts
16
27
18
12
21
-
G
H
I
2b: X = Me (73%)
2c: X = Cl (54%)
2d: X = vinyl (75%)
2e: (79%)b
12
-
Me
Ph
Me
R
J
Ph3PAuNTf2
Ph3PAuCl
AuCl
13
Me
e
-
BzO
BzO
Bn
BzO
Bn
e
-
-
Bn
N
N
N
Ts
-
-
8
-
K
Ts
Ts
2m: (66%)d
e
2f: (73%)
2g: R = 4-Me-C6H4 (63%)
2h: R = 4-Br-C6H4 (66%)
2i: R = 3-thiophenyl (50%)
2j: R = nBu (44%)
PtCl2
a
All reactions were performed at the 0.15 mmol scale with
catalyst:1a ratio = 1:20 and 4Å MS (150 mg) at 80 °C for 24 h. b
Isolated yield. c Reaction carried out at room temperature and 1a
was recovered in 70% yield. d Reaction carried out in the absence
of 4Å MS. e No reaction based on TLC and 1H NMR analysis of
the crude mixture.
2k: R = cyclopentyl (44%)
2l: R = H (-)c
Ph
Ph
BzO
BzO
BzO
Bn
Ts
2n: (60%)
R
( )n
R
N
N
To define the scope of these conditions, we next proceeded
on to assess their generality for a series of monosubstituted
1,7-diyne benzoates prepared from the corresponding L-α-
amino acids, and the results are summarized in Table 2. Over-
all, we were pleased to find the reaction conditions to be
Ts
Ts
N
2o: R = Me (55%)
2p: R = Et (68%)
2q: R = nPr (66%)
2r: R = iPr (48%)
2s: R = iBu (55%)
2t: R = Ph (46%)
2u: R = OTBS
n = 1 (65%)
2v: R = SO2Me
n = 2 (57%)
broad, delivering
a variety of substituted indeno[1,2-
a
All reactions were performed at the 0.15 mmol scale with A:1
c]azepines in 44-79% yield from the corresponding substrates
1b-v. Starting 1,7-diyne benzoates with a pendant alkyl, aryl
or thiophene group at the benzoate or alkyne carbon center
(1b-k) were found to react well, affording the corresponding
tricyclic adducts in 44-79% yield. The presence of a p-styrenyl
at the C3 position or vinyl moiety on the alkyne carbon center
ratio = 1:20 and 4Å MS (150 mg) in toluene at 80 °C for 24 h. Val-
b
ues in parenthesis denote isolated product yields. Isolated as an
c
inseparable mixture of regioisomers in a ratio = 1.2:1. Mixture of
unknown decomposition products afforded based on 1H NMR anal-
ysis of the crude mixture. d Reaction carried out at 120 °C for 20 h.
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The only exception was the cycloisomerization of 1e, which eq 2. This revealed the expected deuterated indeno[1,2-
1
was found to give 2e as a mixture of regioisomers in a ratio of
c]azepine product d1-2a was obtained in 73% yield with deute-
2
3
1.2:1.
rium incorporation solely at the C5 position of the adduct, as
determined by H NMR and LCMS measurements as well as
1
With the reaction conditions for indeno[1,2-c]azepines es-
tablished, we next examined the applicability of this new me-
thodology for the synthesis of azabicyclo[4.2.0]octa-1(8),5-
dines. As shown in Scheme 1, we anticipated that a change in
mode of reactivity should be achievable by switching from a
monosubstituted to a disubstituted 1,7-diyne benzoate sub-
strate. With this in mind, we first tested the reaction of enanti-
opure disubstituted 1,7-diyne benzoate 1w, prepared again
from L-phenylalanine following literature procedures,5 with 5
mol % of A under the standard conditions (Table 3). This re-
vealed that the cyclobutene fused piperidine 3a could be ob-
tained in 80% yield and as a single diastereo- and enantiomer.
Under similar conditions at room temperature, repetition of the
reaction with the disubstituted 1,7-diyne benozates 1x-ζ,5 vari-
ably containing alkyl, phenyl, thiophene and OTBS groups,
gave the corresponding bicyclic N-heterocyclic products 3b-j
in 45-80% yield. The (4S,7S) absolute configurations for 3d
and 3g were determined by X-ray crystallographic analysis.6
X-ray crystal structure analysis.6 Our findings that showed no
intermediates could be trapped when the reaction of 1a was
repeated in the presence of excess amounts of either 1H-indole
or H2O also led us to surmise that a stepwise double cycliza-
tion pathway was unlikely.11 On the other hand, our results
showing the reaction of 1l providing only a mixture of bypro-
ducts in Table 2 suggests that it is more likely steric factors
between the alkyne groups in the substrate with the Au(I) cata-
lyst which play a critical role in controlling the mode of reac-
tivity.
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 2. Control Experiments with Alkynylgold(I) Complex 5
and d1-1a Catalyzed by A
Ph
Ph
BzO
(a) no catalyst: no reaction
(b) A (5 mol %): decomposition
catalyst: (a)-(c)
Bn
N
(1)
(2)
tBu
tBu
Ts
(c) p-TsOH.H2O (1 equiv):
decomposition
Au
4Å MS, PhMe
80 oC, 24 h
P
Table 3. Tandem 1,3-Migration/[2+2] Cycloaddition of Disubsti-
Ph
tuted 1,7-Diyne Benzoates 1w-ζ Catalyzed by Aa
5
Ph
Ph
Ph
D
5
BzO
Bn
A (5 mol %)
R2
BzO
R2
Ph
R3
BzO
7
BzO
R1
A (5 mol %)
4Å MS, PhMe
80 oC, 24 h
N
Ph
3
Bn
N
Ts
D
Ts
d1-2a
4
PhMe, r.t., 15 h
4
N
R1
N
d1-1a
Ts
R3
Ts
96% D-content
73% yield, 96% D-content
1w-ζ
3a-j
A plausible mechanism for the present Au(I)-catalyzed cyc-
loisomerization reactions is outlined in Scheme 3. For mono-
substituted 1,7-diyne benzoates, this could involve selective
activation of the alkyne terminus of the substrate by the
gold(I) catalyst. This gives the gold-coordinated species III,
which undergoes a concerted double cyclization upon nucleo-
philic attack by the aryl moiety situated on the carbinol carbon
center of the substrate.12 Re-aromatization of the resultant
Wheland-type intermediate V followed by protodeauration
would then deliver 2. In the case of the disubstituted substrate,
it is thought that coordination of the gold(I) catalyst at the
estereal triple bond of the 1,7-diyne benzoate preferentially
occurs to give the gold-coordinated species IV. This results in
BzO
BzO
Ph
BzO
Ph
R
Ph
Ph
Ph
Ph
Bn
Ph
Ph
Ph
N
R
N
N
Ts
Ts
3c: R = Me (73%)
Ts
3a: R = Ph (80%)
3g: (56%)
3b: R = 3-thiophenyl (52%) 3d: R = Et (78%)
3e: R = nPr (73%)
3f: R = iBu (75%)
S
BzO
BzO
Ph
Ph
S
BzO
S
Ph
Ph
TBSO
Ph
Bn
Ph
Bn
N
N
Ts
Ts
N
Ts
3i: (45%)b
3j: R = (61%)c
3h: (80%)
a
Scheme 3. Proposed Mechanism for the Cycloisomerizations of
1,7-Diyne Benzoates Catalyzed by A
All reactions were performed at the 0.15 mmol scale with A:1
ratio = 1:20 in toluene at room temperature for 15 h. Values in
b
parenthesis denote isolated product yields. Reaction conducted at
R2
H
80 °C for 15 h. c Reaction conducted for 48 h.
concerted
process
3 = H
−[Au]+
[Au]
R
R2
BzO
R1
1
2
While the above results corroborate the mechanism premise
outlined in Scheme 1, other possible pathways were consi-
dered but then discounted based on the following control ex-
periments (Scheme 2). As gold(I)-activated alkynylgold(I)
species have been proposed in alkyne cycloisomerizations
mediated by the metal catalyst,2a-c,10 the reactions of alkynyl-
gold(I) complex 5 under the various conditions described in
Scheme 2, eq 1 were first examined.5,6 This revealed the orga-
nogold(I) complex was recovered in near quantitative yield in
the absence of a catalyst but decomposed on introducing 5 mol
% of A or 1 equiv of p-TsOH·H2O, as a proton source, to the
reaction conditions. These tests led us to rule out the possible
involvement of a dual activation pathway in which the alkyne
terminus of monosubstituted 1 was activated by two molecules
of the Au(I) catalyst. This was further supported by the out-
come found when a solution of d1-1a in toluene was treated
with 5 mol % of A under the conditions shown in Scheme 2,
[Au]+
BzO
R1
N
N
Ts
Ts
R3 = H [Au]+
[Au]+
III
V
OBz
OBz
R2
OBz
Ph
R1
R2
[Au]+
R2
Ph
R1
1,3-shift
Ph
R1
[Au]+
N
N
N
Ts
R3
Ts
Ts
R3
R3
[Au]+
IV
VI
VII
O
R2
BzO
R3
[Au]
Prins-type
cyclization
Ph
R2
−[Au]+
R1
O
Ph
Ph
R1
3
N
N
R3
VIII
Ts
Ts
[Au]
IX
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Angew. Chem., Int. Ed. 2006, 45, 7896. (k) Zhang, L.; Sun, J.; Koz-
min, S. A.; Adv. Synth. Catal. 2006, 348, 2271.
syn 1,3-migration of the benzoate group and formation of the
corresponding allenyne intermediate VI. Further coordination
by the gold(I) catalyst to the remaining alkyne moiety of this
adduct would give VII, the active species that undergoes the
stepwise [2+2] cycloaddition process involving addition of the
allenic group to the C≡C bond and formation of the piperidine
adduct VIII. In a manner similar to the analogous Au(I)-
catalyzed reactions of 1,6-enynes bearing a carbonyl group,13
subsequent Prins-type cyclization of the vinyl gold moiety to
the carbonyl carbon center in VIII would give the bicyclic
carbocationic species IX. On release of the metal catalyst, this
bicyclic adduct would then provide 3. The diketone 4a could
originate from 1a undergoing a tandem 1,3-migration/6-exo-
dig cyclization/1,5-acyl migration process in a manner similar
to that recently reported for gold(I)-catalyzed cycloisomeriza-
tions of 1,6-diyne acetates.3a The formation of both N-
heterocycles as a single enantiomer from an enantiopure sub-
strate also implies that neither the starting material nor any of
the putative intermediates are prone to racemization. As a con-
sequence, this provides efficient transfer of the retained chiral-
ity at the C4 position that leads to the enantioselectivities ob-
served at the newly formed stereogenic centers.
1
2
3
4
5
6
7
8
(2) For representative examples of gold-catalyzed cycloisomeriza-
tion of 1,n-diynes, see: (a) Ye, L.; Wang, Y.; Aue, D. H.; Zhang, L. J.
Am. Chem. Soc. 2012, 134, 41. (b) Hashmi, A. S. K.; Braun, I.; Nösel,
P.; Schädlich, J.; Wieteck, M.; Rudolph, M.; Rominger, F.; Angew.
Chem., Int. Ed. 2012, 51, 4456. (c) Hashimi, A. S. K.; Wieteck, M.;
Braun, I.; Nösel, P.; Jongbloed, L.; Rudolph, M.; Rominger, F. Adv.
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(f) Sperger, C. A.; Fiksdahl, A. J. Org. Chem. 2010, 75, 4542. (g)
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Chem. Commun. 2007, 1337; (l) Lian, J.-J.; Chen, P.-C.; Lin, Y.-P.;
Ting, H.-C.; Liu, R.-S. J. Am. Chem. Soc. 2006, 128, 11372.
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Gandon, V.; Fensterbank, L. Angew. Chem., Int. Ed. 2011, 50, 6868.
(b) Zhang, D.-H.; Yao, L.-F.; Wei, Y.; Shi, M. Angew. Chem., Int. Ed.
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In summary, we have developed a gold(I)-catalyzed strategy
for the construction of highly functionalized indeno[1,2-
c]azepines and azabicyclo[4.2.0]octa-1(8),5-dines from the
respective mono- and disubstituted 1,7-diyne benzoates. Our
studies suggest that complete control of product selectivity
was found to be possible by exploiting the steric interactions
between the alkyne moieties in the substrate with the gold(I)
catalyst. Efforts to explore the scope and synthetic applica-
tions of the present reactions are currently underway and will
be reported in due course.
(4) Selected examples: (a) Rao, W.; Susanti, D.; Chan, P. W. H. J.
Am. Chem. Soc. 2011, 133, 15248. (b) Kothandaraman, P.; Huang, C.;
Susanti, D.; Rao, W.; Chan, P. W. H. Chem. Eur. J. 2011, 17, 10081.
(c) Sze, E. M. L.; Rao, W.; Koh, M. J.; Chan, P. W. H. Chem. Eur. J.
2011, 17, 1437. (d) Kothandaraman, P.; Rao, W.; Foo, S. J.; Chan, P.
W. H. Angew. Chem., Int. Ed. 2010, 49, 4619. (e) Rao, W.; Chan, P.
W. H. Chem. Eur. J. 2008, 14, 10486.
(5) See the Supporting Information (SI) for details.
(6) See Figures S128-S135 in the SI for ORTEP drawings of the
crystal structures reported in this work.
ASSOCIATED CONTENT
(7) For the synthesis of gold complexes A-K, see: (a) Barabé, F.;
Levesque, P.; Ilia Korobkov, I.; Barriault, L. Org. Lett. 2011, 13,
5580. (b) López-Carrillo, V.; Echavarren, A. M. J. Am. Chem. Soc.
2010, 132, 9292. (c) Amijs, C. H. M.; López-Carrillo, V.; Raducan,
M.; Pérez-Galán, P.; Ferrer, C.; Echavarren, A. M. J. Org. Chem.
2008, 73, 7721. (d) Ricard, L.; Gagosz, F. Organometallics 2007, 26,
4704. (e) Herrero-Gómez, E.; Nieto-Oberhuber, C.; López, S.; Benet-
Buchholz, J.; Echavarren, A. M. Angew. Chem. Int. Ed. 2006, 45,
5455. (f) Hashmi, A. S. K.; Rudolph, M.; Weyrauch, J. P.; Wölfle,
M.; Frey, W.; Bats, J. W. Angew. Chem., Int. Ed. 2005, 44, 2798.
(8) The Z-stereochemistry of the exocyclic double bond in 4a was
assigned based on an earlier work on Au(I)-catalyzed cycloisomeriza-
tion of 1,6-diyne acetates, see ref 3a.
(9) For a review of (N-heterocyclic carbene)gold(I) complexes,
see: Nolan, S. P. Acc. Chem. Res. 2011, 44, 91. For a review on ligand
effects in gold catalysis, see ref 1e.
(10) For dual activation in Au(I)-catalyzed cycloisomerization of
1,n-diynes and allenynes, see ref 2a-c and: Cheong, P. H.-Y.; Morga-
nelli, P.; Luzung, M. R.; Houk, K. N.; Toste, F. D. J. Am. Chem. Soc.
2008, 130, 4517.
(11) For concerted double cyclizations in gold catalysis, see: (a)
Sethofer, S. G.; Mayer, T.; Toste, F. D. J. Am. Chem. Soc. 2010, 132,
8276. (b) Fürstner, A. Morency, L. Angew. Chem., Int. Ed. 2008, 47,
5030. (c) Zhang, L.; Kozmin, S. A. J. Am. Chem. Soc. 2005, 127,
6962.
(12) For recent examples, see ref 2l and: (a) Jin, T.; Uchiyama, J.;
Himuro, M.; Yamamoto Y. Tetrahedron Lett. 2011, 52, 2069. (b) Jin,
T.; Himuro, M.; Yamamoto Y. J. Am. Chem. Soc. 2010, 132, 5590.
(13) For Au(I)-catalyzed Prins-type cyclizations, see: Jimnéz-
Núñez, E.; Claverie, C. K.; Nieto-Oberhuber, C.; Echavarren, A. M.
Angew. Chem., Int. Ed. 2006, 45, 5452.
Supporting Information. Experimental procedures, characteriza-
tion data, crystal structure data (CIF). This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
waihong@ntu.edu.sg
ACKNOWLEDGMENT
This work was supported by a University Research Committee
Grant (RG55/06) from Nanyang Technological University and a
Science and Engineering Research Council Grant (092 101 0053)
from A*STAR, Singapore. We thank Drs. Yongxin Li and Rakesh
Ganguly of this Division for providing the X-ray crystallographic
data reported in this work.
REFERENCES
(1) For selected reviews on gold catalysis: (a) Krause, N.; Winter,
C. Chem. Rev. 2011, 111, 1994. (b) Corma, A.; Leyva-Pérez, A.;
Sabater, M. J.; Chem. Rev. 2011, 111, 1657. (c) Yamamoto Y.; Grid-
nev, I. D.; Patil, N. T.; Jin, T. Chem. Commun. 2009, 5075. (d) Abu
Sohel, S. M.; Liu, R.-S. Chem. Soc.Rev. 2009, 38, 2269. (e) Gorin, D.
J.; Sherry, B. D.; Toste, F. D. Chem. Rev. 2008, 108, 3351. (f) Patil,
N. T.; Yamamoto, Y. Chem. Rev. 2008, 108, 3395. (g) Lipshutz, B.
H.; Yamamoto, Y. Chem. Rev. 2008, 108, 2793. (h) Hashmi, A. S. K.
Chem. Rev. 2007, 107, 3180. (i) Jiménez-Núnẽz, E.; Echavarren, A.
M. Chem. Commun. 2007, 333. (j) Hashmi, A. S. K.; Hutchings, G. J.
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Ph
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R = H
tBu
tBu
N
Ts
BzO
Bn
70% yield
Ph
OBz
N
P
4Å MS
80 ºC, 24 h
PhMe
Au
N
CMe
Ph
Bn
SbF6
BzO
Ph
R = Ph
Ph
Ts
r.t., 15 h
R
Ph
Bn
5 mol %
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N
Ts
80% yield
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