Tandem reactions of cis-2-acyl-1-alkynyl-1-aryl cyclopropanes tuned by gold(i) and silver(i) catalysts: Efficient synthesis of pyran-fused indene cores and 2,4,6-trisubstituted phenols

Article abstract of DOI:10.1039/b909181e

Tandem reactions of cis-2-acyl-1-alkynyl-1-aryl cyclopropanes 1 tuned by gold(i) and silver(i) catalysts are described, which afford selectively the key pyran-fused indene cores 2 and the 2,4,6-trisubstituted phenols 3 in good yields, respectively. The Ro

Full text of DOI:10.1039/b909181e

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Tandem reactions of cis-2-acyl-1-alkynyl-1-aryl cyclopropanes tuned
by gold(I) and silver(I) catalysts: efficient synthesis of pyran-fused indene
cores and 2,4,6-trisubstituted phenolsw
Xiao-Ming Zhang, Yong-Qiang Tu,* Yi-Jun Jiang, Yong-Qiang Zhang, Chun-An Fan
and Fu-Min Zhang*
Received (in Cambridge, UK) 8th May 2009, Accepted 5th June 2009
First published as an Advance Article on the web 29th June 2009
DOI: 10.1039/b909181e
Tandem reactions of cis-2-acyl-1-alkynyl-1-aryl cyclopropanes
1 tuned by gold(I) and silver(I) catalysts are described, which
afford selectively the key pyran-fused indene cores 2 and the
2,4,6-trisubstituted phenols 3 in good yields, respectively.
occurring indenochromone and wrightiadione compounds,6
while in the Ag catalyzed reaction, a cyclization/isomerization
process occurred to deliver substituted phenols 3. Similar
rearrangements under thermal conditions or the catalysis of
group 6 metals have been reported earlier,7 but the reactions
were limited to transform ethynyl-substituted cyclopropanes
to single substituted phenols. It is important that in the
silver(I)-catalyzed reactions, the formed substituted phenols
with three different substituents at C-2, C-4 and C-6 positions
are not easily accessed by known methods, and could be
potentially useful in material science.8 Herein, we present
our experimental results.
Gold- or silver-catalyzed reactions have recently received
increasing attention from chemists.1,2 These metal catalysts
have shown their exceptional ability to activate the alkynyl
species,3,4 among which, carbonyl alkyne-involved transformations
have taken a particularly important part in developing
synthetic methodologies for the construction of furans,5a–c
3(2H)-furanones,5d,e functionalized aromatic compounds,5f–m
as well as 1-allenylisochromenes.5n In these reactions, the key
oxonium intermediates are proposed, which could be termi-
nated by various interesting domino processes. Based on these
pioneering works, we envisaged that cis-2-acyl-1-alkynyl-1-aryl
cyclopropanes 1 might also initiate a cyclic oxonium ion
intermediate under the coordination of an Au or Ag cation
with the triple bond; then, cleavage of the cyclopropane is
expected to trigger some unknown cascade processes to
construct synthetically useful building blocks (Scheme 1).
Interestingly, we found that gold and silver catalysts could
trigger two different processes to give two kind of products 2
and 3 (Scheme 2). In Au-catalyzed reactions, a tandem
cyclization/isomerization/Friedel–Crafts reaction took place
to form a key pyran-fused indene moiety of the naturally
Our initial studies using Au catalysts commenced with the
model substrate, cis-1a, which was readily prepared by the
Simmons–Smith cyclopropanation9 of (Z)-2-en-4-yn-1-ols10
and subsequent oxidation (see the ESIw). As indicated in
Table 1, in the presence of (PPh3)AuOTf in CH2Cl2, cis-1a
was converted to 2a in a good yield of 85% after 2 h. When
AuCl3 or AuCl were employed, the reaction systems became
complex and only less than 10% yield of 2a were obtained in two
cases. Decreasing the catalyst loading to 5 mol% led to a longer
reaction time and gave a lower yield of 2a. Thus, the condition
of entry 1 was selected for further expanding substrate scope.
During our above optimization, we interestingly found in
the presence of AgOTf in CH2Cl2, cis-1a gave rise to 3a in
moderate yield, without 2a being observed (Table 2, entry 1).
This inspired us to make some investigations on this reaction.
When we changed the silver catalysts or the solvents, lower
yields were observed (entries 2–6). Then some additives were
tested, and significantly, when 1.0 equiv NaHCO3 was added,
the yield of 3a increased dramatically (entry 9). Further
experiments showed that decreasing the catalyst loading or
Scheme 1 The formation of two possible oxonium ions.
Table 1 Effect of Au catalysts on the reaction of cis-1a
Scheme 2 Different tandem reactions tuned by gold(I) and silver(I)
Yield (%)ab
catalysts.
Entry
Catalyst
Amount
Time
1
2
3
4
(PPh3)AuOTf
AuCl3
AuCl
10 mol%
10 mol%
10 mol%
5 mol%
2 h
85
o10
o10
74
30 min
1 h
5 h
State Key Laboratory of Applied Organic Chemistry & Department of
Chemistry, Lanzhou University, Lanzhou 730000, P. R. China.
E-mail: tuyq@lzu.edu.cn; Fax: +86 931-8915557
(PPh3)AuOTf
a
b
Isolated yield. Phenol 3a was not observed.
w Electronic supplementary information (ESI) available: Experimental
procedures and characterization data. See DOI: 10.1039/b909181e
ꢀc
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Table 2 Effect of Ag catalysts on the reaction of cis-1a
Table 3 Tandem reactions of various cis-2-acyl-1-alkynyl-1-aryl
cyclopropanes tuned by Au(I) and Ag(I) catalysts
Entry Catalysta Solvent
Additive (equiv.) Time
Yield (%)bc
Entry Product 2
Yield (%)a Product 3
Yield (%)a
1
2
3
4
5
6
7
8
AgOTf CH2Cl2
AgSbF4 CH2Cl2
—
—
—
—
—
—
1.5 h
2 h
2 h
40 min 50
24 h 30
15 min 38
53
20
13
AgBF4
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
CH2Cl2
DCE
Toluene
CH3NO2
CH2Cl2 PPh3 (0.2)
—
—
0
0
CH2Cl2 Cs2CO3 (0.2)
CH2Cl2 NaHCO3 (1.0)
CH2Cl2 NaHCO3 (1.0)
CH2Cl2 NaHCO3 (2.0)
1
2
3
4
R2 = H 2a
85
R2 = H 3a
80
9
50 min 80
14 h
6 h
R2 = 4-OMe 2b 80
R2 = 2-OMe 2c 86
R2 = 4-OMe 3b 81
R2 = 2-OMe 3c 58
10d
11
72
74
R2 = 4-F 2d
94
R2 = 4-F 3d
68
a
b
Conditions: 20 mol% of silver salts were used. Isolated yield.
d
Pyran-fused indene product 2a was not observed. 10 mol% of
c
silver salts were used.
5
6
83
70
increasing the amounts of NaHCO3 led to a longer reaction
time and gave a lower yield of 3a (entries 10 and 11). Thus, the
condition of entry 9 was selected as the general reaction
condition.
90
57
Following the above two optimized conditions, we investi-
gated a range of cis-2-acyl-1-alkynyl-1-aryl cyclopropanes. As
depicted in Table 3, we first performed the Au(I)-catalyzed
reactions, and found that substrates containing both the
electron-rich and electron-deficient groups on the C-1 phenyl
ring were effective in this reaction, and all gave the expected
products 2a–d in good to high yields (entries 1–4). Changing
the C-1 phenyl group to l-naphthyl still gave a good result
(entry 5). Replacing the substituents R1 and R3 with other
aromatic or aliphatic groups did not affect the reaction
significantly, and the corresponding products 2f–h were obtained
in good yields (entries 6–8). As for the Ag(I)-catalyzed
reactions, different substrates were also tolerated just like the
Au(I)-catalyzed reaction, but the yields were lower than the
corresponding Au-catalyzed examples. Notably, in all
Au-catalyzed reactions, phenol products were not detected
and isolated, except for some unknown side products. For the
case of Ag-catalyzed reactions, the pyran-fused indene products
2 were not observed.
7
85
83
53
67
8
a
Isolated yield.
To further expand the substrate scope, employment of the
substrate cis-1i bearing two aliphatic groups R1 and R3 under
Au(I) catalysis led to the formation of two inseparable isomers
2i and 4i in 55% total yield (Scheme 3),11 in which formation
of 4i resulted from a formal 1,3-H shift in 2i. As for the
Ag(I)-catalyzed reaction of 1i, the desired product 3i was only
isolated in 33% yield, wherein an unexpected by-product 5i
was formed.12 Moreover, the substrate with C-1 alkyl
substituent instead of aryl group was examined, neither the
pyran-fused indene product nor the phenol product was
isolated in either reaction.
Scheme 3 Tandem reactions of cis-1i.
triple bond. The subsequent nucleophilic attack of the
carbonyl group took place via a 5-exo-dig cyclization to give
intermediate 7, which generated 8 after cleavage of the cyclo-
propane. Then, gold carbene 8 underwent an intramolecular
Friedel–Crafts reaction and protodemetallation to yield
products 2, with the Au(I) species being regenerated. For
Ag(I)-catalyzed process (cycle B), the coordination of AgOTf
with both the triple bond and the ketone oxygen led to the
cleavage of the cyclopropane to give 10; subsequently,
10 underwent a cyclization to deliver oxepin 11, which
transformed into arene oxide 12.7,13 Then, under the catalysis
of AgOTf, now as a Lewis acid, ring opening of 12 and
migration of R3 finally led to the formation of 3.
Based on the results above together with some literature
reports,4c,5,7,13 two plausible mechanisms were envisioned
(Scheme 4). For Au(I)-catalyzed reaction as presented in cycle
A, a cationic Au(I) species would first coordinate with the
ꢀc
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Scheme 5 Tandem reactions of cis-1j.
Further investigation showed that when there was a ligand
atom near the triple bond, the Au-catalyzed reaction could
also undergo a 6-endo-dig cyclization to give the same product
as the Ag-catalyzed reaction. The substrate cis-1j with a C-1
thienyl group transformed into the phenol product 3j under
Au(I) catalysis, probably because in this case the Au atom
would coordinate with both the sulfur atom and the triple
bond to trigger a 6-endo-dig cyclization process (Scheme 5).
In summary, we have developed two transition-metal
catalyzed tandem reactions of cis-2-acyl-1-alkynyl-1-aryl cyclo-
propanes. These reactions can be tuned by using gold(I) or
silver(I) as the catalyst. From common substrates, structurally
divergent compounds can be readily synthesized by our
tandem protocols.
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Notes and references
11 2i and 4i were obtained as inseparable mixtures and identified by
comparing their spectra with 2a and 4a. 2a could be converted
completely to 4a by heating.
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12 This major by-product might be formed from the intermediate 12i
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4728 | Chem. Commun., 2009, 4726–4728