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Published on the web June 26, 2010
Hg(OTf)2-catalyzed Cycloisomerization of Aryl- and Hetero-substituted 1,3-Dienes
³³
Hirofumi Yamamoto,* Shinya Shiomi, Daiki Odate, Ikuo Sasaki, Kosuke Namba,
Hiroshi Imagawa, and Mugio Nishizawa*,³
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514
(Received May 17, 2010; CL-100473; E-mail: hirofumi@ph.bunri-u.ac.jp)
Table 1. Hg(OTf)2-catalyzed cycloisomerization of 3a
We developed Hg(OTf)2-catalyzed Friedel-Crafts-like cy-
cloisomerization of 7-arylhepta-1,3-dienes to give propenyl-
substituted tetrahydronaphthalenes in excellent catalytic turn-
over under very mild conditions. 1,3-Dienyl sulfonamides and
1,3-dienyl alcohols were also efficiently cyclized to afford
heterocyclic compounds.
Yield/%b
Entry Catalyst
Mol % Solvent
Time/h
3
4
1
2
3
4
5
6
7
8
Hg(OTf)2
Hg(OTf)2
Hg(OTf)2
Hg(OTf)2
Hg(OTf)2
Hg(OTf)2
Hg(OTFA)2
TfOH
1
CH3CN
CH3NO2
C6H5CH3
(CH2Cl)2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
4
4
4
4
4
24
24
12
94
93
98
13
®
®
99
®
®
®
®
63
96
90
0
1
1
1
1
In the last five years Hg(OTf)2 has been increasingly used
for metal-catalyzed cycloisomerization of alkynes to generate
C-C as well as C-heteroatom bonds.1 The key step in these
catalytic reactions is the protonation of vinylmercury intermedi-
ates by TfOH, which is formed in situ.2 Recently the procedure
has been extended to alkene cyclizations by the introduction of
an allylic hydroxy moiety as the protonation site to trigger the
smooth demercuration step that regenerates the catalyst. For
example the reaction of 1 with 0.5 mol % of Hg(OTf)2 in toluene
affords 2 in excellent yield (Scheme 1, eq 1). The vinyl
functionality maintained in the product will be useful for further
molecular modifications such as hydroboration, ozonolysis, and
metathesis.3 Here, we show that Hg(OTf)2-catalyzed cyclo-
isomerization of aryl 1,3-diene 3 affords tetrahydronaphthalene
4 in high catalytic turnover under very mild reaction conditions
(eq 2). 1,3-Dienyl sulfonamides as well as 1,3-dienyl alcohols
were also found to efficiently react in the presence of a catalytic
amount of Hg(OTf)2 to give heterocycles. The Friedel-Crafts-
like metal salt-catalyzed cycloisomerization of aryl-substituted
1,3-diene has not yet been reported,4 although a few catalytic
heterocycle syntheses from 1,3-dienes have been described.5
First, we examined the reaction of 3 with 1 mol % of
Hg(OTf)2 in CH3CN at room temperature. However, no reaction
products were detected (Table 1, Entry 1). After examining a
variety of solvents, CH2Cl2 was found to be the solvent of
choice. Although (CH2Cl)2 provided 4 in 63% yield, CH2Cl2
gave 4 in 96% yield after 4 h at room temperature (Entries 4 and
5). The reaction took place with complete E-selectivity even
0.5
1
1
88
aReactions were carried out at room temperature. bIsolated
yield.
when a mixture of E- and Z-dienes was employed. Complete
reaction was achieved within 24 h using a catalyst loading of
0.5 mol % (Entry 6). By contrast, Hg(OTFA)2 did not afford any
product (Entry 7). Although less effective than Hg(OTf)2, TfOH
acted as a catalyst to give a cyclic product after 12 h (Entry 8).
Table 2 shows the generality of Hg(OTf)2 using a variety of
1,3-diene derivatives. The reaction of m-methoxyphenyl-sub-
stituted heptadiene 5 with 1 mol % of Hg(OTf)2 in CH2Cl2 for
2 h at room temperature afforded the cyclization product 7 at the
p-position for the methoxy group in 71% yield along with the o-
position product 6 in 27% yield. In contrast, the o-substituted 8
gave a complex mixture of reaction products that did not include
9. The m-xylene derivative 10 behaved as a suitable precursor to
afford 11 in good yield. We then examined heterocyclizations to
generate C-N and C-O bonds. The reaction of heptadienyl
sulfonamide 12 with 2 mol % of Hg(OTf)2 was completed in
6 h at room temperature. The homolog 14 also afforded the
piperidine derivative 15 in excellent yield under the same
reaction conditions. The corresponding dienyl alcohols 166 and
187 were found to be less reactive, requiring 8 mol % of
Hg(OTf)2 to obtain 17 in 78% and 19 in 92%, respectively.8
The reaction is likely to be initiated from a mercury-diene
complex. Cation 20, generated by the Friedel-Crafts-like cy-
clization, produces organomercuric intermediate 21 via depro-
tonation (Scheme 2). Protonation of the remaining vinyl moiety
of 21 by TfOH, which is formed in situ, leads to an alternative
cation 22.
OMe
OMe
Hg(OTf)2
(0.5 mol%)
(1)
(2)
toluene
reflux, 5 min
OMe
OMe
OMe
2
96%
1
OH
Demercuration of 22 regenerates the catalyst Hg(OTf)2 and
forms the product 4. In order to confirm the mechanism, we
prepared the isomeric terminal olefin 23 from 6,8-dimethoxy-
3,4-dihydronaphthalen-1(2H)-one.9 When 23 was treated with
either 1 mol % of Hg(OTf)2 or TfOH in CH2Cl2 at room
temperature, no reaction took place even after 24 h. Thus the
potential isomerization of the double bond from the terminal
position to the internal position could be disregarded. It is now
OMe
OMe
Hg(OTf)2
(1 mol%)
CH2Cl2, rt, 4 h
OMe
96%
3
4
Scheme 1. Hg(OTf)2-catalyzed cyclizations.
Chem. Lett. 2010, 39, 830-831
© 2010 The Chemical Society of Japan
Yamamoto, Hirofumi
