Mercuric triflate catalyzed cycloisomerization of alkynyl-1,3- cyclohexanedione and alkynyl-1,3-cyclopentanedione

Article abstract of DOI:10.1055/s-2006-932464

Mercuric triflate was used to catalyze cycloisomerization of alkynyl-1,3-cyclohexanediones and cyclopentanediones to give fused oxabicyclic systems under mild reaction conditions with high catalytic turnover up to 1000 times. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-932464

6
42
LETTER
Mercuric Triflate Catalyzed Cycloisomerization of Alkynyl-1,3-Cyclo-
hexanedione and Alkynyl-1,3-Cyclopentanedione
C
H
ycloisomerizatio
i
n of Alk
r
ynyl-1,3
o
-Cyclohexan
s
e
dione hi Imagawa, Shuhei Kotani, Mugio Nishizawa*
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan
Fax +81(88)6553051; E-mail: mugi@ph.bunri-u.ac.jp
Received 24 December 2005
Table 1 Hg(OTf) -Catalyzed Cyclization of 1
2
Abstract: Mercuric triflate was used to catalyze cycloisomeriza-
tion of alkynyl-1,3-cyclohexanediones and cyclopentanediones to
give fused oxabicyclic systems under mild reaction conditions with
high catalytic turnover up to 1000 times.
Entry
Catalyst (mol%)
Solvent
Time
Yield
(%)a
(
min)
60
40
45
5
1
2
3
4
5
6
7
8
9
Hg(OTf) (1)
CH NO
75
73
81
87
Key words: mercuric triflate, catalytic cycloisomerization, alkyn-
yl-1,3-cyclohexanediones
2
3
2
Hg(OTf) (1)
CH Cl
2
2
2
Hg(OTf) (1)
C H
2
6
6
Alkyne heteroatom cyclization catalyzed by an electro-
philic metal complex is a subject of considerable interest
Hg(OTf) (1)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
2
1
Hg(OTf) (1)
0.5 92
in modern synthetic organic chemistry. Although cyclo-
2
isomerization of alkynyl alcohols, amines, and carboxylic
acids has been studied intensively, cyclization of alkynyl
Hg(OTf) (0.1)
20
300
15
88
0
2
2
ketones has been limited to furan synthesis. We previous-
Hg(OTf) (0.01)
2
3
ly reported a 2-methylfuran synthesis by cyclization of 1-
Hg(OTf) ·TMU (1)
91
93
96
22
0
2
alkyn-5-one. The reaction was catalyzed by mercury(II)
trifluoromethanesulfonate [mercuric triflate, hereafter
Hg(OTf) ·2TMU (1)
20
2
Hg(OTf) ], developed in our group as an olefin cycliza-
2
1
0
Hg(OTf) ·3TMU (1)
30
4
2
tion agent. Recently, we also reported that Hg(OTf) and
2
a Hg(OTf) -tetramethylurea (hereafter TMU) complex 11
Hg(OTf) ·3TMU (0.1) MeCN
180
40
2
2
showed highly efficient catalytic activity for the following
1
1
2
3
4
Hg(OAc) (1)
MeCN
MeCN
MeCN
2
reactions: 1) hydration of terminal alkynes to give methyl
5
ketones, 2) hydroxylative 1,6-enyne cyclization to give
Hg(OTFA) (1)
10
93
85
2
6
exomethylene five-membered ring products, 3) arylal-
1
Hg(OTFA) (0.1)
1200
2
kyne cyclization leading to dihydronaphthalene deriva-
7
tives, and 4) biomimetic tandem cyclization yielding
a
Isolated yield.
8
,9
polycarbocycles. Using a variety of metal complexes
Mascarenas and co-workers described cycloisomerization
of 4-propargyl-1,3-cyclohexanedione and cyclopen-
When the alkynyldione 1 was treated with 1 mol% of
Hg(OTf) in CH NO at room temperature for 1 hour, the
10
tanedione generating dihydropyrane or dihydrofuran. In
the present study, we examined cycloisomerization of
alkynyl-1,3-cyclohexanediones and cyclopentanediones
at ambient temperature using catalytic amounts of
2
3
2
oxabicyclic product 2 was obtained (Scheme 1). Yield of
was 75% after column chromatography on silica gel
Table 1, entry 1). Although comparable yields were ob-
tained by using CH Cl or benzene as the solvent, MeCN
2
(
Hg(OTf) . Notably, we observed very high catalytic effi-
2
2
2
ciencies up to 1000 times catalytic turnover in producing
fused oxabicyclic products.
afforded an improved yield of 87% yield (entries 2–4).
When the reaction of 1 with 1 mol% of Hg(OTf) in
2
MeCN was quenched after 30 seconds by addition of
O
O
O
Hg(OTf)2
O
11
Et N, the yield was 92% (entry 5). Using 0.1 mol% of
3
Hg(OTf) , an 88% yield of 2 was obtained within an
2
1
2
acceptable reaction period (entry 6). Hg(OTf) ·TMU and
2
Hg(OTf) ·2TMU complexes afforded 2 in high yield (en-
tries 8 and 9). However, the highest yield was obtained
2
Scheme 1
using Hg(OTf) ·3TMU complex to produce 2 with a 96%
2
yield after a 30 minutes reaction (entry 10), These results
suggested that the unstable product 2 was partially decom-
posed by the reactive Hg(OTf) . Although Hg(OAc) did
SYNLETT 2006, No. 4, pp 0642–0644
0
2.
0
3.
2
0
0
6
2
2
Advanced online publication: 20.02.2006
DOI: 10.1055/s-2006-932464; Art ID: U31805ST
Georg Thieme Verlag Stuttgart · New York
not catalyze any detectable cycloisomerization (entry 12),
©

LETTER
Cycloisomerization of Alkynyl-1,3-Cyclohexanedione
643
–
conversion to 2 was achieved using Hg(OTFA) (1 mol%)
OTf
H
2
TfOH
+
O
with a 93% yield after 10 minutes in MeCN (entry 13). In-
creased reactivity of Hg(OTf) versus Hg(OTFA) is evi-
O
OH
O
O
O
2
2
HgOTf
HgOTf
Hg(OTf)2
dent when the reactions with 0.1 mol% catalyst are
compared. The reaction of 1 with 0.1 mol% of Hg(OTf)2
afforded an 88% yield of 2 after 20 min (entry 6), howev-
3
4
5
2
+
Hg(OTf)2
er, Hg(OTFA) required 20 hours to give an 85% yield of Scheme 2
2
2
(entry 14).
The cycloisomerization catalyzed by Hg(OTf) is predict-
ed to proceed as shown in Scheme 2. The reaction is initi-
2
Next we examined Hg(OTf) -catalyzed cyclization of var-
ious 1,3-diones (Table 2). Dione 6 (a methyl homologue
2
ated by p-complexation of an alkynyl group with
of 1) was reacted with Hg(OTf) (1 mol%) in MeCN at
2
Hg(OTf) as seen in 3. Participation of an enol group leads
2
room temperature for 30 minutes. This reaction produced
a mixture of exo-cyclization product 7 and endo-cycliza-
tion product 8 in an 88:12 ratio, with a total yield of 84%.
Cyclization of 6 was also achieved using 0.1 mol% of
to vinyl mercury intermediate 4. Protonation of 4 by in
situ generated TfOH leads to oxonium cation 5. Subse-
quent demercuration of 5 yields product 2 and regenerates
the catalyst Hg(OTf)2.
Hg(OTf) producing 7 and 8 with an 80% total yield
2
(
87:13 ratio) after three hours at room temperature.
Table 2 Hg(OTf) -Catalyzed Cyclization of 1,3-Dione
2
Substrate
Hg(OTf)2
Product (yield)a
O
O
O
O
O
O
1
0
mol%, 30 min, 84% (88:12)b
.1 mol%, 3 h, 80% (87:13)
6
7
8
O
O
O
O
O
1 mol%, 25 min, 78%
O
0
.1 mol%, 3 h, 73%
1
0
9
O
O
1
mol%, 5 min, 76%
11
12
O
O
O
O
1
1
mol%, 20 min
mol%, 20 min
13
14 90%
O
O
O
O
15
16 89%
O
O
O
O
O
O
O
O
O
1 mol%, 30 min
1 mol%, 30 min
17
18 48%
19 8%
20 28%
O
O
O
2
2 82%
21
a
Isolated yield.
The ratio was determined by H NMR.
b
1
Synlett 2006, No. 4, 642–644 © Thieme Stuttgart · New York

6
44
H. Imagawa et al.
LETTER
Reaction of 4-propargyl-1, 3-cyclopentanedione (9) with
mol% and 0.1 mol% of Hg(OTf) generated exo-
(2) (a) Wakabayashi, Y.; Fukuda, Y.; Shiragami, H.; Uchimoto,
K.; Nozaki, H. Tetrahedron 1985, 41, 3655. (b) Padwa, A.;
Ishida, M.; Muller, C. L.; Murphree, S. S. J. Org. Chem.
1
2
methylene oxabicyclic product 10 with 78% (25 min) and
3% (3 h) yields, respectively. In contrast, methyl homo-
1992, 57, 1170. (c) Kataoka, Y.; Tezuka, M.; Takai, K.;
7
Uchimoto, K. Tetrahedron 1992, 48, 3495. (d) Arcadi, A.;
Cacchi, S.; Larock, R. C.; Marinelli, F. Tetrahedron Lett.
logue 11 was converted to its endo-mode cyclization
product 12 with a 76% yield using 1 mol% catalyst after
only five minutes. Next, we examined the cyclization of
1993, 34, 2813. (e) Ji, J.; Lu, X. J. Chem. Soc., Chem.
Commun. 1993, 764. (f) Wang, Z.; Lu, X. J. Org. Chem.
1996, 61, 2254. (g) Cacchi, S.; Fabrizi, G.; Moro, L. J. Org.
Chem. 1997, 62, 5327. (h) Picquet, M.; Bruneau, C.;
Dixneuf, P. H. Tetrahedron 1999, 55, 3937. (i) MaGee, D.
I.; Leach, J. D.; Setiadji, S. Tetrahedron 1999, 55, 2847.
2
-propargyl-1,3-cyclohexanedione (13) using 1 mol% of
Hg(OTf) in MeCN at room temperature for five minutes.
2
This reaction gave rise to 2-methylfuran 14 with a 90%
yield. Similarly, methyl homologue 15 was converted to
(
j) Nishibayashi, Y.; Yoshikawa, M.; Inada, Y.; Milton, M.
2
-ethylfuran 16 with an 89% yield. On the other hand, cy-
D.; Hidai, M.; Uemura, S. Angew. Chem. 2003, 42, 2681.
(k) Yoshida, M.; Morishita, Y.; Fujita, M.; Ihara, M.
Tetrahedron Lett. 2004, 45, 1861. (l) Yao, T.; Zhang, X.;
Larock, R. C. J. Am. Chem. Soc. 2004, 126, 11164.
clization of 2-propargyl-1,3-cyclopentanedione (17) pro-
duced a mixture of exo-mode cyclization product 18,
endo-mode cyclization product 19, and 2-methylfuran 20
with 48%, 8%, and 28% yields, respectively. Reaction of
the methyl homologue 21 produced exclusively endo-
mode cyclization product 22 with an 82% yield.
(3) Imagawa, H.; Kurisaki, T.; Nishizawa, M. Org. Lett. 2004,
6, 3679.
(
4) (a) Nishizawa, M.; Takenaka, H.; Nishide, H.; Hayashi, Y.
Tetrahedron Lett. 1983, 24, 2581. (b) Nishizawa, M.;
Morikuni, E.; Asoh, K.; Kan, Y.; Uenoyama, K.; Imagawa,
H. Synlett 1995, 169.
Therefore, Hg(OTf) -catalyzed cycloisomerization of
2
alkynyl-1,3-cyclohexanediones and cyclopentanediones
occurs readily at ambient temperature. In comparison with
previous transition-metal-catalyzed procedures,10 very
high catalytic turnovers were achieved.
(
(
(
(
(
5) Nishizawa, M.; Skwarczynski, M.; Imagawa, H.; Sugihara,
T. Chem. Lett. 2002, 12.
6) Nishizawa, M.; Yadav, V. K.; Skwarczynski, M.; Takao, H.;
Imagawa, H.; Sugihara, T. Org. Lett. 2003, 5, 1609.
7) Nishizawa, M.; Takao, H.; Yadav, V. K.; Imagawa, H.;
Sugihara, T. Org. Lett. 2003, 5, 4563.
Acknowledgment
8) Imagawa, H.; Iyenaka, T.; Nishizawa, M. Org. Lett. 2005, 7,
451.
This study was financially supported by a Grant-in-Aid from the
Ministry of Education, Culture, Sports, Science, and Technology of
Japan.
9) Imagawa, H.; Iyenaka, T.; Nishizawa, M. Synlett 2005, 703.
(
(
10) Gulias, M.; Rodriguez, J. R.; Castedo, L.; Mascarenas, J. L.
Org. Lett. 2003, 5, 1975.
11) Typical Experimental Procedure.
References and Notes
Tetramethylurea (1.15 mg, 0.0099 mmol) and a stock
solution of Hg(OTf) in MeCN (0.01 M solution, 330 mL,
2
(
1) (a) Brown, R. C. D. Angew. Chem. 2005, 44, 850.
b) Aubert, C.; Buisine, O.; Malacria, M. Chem. Rev. 2002,
02, 813. (c) Mendez, M.; Echavarren, A. M. Eur. J. Org.
Chem. 2002, 15. (d) McDonald, F. E. Chem. Eur. J. 1999, 5,
103.
0.0033 mmol) were added to a solution of alkynyldione 1 (50
(
1
mg, 0.333 mmol) in MeCN (3.3 mL, 0.1 M) at r.t. The
solution was stirred for 30 min at r.t., and aq NaHCO was
3
added. The mixture was extracted with CH Cl and dried.
2
2
3
Concentrated extract was subjected to a column
chromatography on silica gel (hexane–EtOAc, 6:1) to give
exclusively the oxabicyclic product 2 (50 mg, 0.333 mmol).
Synlett 2006, No. 4, 642–644 © Thieme Stuttgart · New York