Mercuric triflate·3TMU catalyzed cyclization of ω-alkynoic acids and synthesis of a naturally occurring γ-methylene-γ-lactone

Article abstract of DOI:10.1055/s-2006-926257

Hg(OTf)₂·3TMU showed efficient catalytic activity for the cyclization of ω-alkynoic acid to give ω-methylene-ω-lactone in excellent yield, and the procedure was efficiently applied for the synthesis of naturally occurring γ-methylene-γ-lactone.

Full text of DOI:10.1055/s-2006-926257

LETTER
639
Mercuric Triflate·3TMU Catalyzed Cyclization of w-Alkynoic Acids and
Synthesis of a Naturally Occurring g-Methylene-g-lactone
M
H
ercuric
T
riflate·
3
i
TM
U
C
r
a
talyze
o
d
C
yclization
s
of
w
-Alk
h
ynoic
A
cidsi Imagawa,* Yukari Fujikawa, Atsushi Tsuchihiro, Atsushi Kinoshita, Takayuki Yoshinaga, Hiroko Takao,
Mugio Nishizawa*
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan
Fax +81(88)6229611; E-mail: imagawa@ph.bunri-u.ac.jp
Received 20 December 2005
4
(
2% yield without forming g-methylene-g-lactone 2
Table 1, entry 1). In sharp contrast, 2 mol% of Hg(OAc)2
and Hg(OTFA) afforded 2 in 85% and 93% yield, respec-
Abstract: Hg(OTf) ·3TMU showed efficient catalytic activity for
the cyclization of w-alkynoic acid to give w-methylene-w-lactone in
excellent yield, and the procedure was efficiently applied for the
2
2
9
synthesis of naturally occurring g-methylene-g-lactone. The abso- tively (entries 2 and 3) as reported by Katzenellenbogen.
lute structure of the natural product was established by this synthe- A 2 mol% of Hg(OTf) ·TMU complex, afforded g-meth-
2
sis.
ylene-g-lactone 2 in 3% yield, and the major product was
Key words: catalytic cyclizations, carboxylic acids, alkynes, lac- again isomerized 3 in 62% yield. Hg(OTf) ·2TMU, how-
2
tones, mercury
ever, afforded 2 in 94% yield as the sole product (entries
4
and 5). Moreover, Hg(OTf) ·3TMU (2 mol%) afforded
2
2
in 98% yield after one minute (entry 6). Although the re-
action in CD NO using Hg(OTf) ·3TMU also afforded 2
We found that mercury(II) trifluoromethanesulfonate
3
2
2
1
in 90% yield after one minute (entry 7), CDCl and C D
[
mercuric triflate, hereafter Hg(OTf) ] and Hg(OTf) -tet-
3
6
6
2
2
did not give satisfactory results (entries 8 and 9). When
ramethylurea (hereafter TMU) complex showed potent
catalytic activity for the hydration of terminal alkynes to the quantity of catalyst was reduced to 1 mol%, 15 min-
2
give methyl ketones, hydroxylative 1,6-enyne cycliza- utes were required until all starting material was con-
tion to give exomethylene five-membered ring products,3 sumed and 2 was obtained in 95% yield (entry 10). A 0.1
arylalkyne cyclization leading to dihydronaphthalene mol% of catalyst was not enough to complete the reaction
4
derivatives, cyclization of 1-alkyn-5-ones leading to 2- after five hours to give 2 in 66% yield (entry 11).
5
methylfurans, and biomimetic tandem cyclization of
A second substrate was 5-hexynoic acid (4) and the reac-
6
,7
alkynyl polyene affording polycarbocycles. These reac-
tions involve a protodemercuration step of the vinylmer-
tion with 1 mol% of Hg(OTf) ·3TMU in MeCN at room
2
temperature for 15 minutes afforded d-methylene-d-lac-
tone 5 in 99% yield. The yield was also determined by
NMR using naphthalene as the internal standard. Thus,
the present procedure is highly efficient by comparing it
with reported procedures to prepare d-methylene-d-lac-
cury intermediate induced by TfOH that is generated in
6
situ. We describe herein the Hg(OTf) ·3TMU-catalyzed
2
cycloisomerization of alkynoic acids leading to g-methyl-
ene-g-lactone, d-methylene-d-lactone and e-methylene-e-
lactone in excellent yields with high catalytic turnover of
up to 100 times. Although extensive methodologies for
the synthesis of the g-methylene-g-lactone by the cycliza-
10a,c
tone.
The procedure is also applicable for the cyclization of 6-
heptynoic acid (6) to give e-methylene-e-lactone 7 in
quantitative yield by using 5 mol% of the catalyst in
MeCN at room temperature for 20 hours (Scheme 1). It
must be pointed out that this is the first practical synthesis
8
9
tion of alkynoic acid using silver salts, mercuric salts,
1
0
and transition metals as catalysts have been reported,
synthetic methods of d-methylene-d-lactone and e-meth-
ylene-e-lactone are limited. We have also achieved the
synthesis of a naturally occurring g-methylene-g-lactone
by using Hg(OTf) ·3TMU-catalyzed cyclization of
10d
of e-methylene-e-lactone, though extra dry conditions
1
1
(
substrate, solvent, and reagent) are critical to get high
2
yield. When the procedure was applied for the cyclization
of 7-octynoic acid, z-methylene-z-lactone was not detect-
ed, and the starting material was recovered quantitatively.
alkynyl tert-butyl ester as the key step elucidating the
absolute structure of the natural product.
First, we examined the reaction of 4-pentynoic acid (1)
Finally, we planned to achieve the synthesis of natural oc-
with 2 mol% of Hg(OTf) in CD CN at room temperature.
2
3
curring g-methylene-g-lactone 8 that is isolated from Gor-
1
Yield was determined by H NMR directly by using
naphthalene as the internal standard after adding triethyl-
amine to quench the reaction. The starting material was
consumed within one minute, affording enol lactone 3 in
1
1
gonian Plexaura flava, in order to establish the absolute
12
stereochemistry. Known b-ketoester 9 was reduced with
®
(
R)-Alpine-Borane in THF to give R-alcohol 10 in 21%
13
yield. The R-stereochemistry of 10 was confirmed by
Kusumi’s MTPA method,1 and the optical purity was
established to be 91% ee based on the HPLC experiment
using Daicel Chiralcel OD-H column (0.46 × 25 cm) and
hexane–2-propanol (15:1) as an eluant. The reduction of 9
4a,b
SYNLETT 2006, No. 4, pp 0639–0641
0
2.
0
3.
2
0
0
6
Advanced online publication: 20.02.2006
DOI: 10.1055/s-2006-926257; Art ID: U31705ST
©
Georg Thieme Verlag Stuttgart · New York

6
40
H. Imagawa et al.
LETTER
Table 1 Mercuric Salt Catalyzed Cyclization of 1
1) catalyst
O
O
O
2) Et3N
HO
O
O
1
2
3
Yield (%)a
Entry
Catalyst
mol%
Solvent
Time
1 min
1.5 h
2
3
1
2
3
4
5
6
7
8
9
Hg(OTf)2
Hg(OAc)2
Hg(OTFA)2
2
CD CN
0
85
93
3
42
0
3
2
CD CN
3
2
CD CN
1 min
1 min
1 min
1 min
1 min
10 min
10 min
15 min
5 h
0
3
Hg(OTf) ·TMU
2
CD CN
62
0
2
3
Hg(OTf) ·2TMU
2
CD CN
94
98
90
68
75
95
66
2
3
Hg(OTf) ·3TMU
2
CD CN
0
2
3
Hg(OTf) ·3TMU
2
CD NO
0
2
3
2
Hg(OTf) ·3TMU
2
CDCl3
C D
0
2
Hg(OTf) ·3TMU
2
0
2
6
6
10
Hg(OTf) ·3TMU
1
CD CN
0
2
3
11
Hg(OTf) ·3TMU
0.1
CD CN
0
2
3
a
NMR yield using naphthalene as internal standard.
C16H33
O
Hg(OTf)2·3TMU, MeCN
OH
O
O
a
O
O
O
(
1 mol%), r.t., 15 min
99%
O
TBS
O
21%
OH
O
9
8
4
5
O
OH
OH
b
Hg(OTf)2·3TMU, MeCN
O
O
64%
O
O
TBS
OH
C16H33 TBS
10
11
(1 mol%), r.t., 24 h
75%
99%
OH
O
(5 mol%), r.t., 20 h
C16H33
OH
7
O
6
c
d
O
78%
O
O
Scheme 1 Hg(OTf) ·3TMU-catalyzed cyclization of 4 and 6.
C16H33
2
12
13
α]D1 –19.0 (c 1.3, CH2Cl2)
9
[
lit. [α]D20 +2.8 (c 1.4, CH2Cl2)
1
5
was also examined by using baker’s yeast as well as (R)-
,5¢-diphenyl-2-methyl-3,4-propano-1,3,2-oxazoboroli-
5
1
6
®
Scheme 2 Reagents and conditions: (a) (R)-Alpine-Borane /THF,
r.t., 90 min; (b) C H I, LDA, THF, HMPA, –48 °C, 28 h; (c) Bu NF,
THF, r.t., 1.5 h; (d) Hg(OTf) ·3TMU, MeCN, r.t., 1 h.
dine-BH . The former did not afford reduction product
0 and the latter provided 10 in 67% yield (recovery of
starting material 29%) with 23% ee. Frater’s anti-selec-
tive alkylation of 10 using LDA and HMPA afforded anti-
product 11 in 64% yield. The TBS group was cleaved by Acknowledgment
TBAF in THF to give terminal alkyne 12. Then we tried
3
1
6
33
4
1
2
1
7
This study was financially supported by a Grant-in-Aid from the
Ministry of Education, Culture, Sports, Science, and Technology of
Japanese Government.
direct cyclization of the alkynyl tert-butyl ester 12 using
Hg(OTf) ·3TMU (5 mol%) in MeCN at room tempera-
2
ture. (2R,3S)-g-Methylene-g-lactone 13 was obtained in
7
8% yield after one hour reaction period, and the spectral
References and Notes
data of 13 were identical with those of the reported natural
product (Scheme 2). Although the rotation value of 13
was different from the reported data, the sign of rotation
was opposite. Therefore, we estimated that the absolute
stereochemistry of the natural product is 2R,3S as repre-
(1) (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.
1
8,19
sented by 8.
Synlett 2006, No. 4, 639–641 © Thieme Stuttgart · New York

LETTER
Mercuric Triflate·3TMU Catalyzed Cyclization of w-Alkynoic Acids
641
(
(
(
(
(
2) Nishizawa, M.; Skwarczynski, M.; Imagawa, H.; Sugihara,
(14) (a) Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa, H. J.
Am. Chem. Soc. 1991, 113, 4092. (b) The absolute
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TBAF in THF. The resulting desilylated compound was
acylated by (R)- and (S)-MTPA using EDCI and 4-DMAP in
CH Cl . The Dd (d –d ) values of (R)- and (S)-MTPA esters
5) Imagawa, H.; Kurisaki, T.; Nishizawa, M. Org. Lett. 2004,
2
2
S
R
6
, 3679.
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51.
were shown below (Figure 1).
4
–0.03
+
0.06
∆
δ (δS–δR) MTPAO H O
(
(
7) Imagawa, H.; Iyenaga, T.; Nishizawa, M. Synlett 2005, 703.
8) Silver salt catalyzed reaction, see: (a) Castaner, J.; Pascual,
J. J. Chem. Soc. 1958, 3962. (b) Jong, T. T.; Williard, P. G.
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Wakamatsu, T. Heterocycles 1995, 2587.
R
O
–0.06H
H H
+
0.05 +0.04
Figure 1
(9) Mercuric salt catalyzed reaction, see: (a) Amos, R. A.;
Katzenellenbogen, J. A. J. Org. Chem. 1978, 43, 560.
(15) Cossy, J.; Schmitt, A.; Cinquin, C.; Buisson, D.; Belotti, D.
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1
981, 103, 5459.
(16) Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc.
1987, 109, 5551.
(
(
10) Transition metal-catalyzed reaction, see: (a) Lambert, C.;
Uchimoto, K.; Nozaki, H. Tetrahedron Lett. 1984, 46, 5323.
(17) Frater, G. Helv. Chim. Acta 1979, 62, 2825.
(18) We could obtain neither the natural product nor NMR
spectra and could not check the purity of the natural product.
(19) General Experimental Procedure.
(
b) Yanagihara, N.; Lambert, C.; Iritani, K.; Utimoto, K.;
Nozaki, H. J. Am. Chem. Soc. 1986, 108, 2753. (c) Chan,
D. M. T.; Marder, T. B.; Milstein, D.; Taylor, N. J. J. Am.
Chem. Soc. 1987, 109, 6385. (d) Wakabayashi, T.; Ishii, Y.;
Ishikawa, K.; Hidai, M. Angew. Chem., Int. Ed. Engl. 1996,
To a solution of alkynoic acid (0.30 mmol) in CD CN (3 mL,
3
0.1 M) was added tetramethylurea (0.1 M in CD CN, 90 mL,
3
3
5, 2123.
11) (a) Ravi, B. N.; Wells, R. J. Aust. J. Chem. 1982, 35, 105.
b) Synthesis of racemic 8 was reported. See: Dalla, V.; Pale,
9.0 mmol) and then a 0.1 M CD CN solution of Hg(OTf) (30
3
2
mL, 3.0 mmol) at r.t. After stirring for 15 min at r.t., Et N (100
3
(
mL, 0.14 mmol) and naphthalene (internal standard, 0.3 M
P. New J. Chem. 1999, 23, 803.
CD CN solution, 0.25 mL, 0.075 mmol) were added. The
3
1
(12) Wasserman, H. H.; Frechette, R.; Oida, T.; von Duzer, J. H.
J. Org. Chem. 1989, 54, 6012.
solution was directly subjected to H NMR analysis, and the
yield was calculated from the integral value.
(
13) Midland, M. M.; McDowell, D. C.; Hatch, R. L.;
Tramontano, A. J. Am. Chem. Soc. 1980, 102, 867.
Synlett 2006, No. 4, 639–641 © Thieme Stuttgart · New York