Hg(OTf)2-Catalyzed cyclization of alkynyl tert-butylcarbonate leading to cyclic enol carbonate

Article abstract of DOI:10.1016/j.tetlet.2006.09.067

Mercuric triflate was shown to be a powerful catalyst for the cyclization of alkynyl tert-butylcarbonates giving rise to cyclic enol carbonates under mild conditions. Internal alkynyl carbonate affords endo cyclization product selectively, while terminal alkynyl carbonate provides only exo cyclization product.

Full text of DOI:10.1016/j.tetlet.2006.09.067

Tetrahedron Letters 47 (2006) 8369–8373
Hg(OTf)2-Catalyzed cyclization of alkynyl
tert-butylcarbonate leading to cyclic enol carbonate
Hirofumi Yamamoto, Mami Nishiyama, Hiroshi Imagawa and Mugio Nishizawa*
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan
Received 4 August 2006; revised 12 September 2006; accepted 15 September 2006
Available online 9 October 2006
Abstract—Mercuric triflate was shown to be a powerful catalyst for the cyclization of alkynyl tert-butylcarbonates giving rise to
cyclic enol carbonates under mild conditions. Internal alkynyl carbonate affords endo cyclization product selectively, while terminal
alkynyl carbonate provides only exo cyclization product.
Ó 2006 Elsevier Ltd. All rights reserved.
Mercuric triflate was developed in 1983 as an olefin
cyclization agent,1 and its catalytic activities have been
recently demonstrated for the hydration of terminal
alkynes leading to methyl ketones,2 the hydroxylative
1,6-enyne cyclization to give exomethylene five-mem-
bered ring products,3 cyclization of 1-alkyn-5-ones lead-
ing to 2-methylfurans,4 arylalkyne cyclization leading to
dihydronaphthalene derivatives,5 biomimetic tandem
cyclization of an alkynyl alkenyl aryl derivative to give
polycarbocycles,6 and the reaction of propargyl acetate
with water affording vinyl ketones.7 These reactions
likely involve a protodemercuration step of the vinyl-
mercury intermediate, which is induced by in situ-gener-
ated TfOH.
six-membered ring endo type enol carbonate was pre-
pared by a multi-step synthetic sequence10 (Scheme 1).
We have discovered that Hg(OTf)2 induces endo cycliza-
tion selectively with internal alkynyl carbonates, and
only exo cyclization with terminal alkynes. We first
examined the reaction of an internal alkynyl carbonate,
tert-butyl-2-nonynyl carbonate (1)11 with 5 mol % of
Hg(OTf)2 in acetonitrile at room temperature. An endo
cyclization product 2 was obtained in 35% yield along
with exo cyclization product 3 in 3% yield and fragmen-
tation products 4 and 5 in 29% and 14% yields, respec-
tively (Table 1, entry 1). The Z-configuration of 3 was
confirmed by the NOE experiment. The reaction in tol-
uene, however, afforded 2 in 83% yield along with 5% of
3 (entry 2). Although ether and nitromethane gave lower
yields (entries 3 and 4), dichloromethane was found to
be the solvent of choice affording 2 in 93% yield after
5 min reaction. exo Cyclization product 3 was the only
by-product in 4% yield (entry 5).12 Yields were neither
significantly increased nor decreased with varying
catalyst loadings (entries 6 and 7). However, 1 mol %
We envisioned that Hg(OTf)2-catalyzed cyclizations of
alkynyl tert-butylcarbonates might provide an attractive
and efficient synthesis of cyclic enol carbonates.
Although cyclic enol carbonates can serve as useful
building blocks, the classical preparation of cyclic enol
carbonates by the fixation of CO2 with propargylic alco-
hols requires the presence of catalyst under high temper-
ature or high CO2 pressure.8 Recently, Buzas and
Gagosz demonstrated Au(I)-catalyzed exo cyclizations
of propargylic tert-butyl carbonates to give five-mem-
bered ring 4-alkylidene-1,3-dioxolan-2-ones even from
an internal alkyne after cationic rearrangement.9 There-
fore, most of the known preparations of cyclic alkylid-
ene carbonates are limited to the formation of
five-membered ring compounds. The sole example of a
O
O
O
O
O
C6H13
+
2
Hg(OTf)2
C6H13
O
O
1
O
C6H13
+
C6H13
C6H13
O
HO
+
O
3
4
5
*
Corresponding author. Tel.: +81 886229611; fax: +81 886553051;
e-mail: mugi@ph.bunri-u.ac.jp
Scheme 1.
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.09.067

8370
H. Yamamoto et al. / Tetrahedron Letters 47 (2006) 8369–8373
Table 1. Hg(OTf)2-Catalyzed cyclization of 1
Entry
Solvent
Hg(OTf)2 (mol %)
Time (min)
Yielda (%)
2
3
4
5
1
1
2
3
4
5
6
7
8
9
CH3CN
C6H5CH3
(C2H5)2O
CH3NO2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
5
5
5
5
5
10
3
1
1b
1c
0.5
5d
60
5
15
60
5
35
83
72
58
93
89
77
76
57
17
46
—
3
5
5
2
4
4
4
4
3
1
2
—
29
—
—
6
—
—
—
11
8
14
—
—
2
—
—
—
—
7
17
—
—
—
—
—
—
—
15
69
21
43
5
60
60
120
1440
60
60
10
11
12
—
11
21
—
8
34
a NMR yield using naphthalene as the internal standard.
b Reaction with Hg(OTf)2ÆTMU.
c Reaction with Hg(OTf)2Æ3TMU.
d Reaction with TfOH.
of catalyst was sufficient to consume starting material 1
to give 2 in 76% yield along with significant quantity of
fragmentation product 4 (11%) (entry 8). The cyclization
catalyzed by Hg(OTf)2Ætetramethylurea (hereafter
TMU) also afforded larger amounts of fragmentation
products 4 and 5 (8% and 7%, respectively), however,
Hg(OTf)2Æ3TMU formed neither 4 nor 5, and gave rise
to 2 in only 17% yield after 24 h with a larger amounts
of starting material (entries 9 and 10). The catalyst at
0.5 mol % also produced 4 and 5, indicating that the
fragmentation reaction to give 4 as well as 5 occurred
by the contaminated acidic moiety such as TfOH. Prob-
ably the reaction using 5 mol % catalyst completes the
cyclization before fragmentation. Of course TfOH did
not show any catalytic activity for the cyclization but
provided fragmentation products 4 and 5 in 21% and
34% yields, respectively, along with 43% of starting
material by the reaction in CH2Cl2 for 1 h (entry 12).
will be the major path and producing vinylmercuric
intermediate 9. The protonation of 9 by in situ-gener-
ated TfOH forms the alternative oxonium cation 10
and yields product 2 as well as regenerated catalyst
Hg(OTf)2. Fragmentation as seen in 11 results in the for-
mation of 2-nonynol (5) along with 2-methylpropene
(12) and CO2, and acid mediated coupling of 12 and 5
provides tert-butyl ether 4.
When the standard procedure (5 mol % Hg(OTf)2,
CH2Cl2) was applied to the reaction of the tert-butylcar-
bonate derivative of 4-methyl-2-pentyn-1-ol (13), endo
cyclization product 14 was obtained in 73% yield along
with exo cyclization product 15 in 7% yield (Table 2).
The 4,4-dimethyl-2-pentyn-1-ol derivative 16 also affor-
ded endo cyclization product 17 in 80% yield along with
exo cyclization product 18 in 10% yield. Phenyl substi-
tuted 19 afforded endo cyclization product 20 in 72%
yield along with a significant quantity of less polar com-
plex mixture, however, occurrence of the corresponding
exo cyclization product was not detected. Internal alky-
nyl secondary alcohol derivatives 21 was again con-
verted into endo mode cyclization products 22 in 74%
yield along with exo cyclization product 23 (5%) and
the third product 24 in 12% yields. Compound 22 was
unstable and decomposed through acidic hydrolysis to
The cyclization of 1 is thought to proceed as shown in
Scheme 2. The reaction is initiated by p-complexation
of an alkynyl group with Hg(OTf)2 as seen in 6, followed
by the nucleophilic participation of the carbonyl group
leading to an equilibrium of exo cyclic oxonium cation
7 and endo cyclic oxonium cation 8. Deprotonative frag-
mentation from the thermodynamically more stable 8
O
O+ C6H13
HgOTf
O+
O
O
O
C6H13
HgOTf
C6H13
H
O
6
O
O
O
Hg(OTf)2
7
8
+
O
O
C6H13
O
C6H13
+
Hg(OTf)2
2
O
O
HgOTf
HgOTf
H
TfOH
9
10
O
O
C6H13
+
5
4
O
H
H+
11
12
Scheme 2.

H. Yamamoto et al. / Tetrahedron Letters 47 (2006) 8369–8373
Table 2. Hg(OTf)2-Catalyzed cyclization of alkynyl carbonatesa
8371
Substrate
Time
Productb
O
O
O
O
O
O
O
O
10 min
O
O
O
O
13
14
17
73%
80%
7%
15
O
O
O
O
O
O
60 min
30 min
O
O
16
10%
18
O
O
Ph
Ph
O
O
19
20 72%
O
O
O
C6H13
C6H13
O
O
O
O
O
C6H13
74%
5%
23
22
10 min
O
O
C6H13
21
24 12%
O
O
O
O
O
O
O
O
58%
7%
27
26
30 min
O
O
25
10%
X
28
O
O
O
TMS
O
O
O
O
TMS
O
O
15 min
C6H13
C6H13
20%
C6H13
O
29
30
31a: X = TMS
31b: X = H 64%
O
O
I
24 h
No reaction
C6H13
O
32
O
O
O
C6H13
84%
C6H13
30 min
HN
HN
34
33
a Reaction was carried out using 5 mol % of Hg(OTf)2 in CH2Cl2 at room temperature.
b NMR yield using naphthalene as the internal standard.
form 24 during column chromatography. tert-Butyl
substituted alkyne 25 also produced three products 26–
28 in 58%, 7%, and 10% yield, respectively. The reaction
of TMS substituted alkyne 29 afforded a mixture of endo
cyclization product 30 and exo cyclization product 31a.
Since the separation of 30 and 31a was very difficult and
exo product 31a was shown to be unstable against acid,
we treated the mixture with 0.8 equiv of TfOH in
CH2Cl2 at room temperature for 5 min. The TMS group
of the exo cyclization product 31a was selectively
cleaved to give 31b, and the separation of 30 and 31b
was easily achieved by a column chromatography on sil-
ica gel to give pure 30 and 31b in 20% and 64% yield,
respectively. Iodine substituted alkyne 32 was entirely
inert under these condition and starting material was
recovered after 24 h. The reaction of nitrogen analog
33 with 5 mol % of Hg(OTf)2 afforded endo cyclization
product 34 selectively in 84% yield.

8372
H. Yamamoto et al. / Tetrahedron Letters 47 (2006) 8369–8373
In contrast terminal alkynyl substrates uniformly under-
went exo cyclizations. For instance, substrate 35 affor-
ded exo cyclization product 31b in a quantitative yield
after only after 10 min reaction. The yield was also
observably diminished for the corresponding cyclization
of 1-phenyl analogue 36 affording 37 in 62% yield with
the formation of a complex mixture of less polar prod-
ucts. tert-Alcohol derivatives 38, 40, and 42 afforded
39 (72% yield), 41 (73% yield), and 43 (94% yield),
respectively. The treatment of 44 with 5 mol % of
Hg(OTf)2 afforded complex mixtures, however, the reac-
tion with Hg(OTf)2Æ3TMU with 44 effectively took place
in CDCl3 at room temperature.13 All starting material
was consumed after 5 h and the yield of 45 was deter-
mined to be 80% by direct NMR experiment. The reac-
tion of 3-butynol derivative 46 with Hg(OTf)2Æ3TMU in
CDCl3 also afforded six-membered ring exo cyclization
product 47 in 70% yield (Table 3).
O+
R
O
O
R
O
O
O
R
+
O
O
O
Au
Au
Au
48
49
50
R = alkyl
O+
O
O
O
O
O
O
O
R
O
R
+
Au
R
Au
51
53
52
Scheme 3.
tions. The thermodynamic stability of oxonium cation 8
over 7, which induces endo selective cyclization, may be
the result of stereoelectronic effects. However, exo selec-
tive cyclization occurs with terminal alkynes following
the Markovnikov rule to lead nucleophilic addition at
the more substituted carbon. The Au(I)-catalyzed cycli-
zation of internal alkyne 48 reported by Buzas and Ga-
gosz takes place via exo cyclization generating 49, which
rearranges into cationic carbene 50. A second cycliza-
tion from 51 to 52 furnishes exo olefin 53 after demeta-
lation. The Au(I)-catalyzed reaction should be directed
by carbenoid formation to 50, whereas the Hg(OTf)2-
catalyzed reaction should be controlled by the intensive
cationic character of 8 (Scheme 3).
Therefore, we have developed Hg(OTf)2- and Hg-
(OTf)2Æ3TMU-catalyzed cyclization of alkynyl tert-butyl-
carbonate to give endo cyclized enol carbonates from
internal alkynes and exo cyclized products from termi-
nal alkynes in good to excellent yields under mild condi-
Table 3. Hg(OTf)2-Catalyzed cyclization of alkynyl carbonatesa
Substrate
Time
Productb
O
O
O
O
O
Acknowledgements
10 min
O
We thank Professor Frank E. McDonald of Emory Uni-
versity for stimulating discussion in an early phase of
this project, and for his comments on a draft of this
manuscript. This study was financially supported by a
Grant-in-Aid from the Ministry of Education, Culture,
Sports, Science, and Technology of the Japanese
Government.
C6H13
O
35
C6H13
99%
31b
O
O
O
O
O
30 min
30 min
O
36
Ph
Ph
O
37
62%
O
O
O
O
O
Supplementary data
38
39
72%
O
O
O
O
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2006.09.067.
O
O
5 min
5 min
40
O
41 73%
O
References and notes
O
O
O
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42
94%
43
O
O
O
O
O
O
5 hc
2 hc
O
O
O
80%
70%
44
45
47
O
O
O
46
a Reaction was carried out using 5 mol % of Hg(OTf)2 in CH2Cl2 at
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c Reaction using Hg(OTf)2Æ3TMU in CDCl3.

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flask under argon atmosphere, and the solvent was
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