Mercury(II) triflate-catalyzed cycloisomerization of allenynes to allenenes

Article abstract of DOI:10.1021/jo701591e

(Chemical Equation Presented) Cycloisomerizations of allenynes to allenenes have been studied in the presence of catalytic amounts of [Hg(OTf)₂] in acetonitrile. The catalytic system is quite effective for terminal 1,6-allenynes: allenenes were

Full text of DOI:10.1021/jo701591e

5
Mercury(II) Triflate-Catalyzed
Cycloisomerization of Allenynes to Allenenes
of enyne, arylyne, and yne-en-aryl substrates. Recently, Echa-
6
varren et al. reported the use of Hg(OTf)2 in the cyclization of
,6-enynes. However, they presented only two examples. We
1
chose allenynes as substrates because they are attractive
substrates due to their use in diverse synthetic applications as
well as in new reactions of unsaturated systems. Thus, when
So Hee Sim, Sang Ick Lee, Junhyeok Seo, and
Young Keun Chung*
7
Intelligent Textile System Research Center, Department of
Chemistry, College of Natural Sciences, Seoul National
UniVersity, Seoul 151-747, Korea
allenyne 1a was treated with Hg(OTf) in acetonitrile, allenene
2
1
b was isolated as a major product in 70% yield (eq 1).
ykchung@snu.ac.kr
ReceiVed August 5, 2007
Formation of 1b was also confirmed by an X-ray diffraction
study (Figure 1). This was the first observation on a mercury-
catalyzed cycloisomerization of allenyne. Encouraged by this
result, we initially screened various metal catalysts such as Hg-
(CN)2, HgCl2, Hg(OAc)2, and Hg(OTf)2 with/without tetram-
ethylurea (TMU), Cu(OTf)2, Yb(OTf)3, and Sc(OTf)3 for the
cycloisomerization of allenynes. Results are summarized in
Table 1.
Neither Hg(CN)2 nor HgCl2 had any catalytic activity. When
Hg(OAc)2 was used as a catalyst, a dimeric product 1c was
obtained in 20% yield with recovery of 40% of the reactant.
Formation of 1c was confirmed by H and C NMR and high-
resolution mass spectroscopy. Treatment of 1c with trifluo-
romethanesulfonic acid in acetonitrile at 15-20 °C for 30 min
gave 1b in 92% yield (eq 2).
Cycloisomerizations of allenynes to allenenes have been
studied in the presence of catalytic amounts of [Hg(OTf)
2
]
1
13
in acetonitrile. The catalytic system is quite effective for
terminal 1,6-allenynes: allenenes were obtained in reasonable
to high yields. However, treatment of allenynes with disub-
stituents at the allenic terminal carbon yielded a triene and/
or allenene as a major product(s) depending upon the
substituents.
The transition-metal-catalyzed cyclization of enyne systems
1
has recently experienced tremendous developments. However,
Chatani’s study on the use of gallium compound as a catalyst
When 10 mol % of Hg(OTf)2 was used as a catalyst, the reaction
time was shortened to 1 h and the expected product 1b was
obtained in 70% yield. However, when we lowered the catalyst
loading to 5 mol %, product 1b was obtained 38% yield. The
catalytic activity in acetonitrile solvent was better than that in
THF (77% of the reactant recovered) or dichloromethane (33%
2
in the skeletal rearrangement reaction turned our attention from
transition metal catalysts to main group and even lanthanide
compounds, such as main group and lanthanide Lewis acids.
3
+
We recently reported the use of Au(PPh3) or GaCl3 as a
catalyst in the cycloisomerization of allenynes to allenenes and
initiated studying the use of Hg(OTf)2 as a catalyst in the
cycloisomerization. Hg(OTf)2, developed by Nishizawa’s group
(5) For recent papers, see: (a) Nishizawa, M.; Imagawa, H. J. Synth.
Org. Chem. Jpn. 2006, 64, 744-751. (b) Imagawa, H.; Kinoshita, A.;
Fukuyama, T.; Yamamoto, H.; Nishizawa, M. Tetrahedron Lett. 2006, 47,
4
in 1983 as an olefin cyclization agent, now has been developed
4
6
729-4731. (c) Imagawa, H.; Kotani, S.; Nishizawa, M. Synlett 2006, 642-
further into a powerful catalyst for many useful reactions
including the hydration of terminal alkynes and the cyclization
44. (d) Imagawa, H.; Asai, Y.; Takano, H.; Hamagaki, H.; Nishizawa, M.
Org. Lett. 2006, 8, 447-450. (e) Imagawa, H.; Iyenaga, T.; Nishizawa, M.
Org. Lett. 2005, 7, 451-453. (f) Imagawa, H.; Kurisaki, T.; Nishizawa,
M. Org. Lett. 2004, 6, 3679-3681.
(6) Nieto-Oberhuber, C.; Mu n˜ oz, M. P.; L o´ pez, S.; Jim e´ nez-N u´ n˜ ez, E.;
Nevado, C.; Herrero-G o´ mez, E.; Raducan, M.; Echavarren, A. M. Chem.s
Eur. J. 2006, 12, 1677-1693.
(7) (a) Brummond, K. M.; You, L. Tetrahedron 2005, 61, 6180-6185.
(b) Gupta, A. K.; Rhim, C. Y.; Oh, C. H. Tetrahedron Lett. 2005, 46, 2247-
2250. (c) Oh, C. H.; Park, D. I.; Jung, S. H.; Reddy, V. R.; Gupta, A. K.;
Kim, Y. M. Synlett 2005, 2092-2094. (d) Kumareswaran, R.; Shin, S.;
Gallou, I.; RajanBabu, T. V. J. Org. Chem. 2004, 69, 7157-7170. (e)
Shibata, T.; Kadowaki, S.; Takagi, K. Organometallics 2004, 23, 4116-
4120. (f) Mukai, C.; Inagaki, F.; Yoshida, T.; Kitagaki, S. Tetrahedron
Lett. 2004, 45, 4117-4121. (g) Oh, C. H.; Jung, S. H.; Park, D. I.; Choi,
J. H. Tetrahedron Lett. 2004, 45, 2499-2502. (h) Oh, C. H.; Jung, S. H.;
Rhim, C. Y. Tetrahedron Lett. 2001, 42, 8669-8671. (i) Urabe, H.; Takeda,
T.; Hideura, D.; Sato. F. J. Am. Chem. Soc. 1997, 119, 11295-11305.
(
1) For reviews, see: (a) Nakamura, I.; Yamamoto, Y. Chem. ReV. 2004,
1
04, 2127-2198. (b) Fr u¨ hauf, H.-W. Chem. ReV. 1997, 97, 523-596. (c)
Ojima, I.; Tzamarioudaki, M.; Li, Z.; Donovan, R. J. Chem. ReV. 1996, 96,
6
9
35-662. (d) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49-
2.
(
2) (a) Miyanohana, Y.; Chatani, N. Org. Lett. 2006, 8, 2155-2158. (b)
Chatani, N.; Oshita, M.; Tobisu, M.; Ishii, Y.; Murai, S. J. Am. Chem. Soc.
2
003, 125, 7812-7813. (c) Chatani, N.; Inoue, H.; Kotsuma, T.; Murai, S.
J. Am. Chem. Soc. 2002, 124, 10294-10295. (d) Inoue, H.; Chatani, N.;
Murai, S. J. Org. Chem. 2002, 67, 1414-1417.
(3) Lee, S. I.; Sim, S. H.; Kim, S. M.; Kim, K.; Chung, Y. K. J. Org.
Chem. 2006, 71, 7120-7123.
4) (a) Nishizawa, M.; Takenaka, H.; Hayashi, Y. Chem. Lett. 1983,
459-1460. (b) Nishizawa, M.; Takenaka, H.; Nishide, H.; Hayashi, Y.
Tetrahedron Lett. 1983, 24, 2581-2584.
(
1
10.1021/jo701591e CCC: $37.00 © 2007 American Chemical Society
9
818
J. Org. Chem. 2007, 72, 9818-9821
Published on Web 11/14/2007

Terminal allenynes (entries 1-3) were found to serve as good
substrate. This is quite similar to the results of GaCl3- and Au-
3
(
I)-catalyzed reactions. However, it is in sharp contrast to
previously reported results of the Mo-catalyzed RCM of
9
allenynes, where no reaction occurred with allenynes bearing
the allenic terminus unsubstituted. Allenynes 4a-6a having a
substituent on the 3 position (entries 4 and 5) or having a
substituent on the 5 position (entry 6) were also good substrates.
Treatment of an allenyne (7a) bearing a monosubstituent at the
allenic terminal carbon resulted in 7b in 48% yield. Interestingly,
allenynes with disubstituents at the allenic terminal carbon
showed a different reaction behavior depending upon the
substituents. Allenyne 8a (entry 7) afforded a mixture of 8b
and 8d in 34 and 26% yields, respectively. Reaction of allenyne
FIGURE 1. X-ray structure of 1b (30% thermal ellipsoid).
TABLE 1. Hg-Catalyzed Cycloisomerization of Allenynes to
a
Allenenes
9a bearing a cyclic butyl group gave only 9b as the sole product,
although the yield was low (22%). However, treatment of
allenyne 10a with a cyclohexyl group afforded 10d as the sole
1
0
product in 46% yield.
Unfortunately, reactions of the substrates shown in Scheme
gave no reaction products under the conditions described here.
1
T
Interestingly, hydration of alkyne 15d was observed in the
reaction of 15a, although the yield was quite poor (8%).
b
entry
catalyst
solvent (h)
yield (%)
1
2
3
4
5
6
7
8
10 mol % Hg(CN)2
10 mol % HgCl2
CH3CN 24
CH3CN 24 73(1a)/(trace)(1c)
CH3CN 24 40(1a)/20(1c)
c
SCHEME 1. Unreactive Substrates for Hg(OTf) -Catalyzed
Cycloisomerization of Allenynes
2
10 mol % Hg(OAc)2
10 mol % Hg(OTf)2
5 mol % Hg(OTf)2
10 mol % Hg(OTf)2
10 mol % Hg(OTf)2
CH3CN
1
70(1b)
CH3CN 24 38(1b)
THF
CH2Cl2
24 77(1a)
24 33(1b)
10 mol % Hg(OTf)2 + CH3CN 18 38(1a)/18(1b)/18(1c)
d
20 mol % TMU
9
0
1
20 mol % Tf2O
10 mol % Cu(OTf)2
10 mol % M(OTf)3
CH3CN 24
CH3CN 24 80(1a)/8(1b)
CH3CN 24
c
1
1
c
(M ) Yb, Sc)
a
1
a (0.4 mmol) in 2 mL of CH3CN was added dropwise to the 1 mL
solution of 10 mol % of Hg(OTf)2. Isolated yield. No reaction. d TMU
b
c
)
tetramethylurea.
8
When allenyne 1a-d with the alkyne terminus deuterated was
used, the deuterium was labeled at the 1 position of the produced
allenene (eq 3). The same deuterated reaction product was also
observed in the GaCl3-catalyzed cycloisomerization of allenynes.
When allenyne 8a-d with the deuterated allenene was used, a
mixture of the deuterated allenene 8b-d and triene 8d-d was
obtained (eq 4).
yield for 1b). Recently, Nishizawa reported that the Hg(OTf)2-
TMU complex showed effective catalytic activity for the
hydration of terminal alkynes and cyclization. Thus, we used
the Hg(OTf)2/TMU system as a catalyst. After 18 h of reaction
time, a mixture of 1b and 1c (18 and 18%, respectively) was
obtained with a recovery of the reactant (38%). When Cu(OTf)2
was used as a catalyst, only 8% of 1b was isolated with 80%
recovery of the reactant. Strangely, no noticeable increase in
the yield was found, although 1 equiv of Cu(OTf)2 was used.
Disappointingly, neither Yb(OTf)3 nor Sc(OTf)3 was active as
a catalyst. Thus, the cycloisomerization of 1a to 1b was unique
to Hg(OTf)2.
With this result in mind, we screened other allenynes in the
presence of a catalytic amount of Hg(OTf)2 in acetonitrile. The
results are summarized in Table 2. The reactivity of Hg(OTf)2
was slightly dependent upon the freshness of Hg(OTf)2.
However, most of the reactions went to completion within 2 h.
(8) (a) M e´ nard, D.; Vidal, A.; Barthomeuf, C.; Lebreton, J.; Gosselin,
P. Synlett 2006, 57-60. (b) Imagawa, H.; Fujikawa, Y.; Tsuchihiro, A.;
Kinoshita, A.; Yoshinaga, T.; Takao, H.; Nishizawa, M. Synlett 2006, 639-
6
41. (c) Nishizawa, M.; Takao, H.; Yadav, V. K.; Imagawa, H.; Sugihara,
(9) Murakami, M.; Kadowaki, S.; Matsuda, T. Org. Lett. 2005, 7, 3953-
3956.
(10) The migrations of H on the allenic substituents were also observed
in other literature. See: Matsuda, T.; Kadowaki, S.; Goya, T.; Murakami,
M. Synlett 2006, 575-578.
T. Org. Lett. 2003, 5, 4563-4565. (d) Nishizawa, M.; Skwarczynski, M.;
Imagawa, H.; Sugihara, T. Chem. Lett. 2002, 12-13. (e) Nishizawa, M.;
Yadav, V. K.; Skwarczynski, M.; Takao, H.; Imagawa, H.; Sugihara, T.
Org. Lett. 2003, 5, 1609-1611.
J. Org. Chem, Vol. 72, No. 25, 2007 9819

TABLE 2. Hg(OTf)2-Catalyzed Cycloisomerization of Allenynes to Allenenesa
a
Allenyne (0.4 mmol) in 2 mL of CH3CN was added dropwise to the 1 mL solution of 10 mol % of Hg(OTf)2. b Isolated yield.
SCHEME 2. Proposed Mechanism for Hg-Catalyzed Cycloisomerization of Allenynes
A general mechanistic view has so far remained elusive.
However, on the basis of our experimental observations and
the previous studies,2c,3,11 a plausible reaction mechanism is
shown in Scheme 2. A π-complexation of Hg(OTf)2 with alkyne
generates I as a major intermediate and II as a minor
intermediate. The intermediate II was transformed into I in the
presence of generated HOTf. Vinylmercuration (III) followed
by demercuration provides V, eventually leading to the genera-
tion of b. When a substituent on the allenic terminal carbon
has protons which can be easily deprotonated, the reaction path
will follow the other pathway to the intermediates VI and VII,
and finally to d.
effective for terminal 1,6-allenynes: allenenes were obtained
in reasonable to high yields. However, for allenynes with
disubstituents at the allenic terminal carbon, two mechanistic
pathways (to triene vs allenene) operate and the pathway is
dependent upon the substituents.
Experimental Section
General Procedure for Hg(OTf)
tion of Allenynes. A solution of Hg(OTf)
2
-Catalyzed Cycloisomeriza-
in CH CN (0.04 M, 1
2
3
mL) was transferred to a flame-dried 10 mL Schlenk flask. To the
flask was added slowly a solution of allenyne (0.4 mmol) in 1 mL
of CH
mixture was quenched by the addition of an aqueous NaCl-
NaHCO solution. The organic layer was extracted with Et O, dried
over anhydrous MgSO , and concentrated. Flash column chroma-
3
CN. The reaction mixture was stirred for 1 h. The reaction
In summary, Hg(OTf)2 is also an efficient catalyst for the
cycloisomerization of allenynes. The catalytic system is quite
3
2
4
tography on a silica gel column using hexane and EtOAc gave the
product.
(
11) (a) Soriano, E.; Marco-Contelles, J. J. Org. Chem. 2005, 70, 9345-
353. (b) Bruneau, C. Angew. Chem., Int. Ed. 2005, 44, 2328-2334. (c)
Oi, S.; Tsukamoto, I.; Miyano, S.; Inoue, Y. Organometallics 2001, 20,
704-3709.
9
1c: 1H NMR (CDCl
3
, 300 MHz) δ 2.46 (s, 6H), 3.91 (m, 4H),
3
4.16 (s, 4H), 4.80 (m, 4H), 5.06 (m, 2H), 7.29 (d, J ) 8.0 Hz, 4H),
9
820 J. Org. Chem., Vol. 72, No. 25, 2007

7
3
.73 (d, J ) 8.0 Hz, 4H) ppm; 13C NMR (CDCl
6.5, 45.9, 76.8, 85.6, 99.1, 116.3, 128.2, 129.6, 136.6, 143.7, 209.9
3
, 75 MHz) δ 21.8,
(m, 2H), 7.77 (d, J ) 8.0 Hz, 2H) ppm; 13C NMR (CDCl
, 75
3
MHz) δ 21.8, 35.8, 47.0, 74.3, 76.1, 79.2, 99.8, 126.6, 127.6, 128.2,
128.8, 129.7, 133.3, 135.5, 143.9, 210.2 ppm. Exact mass for
C H N S O (EI): calcd 337.1136, found 337.1137.
ppm. Exact mass for C28
found 723.1287.
H
28Hg
1
N
2
S
2
O
4
(FAB+): calcd 723.1276,
a-d: 1H NMR (CDCl
, 300 MHz) δ 1.66 (s, 6H), 2.00 (t, J )
3
20
19
1
1
2
8
5d: 1H NMR (CDCl
3
, 300 MHz) δ 2.09 (s, 3H), 2.36 (s, 3H),
1
2
.3 Hz, 1H), 2.41 (s, 3H), 3.79 (s, 2H), 4.15 (d, J ) 2.3 Hz, 2H),
2
1
.77 (m, 2H), 3.29 (m, 2H), 3.76 (m, 2H), 4.64 (m, 2H), 4.83 (m,
13
7
.28 (d, J ) 8.0 Hz, 2H), 7.72 (d, J ) 8.0 Hz, 2H) ppm; C NMR
, 75 MHz) δ 20.4, 21.7, 35.7, 46.7, 73.6, 76.7, 97.3, 127.8,
18 1 1 1 2
29.6, 136.3, 143.6, 204.1 ppm. Exact mass for C16H D N S O
13
H), 7.22 (d, J ) 8.0 Hz, 2H), 7.68 (d, J ) 8.0 Hz, 2H) ppm;
, 75 MHz) δ 21.6, 30.3, 42.2, 43.5, 47.9, 76.5, 86.0,
27.3, 129.8, 136.4, 143.5, 207.0, 209.4 ppm. Exact mass for
(HRFAB): calcd 294.1164, found 294.1166. IR
C
(CDCl
3
NMR (CDCl
3
1
1
C
(
(EI): calcd 290.1199, found 290.1195.
15
H
19
-1
N
1
S
1
O
3
8
d: 1H NMR (CDCl
3
, 300 MHz) δ 1.75 (s, 3H), 2.42 (s, 3H),
cm ) 2256 (m), 1705 (s), 1632 (br), 1459 (m).
3
5
8
4
1
.80 (d, J ) 3.6 Hz, 2H), 3.84 (s, 2H), 4.70 (s, 1H), 4.95 (s, 1H),
.01 (m, 2H), 5.51 (m, 1H), 7.28 (d, J ) 8.0 Hz, 2H), 7.67 (d, J )
.0 Hz, 2H) ppm; 1 C NMR (CDCl
9.7, 113.8, 115.5, 121.2, 128.1, 129.8, 133.8, 135.8, 140.8, 143.0,
43.8 ppm. Exact mass for C16 (EI): calcd 289.1136,
3
Acknowledgment. This work was supported by the Korea
3
, 75 MHz) δ 21.7, 22.9, 45.7,
Research Foundation grant funded by the Korean Government
(MOEHRD) (R02-2004-000-10005-0 and KRF-2005-070-
C00072) and the SRC/ERC program of MOST/KOSEF (R11-
2005-065). S.H.S. thanks to the BK21 fellowship.
19 1 1 2
H N S O
found 289.1136.
1
2a: 1H NMR (CDCl
3
, 300 MHz) δ 1.71 (m, 3H), 1.96 (t, J )
2
4
.4 Hz, 1H), 2.42 (s, 3H), 3.78 (m, 2H), 4.11 (d, J ) 2.4 Hz, 2H),
.68 (m, 2H), 7.28 (d, J ) 8.0 Hz, 2H), 7.73 (d, J ) 8.0 Hz, 2H)
Supporting Information Available: Detailed experimental
13
ppm; C NMR (CDCl
3
, 75 MHz) δ 16.0, 21.8, 35.8, 50.1, 73.8,
1
13
procedures, new characterization data, H and C NMR spectra of
all compounds, and crystallographic data (CIF) of 1b. This material
is available free of charge via the Internet at http://pubs.acs.org.
7
5.4, 76.8, 93.5, 128.0, 129.7, 136.2, 143.7, 207.8 ppm. Exact mass
for C15 (EI): calcd 275.0980, found 275.0980.
3a: 1H NMR (CDCl
, 300 MHz) δ 1.93 (m, 1H), 2.44 (s, 3H),
.01(m, 2H), 4.30 (s, 2H), 5.13 (s, 2H), 7.24-7.37 (m, 5H), 7.52
17 1 1 2
H N S O
1
3
4
JO701591E
J. Org. Chem, Vol. 72, No. 25, 2007 9821