Cationic Rh(I) catalyst in fluorinated alcohol: Mild intramolecular cycloaddition reactions of ester-tethered unsaturated compounds

Article abstract of DOI:10.1021/jo060827x

In fluorinated alcohols, the cationic Rh(I) species, which is derived from [Rh(COD)Cl]₂ and AgSbF₆, efficiently catalyzed intramolecular [4+2] cycloaddition reactions of ester-tethered 1,3-diene-8-yne derivatives. The catalytic syste

Full text of DOI:10.1021/jo060827x

Cationic Rh(I) Catalyst in Fluorinated Alcohol: Mild
Intramolecular Cycloaddition Reactions of Ester-Tethered
Unsaturated Compounds
Akio Saito,* Takamitsu Ono, and Yuji Hanzawa*
Laboratory of Organic Reaction Chemistry, Showa Pharmaceutical UniVersity,
3-3165 Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan
hanzaway@ac.shoyaku.ac.jp
ReceiVed April 19, 2006
In fluorinated alcohols, the cationic Rh(I) species, which is derived from [Rh(COD)Cl]2 and AgSbF6,
efficiently catalyzed intramolecular [4+2] cycloaddition reactions of ester-tethered 1,3-diene-8-yne
derivatives. The catalytic system was also effective in intramolecular [5+2] cycloaddition reactions of
ester-tethered ω-alkynyl vinylcyclopropane compounds.
SCHEME 1
Introduction
The intramolecular cycloaddition reaction provides a straight-
forward procedure for the potentially stereocontrolled construc-
tion of bicyclic and polycyclic compounds, and the reaction has
been applied to the synthesis of a variety of molecules including
natural products.1 In intramolecular cycloaddition, the reactivity
of the substrate and the stereochemical outcome of the product
are strongly influenced by the tethering chain which links
reaction sites. For example, ester-tethered diene-ene compounds
often show low reactivity in the intramolecular Diels-Alder
(IMDA) reaction. The reduced reactivity of the ester-tethered
compound is due to the difficulty in adopting a cisoid form, in
which the diene and the dienophile are in close proximity.2,3
Such a conformational disadvantage is explained by the steric
repulsion between the two substituents (R1 and R2) and by the
dipole-dipole repulsion between the carbonyl and ethereal
oxygen groups (Scheme 1).4 To overcome this conformational
difficulty, the use of a polar solvent5 or the modification of the
tether of the substrates from ester to acetal6 or to hydroxamate7
has been reported. These methodologies, however, have draw-
backs such as limited availability or requiring laborious synthesis
(2) Reviews on intramolecular Diels-Alder reactions: (a) Ciganek, E.
In Organic Reactions; Dauben, W. G., Ed.; John Wiley & Sons: New York,
1984; Vol. 32, pp 1-374. (b) Craig, D. Chem. Soc. ReV. 1987, 16, 187. (c)
Roush, W. R. In AdVances in Cycloaddition; Curran, D. P., Ed.; JAI Press:
Greenwich, CT, 1990; Vol. 2, pp 91-146. (d) Roush, W. R. In Compre-
hensiVe Organic Synthesis; Trost, B. M., Fleming, I. Eds.; Pergamon
Press: Oxford, U.K., 1991; Vol. 5, pp 513-550.
(3) For recent examples on IMDA reactions of ester-tethered triene
compounds, see: (a) Jung, M. E.; Huang, A.; Johnson, T. W. Org. Lett.
2000, 2, 1835. (b) Kim, P.; Nantz, M.; Kurth, M. J.; Olmsteas, M. M. Org.
Lett. 2000, 2, 1831. (c) Jones, G. A.; Paddon-Row, M. N.; Sherburn, M.
S.; Turner, C. I. Org. Lett. 2002, 4, 3789. (d) Turner, C. I.; Wong, L. S.-
M.; Turner, P.; Paddon-Row, M. N.; Sherburn, M. S. Chem.-Eur. J. 2002,
8, 739. (e) Turner, C. I.; Paddon-Row, M. N.; Moran, D.; Payne, A. D.;
Sherburn, M. S.; Turner, P. J. Org. Chem. 2005, 70, 5561.
* To whom correspondence should be addressed. Tel./fax: Fax: +81 (0)42
721 1569.
(1) (a) Fallis, A. G. Acc. Chem. Res. 1999, 32, 464-474. (b) Suzuki,
Y.; Murata, T.; Takao, K.: Tadano, K. Synth. Org. Chem., Jpn. 2002, 60,
679-689. (c) Takao, K.; Murata, T.; Munakata, R.; Tadano, K. Chem. ReV.
2005, 105, 4779-4807.
(4) (a) Cain, D.; Pawar, D. M.; Stewart, M.; Billings, H., Jr.; Noe, E. A.
J. Org. Chem. 2001, 66, 6092. (b) Review on the conformation and
stereoelectric effect of ester compounds; see: Deslongchamps, P. in
Stereoelectric Effects in Organic Chemistry; Pergamon Press: Oxford, 1983;
pp 54-100.
10.1021/jo060827x CCC: $33.50 © 2006 American Chemical Society
Published on Web 07/27/2006
J. Org. Chem. 2006, 71, 6437-6443
6437

Saito et al.
SCHEME 2
of reactants. It should be mentioned that a Lewis acid, which is
effective for intermolecular Diels-Alder reactions, does not
necessarily work well in the IMDA reactions of the ester-
tethered substrates.3a,8
Recently, we reported that a novel bidentate Lewis acid,
bisaluminated triflic amide TfN[Al(Me)Cl]2, efficiently pro-
motes the IMDA reaction of 1,7,9-decatrienoate derivatives.9
This bidentate Lewis acid, however, essentially requires a
stoichiometric or a substoichiometric amount for the reaction.
We assumed that ester-tethered unsaturated compounds would
take a preferable cisoid form through the coordination of
transition metal to carbon-carbon unsaturated bonds (Scheme
1), and we reported in a communication that intramolecular
[4+2] cycloaddition reactions of ester-tethered 1,3-diene-8-yne
compounds can be efficiently catalyzed by the cationic Rh(I)
complex in fluorinated alcohols.10
TABLE 1. [4+2] Cycloaddition of Sorbatesa
Although the usefulness of Rh(I) catalysts has been reported
in regard to the formation of medium-sized ring compounds
through cycloaddition such as [4+2] cycloadditions of alkyne-
diene compounds11,12 and/or [5+2] cycloadditions of alkyne-
vinylcyclopropane compounds,13 there has been no report about
transition-metal-catalyzed intramolecular cycloadditions of ester-
tethered alkyne-unsaturated compounds. The efficiency of
cationic Rh(I) encouraged us to examine the scope of [4+2]
cycloadditions of ester-tethered ω-alkynyl dienes as well as the
application to [5+2] cycloadditions of ester-tethered ω-alkynyl
vinylcyclopropane derivatives. In this paper, we describe in
detail the mild intramolecular cycloadditions of such ester-
tethered substrates catalyzed by cationic Rh(I) in fluorinated
alcohol media (Scheme 2).
entry
1
R
solvent
time (h)
3 (%)b
1c
2c
3c
4c,d
5
1a
1b
1c
1d
1a
1b
1c
1d
Me
H
Ph
HFIP
HFIP
TFE
5
1
27
48
2
1
24
24
3a 67
3b 81
3c 63
3d 51
3a 84
3b 81
3c 77
3d 60
tBuMe2Si
TFE
Me
H
Ph
HFIP
HFIP
TFE
6
7
8d
tBuMe2Si
TFE
a Immediately after mixing [Rh(COD)Cl]2 with AgSbF6, 1 was added,
unless otherwise noted. b Isolated yield. c [Rh(COD)Cl]2 was treated with
AgSbF6 for 30 min prior to the addition of 1. d Reaction temperature:
50 °C.
Results and Discussion
[4+2] Cycloaddition Reaction. The cationic Rh(I)-catalyzed
[4+2] cycloaddition reactions of sorbates 1a-d are shown in
Table 1. In the presence of the cationic Rh(I) catalyst generated
in situ by mixing 5 mol % of [Rh(COD)Cl]2 and 13 mol % of
AgSbF6 in hexafluoroisopropanol (HFIP) for 30 min, the
reaction of 1a proceeded in HFIP at room temperature for 5 h
to give the corresponding cycloadduct 2a. Because the initially
formed 2a was readily oxidized to benzofuranone 3a during
the workup and was difficult to be separated from 3a, the crude
reaction mixture was directly treated with DDQ. Thus, after
the DDQ oxidative workup, 3a was isolated in 67% yield (entry
1). In addition to the reaction of methyl-substituted 2a, the
formation of hydrogene-substituted 2b was efficiently achieved
in HFIP, and the subsequent DDQ oxidative workup gave 3b
in 81% yield (entry 2). Interestingly, for the reaction of phenyl-
or tert-butyldimethylsilyl-substituted compound 1c or 1d, trif-
luoroethanol (TFE) was found to be more suitable than HFIP
(entries 3 and 4). Furthermore, it turns out that the yield of 3
was improved by the addition of substrate 1 immediately after
mixing [Rh(COD)Cl]2 with AgSbF6 (see Experimental Section).
A similar observation in regard to the preparation of the cationic
Rh catalyst has been reported to provide good results in the
cycloisomerization of 1,6-enynes.14 Thus, 3a was obtained in
84% yield after the DDQ oxidative workup and 3c or 3d was
obtained in a good yield (entries 5-8). Because the sole use of
a catalytic amount of [Rh(COD)Cl]2 or AgSbF6 did not yield
(5) (a) Jung, M. E.; Gervay, J. J. Am. Chem. Soc. 1989, 111, 5469. (b)
Jung, M. E. Synlett 1999, 843. (c) Yanai, H.; Saito, A.; Taguchi, T.
Tetrahedron 2005, 61, 7987. (d) See also intramolecular radical addition
of allyl R-iodoalkanoates in water: Yoshimitsu, H.; Nakamura, T.;
Shinokubo, H.; Oshima, K.; Omote, K.; Fujimoto, H. J. Am. Chem. Soc.
2000, 122, 11041.
(6) (a) Taillefumier, C.; Chapleur, Y.; Bayeul, D.; Aubry, A. J. Chem.
Soc., Chem. Commun. 1995, 937. (b) Taillefumier, C.; Chapleur, Y. Can.
J. Chem. 2000, 78, 708.
(7) (a) Ichikawa, T.; Senzaki, M.; Kadoya, R.; Morimoto, T.; Miyake,
N.; Izawa, M.; Saito, S.; Kobayashi, H. J. Am. Chem. Soc. 2001, 123, 4607.
(b) Ishikawa, T.; Kudoh, T.; Saito, S. J. Synth. Org. Chem. 2003, 61, 1186.
(8) Toyota, M.; Wada, Y.; Fukumoto, K. Heterocycles 1993, 35, 111.
(9) (a) Saito, A.; Ito, H.; Taguchi, T. Org. Lett. 2002, 4, 4619. (b) Saito,
A.; Yanai, H.; Taguchi, T. Tetrahedron 2004, 60, 12239. (c) Saito, A.;
Yanai, H.; Taguchi, T. Tetrahedron Lett. 2004, 45, 9439.
(10) A preliminary communication: Saito, A.; Ono, T.; Takahashi, A.;
Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 2006, 47, 891.
(11) (a) Jolly, R. S.; Luedtke, G.; Sheehan, D.; Livinghouse, T. J. Am.
Chem. Soc. 1990, 112, 4965. (b) Wender, P. A.; Jenkins, T. E.; Suzuki, S.
J. Am. Chem. Soc. 1995, 117, 1843. (c) Gilbertson, S. R.; Hoge, G.; Genov,
D. G. Tetrahedron Lett. 1998, 39, 2075. (d) O’Mahony, D. J. R.; Belanger,
D. B.; Livinghouse, T. Synlett 1998, 443. (e) Motoda, D.; Kinoshita, H.;
Shinokubo, H.; Oshima, K. Angew. Chem., Int. Ed. 2004, 43, 1860. (f)
Lee, S. I.; Park, S. Y.; Park, J. H.; Jung, I. G.; Choi, S. Y.; Chung, Y. K.
J. Org. Chem. 2006, 71, 91.
(13) (a) Wender, P. A.; Takahashi, H.; Witulski, B. J. Am. Chem. Soc.
1995, 117, 4720. (b) Wender, P. A.; Rieck, H.; Fuji, M. J. Am. Chem. Soc.
1998, 120, 10976. (c) Wender, P. A.; Dyckman, A. J.; Husfeld, C. O.;
Scanio, M. J. C. Org. Lett. 2000, 2, 1609. (d) Wender, P. A.; Gamber, G.
G.; Scanio, M. J. C. Angew. Chem., Int. Ed. 2001, 40, 3895. (e) Wender,
P. A.; Barzilay, C. M.; Dyckman, A. J. J. Am. Chem. Soc. 2001, 123, 179.
(f) Wender, P. A.; Gamber, G. G.; Hubbard, R. D.; Zhang, L. J. Am. Chem.
Soc. 2002, 124, 2876. (g) Wender, P. A.; Pedersen, T. M.; Scanio, M. J. C.
J. Am. Chem. Soc. 2002, 124, 15154. (h) Wegner, H. A.; de Meijere, A.;
Wender, P. A. J. Am. Chem. Soc. 2005, 127, 6530.
(12) Ni-catalyzed intramolecular [4+2] cycloaddition reaction of diene-
alkene; see: Wender, P. A.; Jenkins, T. E. J. Am. Chem. Soc. 1989, 111,
6432.
(14) (a) Cao, P.; Wang, B.; Zhang, X. J. Am. Chem. Soc. 2000, 122,
6490. (b) Lei, A.; He, M.; Zhang, X. J. Am. Chem. Soc. 2002, 124, 8198.
(c) He, M.; Lei, A.; Zhang, X. Tetrahedron Lett. 2005, 46, 1823.
6438 J. Org. Chem., Vol. 71, No. 17, 2006

Intramolecular Cycloadditions of Ester-Tethered Compounds
SCHEME 3. [4+2] Cycloaddition of Sorbates 1a,b Followed
by Silica Gel Workup
SCHEME 4. Synthesis of Tricyclic Lactone
TABLE 2. [4+2] Cycloadditions of Propiolates
TABLE 3. [5+2] Cycloadditions of â-Cyclopropylacrylatesa
entry
5
R
solvent
TFE
HFIP
HFIP-CH2Cl2
TFE
time (h)
6 (%)a
time (h)
1
2
3
4
5a
5a
5a
5b
5c
5a
5b
5c
H
H
H
Me
Ph
H
Me
Ph
1
1
1
1
2
12
24
3
6a quant.
6a 11
6a 73
6b 98
6c quant.
6a 94
entry
7
R
addition
total
9 (%)b
1
7a
7a
7a
7a
7b
7c
7d
Me
Me
Me
Me
H
3
3
5
24
2
2
9a 84
9a 80
9a 50
9a -f
9b 73
9c 87
9d 70
2c
3d,e
4
5
TFE
6b
7b,c
8b
toluene
xylene
xylene
6b 96
6c 98
5
6
7
1
1
1
CH2OMe
n-Bu
a Isolated yield. b No catalyst under refluxing conditions. c Ref 15a.
3
a Immediately after mixing [Rh(COD)Cl]2 with AgSbF6, 7 was added,
unless otherwise noted. b Isolated yield. c [Rh(COD)Cl]2 was treated with
AgSbF6 in the presence of 7. d [Rh(COD)Cl]2 was treated with AgSbF6
for 30 min prior to the addition of 7. e Solvent: TFE. f Recovery of 7a:
23%.
2a, the cationic Rh catalyst in the present reaction is suggested
to be an active catalyst. It is worth noting that the addition of
a phosphine ligand (Ph3P, dppb, or ((CF3)2CHO)3P) to the
cationic Rh catalyst or the thermal reaction of 1a in TFE or
HFIP at refluxing temperature without the use of the catalyst
did not give a cyclized product.15
As shown in the [4+2] cycloaddition reaction of 1a or 1b
(Scheme 3), the addition of silica gel to the reaction mixture
after the consumption of the starting ester (by TLC) gave
conjugated dienelactone 4a or 4b, which was derived from
initially formed 2a or 2b through isomerization.
In the [4+2] reaction of propiolate 5, the cationic Rh(I)-
TFE system showed particular efficiency (Table 2). That is,
treatment of propiolate 5a with the cationic Rh(I) catalyst in
TFE at room temperature for 1 h afforded the corresponding
adduct 6a in quantitative yield (entry 1). In contrast to the case
of sorbate 1, the use of HFIP solvent lowered the yield of 6a
because of the decomposition of 5a (entries 2 and 3). In the
cases of methyl- and phenyl-substituted compounds 5b and 5c,
TFE was found to be an efficient solvent, and adducts 6b and
6c were obtained in excellent yields, respectively (entries 4 and
5). It should be noted that the thermal IMDA reactions of 5 in
the absence of the cationic Rh(I) catalyst showed excellent
results for the formation of 6. It, however, required a higher
temperature and longer time to complete the reaction (by TLC)
(entries 6-8).16 In all cases examined, each adduct 6a-c was
obtained as a single isomer with illustrated trans stereochemistry.
On the basis of the described procedure, tricyclic lactones
3e and 6d were prepared in good yields (Scheme 4). Thus, 3e
was obtained in 90% yield after the cycloaddition of 1e in HFIP
at 50 °C for 4 h and the subsequent DDQ oxidative workup,
and 6d was obtained in 96% yield in TFE at room temperature
for 3 h.
[5+2] Cycloaddition Reaction. The Rh(I)-catalyzed inter-
or intramolecular [5+2] cycloaddition reactions of vinylcyclo-
propane and alkyne compounds have been reported to give
seven-membered ring compounds.13 To our knowledge, how-
ever, no successful examples of the intramolecular reaction of
the ester-tethered substrates have been reported. The established
efficiency of the cationic Rh(I) species in fluorinated alcohol
for the [4+2] cycloaddition of ester-tethered diene-yne com-
pounds encouraged us to examine the [5+2] cycloaddition of
â-cyclopropylacrylates 7 (Table 3). As expected, the cationic
Rh(I) catalyst prepared in situ from [Rh(COD)Cl]2 and AgSbF6
was efficient in bringing about cycloaddition, and lactone 9a
was obtained in 84% yield from 7a in HFIP at room temperature
for 5 h (entry 1). The obtained 9a would be generated by the
isomerization of initially formed [5+2] adduct 8a during the
workup. The premixing of [Rh(COD)Cl]2 and AgSbF6 for 30
min prior to the addition of 2a decreased the yield of 9a to
50% (entry 2). The reaction of 7a in TFE did not give the
cyclized product because of alcoholysis of the starting material
(16) Thermal IMDA reactions of 2,4-pentadienyl propiolates are known;
see: (a) White, J. D.; Sheldon, B. G. J. Org. Chem. 1981, 46, 2273. (b)
Birtwhistle, D. H.; Brown, J. M.; Foxton, M. W. Tetrahedron 1998, 44,
7309. (c) Turner, C. I.; Williamson, R. M.; Paddon-Row, M. N.; Sherburn,
M. S. J. Org. Chem. 2001, 66, 3963. (d) Pradilla, R. F.; Baile, R.; Tortosa,
S. Chem. Commun. 2003, 2476.
(15) Thermal IMDA reactions of sorbate derivatives require a very high
temperature (200 °C) to give the products; see: (a) Boeckman, R. K., Jr.;
Demko, D. M. J. Org. Chem. 1982, 47, 1789. (b) Martin, S. F.; Williamson,
S. A.; Gist, R. P.; Smith, K. M. J. Org. Chem. 1983, 48, 5170.
J. Org. Chem, Vol. 71, No. 17, 2006 6439

Saito et al.
TABLE 4. [5+2] Cycloadditions of Propiolatesa
entry
10
R
solvent
TFE
HFIP
CH2Cl2
HFIP-CH2Cl2
HFIP-CH2Cl2
HFIP-CH2Cl2
HFIP-CH2Cl2
HFIP-CH2Cl2
time (h)
11 (%)b
1c
2c
3c
4c
5
10a
10a
10a
10a
10a
10b
10c
10d
H
H
H
H
2
2
4
2
1
1
3
3
11a 20
11a 23
11a 12
11a 41
11a 78
11b 97
11c 56
11d 58
H
6
Me
Ph
i-Pr
FIGURE 1. Catalytic cycle of [4+2] cycloaddition.
7d
8d
a Immediately after mixing [Rh(COD)Cl]2 with AgSbF6, 10 was added,
unless otherwise noted. b Isolated yield. c [Rh(COD)Cl]2 was treated with
AgSbF6 for 30 min prior to the addition of 10. d Slow addition (1 h) of 10.
SCHEME 5. [5+2] Cycloaddition of Propiolate 12
SCHEME 6. Cycloisomerization of Propiolate 15
FIGURE 2. Catalytic cycle of [5+2] cycloaddition.
The formation of eight-membered ring-fused lactones by the
[6+2] cycloaddition of propiolate 15 under the present condi-
tions could be considered to be difficult to take place according
to Wender et al.’s observations.17 Thus, an attempted reaction
of 15, by means of the slow addition of a substrate for 2 h at
50 °C and the further stirring for 3 h, did not yield the bicyclic
lactone 17 but afforded the 1,4-dienelactone 16 in 55% yield
as a major product (Scheme 6).
(entry 3). As shown in entries 4-6, the cationic Rh(I)-HFIP
system worked well in the reactions of 7b-d to give 9b-d. In
particular, the slow addition of 7 (0.5 mmol/2 mL in HFIP, 1 h
addition) exerted a preferable effect, and thus terminal alkynyl
compound 9b was obtained in 73% yield at room temperature
for 2 h. Likewise, 9c and 9d were obtained in good yields (9c,
87%; 9d, 70%).
Catalytic Cycles. On the basis of previous reports about the
transition-metal-catalyzed [4+2] cycloadditions of alkyne-diene
compounds12,13 and [5+2] cycloadditions of alkene-vinyl-
cyclopropane compounds,14 plausible catalytic cycles for the
cationic Rh(I)-catalyzed [4+2] and [5+2] reactions of the
present ester-tethered substrates are shown in Figures 1 and 2,
respectively. Thus, in the [4+2] reaction of the ester-tethered
ω-alkynyl diene derivatives (Figure 1), the formation of
metallacyclic intermediate B and the reductive elimination of
Rh(I) gave cycloadducts. As shown in the [5+2] reaction of
the ester-tethered ω-alkynyl vinylcyclopropanes (n ) 1, Figure
2), metallacycle C was converted to metallacycle D through a
cyclopropane ring opening, and bicyclic lactones were obtained
by the reductive elimination of Rh(I). In the case of ω-alkynyl
vinylcyclobutane (n ) 2, Figure 2), because of the difficulty of
the cyclobutane ring opening in intermediate C, â-hydrogen
elimination and subsequent reductive elimination of Rh(I) in
rhodium hydride E occurred to give 1,4-dienelactone. A similar
result was observed in the Ru-catalyzed cycloisomerization of
the alkyne-vinylcyclobutane compound, in which an analogous
catalytic cycle has been proposed.18
The cationic Rh(I)-catalyzed [5+2] cycloaddition of propi-
olates 10 and 12 in an analogous method to 7 was also examined
(Table 4 and Scheme 5). In the reaction of 10a in TFE, which
was a suitable solvent in the [4+2] cycloaddition of propiolate
5, an incomplete reaction took place (by TLC analysis), and
[5+2] adduct 11a was obtained in 20% yield together with the
recovered 10a (Table 4, entry 1). Because the use of HFIP as
a solvent lead to the decomposition of 10a, the reaction in HFIP
scarcely provided an improved result even in the absence of a
catalyst (entry 2). However, the addition of a solution of 10a
in CH2Cl2 to the cationic Rh(I) catalyst prepared in HFIP
increased the yield of 11a up to 41% (entry 4). A better yield
of 11a (78%) was obtained with the addition of a solution of
10a in CH2Cl2 to the catalyst solution immediately after the
preparation of the cationic Rh(I) catalyst (entry 5). The reaction
of Me-substituted 10b also proceeded smoothly under similar
conditions to 10a giving rise to the corresponding adduct 11b
quantitatively (entry 6). In the cases of Ph-substituted 10c and
i-Pr-substituted 10d, by the slow addition of a substrate (0.5
mmol/2 mL in CH2Cl2, 1 h addition), 11c and 11d were obtained
in 56 and 58% yields, respectively (entries 8 and 9). The [5+2]
cycloaddition of propiolate 12 with a MOM-oxy-substituted
cyclopropane ring gave the corresponding adduct 13 in 91%
yield, and the product was converted to ketone 14 quantitatively
(Scheme 5).13c,d
(17) As far as we know, the [6+2] cycloaddition with simple vinylcy-
clobutane has never been successful; see: Wender, P. A.; Correa, A. G.;
Sato, Y.; Sun, R. J. Am. Chem. Soc. 2000, 122, 7815.
(18) Trost, B. M.; Toste, F. D. J. Am. Chem. Soc. 2002, 124, 5025.
6440 J. Org. Chem., Vol. 71, No. 17, 2006

Intramolecular Cycloadditions of Ester-Tethered Compounds
m/z: 149 (M+ + H). FAB-HM Calcd for C9H9O2, 149.0585; found,
149.0620. Anal. Calcd for C9H8O2: C, 72.96; H, 5.44. Found: C,
72.79; H, 5.55.
Although the significant effect of the fluorinated alcohols in
our case is quite notable, no evident advantage to the use of
TFE has been reported in cationic Rh(I)-catalyzed cyclizations
of 1,3-diene-8-yne derivatives.11c At present, we believe that
fluorinated alcohols might increase the cisoid conformation of
an ester-tethered substrate by the polar effect5 and/or accelerate
in the generation and reactivity of the cationic Rh(I) catalyst,
which coordinates to unsaturated bonds.19 Thus, the adverse
effect caused by the addition of phosphine ligands would be a
result of a decrease in the electrophilicity of the cationic Rh(I)
by coordination of the added phosphine ligand to the cationic
metal center.
5-Methyl-4-phenylisobenzofuran-1(3H)-one (3c). White solid.
1
Mp 111-112 °C. IR (neat) ν cm-1; 1760. H NMR (300 MHz,
CDCl3) δ: 2.30 (s, 3H), 5.04 (s, 2H), 7.28-7.27 (m, 2H), 7.40-
7.51 (m, 4H), 7.81 (d, 1H, J ) 7.7 Hz). 13C NMR (75 MHz, CDCl3)
δ: 20.2, 69.2, 123.4, 124.3, 128.1, 128.3, 128.9, 131.4, 136.4, 136.5,
142.8, 146.0, 171.3. FAB-LM m/z: 225 (M+ + H). FAB-HM Calcd
for C15H13O2, 225.0915; found, 225.0915. Anal. Calcd for
C15H12O2: C, 80.34; H, 5.39. Found: C, 80.44; H, 5.46.
4-(tert-Butyldimethylsilyl)-5-methylisobenzofuran-1(3H)-
one (3d). White solid. Mp 135-137 °C. IR (neat) ν cm-1: 1706.
1H NMR (300 MHz, CDCl3) δ: 0.42 (s, 6H), 0.91 (s, 9H), 2.58 (s,
3H), 5.31 (s, 2H), 7.31 (d, 1H, J ) 7.8 Hz), 7.89 (d, 1H, J ) 7.8
Hz). 13C NMR (75 MHz, CDCl3) δ: -1.1, 19.4, 25.4, 26.8, 72.0,
122.5, 126.2, 130.8, 131.8, 152.0, 153.9, 171.4. FAB-LM m/z: 263
(M+ + H). FAB-HM Calcd for C15H23O2Si, 263.1483; found,
263.1467.
Conclusion
For the purpose of the mild intramolecular [4+2] cycload-
dition reaction of ester-tethered alkyne-diene compounds,
which usually requires high temperatures and long reaction times
in the thermal Diels-Alder reactions, the cationic Rh(I) catalyst
in fluorinated alcohols was found to be very efficient. The
cationic Rh(I) was generated in situ from [Rh(COD)Cl]2 and
AgSbF6 in fluorinated alcohols. The cationic Rh(I)-fluorinated
alcohol system was applied to the [5+2] cycloaddition of ester-
tethered substrates giving seven-membered ring fused lactones.
We believe that the present reactions of ester compounds provide
an attractive procedure for the formation of medium-sized ring
fused five-membered lactones under mild conditions. Further
studies on the reaction of ester-tethered enyne compounds and
application to the synthesis of natural products are under way.
General Procedure for the [4+2] Cycloaddition of Sorbate 1
Followed by Treatment with Silica Gel (Scheme 3): 4,5-Dihydro-
5-methylisobenzofuran-1(3H)-one (4a). Under an argon atmo-
sphere, immediately after treatment of a solution of bis(1,5-
cyclooctadiene)-µ,µ′-dichloro dimmer (12.4 mg, 25 µmol) in HFIP
(3 mL) with silver hexafluoroantimonate (0.25 M in CH2Cl2
solution, 0.26 mL, 65 µmol) at room temperature, 1a (82 mg, 0.5
mmol) in HFIP (2 mL) was added. After being stirred for 2 h at
the same temperature, the reaction mixture was treated with silica
gel (2 g) for 1 h. After filtration of the silica gel and concentration
of the filtrate to dryness, the residue was purified by silica gel
column chromatography (hexane/AcOEt ) 6:1) to give 4a (70.3
mg, 75% yield) as a white solid. Mp 44-45 °C. IR (neat) ν cm-1
:
1
1751. H NMR (300 MHz, CDCl3) δ: 1.28 (d, 3H, J ) 7.5 Hz),
2.22 (s, 3H), 2.91-2.96 (m, 1H), 3.44-3.54 (m, 1H), 3.77 (dd,
1H, J ) 8.2, 10.8 Hz), 4.52 (dd, 1H, J ) 8.2, 8.2 Hz), 5.66 (d, 1H,
J ) 9.8 Hz), 5.74 (d, 1H, J ) 9.8 Hz). 13C NMR (75 MHz, CDCl3)
δ: 14.6, 18.3, 36.5, 38.8, 69.6, 119.9, 122.1, 133.7, 150.4, 169.2.
FAB-LM m/z: 165 (M+ + H). FAB-HM Calcd for C10H13O2,
165.0923; found, 165.0915. Anal. Calcd for C10H12O2: C, 71.98;
H, 6.71. Found: C, 71.72; H, 6.73.
Experimental Section
General Information. For details, see Supporting Information.
General Procedure for the [4+2] Cycloaddition of Sorbate 1
Followed by DDQ Oxidation (Table 1): 4,5-Dimethylisoben-
zofuran-1(3H)-one (3a). Under an argon atmosphere, immediately
after treatment of a solution of bis(1,5-cyclooctadiene)-µ,µ′-dichloro
dimmer (12.4 mg, 25 µmol) in HFIP (3 mL) with silver hexafluo-
roantimonate (0.25 M in a CH2Cl2 solution, 0.26 mL, 65 µmol) at
room temperature, 1a (82 mg, 0.5 mmol) in HFIP (2 mL) was
added. After being stirred for 2 h at the same temperature, the
reaction mixture was diluted with ether and filtered through a Celite
pad. After concentration of the filtrate to dryness, to a solution of
the residue in toluene (5 mL) was added 2,3-dichloro-5,6-dicyano-
p-benzoquinone (113 mg, 0.5 mmol). After being stirred at room
temperature for 1 h, the reaction mixture was quenched by saturated
NaHCO3 and extracted with AcOEt. The organic layer was washed
with brine and dried over MgSO4, and subsequent purification by
silica gel column chromatography (hexane/AcOEt ) 6:1) gave 3a
(60.0 mg, 84% yield) as a white solid. Mp 126-128 °C. IR (neat)
ν cm-1: 1758. 1H NMR (300 MHz, CDCl3) δ: 2.15 (s, 3H), 2.32
(s, 3H), 5.13 (s, 2H), 7.23 (d, 1H, J ) 7.7 Hz), 7.53 (d, 1H, J )
7.7 Hz). 13C NMR (75 MHz, CDCl3) δ: 14.5, 19.6, 69.0, 122.6,
122.9, 130.5, 130.8, 143.4, 145.8, 171.5. FAB-LM m/z: 163 (M+
+ H). FAB-HM calcd for C10H11O2, 163.0761; found, 163.0759.
Anal. Calcd for C10H10O2: C, 74.06; H, 6.21. Found: C, 74.09; H,
6.21.
3a,4-Dihydro-4,5-dimethylisobenzofuran-1(3H)-one (4b). White
solid. Mp 41-42 °C. IR (neat) ν cm-1: 1720. 1H NMR (300 MHz,
CDCl3) δ: 1.31 (d, 3H, J ) 7.2 Hz), 2.28-2.36 (m, 1H), 2.63-
2.71 (m, 2H), 4.75 (d, 1H, J ) 18.0 Hz), 4.84 (d, 1H, J ) 18.0
Hz), 5.83 (dd, 1H, J ) 2.8, 9.6 Hz), 6.15 (d, 1H, J ) 9.6 Hz). 13
C
NMR (75 MHz, CDCl3) δ: 20.3, 28.5, 29.4, 71.4, 115.5, 124.1,
135.1, 158.3, 171.6. FAB-LM m/z: 151 (M+ + H). FAB-HM
Calcd for C9H11O2, 151.0750; found, 151.0759. Anal. Calcd for
C9H10O2: C, 73.15; H, 7.37. Found: C, 73.13; H, 7.43.
General Procedure for the [4+2] Cycloaddition Reaction of
Propiolate 6 (Table 2): (3aS*,6R*)-3,3a-Dihydro-6-methyl-
isobenzofuran-1(6H)-one (6a). Under an argon atmosphere, im-
mediately after treatment of a solution of bis(1,5-cyclooctadiene)-
µ,µ′-dichloro dimmer (12.4 mg, 25 µmol) in TFE (3 mL) with silver
hexafluoroantimonate (0.25 M in CH2Cl2 solution, 0.26 mL, 65
µmol) at room temperature, 5a (75 mg, 0.5 mmol) in TFE (2 mL)
was added. After being stirred for 1 h at the same temperature, the
reaction mixture was diluted with ether and filtered through a Celite
pad. Concentration of the filtrate to dryness and subsequent
purification by silica gel column chromatography (hexane/AcOEt
) 6:1) gave 6a (75.0 mg, quant.) as a colorless oil. IR (neat) ν
cm-1: 1760. 1H NMR (300 MHz, CDCl3) δ: 1.26 (d, 3H, J ) 7.7
Hz), 2.99-3.06 (m, 1H), 3.48-3.54 (m, 1H), 3.84 (dd, 1H, J )
8.8, 10.3 Hz), 4.65 (dd, 1H, J ) 8.8, 8.8 Hz), 5.64-5.73 (m, 2H),
6.61 (br. s, 1H). 13C NMR (75 MHz, CDCl3) δ: 20.4, 32.1, 37.1,
70.7, 121.8, 127.5, 133.1, 138.6, 169.5. FAB-LM m/z: 151 (M+
+ H). FAB-HM Calcd for C9H11O2, 151.0781; found, 151.0759.
Anal. Calcd for C9H10O2: C, 71.97; H, 6.71. Found: C, 71.66; H,
6.71.
5-Methylisobenzofuran-1(3H)-one (3b). White solid. Mp 104-
106 °C. IR (neat) ν cm-1: 1716. H NMR (300 MHz, CDCl3) δ:
1
2.50 (s, 3H), 5.27 (s, 2H), 7.29 (s, 1H), 7.33 (d, 1H, J ) 7.7 Hz),
7.79 (d, 1H, J ) 7.7 Hz). 13C NMR (75 MHz, CDCl3) δ: 22.1,
69.4, 122.4, 123.1, 125.4, 130.2, 145.3, 147.1, 171.2. FAB-LM
(19) A rhodium chloride complex such as Willkinson’s catalyst acceler-
ates the [4+2] cycloaddition of 1,3-diene-8-yne or 1,3,8-triene derivatives
in TFE. It has been suggested that TFE enhances the polarizability of the
Rh-Cl bond. See, refs 11a and 11d.
J. Org. Chem, Vol. 71, No. 17, 2006 6441

Saito et al.
(3aS*,6R*)-3,3a-Dihydro-6,7-dimethylisobenzofuran-1(6H)-
one (6b). The 1H NMR spectra of 7b were identical to those
reported in the literature.15a
2.00 (m, 2H), 2.48-2.51 (m, 2H), 2.51-2.63 (m, 2H), 4.68 (s,
2H), 6.07 (d, 1H, J ) 11.7 Hz), 6.16 (dt, 1H, J ) 11.7, 5.3 Hz).13C
NMR (75 MHz, CDCl3) δ: 22.4, 29.8, 31.0, 71.8, 118.0, 123.6,
160.6, 174.1. FAB-LM m/z: 151 (M+ + H). FAB-HM Calcd for
C9H11O2, 151.0746; found, 151.0801. Anal. Calcd for C10H12O2:
C, 71.98; H, 6.71. Found: C, 71.69; H, 6.81.
(3aS*,6R*)-3,3a-Dihydro-6-methyl-7-phenylisobenzofuran-
1(6H)-one (6c). White solid. Mp 95-97 °C. IR (neat) ν cm-1
:
1
1756. H NMR (300 MHz, CDCl3) δ: 0.96 (d, 3H, J ) 7.5 Hz),
3.26-3.37 (m, 1H), 3.60-3.67 (m, 1H), 3.88 (dd, 1H, J ) 8.0,
10.8 Hz), 4.56 (dd, 1H, J ) 8.0, 8.0 Hz), 5.80 (s, 2H), 7.01-7.12
(m, 2H), 7.30-7.36 (m, 3H). 13C NMR (75 MHz, CDCl3) δ: 19.5,
36.0, 39.1, 69.3, 121.4, 121.8, 127.1, 127.7, 127.9, 133.8, 136.5,
150.9, 167.7. FAB-LM m/z: 227 (M+ + H). FAB-HM Calcd for
C15H15O2, 227.1065; found, 227.1072.
5,6-Dihydro-4-(methoxymethyl)-3H-cyclohepta[c]furan-1(4H)-
1
one (9c). Colorless oil. IR (neat) ν cm-1: 1754. H NMR (300
MHz, CDCl3) δ: 1.80-1.90 (m, 1H), 1.95-2.05 (m, 1H), 2.43-
2.50 (m, 2H), 2.92-3.01 (m, 1H), 3.35 (s, 3H), 3.41 (dd, 1H,
J ) 9.0, 7.9 Hz), 3.48 (dd, 1H, J ) 9.0, 5.5 Hz), 4.72 (d, 1H, J )
18.3 Hz), 4.89 (d, 1H, J ) 18.3 Hz), 6.09 (dt, 1H, J ) 11.5, 5.5
Hz), 6.22 (d, 1H, J ) 11.5 Hz). 13C NMR (75 MHz, CDCl3) δ:
25.7, 28.2, 40.3, 58.9, 71.8, 74.8, 118.0, 123.3, 136.6, 161.7, 174.1.
FAB-LM m/z: 195 (M+ + H). FAB-HM Calcd for C11H15O3,
195.1038; found, 195.1021.
Synthesis of Tricyclic Lactone (Scheme 4): Preparations of
3-Cyclohex-1-enyl-acrylic Acid But-2-ynyl Ester (1e) and (2E)-
3-Cyclohexenylallyl But-2-ynoate (5d). For details, see Supporting
Information.
4-Butyl-5,6-dihydro-3H-cyclohepta[c]furan-1(4H)-one (9d).
Preparation of 2,3,5,6,7,8-Hexahydro-1H-cyclopenta[b]naph-
thalen-1-one (3e). In a manner similar to 3a, the [4+2] cycload-
dition of 1e (102 mg, 0.5 mmol) was carried out at 50 °C for 4 h.
After the usual workup, to a solution of the obtained residue in
toluene (5 mL) was added 2,3-dichloro-5,6-dicyano-p-benzoquinone
(113 mg, 0.5 mmol). After being stirred at room temperature for 1
h, the reaction mixture was quenched by saturated NaHCO3 and
extracted with AcOEt. The organic layer was washed with brine
and dried over MgSO4, and subsequent purification by silica gel
column chromatography (hexane/AcOEt ) 6:1) gave 3e (93 mg,
90%) as a white solid. Mp 138-140 °C. IR (neat) ν cm-1: 1752.
1H NMR (300 MHz, CDCl3) δ: 1.68-1.88 (m, 4H), 2.89 (s, 3H),
2.65 (t, 2H, J ) 6.1 Hz), 2.71 (t, 2H, J ) 6.1 Hz), 5.20 (s, 2H),
7.48 (s, 1H). 13C NMR (75 MHz, CDCl3) δ: 14.5, 22.4, 22.8,
27.1, 30.3, 69.1, 122.2, 123.4, 130.3, 138.8, 142.6, 142.8, 171.9.
FAB-LM m/z: 203 (M+ + H). FAB-HM Calcd for C13H15O2,
203.1064; found, 203.1072. Anal. Calcd for C13H14O2: C, 77.20;
H, 6.98. Found: C, 77.32; H, 7.08.
Colorless oil. IR (neat) ν cm-1
:
1724. 1H NMR (300 MHz,
CDCl3) δ: 0.91 (t, 3H, J ) 7.0 Hz), 1.20-1.59 (m, 6H), 1.76-
1.83 (m, 1H), 1.92-2.04 (m, 1H), 2.46-2.47 (m, 2H), 2.61-2.70
(m, 1H), 4.65 (d, 1H, J ) 17.6 Hz), 4.83 (d, 1H, J ) 17.6 Hz),
6.08 (dd, 1H, J ) 11.5, 5.4 Hz), 6.19 (d, 1H, J ) 11.5 Hz).13C
NMR (75 MHz, CDCl3) δ: 13.9, 22.6, 26.1, 27.3, 28.8, 32.4, 38.8,
71.2, 117.8, 122.5, 136.7, 164.4, 174.2. FAB-LM m/z: 207 (M+
+ H). FAB-HM Calcd for C13H19O2, 207.1397; found 207.1353.
Anal. Calcd for C13H18O2: C, 75.69; H, 8.80. Found: C, 75.80; H,
8.66.
General Procedure for the [5+2] Cycloaddition of Propiolate
10 or 12 (Table 4 and Scheme 5): 3,3a,6,7-Tetrahydrocyclo-
hepta[c]furan-1-one (11a). Under an argon atmosphere, im-
mediately after treatment of a solution of bis(1,5-cyclooctadiene)-
µ,µ′-dichloro dimmer (12.4 mg, 25 µmol) in HFIP (3 mL) with
silver hexafluoroantimonate (0.25 M in CH2Cl2 solution, 0.26 mL,
65 µmol) at room temperature, 10a (75 mg, 0.5 mmol) in CH2Cl2
(2 mL) was added. After being stirred for 1 h at the same
temperature, the reaction mixture was diluted with ether and filtered
through a Celite pad. Concentration of the filtrate to dryness and
subsequent purification by silica gel column chromatography
(hexane/AcOEt ) 6:1) gave 11a (58.2 mg, 84%) as a white solid.
Mp 51-54 °C. IR (neat) ν cm-1: 1741. 1H NMR (300 MHz,
CDCl3) δ: 2.09-2.33 (m, 2H), 2.40-2.53 (m, 2H), 3.89 (dd, 1H,
J ) 8.8, 8.8 Hz), 4.04-4.22 (m, 1H), 4.52 (dd, 1H, J ) 8.8, 8.8
Hz), 5.53 (dt, 1H, J ) 10.3, 2.2 Hz), 5.83-5.92 (m, 1H), 6.89 (dd,
1H, J ) 8.8, 3.7 Hz). 13C NMR (75 MHz, CDCl3) δ: 24.8, 26.2,
37.1, 70.5, 128.6, 129.9, 132.2, 140.8, 170.9. FAB-LM m/z: 151
(M+ + H). FAB-HM Calcd for C9H11O2, 151.0766; found,
151.0719. Anal. Calcd for C9H10O2: C, 71.98; H, 6.71. Found: C,
71.79; H, 6.81.
Preparation of 9-Methyl-3a,5,6,7,8,8a-hexahydro-3H-naph-
tho[2,3-c]furan-1-one (6d). In a manner similar to 6a, the [4+2]
cycloaddition of 1e (102 mg, 0.5 mmol) and subsequent usual
workup gave 6d (98 mg, 96%) as a white solid. Mp 41-43 °C. IR
1
(neat) ν cm-1: 1756. H NMR (300 MHz, CDCl3) δ: 1.01 (m,
1H), 1.24 (m, 1H), 1.49 (m, 1H), 1.74-2.17 (m, 3H), 2.32 (s, 3H),
2.32-2.38 (m, 2H), 2.68-2.73 (m, 1H), 3.47-3.56 (m, 1H), 3.73
(dd, 1H, J ) 7.8, 11.2 Hz), 4.46 (dd, 1H, J ) 7.8, 7.8 Hz), 5.40 (q,
1H, J ) 1.7 Hz). 13C NMR (75 MHz, CDCl3) δ: 14.5, 26.4, 26.9,
32.0, 35.5, 38.9, 43.5, 70.4, 114.2, 119.6, 140.8, 148.1, 170.0.
FAB-LM m/z: 205 (M+ + H). FAB-HM Calcd for C13H17O2,
205.1233; found, 205.1229.
General Procedure for the [5+2] Cycloaddition of â-Cyclo-
propylacrylate 7 (Table 3): 5,6-Dihydro-4-methyl-3H-cyclo-
hepta[c]furan-1(4H)-one (9a). Under an argon atmosphere, im-
mediately after treatment of a solution of bis(1,5-cyclooctadiene)-
µ,µ′-dichloro dimmer (12.4 mg, 25 µmol) in HFIP (3 mL) with
silver hexafluoroantimonate (0.25 M in CH2Cl2 solution, 0.26 mL,
65 µmol) at room temperature, 7a (82 mg, 0.5 mmol) in HFIP (2
mL) was added. After being stirred for 3 h at the same temperature,
the reaction mixture was treated with silica gel (2 g) for 1 h.
Filtration of silica gel, concentration of the filtrate to dryness, and
subsequent purification by silica gel column chromatography
(hexane/AcOEt ) 6:1) gave 9a (68.9 mg, 84%) as a colorless
oil. IR (neat) ν cm-1: 1718. 1H NMR (300 MHz, CDCl3) δ:
1.12 (d, 3H, J ) 7.2 Hz), 1.51 (m, 2H), 1.76-1.87 (m, 2H),
2.39-2.43 (m, 1H), 4.55 (d, 1H, J ) 17.6 Hz), 4.75 (d, 1H,
J ) 17.6 Hz), 6.03 (dt, 1H, J ) 11.4, 5.3 Hz), 6.13 (d, 1H, J )
11.4 Hz).13C NMR (75 MHz, CDCl3) δ: 19.3, 27.6, 30.1, 34.3,
70.8, 118.0, 122.3, 136.8, 164.3, 174.2. FAB-LM m/z: 165 (M+
+ H). FAB-HM Calcd for C10H13O2,165.0919; found, 165.0916.
Anal. Calcd for C10H12O2: C, 73.15; H, 7.37. Found: C, 72.93;
H, 7.35.
3,3a,6,7-Tetrahydro-8-methylcyclohepta[c]furan-1-one (11b).
1
IR (neat) ν cm-1: 1743. H NMR (300 MHz, CDCl3) δ: 2.09-
2.39 (m, 2H), 2.27 (s, 3H), 2.68-2.78 (m, 1H), 3.85 (dd, 1H, J )
8.8, 8.8 Hz), 4.11 (m, 1H), 4.48 (dd, 1H, J ) 8.8, 8.8 Hz), 5.53
(ddd, 1H, J ) 11.0, 3.7, 1.5 Hz), 5.67-5.75 (m, 1H). 13C NMR
(75 MHz, CDCl3) δ: 19.8, 24.8, 35.4, 37.8, 70.4, 123.3, 128.3,
130.7, 156.1, 170.1. FAB-LM m/z: 165 (M+ + H). FAB-HM
Calcd for C10H13O2, 165.0915; found, 165.0916. Anal. Calcd for
C10H12O2: C, 73.15; H, 7.37. Found: C, 73.29; H, 7.30.
3,3a,6,7-Tetrahydro-8-phenylcyclohepta[c]furan-1-one (11c).
Colorless oil. IR (neat) ν cm-1: 1745. 1H NMR (300 MHz, CDCl3)
δ: 2.28-2.47 (m, 3H), 2.29-3.08 (m, 1H), 3.90 (dd, 1H, J ) 8.1,
8.1 Hz), 4.21 (m, 1H), 4.50 (dd, 1H, J ) 8.1, 8.1 Hz), 5.40 (ddd,
1H, J ) 11.0, 3.7, 2.2 Hz), 5.74-5.78 (m, 1H), 7.16-7.32 (m,
5H). 13C NMR (75 MHz, CDCl3) δ: 25.4, 36.2, 38.3, 70.2, 125.1,
127.5, 127.8, 127.9, 128.2, 131.1, 139.8, 156.2, 168.5. FAB-LM
m/z: 227 (M+ + H). FAB-HM Calcd for C15H15O2, 227.1069;
found, 227.1084. Anal. Calcd for C15H14O2: C, 79.62; H, 6.24.
Found: C, 79.73; H, 6.38.
5,6-Dihydro-3H-cyclohepta[c]furan-1(4H)-one (9b). Colorless
3,3a,6,7-Tetrahydro-8-isopropylcyclohepta[c]furan-1-one (11d).
oil. IR (neat) ν cm-1: 1741. 1H NMR (300 MHz, CDCl3) δ: 1.92-
Colorless oil. IR (neat) ν cm-1: 1743. 1H NMR (300 MHz, CDCl3)
6442 J. Org. Chem., Vol. 71, No. 17, 2006

Intramolecular Cycloadditions of Ester-Tethered Compounds
δ: 1.00 (d, 3H, J ) 6.8 Hz), 1.05 (d, 3H, J ) 6.8 Hz), 2.06-2.18
(m, 1H), 2.31-2.59 (m, 2H), 3.88 (dd, 1H, J ) 8.5, 8.5 Hz), 4.40
(seotet, 1H, J ) n6.8 Hz), 5.30 (ddd, 1H, J ) 11.4, 4.2, 2.0 Hz),
5.62-5.7 (m, 1H). 13C NMR (75 MHz, CDCl3) δ: 19.6, 20.2, 26.6,
27.1, 27.8, 38.1, 70.6, 123.3, 127.4, 130.6, 165.4, 169.6. FAB-LM
m/z: 193 (M+ + H). FAB-HM Calcd for C12H17O2, 193.1240;
found, 193.1229. Anal. Calcd for C12H17O2: C, 74.97; H, 8.39.
Found: C, 74.75; H, 8.44.
Cycloisomerization of Propiolate 15 (Scheme 6): (3Z)-4-
(Cyclobutylidenemethyl)-3-ethylidenedihydrofuran-2(3H)-one
(16). Under an argon atmosphere, immediately after treatment of a
solution of bis(1,5-cyclooctadiene)-µ,µ′-dichloro dimmer (12.4 mg,
25 µmol) in HFIP (3 mL) with silver hexafluoroantimonate (0.25
M in CH2Cl2 solution, 0.26 mL, 65 µmol) at room temperature, 15
(44.5 mg, 0.25 mmol) in CH2Cl2 (2 mL) was slowly added for 2 h
at 50 °C. After being stirred for 3 h at the same temperature, the
reaction mixture was diluted with ether and filtered through a Celite
pad. Concentration of the filtrate to dryness and subsequent
purification by silica gel column chromatography (hexane/AcOEt
3,3a,6,7-Tetrahydro-5-(methoxymethoxy)cyclohepta[c]furan-
1
1-one (13). Colorless oil. IR (neat) ν cm-1: 1743. H NMR (300
MHz, CDCl3) δ: 2.17-2.33 (m, H), 2.26 (s, 3H), 2.46-2.62 (m,
2H), 3.39 (s, 3H), 3.85 (dd, 1H, J ) 8.2, 8.2 Hz), 3.91-4.05 (m,
1H), 4.51 (dd, 1H, J ) 8.2, 8.2 Hz), 4.73 (br.s, 1H), 4.84 (d, 1H,
J ) 6.6 Hz), 4.92 (d, 1H, J ) 6.6 Hz). 13C NMR (75 MHz, CDCl3)
δ: 19.8, 28.5, 33.9, 35.3, 56.0, 71.0, 93.6, 100.5, 123.7, 154.6,
155.8, 170.2. FAB-LM m/z: 225 (M+ + H). FAB-HM Calcd for
C12H17O4, 225.1114; found, 225.1161.
) 6:1) gave 16 (24.5 mg, 55%) as a colorless oil. IR (neat) ν cm-1
:
1
1716. H NMR (300 MHz, CDCl3) δ: 1.99 (dddd, 2H, J ) 8.0,
8.0, 8.0, 8.0 Hz), 2.42 (dd, 3H, J ) 7.4, 2.8 Hz), 2.65-2.73 (m,
4H), 3.60-3.65 (m, 1H), 4.83 (dd, 1H, J ) 8.7, 8.7 Hz), 4.39 (dd,
1H, J ) 8.7, 8.7 Hz), 4.93 (m, 1H), 6.13 (qd, 1H, J ) 2.7, 7.3 Hz).
13C NMR (75 MHz, CDCl3) δ: 13.8, 16.9, 29.3, 30.9, 40.4. 70.2,
117.7, 128.4, 139.1, 145.5, 170.2. FAB-LM m/z: 179 (M+ + H).
FAB-HM Calcd for C11H15O2, 179.1060; found, 179.1072.
Preparation of 3a,4,6,7-Tetrahydro-8-methyl-3H-cyclohepta-
[c]furan-1,5-dione (14). To a solution of lactone 13 (38 mg, 16.8
mmol) in EtOH (3 mL) was added 10% HCl-MeOH (0.3 mL) at
room temperature. After being stirred for 3 h at the same
temperature, concentration of the reaction mixture to dryness and
subsequent purification by silica gel column chromatography
(hexane/AcOEt ) 1:1) gave 11a (29 mg, 96%) as a colorless oil.
Acknowledgment. This work was supported by a Grant-
in-Aid for Young Scientists (B), MEXT Japan (No. 17790021).
A generous donation of HFIP by Central Glass Co., Ltd is
gratefully acknowledged.
1
IR (neat) ν cm-1: 1743, 1708. H NMR (300 MHz, CDCl3) δ:
Supporting Information Available: Physical data of 1, 3, 5,
7, 10, 12, and 15 and stereochemical determination of 7a and 7c.
1H/13C NMR spectra of new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
2.32 (d, 3H, J ) 2.2 Hz), 2.42-2.48 (m, 1H), 2.54-2.66 (m, 4H),
2.89-2.98 (m, 1H), 3.50-3.55 (m, 1H), 3.77 (dd, 1H, J ) 8.9, 8.9
Hz), 4.47 (dd, 1H, J ) 8.9, 8.9 Hz). 13C NMR (75 MHz, CDCl3)
δ: 20.4, 33.9, 35.0, 40.9, 46.8, 69.1, 123.6, 154.4, 169.9, 208.4.
FAB-LM m/z: 181 (M+ + H). FAB-HM Calcd for C10H13O3,
181.0866; found, 181.0865.
JO060827X
J. Org. Chem, Vol. 71, No. 17, 2006 6443