Dimethylaluminum methide complex Tf2CHAlMe2: an effective catalyst for Diels-Alder reaction of α,β-unsaturated lactone derivatives with cyclopentadiene

Article abstract of DOI:10.1016/j.tet.2007.09.061

Lewis acid derived by mixing Tf₂CH₂ and Me₃Al was found to be an effective catalyst system for the catalytic DA reaction of less reactive α,β-unsaturated lactone derivative with cyclopentadiene (CP). In this catalyst system, Tf₂CHAlMe₂ is an active species and an excess amount of Me₃Al plays an important role to lower the catalyst loading. Substituent effect of the lactone framework on π-facial selectivity was also examined. In the reactions of both γ-substituted 5-membered lactone derivatives and γ- or δ-methylated 6-membered lactone derivatives with CP, selective attack on the anti face of γ- or δ-substituent was observed. On the other hand, in the cases of γ- or ε-methylated 7-membered lactone derivatives, CP favorably attacked on the syn face.

Full text of DOI:10.1016/j.tet.2007.09.061

Tetrahedron 63 (2007) 12149–12159
Dimethylaluminum methide complex Tf2CHAlMe2: an
effective catalyst for Diels–Alder reaction of a,b-unsaturated
lactone derivatives with cyclopentadiene
*
Hikaru Yanai, Arata Takahashi and Takeo Taguchi
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1423-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Received 27 August 2007; revised 18 September 2007; accepted 22 September 2007
Available online 29 September 2007
Abstract—Lewis acid derived by mixing Tf2CH2 and Me3Al was found to be an effective catalyst system for the catalytic DA reaction of less
reactive a,b-unsaturated lactone derivative with cyclopentadiene (CP). In this catalyst system, Tf2CHAlMe2 is an active species and an excess
amount of Me3Al plays an important role to lower the catalyst loading. Substituent effect of the lactone framework on p-facial selectivity was
also examined. In the reactions of both g-substituted 5-membered lactone derivatives and g- or d-methylated 6-membered lactone derivatives
with CP, selective attack on the anti face of g- or d-substituent was observed. On the other hand, in the cases of g- or 3-methylated 7-membered
lactone derivatives, CP favorably attacked on the syn face.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
cyclopentadiene (CP) but also with acyclic dienes, such as
isoprene and 2,3-dimethyl-1,3-butadiene, under mild condi-
tions.9 By the bidentate Lewis acids, a significant activation
of a,b-unsaturated lactone derivatives was realized, but high
catalyst loading (110 mol %) remained a serious problem.10
In general, since Lewis basicity of lactone derivatives con-
formationally locked in cisoid form is higher than that of
the corresponding acyclic ester derivatives, the dissociation
of Lewis acid from Lewis acid–product complex is difficult.
Thereby, high catalyst loading is needed for the smooth re-
action. In fact, we observed that in the presence of sub-
stoichiometric amount (50 mol %) of TfN[Al(Me)Cl]2 the
DA reaction of g-crotonolactone 1a with isoprene in 1,2-di-
chloroethane gave DA product 2 in only 29% yield (Scheme 1).
Diels–Alder (DA) reaction is one of the most powerful syn-
thetic reactions to construct complex polycyclic systems.1 It
is well known that as a dienophile electron-deficient alkene
derivatives are more reactive than electron-neutral and elec-
tron-rich alkene derivatives. For example, acyclic a,b-unsat-
urated ester derivatives are used for the synthesis of natural
products and functional molecules.1 a,b-Unsaturated lac-
tone derivatives, which are cyclic analogues of a,b-unsatu-
rated ester derivatives, can also be used as dienophiles.
a,b-Unsaturated lactone derivatives are less reactive than
acyclic ester derivatives, and thus the DA reaction of a,b-un-
saturated lactone derivatives is not necessarily general
approach to polycyclic lactone derivatives.2–5 For instance,
Ortun˜o and co-workers have reported the DA reaction of
g-substituted g-crotonolactone derivatives with 1,3-dienes
under various conditions including simply thermal or high-
pressure reactions, but, compared to 6- and 7-membered
a,b-unsaturated lactone derivatives, only relatively reactive
5-membered lactone derivatives were used as substrates.
O
H
O
TfN[Al(Me)Cl]2
ClCH2CH2Cl
60 °C
O
O
Me
H
(10 eq)
TfN[Al(Me)Cl]2 (50 mol%)
1a
2
5 h
TfN[Al(Me)Cl]2 (110 mol%) 7 h
29% (para/meta = >20 : 1)
76% (para/meta = >20 : 1)
Related to our ongoing study on the development of Lewis
acids having unique properties,6–8 we have reported that
bis-aluminated triflic amides [TfN(AlR1R2)2, Tf¼CF3SO2],
as bidentate Lewis acids, highly promote the DA reaction of
5- and 6-membered lactone derivatives not only with
Scheme 1.
To solve these synthetic problems, development of an effi-
cient Lewis acid catalyst for the catalytic DA reaction of
a,b-unsaturated lactone derivatives is an important task.
However, there have been only a few studies on this issue.11
Recently, Corey et al. reported catalytic enantioselective DA
reaction of g-crotonolactone with CP using chiral cationic
Keywords: Lewis acid; Bis(trifluoromethanesulfonyl)methane; Diels–Alder
reaction; a,b-Unsaturated lactones.
* Corresponding author. E-mail: taguchi@ps.toyaku.ac.jp
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.09.061

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H. Yanai et al. / Tetrahedron 63 (2007) 12149–12159
oxazaborolidine catalyst, but scope and limitations with re-
spect to a structural variation of unsaturated lactones and
1,3-dienes are not clear.12
portion at room temperature, almost the same result, namely,
only 1 mol of methane liberation, was observed.16 13C NMR
spectrum (100 MHz) of a 1:1.1 mixture of Tf2CH2 and
Me3Al in CDCl3 at room temperature showed clean forma-
tion of the single complex (ꢀ10.9, 47.9, and 119.6 ppm)
with complete consumption of Tf2CH2.17 On the other
hand, 13C NMR spectrum of a 1:2 mixture of Tf2CH2 and
Me3Al showed two kinds of the complexes, that is, major
one is the same as above and the other newly formed com-
We have also reported an effective Lewis acid system de-
rived from bis(trifluoromethanesulfonyl)methane (Tf2CH2)
and Me3Al for the catalytic DA reaction of less reactive 6-
and 7-membered lactonic dienophiles with CP.13 It is likely
that the following two characteristics of this Lewis acid sys-
tem contribute to realize catalytic activation of a,b-unsatu-
rated lactone derivatives: (1) high Lewis acidity for high
activation of less reactive a,b-unsaturated lactones14 and
(2) steric bulk of Lewis acid having sterically hindered
bis(trifluoromethanesulfonyl)methide ligand for catalyst
loading.15 In this paper, we would like to report a full detail
on this Lewis acid system and the application to the catalytic
DA reaction of a,b-unsaturated lactone derivatives with CP.
1
plex has a signal of CF3 moiety at 119.8 ppm. In H NMR
spectrum, a 1:1.1 mixture of Tf2CH2 and Me3Al showed
two sharp peaks at 4.42 ppm (Tf2CH) and ꢀ0.53 ppm
(AlCH3). Up-field shifts of Tf2C carbon by 16.3 ppm and
Tf2CH proton by 0.54 ppm possibly indicate the formation
of Tf2CHAlMe2 A having a carbon–aluminum bond. NMR
study of the complex derived from the present aluminum
methide A and g-crotonolactone 1a would provide further
information on the structure of the complex and the qualita-
tive Lewis acidity of A (Table 1). Thus, a mixture of 1a and
the aluminum methide A (1.0 equiv) in CDCl3 brought about
new signals presumably due to the formation of a complex
such as D (simple Lewis acid coordination model) or D0
(a bidentate model for Lewis acid coordination with hydro-
gen bonding), although the exact structure was not clear at
this moment.18 Compared to crotonolactone 1a, complex
D (or D0) showed down-field shifts of carbonyl, b- and g-
carbons by 9.6, 11.3, and 7.2 ppm, respectively, and up-field
shift of a-carbon by 1.4 ppm in 13C NMR spectrum (entry 2).
In the case of a mixture of 1a and ‘Tf2CH2+2.0Me3Al’ sys-
tem, essentially the same peaks were observed in 13C NMR
2. Results and discussions
Since the formation of aluminum methide through the reac-
tion of carbon acids with alkylaluminum reagents was not
reported, we examined the reaction of Tf2CH2 with Me3Al.
As shown in Scheme 2, treatment of Tf2CH2 (1 mol) with
Me3Al (1 mol) in CH2Cl2 at room temperature for 30 min
liberated 1 mol of methane gas. Further addition of Me3Al
(1 mol) to this reaction mixture resulted in no liberation of
gas. In a separate experiment, when to a solution of 1 mol
of Tf2CH2 in CH2Cl2, 2 mol of Me3Al was added in one-
F3C
O
Tf
Tf
S
S
O
SO2CF3
SO2CF3
SO2CF3
H
Al
Me
H
Me2Al
H
H
Me3Al (1 mol)
rt, 30 min
H
Me2Al
Me3Al (1 mol)
rt, 30 min
Me
Me
AlMe3
+
A
or
Me2Al
O
O
SO2CF3
(1 mol)
F3C
CH4 (ca. 1 mol)
A
C
B
O
1a
O
O
1a
O
Tf
Al
Tf
O
Tf
Al
Tf
O
or
H
O
O
D
D'
Scheme 2.
Table 1. Chemical shifts of Lewis acid–1a complexes in 13C NMRa
O
CC=O
O
Cα
Cβ
Cγ
1a
Entry
Lewis acid (1.0 equiv)
Chemical shifts
Cb
CC]O
DCC]O
Ca
DCa
DCb
Cg
DCg
DCbꢀCa
1
2
3
4
None
173.6
183.2
183.2
180.9
—
121.5
120.1
120.4
120.9
—
152.7
164.0
163.5
158.9
—
72.1
79.3
79.1
76.5
—
31.2
43.9
43.1
38.0
Tf2CH2+1.1 Me3Al
Tf2CH2+2.0 Me3Al
Me3Alb
+9.6
+9.6
+7.3
ꢀ1.4
ꢀ1.1
ꢀ0.6
+11.3
+10.8
+6.2
+7.2
+7.0
+4.4
a
In CDCl3, rt (100 MHz, ppm).
1.1 equiv of Me3Al was used.
b

H. Yanai et al. / Tetrahedron 63 (2007) 12149–12159
12151
spectrum (entry 3). These data may indicate that the dissoci-
ation of Me3Al from the complex possibly such as B or C by
Lewis basic g-crotonolactone 1a easily takes place. Since
the chemical shift difference between Cb and Ca reflects
the reactivity as a dienophile, the observed DCbꢀCa value
(43.9 ppm) in Tf2CHAlMe2–1a complex also means signifi-
cantly high activation of 1a by Tf2CHAlMe2, compared to
the use of 1.1 equiv of Me3Al (DCbꢀCa¼38.0 ppm).
of 3a (entries 4, 5).19 To check effects of an excess amount of
Me3Al over Tf2CH2, the DA reaction of 1a was conducted in
the presence of only Me3Al (40 mol %) for 8 h, but the yield
of 3a was only 21% (entry 9, endo/exo¼9.7:1). This result
indicates that catalytic amount of Me3Al does not effectively
catalyze the DA reaction of 1a under the present conditions.
Without addition of Lewis acid DA product 3a was not ob-
tained after stirring for 14 h at room temperature (entry 7).
While we have reported that bidentate Lewis acid,
TfN(Ali-Bu2)2, promoted the DA reaction of 1a with CP,
compared with the present ‘Tf2CH2+2.0Me3Al’ system,
the use of stoichiometric amount of this sulfonamide-based
Lewis acid (110 mol %) and longer reaction time (13 h)
were needed for the smooth reaction (entry 8).9
To find out the efficiency of Tf2CHAlMe2, in the presence of
a mixture of Tf2CH2 and Me3Al in various ratios, reaction of
g-crotonolactone 1a with CP was conducted. These results
are summarized in Table 2. As shown in entry 1, catalytic
amount of Tf2CHAlMe2 (20 mol %), which was generated
by a 1:1 reaction of Tf2CH2 and Me3Al, catalyzed the reac-
tion of 1a with CP (10 equiv) in CH2Cl2 for 8 h at room tem-
perature to give cycloadduct 3a in 52% yield as an endo/exo
mixture in a ratio of 6.8:1. A 1:1 mixture of Tf2CH2 and
i-Bu2AlH instead of Me3Al did not promote the DA reaction
(entry 2). The use of a 1:2 mixture of Tf2CH2 and Me3Al dra-
matically increased the yield of 3a to 89% only after 4 h
without an appreciable change in endo/exo selectivity (entry
3). Catalyst loading of ‘Tf2CH2+2.0Me3Al’ system could be
reduced to 10 mol % without significant decrease in the yield
To see the influence of lactone ring-size to the reactivity and
the endo/exo selectivity, we examined the reaction of various
a,b-unsaturated lactone derivatives with CP (Table 3).20 We
found that by expanding lactone ring-size, reactivity of a,b-
unsaturated lactones as dienophiles reduces but endo-selec-
tivity notably increases. The reaction of 6-membered lactone
1b in the presence of 20 mol % of ‘Tf2CH2+1.3Me3Al’ sys-
tem required higher reaction temperature (60 ꢁC) for the
smooth reaction to give DA adduct 3b in 76% yield as
a 14:1 mixture of endo/exo isomers (entry 1). The use of
‘Tf2CH2+2.0Me3Al’system in place of ‘Tf2CH2+1.3Me3Al’
system increased the product yield to 81% with a small de-
crease in endo/exo selectivity (entry 2, endo/exo¼9.4:1).
The reactivity of 7-membered lactone derivative 1c was
lower than that of 5- and 6-membered lactone substrates,
that is, in the presence of 30 mol % of ‘Tf2CH2+1.3Me3Al’
system the reaction with 20 equiv of CP yielded 3c in only
56% yield with fairly high endo/exo selectivity (entry 3,
endo/exo¼17:1). On the other hand, the use of ‘Tf2CH2+
2.0Me3Al’ system improved both the product yield and
endo/exo selectivity (entry 4, 85% yield, endo/exo¼21:1).
Table 2. Effects of Lewis acids on DA reaction of 1a with CP
O
O
O
H
H
Lewis acid
rt
O
O
+
+
O
H
H
(10 equiv.)
1a
endo-3a
exo-3a
Entry Lewis acid (mol %)
Solvent Time Yielda Ratiob
(h)
(%)
(endo/exo)
1
2
3
4
5
6
7
8d
9
Tf2CH2+1.0 Me3Al (20)
Tf2CH2+1.0 DIBAL–H (20) CH2Cl2 12
CH2Cl2
8
52
6.8:1
Trace ndc
Tf2CH2+2.0 Me3Al (20)
Tf2CH2+2.0 Me3Al (10)
Tf2CH2+1.3 Me3Al (20)
Tf2CHMe+1.3 Me3Al (20) CH2Cl2
None
CH2Cl2
CH2Cl2
CH2Cl2
4
5
3
3
89
83
88
76
0
6.8:1
7.8:1
8.3:1
8.1:1
—
5.5:1
9.7:1
Next, we examined the substituent effects of the lactone ring
systems on the stereochemical outcomes. Results are sum-
marized in Table 4. It is well known that in the DA reaction
of g-substituted 5-membered lactones, 1,3-dienes perfectly
attack on the opposite face to the g-substituents under
both simply thermal conditions and Lewis acid mediated
conditions (anti addition).3,9 Under ‘Tf2CH2+1.3Me3Al’
catalyzed conditions, the reaction of g-methyl-g-butenolide
Toluene 14
Toluene 13
TfN(Ali-Bu2)2 (110)
Me3Al (40)
97
21
CH2Cl2
8
a
b
c
d
Isolated yield.
Determined by 1H NMR.
Not determined.
Ref. 9.
Table 3. Effect of lactone ring-size on DA reaction with CP
O
O
O
H
H
H
H
"Tf2CH2 + Me3Al"
+
+
O
n
O
n
O
n
(10 equiv.)
1
endo-3
exo-3
Entry
1
Lewis acid (mol %)
Temp (ꢁC)
Time (h)
Solvent
3
Yielda (%)
Ratio of 3b
(endo/exo)
1
1b (n¼2)
1b (n¼2)
1c (n¼3)
1c (n¼3)
1a (n¼1)
Tf2CH2+1.3 Me3Al (20)
Tf2CH2+2.0 Me3Al (20)
Tf2CH2+1.3 Me3Al (30)
Tf2CH2+2.0 Me3Al (30)
Tf2CH2+1.3 Me3Al (20)
60
60
60
60
rt
4
4
4
4
3
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
CH2Cl2
3b
3b
3c
3c
3a
76
81
56
85
88
14:1
9.4:1
17:1d
21:1d
8.3:1
2
3c
4c
5
a
Isolated yield.
Determined by 1H NMR.
CP of 20 equiv was used.
Determined by isolated yield.
b
c
d

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H. Yanai et al. / Tetrahedron 63 (2007) 12149–12159
Table 4. Diastereoselective DA reaction of various a,b-unsaturated lactones with CP
O
O
O
O
H
H
H
H
"Tf2CH2 + Me3Al"
ClCH2CH2Cl
O
R
O
R
O
R
+
+
+
O
R
H
endo-cis-3
H
endo-trans-3
(10 equiv.)
1
exo-3
Entry
1
Lewis acid
(mol %)
Temp Time (h)
(ꢁC)
Products 3
Yielda (%) endo/exob,c
(endo-cis/endo-trans)
O
O
H
H
H
O
1d
2d
Tf2CH2+1.3 Me3Al (20) rt
Tf2CH2+2.0 Me3Al (20) rt
4
4
+
80
90
6.7:1
5.9:1
O
O
O
1d
H
endo-3d
exo-3d
O
O
H
H
O
+
O
O
1e
O
3
Tf2CH2+2.0 Me3Al (30) 60
24
63
5.9:1
H
endo-3e
H
exo-3e
OTBS
OTBS
OTBS
O
O
O
H
H
H
H
H
O
O
+
O
O
4
5
Tf2CH2+1.3 Me3Al (20) 60
Tf2CH2+2.0 Me3Al (20) 60
7
7
84
93
9.9:1 (2.3:1)
13:1 (2.4:1)
O
+
+
1f
H
exo-3f
endo-cis-3f
endo-trans-3f
O
H
O
H
O
H
O
6e
7e
Tf2CH2+1.3 Me3Al (30) 60
Tf2CH2+2.0 Me3Al (30) 60
4
4
92
92
25:1 (11:1)
25:1 (14:1)
O
O
O
+
+
O
O
1g
H
endo-cis-3g
H
endo-trans-3g
H
exo-3g
O
H
O
H
O
H
O
O
O
O
8f
9f
Tf2CH2+1.3 Me3Al (50) 60
Tf2CH2+2.0 Me3Al (50) 60
8
8
80
80
17:1 (1:1.8)
12:1 (1:1.7)
+
1h
H
H
H
endo-cis-3h
endo-trans-3h
exo-3h
O
H
O
H
O
H
O
O
O
O
10g,h
11g,h
Tf2CH2+1.3 Me3Al (30) 60
Tf2CH2+2.0 Me3Al (30) 60
4
4
70
70
19:1 (1:3.8)
>20:1 (1:5.5)
O
1i
+
+
H
endo-cis-3i
H
endo-trans-3i
H
exo-3i
a
Isolated yield.
Determined by 1H NMR.
A ratio of endo-cis/endo-trans isomers is shown in parentheses.
Solvent: CH2Cl2.
CP of 20 equiv was used.
CP of 30 equiv of was used.
CP of 40 equiv was used.
Solvent; toluene (0.5 M).
b
c
d
e
f
g
h
1d with 10 equiv of CP gave an endo/exo mixture of anti
adducts 3d in 80% yield (entry 1, endo/exo¼6.7:1). As
shown in entry 2, the use of ‘Tf2CH2+2.0Me3Al’ system in-
stead of ‘Tf2CH2+1.3Me3Al’ system improved the product
yield to 90%, although endo/exo selectivity was decreased
to 5.9:1. The reaction of silyloxymethylated g-butenolide
1e also proceeded in the presence of 20 mol % of
‘Tf2CH2+2.0Me3Al’ system for 24 h at 60 ꢁC to give the
desired cycloadduct 3e in reasonable yield with the perfect
p-facial selectivity (entry 3, 63% yield, endo/exo¼5.9: 1).
Compared to 5-membered lactone derivatives, there have
been reported only a few studies on the reactivity and on
the p-facial selectivity of substituted 6- or 7-membered
lactonederivatives.21 Inthepresenceof20 mol %of‘Tf2CH2+
1.3Me3Al’ the reaction of g-methylated 6-membered lac-
tone derivative 1f with CP for 7 h at 60 ꢁC gave the desired
adduct 3f in 84% yield as a mixture of three isomers (entry
4). Based on NOESY data or X-ray crystallographic analysis,
structures of these products were determined as two endo
isomers and one exo isomer (endo/exo¼9.9:1, endo-cis/
endo-trans¼2.3:1).22,23 Under the similar conditions, the use
of ‘Tf2CH2+2.0Me3Al’ system gave a better result in both
the product yield and the endo/exo selectivity (entry 5, 93%
yield,endo/exo¼13:1, endo-cis/endo-trans¼2.4:1). Compared
to g-methyl group on the d-pentenolide structure, d-methyl
group dramatically improved not only the reactivity and the

H. Yanai et al. / Tetrahedron 63 (2007) 12149–12159
12153
endo/exo selectivity but also the endo-cis/endo-trans selec-
tivity. As shown in entry 6, in the presence of
‘Tf2CH2+1.3Me3Al’ system (30 mol %) the reaction of d-
methylated 6-membered substrate 1g with 20 equiv of CP
gave DA product 3g in 92% yield as a mixture of four isomers
with excellent endo/exo selectivity (endo/exo¼25:1) and
high p-facial selectivity between two endo isomers (endo-
cis/endo-trans¼11:1). Furthermore, in the reaction using
‘Tf2CH2+2.0Me3Al’ system instead of ‘Tf2CH2+1.3Me3Al’
system, the p-facial selectivity between two endo isomers
improved to 14:1 without decrease in both the product yield
and the endo/exo selectivity (entry 7). In the presence of
50 mol % of ‘Tf2CH2+1.3Me3Al’ system g-methyl-7-mem-
bered lactone 1h reacted with 40 equiv of CP to give the
cycloadduct 3h in 80% yield as a mixture of two endo adducts
and one exo-adduct (endo/exo¼17:1, entry 8). The major
endo adduct had endo-trans structure (endo-cis/endo-
trans¼1:1.8), which was determined by X-ray crystallo-
graphic analysis.22 This result on the p-facial selectivity is
a sharp contrast to those in the reactions of methylated
5- and 6-membered lactone substrates with CP. The use of
‘Tf2CH2+2.0Me3Al’ system instead of ‘Tf2CH2+1.3Me3Al’
system decreased the endo/exo selectivity to 12:1 without
any change of the yield and endo-cis/endo-trans selectivity
(entry 9). The similar tendency on the endo-cis/endo-trans
selectivity was also observed in the case of 3-methylated
7-membered substrate 1i. That is, the reaction of 1i with
30 equiv of CP in the presence of 30 mol % of ‘Tf2CH2+
1.3Me3Al’ system gave a mixture of two endo adducts and
one exo-adduct in 70% yield (endo/exo¼19:1, entry 10).
Interestingly, compared to the case of 1h having g-methyl
group, endo-cis/endo-trans selectivity in the reaction of 1i
was increased to 1:3.8. The reaction using 30 mol % of
‘Tf2CH2+2.0Me3Al’ improved the stereoselectivity without
loss of the yield (70% yield, endo/exo¼ >20:1, endo-cis/
endo-trans¼1:5.5, entry 11).
Concerning the observed p-facial selectivity, we propose the
transition state models as shown in Figure 1.24 In the DA re-
action of g-substituted 5-membered lactone derivatives with
CP under simply thermal conditions, it is known that CP
attacks on the opposite p-face to avoid steric repulsion of
g-substituents.3a Under the present Lewis acid-catalyzed
conditions, similar selectivity was also observed (Fig. 1,
TS-1). On the other hand, in the case of 3-methylated 7-mem-
bered lactone 1i the p-facial selectivity was inversed to that
of g-methylated 5-membered lactone 1d. This result can be
explained by considering transition state model TS-2. Since
in TS-2, sterically bulky 3-methyl group occupies pseudo-
equatorial position and thus the anti face to 3-methyl group
is sterically shielded by 3-proton and g-axial proton, CP
favorably attacks on the syn face of lactone substrate leading
endo-trans isomer as a major product. Sammakia and co-
workers reported a similar stereoselectivity in the cationic
intramolecular DA reaction of 7-membered oxocarbenium
species.25 In contrast, anti addition of nitrile oxide to 3-
methyl lactone 1i was also reported.26 The observed p-facial
selectivity controlled by the remote substituent effect in the
7-membered cyclic system is the first example of kinetically
controlled syn addition in the intermolecular cycloadditions.
Regarding the reactivity and stereoselectivity, 6-membered
lactone derivatives showed intermediate nature between 5-
membered lactones and 7-membered lactones. The DA reac-
tion of d-methylated lactone derivative 1g should proceed via
TS-3, in which d-methyl group occupies a pseudo-equatorial
position and g-axial proton shields the syn face to d-methyl
group, that is, the moderate anti-selectivity was observed.27
O H
O
O
H
ε
H
Me
H
O
O
O
Me
γ
H
δ
R
H
H
In the present Lewis acid system, the ratio of Tf2CH2 and
Me3Al affected notably the yield of DA adducts. Concerning
these results, we propose the catalytic cycle as shown in
Figure 2. Based on the above NMR studies, the reaction of
Tf2CH2 and Me3Al gave Tf2CHAlMe2 A, which highly
activates a,b-unsaturated lactone derivatives, compared to
Me3Al. While, complexation of aluminum methide A with
a,b-unsaturated lactone derivatives promotes the DA
TS-1
TS-2
TS-3
Figure 1. Proposed transition models of DA reactions of a,b-unsaturated
lactones with CP. TS-1 and TS-3 show that CP attacks on the opposite
face from g-methyl group on 5-membered lactone structure or d-methyl
group on 6-membered lactone structure (anti addition), respectively. On
the other hand, in the case of 7-membered lactone 1i, CP attacks on the
same face (syn addition) to 3-methyl group as shown in TS-2.
3
Tf
Me3Al
Me3Al
Tf
Al
O
H
O
H
Tf
O
O
Tf
Al
H
O
H
E
F
path a
path b
O
O
O
Tf2CHAlMe2
A
D
H
O
O
- CH4 (1 mol)
Tf2CH2 + Me3Al
H
3
1
Figure 2. Proposed catalytic cycle on the catalytic DA reaction of a,b-unsaturated lactones.

12154
H. Yanai et al. / Tetrahedron 63 (2007) 12149–12159
reaction with CP to give complex E. Since complex E, which
have sterically bulky bis(trifluoromethanesulfonyl)methide
ligand and DA adduct part, is thermodynamically less stable,
both direct dissociation of A (path a) and Lewis acid
exchange reaction with Me3Al (path b), which provides ther-
modynamically more stable complex F, result in regenera-
tion of A with formation of DA product 3. That is, excess
amount of Me3Al in the present Lewis acid systems should
improve the turnover of complex A.
respectively. 19F NMR spectra were taken on a Bruker
dpx400 spectrometer, and chemical shifts were reported in
parts per million using benzotrifluoride (0 ppm) as a standard.
Infrared (IR) spectra were recorded on a JASCO FT/IR-620
infrared spectrophotometer. Mass spectra (MS) were ob-
tained on a Micromass LCT (ESI) or Micromass AutoSpec
(EI). Medium pressure liquid chromatography (MPLC) was
performed using prepacked column (KUSANO Prepacked
column Si-10, 40ꢂ300 mm I.D., silica gel, 50 mm) with RI
detector.
According to this concept laying in the use of combination of
a catalytic amount of bulky ligand and catalytic/sub-
stoichiometric amount of alkylaluminum, we examined the
efficiency of other mononuclear aluminum Lewis acid cata-
lyst. For example, in the presence of 20 mol % of
Tf2NAlMe2 generated in situ by mixing Tf2NH and 1 M
equivalent of Me3Al, the reaction of 1b with CP gave DA
adduct 3b in only 40% yield, but the use of 20 mol %
of ‘Tf2NH+2.0Me3Al’ system significantly improved the
product yield to 67% (Scheme 3).28
3.1.1. Preparation of bis(trifluoromethanesulfonyl)me-
thane. To a solution of trimethylsilylmethyllithium (1.0 M
in pentane, 100 mL, 100 mmol), trifluoromethanesulfonic
anhydride (18.6 g, 67 mmol) was added dropwise at 0 ꢁC
over 2 h. Reaction mixture was stirred at the same tempera-
ture for 30 min, then quenched with saturated aqueous
NaHCO3 solution (100 mL) at 0 ꢁC. After being washed
with CH2Cl2 (100 mLꢂ2), the pH of the aqueous layer
was adjusted to 2–3 by careful addition of concd HCl, and
the resulting mixture was extracted with CH2Cl2
(150 mLꢂ3). The organic layer was dried over MaSO4 and
evaporated. To remove impurities, additional extractive
work-up using H2O (20 mL), concd HCl (20 mL), and
CH2Cl2 (50 mLꢂ3) and evaporation were carried out to
give bis(trifluoromethanesulfonyl)methane as colorless
crystals. The structure was confirmed by comparison of
spectrum data reported in the literature.14 1H NMR
(400 MHz, CDCl3) d: 4.96 (2H, s). 13C NMR (100.6 MHz,
CDCl3) d: 64.2, 118.8 (q, J¼327.8 Hz). 19F NMR
(386 MHz, CDCl3) d: ꢀ13.0 (6F, s).
O
O
O
Lewis acids
(20 mol%)
H
H
H
H
O
O
+
+
O
ClCH2CH2Cl
60 °C, 4 h
(10 equiv.)
1b
endo-3b
exo-3b
Tf2NH + 1.0 Me3Al
Tf2NH + 2.0 Me3Al
Tf2CH2 + 2.0 Me3Al
40% (endo/exo = 10 : 1)
67% (endo/exo = 9.6 : 1)
81% (endo/exo = 9.4 : 1)
Scheme 3.
In summary, we found efficient catalytic systems derived by
mixing Tf2CH2 and Me3Al for the DA reactions of a,b-
unsaturated lactone derivatives with CP. Aluminum methide
complex, Tf2CHAlMe2, is an active species in these catalytic
systems and a small excess of Me3Al plays an important role
to improve catalyst loading. The present catalytic systems
activate not only relatively reactive 5-membered lactone de-
rivatives but also less reactive 6- and 7-membered lactone
derivatives. Lactone ring-size influences both reactivity
and the endo/exo selectivity. Thus, by expanding ring-size,
reactivity of a,b-unsaturated lactone derivatives reduced
but endo-selectivity notably increased. Furthermore, substit-
uent effects of the lactone framework on p-facial selectivity
were also examined. In the reactions of both g-substituted
5-membered lactone derivatives and g- or d-methylated
6-membered lactone derivatives with CP, CP attacked on
anti face of g- or d-substituted groups. On the other hand,
in the cases of g- or 3-methylated 7-membered lactone
derivatives, CP favorably attacked on the syn face.
3.1.2. NMR data of dimethylaluminum bis(trifluorome-
thanesulfonyl)methide complex. For Tf2CHAlMe2: 1H
NMR (400 MHz, CDCl3) d: ꢀ0.53 (6H, s), 4.42 (1H, s).
13C NMR (100.6 MHz, CDCl3) d: ꢀ10.9 (br), 47.9, 119.6
(q, J¼319.0 Hz).
For Tf2CHAlMe2–1a complex: 1H NMR (400 MHz, CDCl3)
d: ꢀ0.62 (6H, s, AlCH3), 4.09 (1H, s, Tf2CH), 5.47 (2H, s,
CgH2), 6.52 (1H, dt, J¼5.7, 1.8 Hz, CaH), 8.26 (br d,
J¼5.7 Hz, CbH). 13C NMR (100.6 MHz, CDCl3) d: ꢀ10.9,
51.3, 79.3, 120.1, 120.2 (q, J¼323.8), 164.0, 183.2.
3.1.3. Preparation of a,b-unsaturated lactones (1). 5H-
Furan-2-one 1a and 5,6-dihydro-2H-pyran-2-one 1b are
available commercially. 6,7-Dihydro-5H-oxepin-2-one 1c,29
5-methyl-5H-furan-2-one 1d,30 5-({[tert-butyl(dimethyl)sil-
yl]oxy}methyl)-5H-furan-2-one 1e,31 6-methyl-5,6-dihydro-
2H-pyran-2-one 1g,32 and 7-methyl-6,7-dihydro-5H-oxepin-
2-one 1i33 were prepared by the reported procedure.
3.1.4. 5-Methyl-5,6-dihydro-2H-pyran-2-one (1f). This
compound was prepared by extending a method described
in the literature.34 To a solution of 2-methyl-3-buten-1-ol
(1.0 mL, 10.0 mmol) in CH2Cl2 (30 mL), acryloyl chloride
(2.2 mL, 11.0 mmol) and Et3N (1.8 mL, 12.0 mmol) were
added at 0 ꢁC. After being stirred at the same temperature
for 3 h, extractive work-up and purification by silica gel
column chromatography (pentane/Et2O¼50:1) gave 2-methyl-
3-butenyl acrylate (953 mg, 6.8 mmol, 68% yield) as color-
less oil. IR (neat) n cmꢀ1: 1730. 1H NMR (400 MHz, CDCl3)
d: 1.06 (3H, d, J¼6.9 Hz), 2.50–2.64 (1H, m), 4.03 (1H, dd,
3. Experimental
3.1. General and materials
All reactions were carried out under Ar atmosphere. 1H and
13C NMR spectra were taken on a Varian Mercury 300,
Bruker DPX400 or Brucker AV600 spectrometers, and
chemical shifts were reported in parts per million (ppm) us-
1
ing CHCl3 (7.26 ppm) in CDCl3 for H NMR, and CDCl3
(77.01 ppm) for 13C NMR as an internal standard,

H. Yanai et al. / Tetrahedron 63 (2007) 12149–12159
12155
J¼10.8, 6.6 Hz), 4.08 (1H, dd, J¼10.8, 6.9 Hz), 5.04 (1H,
d, J¼10.4 Hz), 5.08 (1H, br d, J¼17.4 Hz), 5.76 (1H, ddd,
J¼17.4, 10.4, 6.9 Hz), 5.81 (1H, dd, J¼10.3, 1.3 Hz), 6.12
(1H, dd, J¼17.3, 10.4 Hz), 6.39 (1H, dd, J¼17.3, 1.3 Hz).
13C NMR (100.6 MHz, CDCl3) d: 16.4, 37.0, 68.4, 115.0,
128.5, 130.6, 139.9, 166.2. Anal. Calcd for C8H12O2: C,
68.54; H, 8.63. Found: C, 68.38; H, 8.59. To a solution of
the above acrylate (641 mg, 4.58 mmol) in CH2Cl2
(900 mL), Grubbs II catalyst (170 mg, 0.19 mmol) was added
at room temperature. After being stirred at 40 ꢁC for 2 h,
evaporation of the reaction mixture followed by purification
by column chromatography on silica gel (pentane/Et2O¼
1:1) gave 5-methyl-5,6-dihydro-2H-pyran-2-one 1f (370 mg,
3.30 mmol, 73% yield). The structure was confirmed by
comparison of spectrum data with the authentic sample.35
Tf2CH2 (28.1 mg, 0.10 mmol) in CH2Cl2 (1.0 mL), Me3Al
(1.05 M in hexane, 0.12 mL, 0.13 mmol) was stirred for
1 h at room temperature. To this reaction mixture, a solution
of 2(5H)-furan-2-one 1a (42.0 mg, 0.50 mmol) in CH2Cl2
(1.0 mL) and freshly prepared CP were added. After being
stirred for 3 h at same temperature, the resulting mixture
was quenched with H2O (10 mL), and extracted with Et2O
(10 mLꢂ3). The organic layer was dried over MgSO4,
concentrated under reduced pressure, and purified by flash
column chromatography (silica gel, hexane/EtOAc¼3:1)
to give endo-3a (58.9 mg, 0.39 mmol, 78% yield) and
exo-3a (7.1 mg, 0.05 mmol, 10% yield). The structure
was confirmed by comparison of spectrum data with the
literature.36
3.2.2. (1S*,2S*,7S*,8R*)-4-Oxatricyclo[6.2.1.02,7]undec-
9-en-3-one (endo-3b) and (1R*,2S*,7S*,8S*)-4-oxatricy-
clo[6.2.1.02,7]undec-9-en-3-one (exo-3b). endo-3b: Color-
less oil. IR (neat) n cmꢀ1: 1726. 1H NMR (400 MHz,
CDCl3) d: 1.12–1.21 (1H, m), 1.35 (1H, d, J¼8.5 Hz),
1.52 (1H, dd, J¼8.5, 1.5 Hz), 1.91–2.00 (1H, m), 2.63–
2.74 (1H, m), 2.88–2.95 (1H, m), 3.32 (1H, br s), 4.06
(1H, td, J¼11.7, 1.5), 4.20 (1H, dt, J¼11.7, 3.1 Hz), 6.06
(1H, dd, J¼5.5, 2.9 Hz), 6.28 (1H, dd, J¼5.5, 2.6 Hz). 13C
NMR (100.6 MHz, CDCl3) d: 27.8, 388.8, 43.4, 45.6, 45.6,
48.2, 67.7, 135.0, 138.1, 174.2. ESI-MS m/z: 165 [M+H]+.
HRMS: calcd for C10H13O2: 165.0916 [M+H]+, found:
165.0917.
3.1.5. 5-Methyl-6,7-dihydro-5H-oxepin-2-one (1h). To
a solution of LDA prepared from n-BuLi (1.59 M in hexane,
6.3 mL, 10.0 mmol) and diisopropylamine (6.3 mL,
10.0 mmol) in THF (30 mL), 5-methyl-6,7-dihydro-5H-
oxepin-2-one (1.28 g, 10.0 mmol) was added at ꢀ78 ꢁC
over 15 min. After being stirred at the same temperature
for 30 min, the reaction mixture was treated with benzene-
selenyl chloride (2.50 g, 13.0 mmol) at ꢀ78 ꢁC for 3 h and
quenched with H2O (20 mL) at 0 ꢁC. After usual extractive
work-up and evaporation, purification of the resulting resi-
due by silica gel column chromatography (hexane/
EtOAc¼3:1) gave 5-methyl-3-(phenylselenyl)-2-oxepanone
(950 mg, 3.40 mmol). Light yellow oil. IR (neat) n cmꢀ1
:
1715. 1H NMR (400 MHz, CDCl3) d: 1.00 (3H, d,
J¼6.5 Hz), 1.44–1.57 (1H, m), 1.83 (1H, ddd, J¼13.7,
11.1, 2.5 Hz), 1.90–2.07 (2H, m), 2.10–2.19 (1H, m), 4.20
(1H, dd, J¼6.5, 2.5 Hz), 4.32 (1H, ddd, J¼13.1, 5.9,
1.8 Hz), 4.75 (1H, dd, J¼13.1, 10.1 Hz), 7.25–7.36 (3H,
m), 7.58–7.62 (2H, m). 13C NMR (100.6 MHz, CDCl3) d:
22.0, 32.1, 37.2, 37.4, 45.5, 68.1, 128.4, 128.7, 129.4,
134.3, 173.0. ESI-MS (m/z): 285 [M+H]+. HRMS: calcd
for C13H16O2Se: 285.0394 [M+H]+, found: 285.0390.
Anal. Calcd for C13H16O2Se: C, 55.13; H, 5.69. Found: C,
55.05; H, 5.67. The above phenylselenide was treated with
30% H2O2 (0.57 mL) in THF (24 mL) at room temperature
for 4 h. Resulting mixture was quenched with saturated
aqueous Na2S2O7 solution (10 mL) at 0 ꢁC and extracted
with Et2O (20 mLꢂ3). The combined organic layer was
dried over MgSO4, and concentrated under reduced pres-
sure. Chromatographic purification (pentane/Et2O¼1:1) of
resulting residue gave 5-methyl-6,7-dihydro-5H-oxepin-2-
exo-3b: Colorless oil. IR (neat) n cmꢀ1: 1732. H NMR
1
(400 MHz, CDCl3) d: 1.31 (1H, br s), 1.45 (2H, m), 2.01
(1H, m), 2.14 (1H, ddd, J¼8.6, 5.4, 1.6 Hz), 2.47 (1H, br
d, J¼9.1 Hz), 2.71 (1H, br s), 3.47 (1H, br s), 4.08 (1H,
ddd, J¼12.4, 11.0, 1.4 Hz), 4.33 (1H, m), 6.14 (1H, dd,
J¼5.3, 2.8 Hz), 6.19 (1H, dd, J¼5.3, 2.7 Hz). 13C NMR
(100.6 MHz, CDCl3) d: 29.7, 40.0, 42.8, 44.5, 46.2, 46.3,
67.2, 135.4, 137.6, 174.4. EIMS m/z: 165 [M]+. HRMS:
calcd for C10H13O2: 165.0916 [M]+, found: 165.0917.
3.2.3. (1S*,2S*,8S*,9R*)-4-Oxatricyclo[7.2.1.02,8]dodec-
10-en-3-one (endo-3c) and (1R*,2S*,8S*,9S*)-4-oxatricy-
clo[7.2.1.02,8]dodec-10-en-3-one (exo-3c). endo-3c: Color-
less crystals. Mp 66.8–67.0 ꢁC. IR (KBr) n cmꢀ1: 1726. 1H
NMR (400 MHz, CDCl3) d: 1.00 (1H, td, J¼14.0, 6.5 Hz),
1.34 (1H, d, J¼8.5 Hz), 1.49 (1H, d, J¼8.5 Hz), 1.47–1.58
(1H, m), 1.75 (1H, dd, J¼14.0, 7.2 Hz), 1.88–2.01 (1H,
m), 2.26–2.38 (1H, m), 2.76 (1H, br s), 3.15 (1H, br s),
3.27 (1H, dd, J¼10.0, 3.5 Hz), 4.15 (1H, dd, J¼12.4,
6.6 Hz), 4.29 (1H, td, J¼12.4, 3.9 Hz), 6.01 (1H, dd,
J¼5.6, 3.0 Hz), 6.39 (1H, dd, J¼5.6, 2.9 Hz). 13C NMR
(100.6 MHz, CDCl3) d: 25.6, 26.2, 40.2, 45.5, 47.2, 48.3,
49.3, 64.9, 133.2, 137.6, 174.9. ESI-MS (m/z): 179
[M+H]+. HRMS: calcd for C11H15O2: 179.1072 [M+H]+,
found: 179.1069. Anal. Calcd for C11H14O2: C, 74.13; H,
7.92. Found: C, 74.36; H, 8.16.
1
one 1h as colorless oil. IR (neat) n cmꢀ1: 1706. H NMR
(400 MHz, CDCl3) d: 1.09 (3H, d, J¼7.2 Hz), 1.66–1.78
(1H, m), 2.14–2.26 (1H, m), 2.56–2.68 (1H, m), 4.15–4.33
(1H, m), 5.83 (1H, dd, J¼12.4, 2.3 Hz), 6.21 (1H, dd,
J¼12.4, 3.8 Hz). 13C NMR (100.6 MHz, CDCl3) d: 20.3,
34.7, 35.5, 66.0, 119.6, 149.2, 168.6. EIMS (m/z): 126
[M]+. Anal. Calcd for C7H10O2: C, 66.65; H, 7.99. Found:
C, 66.49; H, 8.00.
1
3.2. General procedure of Tf2CH2DMe3Al catalyzed
Diels–Alder reaction of a,b-unsaturated lactones (1)
with CP
exo-3c: Colorless oil. IR (neat) n cmꢀ1: 1730. H NMR
(400 MHz, CDCl3) d: 1.29–1.48 (1H, m), 1.45 (1H, dt,
J¼9.4, 1.7 Hz), 1.54 (1H, d, J¼9.4 Hz), 1.52–1.63 (1H, m),
1.64–1.73 (1H, m), 1.87–1.96 (1H, m), 2.02–2.14 (1H,
m), 2.52–2.62 (2H, m), 3.32 (1H, br s), 4.16–4.30 (2H,
m), 6.13 (1H, dd, J¼5.7, 3.0 Hz), 6.28 (1H, dd, J¼5.7,
3.0 Hz). 13C NMR (100.6 MHz, CDCl3) d: 25.9, 27.6,
3.2.1. (1S*,2R*,6S*,7R*)-4-Oxatricyclo[5.2.1.02,6]dec-8-
en-3-one (endo-3a) and (1R*,2R*,6S*,7S*)-4-oxatricy-
clo[5.2.1.02,6]dec-8-en-3-one (exo-3a). To a solution of

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H. Yanai et al. / Tetrahedron 63 (2007) 12149–12159
39.9, 44.8, 45.1, 47.4, 48.2, 65.0, 135.5, 139.5, 176.1. ESI-
MS (m/z): 179 [M+H]+. HRMS: calcd for C11H15O2:
179.1072 [M+H]+, found: 179.1082.
47.4, 51.1, 71.5, 135.7, 136.6, 173.4. ESI-MS (m/z): 179
[M+H]+. HRMS: calcd for C11H15O2: 179.1072 [M+H]+,
found: 179.1058.
3.2.4. (1S*,2R*,5R*,6S*,7R*)-5-Methyl-4-oxatricyclo-
[5.2.1.02,6]dec-8-en-3-one (endo-3d) and (1R*,2R*,
5R*,6S*,7S*)-5-methyl-4-oxatricyclo[5.2.1.02,6]dec-8-en-
3-one (exo-3d). The structure of these compounds was con-
firmed by comparison of spectrum data with the literature.3d
exo-3f: Colorless crystals. Mp 31.1–33.1 ꢁC. IR (neat)
n cmꢀ1: 1736. 1H NMR (400 MHz, CDCl3) d: 1.07 (3H, d,
J¼6.2 Hz), 1.26 (1H, d, J¼8.9 Hz), 1.41 (1H, br d,
J¼8.9 Hz), 1.45–1.63 (2H, m), 2.25 (1H, dd, J¼8.9,
1.7 Hz), 2.78 (1H, br s), 3.46 (1H, br s), 3.80 (1H, t,
J¼10.6 Hz), 4.12 (1H, dd, J¼5.6, 3.1 Hz), 6.16 (1H, dd,
J¼5.6, 3.0 Hz), 6.19 (1H, dd, J¼5.6, 2.9 Hz). 13C NMR
(100.6 MHz, CDCl3) d: 16.2, 34.7, 42.3, 44.6, 45.0, 45.9,
46.0, 72.4, 135.4, 137.6, 174.5. ESI-MS (m/z): 179
[M+H]+. HRMS: calcd for C11H15O2: 179.1072 [M+H]+,
found: 179.1064.
3.2.5. (1S*,2R*,5S*,6S*,7R*)-5-({[tert-Butyl(dimethyl)sil-
yl]oxy}methyl)-4-oxatricyclo[5.2.1.02,6]dec-8-en-3-one
(endo-3e) and (1R*,2R*,5S*,6S*,7S*)-5-({[tert-butyl(di-
methyl)silyl]oxy}methyl)-4-oxatricyclo[5.2.1.02,6]dec-8-
en-3-one (exo-3e). endo-3e: Colorless crystals. Mp
51.1–52.0 ꢁC. IR (KBr)
n :
cmꢀ1 1753. 1H NMR
(400 MHz, CDCl3) d: 0.04 (6H, s), 0.88 (9H, s), 1.44 (1H,
br d, J¼8.4 Hz), 1.64 (1H, br d, J¼8.4 Hz), 2.93–3.00
(1H, m), 3.07 (1H, br s), 3.20 (1H, dd, J¼9.0, 4.6 Hz),
3.28 (1H, br s), 3.63 (1H, dd, J¼11.0, 2.8 Hz), 3.72 (1H,
dd, J¼11.0, 3.4 Hz), 3.92–3.97 (1H, m), 6.22 (1H, dd,
J¼5.4, 2.9 Hz), 6.28 (1H, dd, J¼5.5, 2.9 Hz). 13C NMR
(100.6 MHz, CDCl3) d: ꢀ5.6, ꢀ5.6, 18.1, 25.8, 42.9, 45.5,
45.8, 51.7, 65.0, 82.2, 134.5, 136.7, 177.9. ESI-MS (m/z):
295 [M+H]+. HRMS: calcd for C16H27O3: 295.1729
[M+H]+, found: 295.1729.
3.2.7. (1S*,2R*,7R*,8R*)-5-Methyl-4-oxatricyclo-
[6.2.1.02,7]undec-9-en-3-one (endo-3g), (1S*,2R*,5R*,
7R*,8S*)-5-methyl-4-oxatricyclo[6.2.1.02,7]undec-9-en-
3-one (exo-cis-3g), and (1R*,2S*,5R*,7S*,8R*)-5-methyl-
4-oxatricyclo[6.2.1.02,7]undec-9-en-3-one (exo-trans-3g).
endo-3g (as an mixture of two diastereomers): IR (neat) n
1
cmꢀ1: 1721. H NMR (400 MHz, CDCl3) d: for endo-cis-
3g 1.30–1.45 (2H, m), 1.36 (3H, d, J¼6.7 Hz), 1.46–1.62
(1H, m), 1.87 (1H, ddd, J¼14.0, 7.0, 3.2 Hz), 2.65–2.78
(1H, m), 2.93 (1H, br s), 2.85–3.00 (1H, dd, J¼10.0,
4.0 Hz), 3.38 (1H, br s), 4.47–4.59 (1H, m), 6.13 (1H, dd,
J¼5.6 Hz), 6.28 (1H, dd, J¼5.6 Hz); for endo-trans-3g
1.25 (3H, d, J¼6.3 Hz), 1.94 (1H, dd, J¼13.7, 6.9 Hz),
4.20–4.30 (1H, m), 6.04 (1H, dd, J¼5.6, 3.0 Hz). Other sig-
nals could not be assigned through peak overlapping. 13C
NMR (100.6 MHz, CDCl3) d: for endo-cis-3g 20.7, 32.0,
34.9, 42.8, 46.1, 46.2, 48.6, 74.7, 135.4, 137.6, 173.7; for
endo-trans-3g 21.0, 35.1, 38.6, 42.9, 45.4, 45.4., 48.3,
75.1, 134.9, 138.2, 174.5. ESI-MS (m/z): 179 [M+H]+.
HRMS: calcd for C11H15O2: 179.1072 [M+H]+, found:
179.1051. Anal. Calcd for C11H14O2: C, 74.13; H, 7.92.
Found: C, 74.03; H, 7.83.
exo-3e: Colorless crystals. Mp 52.0–53.2 ꢁC. IR (KBr)
1
n cmꢀ1: 1766. H NMR (400 MHz, CDCl3) d: 0.06 (6H,
s), 0.87 (9H, s), 1.50 (2H, br s), 2.40 (1H, dd, J¼8.1,
2.2 Hz), 2.62 (1H, br d, J¼8.1 Hz), 2.88 (1H, br s), 3.24
(1H, br s), 3.67 (1H, dd, J¼11.0, 2.8 Hz), 3.82 (1H, dd,
J¼11.0, 3.2 Hz), 4.16–4.19 (1H, m), 6.18 (1H, dd, J¼5.6,
3.0 Hz), 6.22 (1H, dd, J¼5.6, 3.0 Hz). 13C NMR
(100.6 MHz, CDCl3) d: ꢀ5.5, ꢀ5.5, 18.2, 25.8, 43.6, 44.6,
46.5, 47.5, 49.1, 65.0, 83.5, 137.5, 137.8, 177.5. ESI-MS
(m/z): 295 [M+H]+. HRMS: calcd for C16H27O3: 295.1729
[M+H]+, found: 295.1715.
3.2.6. (1S*,2R*,6R*,7R*,8R*)-6-Methyl-4-oxatricyclo-
[6.2.1.02,7]undec-9-en-3-one (endo-cis-3f), (1R*,2S*,6R*,
7S*,8S*)-6-methyl-4-oxatricyclo[6.2.1.02,7]undec-9-en-3-
one (endo-trans-3f), and (1R*,2R*,7R*,8S*)-6-methyl-4-
oxatricyclo[6.2.1.02,7]undec-9-en-3-one (exo-3f). endo-cis-
exo-trans-3g: Colorless oil. IR (neat) n cmꢀ1: 1724. 1H NMR
(400 MHz, CDCl3) d: 1.36 (3H, d, J¼6.8 Hz), 1.40 (1H, d,
J¼9.4 Hz), 1.32–1.43 (1H, m), 1.55–1.68 (1H, m), 1.98–
2.12 (1H, m), 2.22–2.30 (1H, m), 2.66 (1H, br s), 3.47
(1H, br s), 4.65–4.74 (1H, m), 6.17 (1H, dd, J¼5.6,
2.9 Hz), 6.21 (1H, dd, J¼5.6, 3.0 Hz). 13C NMR
(100.6 MHz, CDCl3) d: 19.6, 33.7, 33.8, 42.4, 44.4, 46.4,
46.6, 74.3, 135.7, 137.6, 173.9. ESI-MS (m/z): 179
[M+H]+. HRMS: calcd for C11H15O2: 179.1072 [M+H]+,
found: 179.1069.
3f: Colorless crystals. Mp 68.9–69.0 ꢁC. IR (neat) n cmꢀ1
:
1727. 1H NMR (400 MHz, CDCl3) d: 1.01 (3H, d,
J¼7.0 Hz), 1.23–1.35 (1H, m), 1.33 (1H, d, J¼8.4 Hz),
1.55 (1H, dt, J¼8.4, 1.8 Hz), 2.20 (1H, td, J¼10.7, 3.9 Hz),
2.92 (1H, dd, J¼6.5, 3.9 Hz), 3.01 (1H, br s), 3.34 (1H, br
s), 3.81 (1H, dd, J¼11.0, 10.8 Hz), 4.00 (1H, dd, J¼10.8,
3.6 Hz), 6.05 (1H, dd, J¼5.7, 3.0 Hz), 6.28 (1H, dd, J¼5.7,
2.9 Hz). 13C NMR (100.6 MHz, CDCl3) d: 15.6, 33.2, 43.1,
44.0, 45.5, 46.9, 48.1, 73.0, 135.0, 138.0, 174.4. ESI-MS
m/z: 179 [M+H]+. HRMS: calcd for C11H15O2: 179.1072
[M+H]+, found: 179.1057.
exo-cis-3g: Colorless crystals. Mp 30.0–30.5 ꢁC. IR (KBr)
n cmꢀ1: 1723. 1H NMR (400 MHz, CDCl3) d: 1.36 (3H, d,
J¼6.3 Hz), 1.10–1.44 (3H, m), 1.95–2.06 (1H, m), 2.12
(1H, dd, J¼13.8, 7.2 Hz), 2.22 (1H, dd, J¼9.4, 1.6 Hz),
2.67 (1H, br s), 3.47 (1H, br s), 4.22–4.33 (1H, m), 6.15
(1H, dd, J¼5.5, 3.0 Hz), 6.19 (1H, dd, J¼5.5, 2.9 Hz). 13C
NMR (100.6 MHz, CDCl3) d: 21.1, 36.9, 37.9, 42.3, 44.5,
46.1, 46.2, 74.6, 135.5, 137.7, 174.7. ESI-MS (m/z): 179
[M+H]+. HRMS: calcd for C11H15O2: 179.1072 [M+H]+,
found: 179.1063.
endo-trans-3f: Colorless crystals. Mp 49.5–49.8 ꢁC. IR
1
(neat) n cmꢀ1: 1735. H NMR (400 MHz, CDCl3) d: 1.00
(3H, d, J¼7.0 Hz), 1.39 (1H, d, J¼8.7 Hz), 1.53 (1H, dt,
J¼8.7, 1.7 Hz), 2.26–2.40 (1H, m), 2.60 (1H, ddd, J¼9.4,
6.5, 3.1 Hz), 3.08 (1H, br s), 3.11 (1H, dd, J¼9.4, 4.4 Hz),
3.33 (1H, br s), 3.88–3.99 (2H, m), 6.23 (2H, br s). 13C
NMR (100.6 MHz, CDCl3) d: 14.2, 29.1, 42.3, 43.1, 45.4,
3.2.8. (1S*,2S*,7S*,8S*,9R*)-7-Methyl-4-oxatricyclo-
[7.2.1.02,8]dodec-10-en-3-one (endo-cis-3h), (1R*,2R*,

H. Yanai et al. / Tetrahedron 63 (2007) 12149–12159
12157
7S*,8R*,9S*)-7-methyl-4-oxatricyclo[7.2.1.02,8]dodec-
10-en-3-one (endo-trans-3h), and (1R*,2S*,8S*,9S*)-7-
methyl-4-oxatricyclo[7.2.1.02,8]dodec-10-en-3-one (exo-
3h). endo-cis-3h: Colorless crystals. Mp 50.0–50.9 ꢁC. IR
1.49 (1H, br d, J¼8.4 Hz), 1.58–1.74 (3H, m), 2.26–2.36
(1H, m), 2.75 (1H, br s), 3.16 (1H, br s), 3.26 (1H, dd,
J¼10.0, 3.6 Hz), 4.49–4.62 (1H, m), 6.00 (1H, dd, J¼5.6,
3.0 Hz), 6.41 (1H, dd, J¼5.6, 2.9 Hz). 13C NMR
(100.6 MHz, CDCl3) d: 20.9, 26.8, 33.8, 40.6, 45.5, 47.3,
48.3, 49.9, 72.3, 133.0, 137.8, 174.5. ESI-MS (m/z): 193
[M+H]+. HRMS: calcd for C12H17O2: 193.1229 [M+H]+,
found: 193.1214.
1
(KBr) n cmꢀ1: 1725. H NMR (400 MHz, CDCl3) d: 0.96
(3H, d, J¼6.1 Hz), 1.09–1.23 (2H, m), 1.30 (1H, d,
J¼8.5 Hz), 1.51 (1H, d, J¼8.5 Hz), 1.97–2.11 (2H, m),
2.92 (1H, br s), 3.15 (1H, br s), 3.30 (1H, dd, J¼9.9,
3.5 Hz), 4.14 (1H, dd, J¼12.5, 6.6 Hz), 4.32 (1H, td,
J¼12.5, 3.3 Hz), 6.04 (1H, dd, J¼5.7, 2.9 Hz), 6.42 (1H,
dd, J¼5.7, 2.9 Hz). 13C NMR (100.6 MHz, CDCl3) d: 19.8,
31.4, 35.0, 45.0, 45.2, 46.8, 47.5, 49.1, 64.5, 132.2, 138.1,
175.0. ESI-MS (m/z): 193 [M+H]+. HRMS: calcd for
C12H17O2: 193.1229 [M+H]+, found: 193.1235. Anal. Calcd
for C12H16O2: C, 74.97; H, 8.39. Found: C, 74.71; H, 8.39.
exo-3i: Colorless crystals. Mp 30.0–31.0 ꢁC. IR (KBr)
1
n cmꢀ1: 1728. H NMR (400 MHz, CDCl3) d: 1.29–1.42
(1H, m), 1.34 (3H, d, J¼6.2 Hz), 1.44 (1H, dt, J¼9.2,
1.7 Hz), 1.52–1.58 (1H, m), 1.62–1.82 (3H, m), 1.83–1.89
(1H, m), 2.51–2.59 (1H, m), 2.56 (1H, br s), 3.32 (1H, br
s), 4.47–4.56 (1H, m), 6.12 (1H, dd, J¼5.7, 3.0 Hz), 6.27
(1H, dd, J¼5.7, 3.0 Hz). 13C NMR (100.6 MHz, CDCl3) d:
20.7, 28.1, 34.1, 40.2, 44.8, 45.0, 47.9, 48.3, 72.4, 135.5,
139.5, 175.8. ESI-MS (m/z): 193 [M+H]+. HRMS: calcd
for C12H17O2: 193.1229 [M+H]+, found: 193.1239.
endo-trans-3h: Colorless crystals. Mp 119.5–120.2 ꢁC. IR
1
(KBr) n cmꢀ1: 1723. H NMR (400 MHz, CDCl3) d: 0.81
(3H, d, J¼7.7 Hz), 1.40 (1H, d, J¼8.3 Hz), 1.52 (1H, br d,
J¼8.5 Hz), 1.84–1.95 (2H, m), 2.37–2.44 (1H, m), 2.73
(1H, dt, J¼11.1, 3.5 Hz), 2.82 (1H, br s), 3.12 (1H, br s),
3.34 (1H, dd, J¼11.1, 3.5 Hz), 4.26 (1H, dd, J¼12.8,
6.8 Hz), 4.47 (1H, td, J¼12.8, 5.1 Hz), 6.08 (1H, dd,
J¼5.6, 3.0 Hz), 6.37 (1H, dd, J¼5.6, 3.1 Hz). 13C NMR
(100.6 MHz, CDCl3) d: 21.3, 31.4, 35.3, 44.8, 45.0, 46.6,
47.8, 50.9, 66.2, 135.2, 135.7, 176.1. ESI-MS (m/z): 193
[M+H]+. HRMS: calcd for C12H17O2: 193.1229 [M+H]+,
found: 193.1210. Anal. Calcd for C12H16O2: C, 74.97; H,
8.39. Found: C, 74.72; H, 8.42.
3.3. The structure determination of endo/exo-3e and
endo-cis-3h
3.3.1. (1S*,2R*,5S*,6S*,7R*)-5-(Hydroxymethyl)-4-oxa-
tricyclo[5.2.1.02,6]dec-8-en-3-one and (1R*,2R*,5S*,
6S*,7S*)-5-(hydroxymethyl)-4-oxatricyclo[5.2.1.02,6]-
dec-8-en-3-one. To a solution of pure endo-3e (88.7 mg,
0.30 mmol) in THF (0.4 mL), tetrabutylammonium fluoride
(TBAF, 0.62 mL, 1.0 M solution in THF, 0.62 mmol) was
added dropwise at 0 ꢁC, and then stirred for 3 h at the same
temperature. The reaction mixture was poured into H2O
(5 mL), and extracted with EtOAc (10 mLꢂ3). The organic
layer was dried over anhydrous MgSO4, and the filtrate was
evaporated. The residue was purified by column chromato-
graphy (hexane/EtOAc¼2:1) to give (1S*,2R*,5S*,6S*,7R*)-
5-(hydroxymethyl)-4-oxatricyclo[5.2.1.02,6]dec-8-en-3-one
(41.1 mg, 0.23 mmol, 76% yield) as a single diastereomer.
Under the same conditions, (1R*,2R*,5S*,6S*,7S*)-isomer
was also obtained from pure exo-3e in 84% yield. The
structures both (1S*,2R*,5S*,6S*,7R*)-isomer and (1R*,
2R*,5S*,6S*,7S*)-isomer were confirmed by comparison
of spectrum data with the authentic samples, respectively.3d
1
exo-3h: Colorless oil. IR (neat) n cmꢀ1: 1732. H NMR
(400 MHz, CDCl3) d: 1.05 (3H, d, J¼6.2 Hz), 1.19 (1H,
ddd, J¼13.9, 10.2, 4.0 Hz), 1.37–1.48 (2H, m), 1.49 (1H,
d, J¼8.9 Hz), 1.49–1.62 (1H, m), 2.12–2.23 (1H, m), 2.59
(1H, d, J¼10.2 Hz), 2.91 (1H, br s), 3.31 (1H, br s), 4.15
(1H, dd, J¼12.5, 6.9 Hz), 4.27 (1H, td, J¼12.5, 4.0 Hz),
6.16 (1H, dd, J¼5.6, 3.0 Hz), 6.23 (1H, dd, J¼5.6,
3.0 Hz). 13C NMR (100.6 MHz, CDCl3) d: 19.8, 31.4,
35.9, 43.7, 44.0, 44.7, 46.5, 47.4, 64.3, 136.3, 139.3,
176.3. ESI-MS (m/z): 193 [M+H]+. HRMS: calcd for
C12H17O2: 193.1229 [M+H]+, found: 193.1229.
3.2.9. (1S*,2S*,5R*,8S*,9R*)-5-Methyl-4-oxatricyclo-
[7.2.1.02,8]dodec-10-en-3-one (endo-cis-3i), (1R*,2R*,
5R*,8R*,9S*)-5-methyl-4-oxatricyclo[7.2.1.02,8]dodec-
10-en-3-one (endo-trans-3i), and (1R*,2S*,8S*,9S*)-5-
methyl-4-oxatricyclo[7.2.1.02,8]dodec-10-en-3-one (exo-
3i). endo-cis-3i: Colorless crystals. Mp 60.0–60.6 ꢁC. IR
3.3.2. (1S*,2S*,3S*,4R*)-N-(4-Bromophenyl)-3-[(2R*)-2-
hydroxypropyl]bicyclo[2.2.1]hept-5-ene-2-carboxamide.
To a solution of p-bromoaniline (119 mg, 0.69 mmol) in
toluene (0.3 mL), Me3Al (1.05 M in hexane, 0.66 mL,
0.69 mmol) was added at 0 ꢁC. After being stirred at room
temperature for 30 min, this mixture was treated with a solu-
tion of endo-cis-3h (40.0 mg, 0.23 mmol) in toluene
(0.5 mL) at room temperature for 3 h. Reaction mixture
was quenched with 1 M HCl (10 mL), extracted with EtOAc
(10 mLꢂ3), and dried over MgSO4. After evaporation of
the combined organic layers, the residue was purified by
silica gel column chromatography (hexane/EtOAc¼2:1)
and additional recrystallization to give (1S*,2S*,3S*,4R*)-
N-(4-bromophenyl)-3-[(2R*)-2-hydroxypropyl]bicyclo[2.2.1]-
hept-5-ene-2-carboxamide (77.0 mg, 0.22 mmol, 96% yield)
as colorless crystals. To determine relative stereochemistry
of endo-cis-3h, this compound was submitted to the X-ray
1
(KBr) n cmꢀ1: 1712. H NMR (400 MHz, CDCl3) d: 1.03–
1.17 (1H, m), 1.34 (1H, d, J¼8.4 Hz), 1.51 (3H, d,
J¼7.2 Hz), 1.49–1.59 (2H, m), 1.75–1.84 (1H, m), 1.96–
2.06 (1H, m), 2.42 (1H, ddt, J¼13.0, 10.2, 2.9 Hz), 2.74
(1H, br s), 3.13 (1H, br s), 3.25 (1H, dd, J¼10.2, 3.5 Hz),
4.49 (1H, qdd, J¼7.2, 7.0, 4.0 Hz), 6.05 (1H, dd, J¼5.6,
3.0 Hz), 6.40 (1H, J¼5.6, 2.9 Hz). 13C NMR (100.6 MHz,
CDCl3) d: 22.6, 29.0, 32.9, 41.3, 45.5, 47.7, 48.7, 51.9,
75.3, 133.6, 137.7, 176.3. ESI-MS (m/z): 193 [M+H]+.
HRMS: calcd for C12H17O2: 193.1229 [M+H]+, found:
193.1222.
endo-trans-3i: Colorless crystals. Mp 104.5–105.2 ꢁC. IR
(KBr) n cmꢀ1: 1725. 1H NMR (400 MHz, CDCl3) d: 1.02–
1.04 (1H, m), 1.32 (3H, d,J¼6.2 Hz), 1.30–1.36 (1H, m),
crystallographic analysis.21 Mp 174.8 ꢁC. IR (KBr) n cmꢀ1
:
3451, 1668. H NMR (400 MHz, methanol-d4) d: 1.17 (3H,
1
d, J¼6.2 Hz), 1.29–1.52 (4H, m), 2.64–2.74 (1H, m), 2.89

12158
H. Yanai et al. / Tetrahedron 63 (2007) 12149–12159
Minuti, L.; Piermatti, O.; Pizzo, F.; Vaccaro, L. J. Org. Chem.
2005, 71, 70–74.
(1H, br s), 3.04 (1H, br s), 3.17 (1H, dd, J¼10.1, 3.1 Hz), 3.73
(1H, sex., J¼6.2 Hz), 6.15 (1H, dd, J¼5.6, 3.0 Hz), 6.40 (1H,
dd, J¼5.6, 3.0 Hz), 7.42–7.52 (4H, m). 13C NMR (100.6 MHz,
methanol-d4) d: 23.7, 41.0, 43.5, 48.7, 48.7, 50.5, 51.6,
68.1, 117.4, 123.0, 133.0, 134.3, 137.8, 139.6, 174.7. ESI-MS
(m/z): 350 [M+H]+. HRMS: calcd for C17H20BrNO2: 350.0756
[M+H]+, found: 350.0764. Anal. Calcd for C17H20BrNO2: C,
58.13; H, 5.76; N, 4.00. Found: C, 57.95; H, 5.86; N, 3.71.
5. (a) Ferroud, C.; Revial, G.; d’Angelo, J. Tetrahedron 1985, 26,
3981–3984; (b) Ortun˜o, R. M.; Guingant, A.; d’Angelo, J.
Tetrahedron Lett. 1988, 29, 6989–6992; (c) Caarretero, J. C.;
Ruano, J. L. G.; Lorente, A.; Yuste, F. Tetrahedron:
Asymmetry 1993, 4, 177–180; (d) Carretero, J. C.; Ruano,
J. L. G.; Cabrejas, L. M. M. Tetrahedron 1997, 53, 14115–
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Stewart, S. G. Aust. J. Chem. 2004, 57, 641–644.
6. For a review on bis-aluminated Lewis acids, see: Taguchi, T.;
Saito, A.; Yanai, H. Chem. Rec. 2007, 7, 167–179.
7. (a) Saito, A.; Ito, H.; Taguchi, T. Org. Lett. 2002, 4, 4619–4621;
(b) Saito, A.; Yanai, H.; Taguchi, T. Tetrahedron 2004, 60,
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Acknowledgements
The authors would like to thank Dr. Motoo Shiro (Rigaku
Corporation) for the X-ray crystallographic analysis.
References and notes
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ꢀ
Ballesteros, M.; Monsalvatje, M.; Corbera, J.; Sanchez-
16. This is a sharp contrast to TfNH2, since reaction of TfNH2
(1 mol) with Me3Al (2 mol) gave TfN(AlMe2)2 with liberation
of 2 mol of methane gas.
17. Previously, in the 1:2 reaction of TfNH2 and Me2AlCl in
CDCl3, we observed the formation of three kinds of complexes
in 13C NMR study.7a Jonas and co-workers also reported a rapid
equilibrium of bis-silylated triflic amide between N,N-bis-
silylated form and N,O-bis-silylated form: Jonas, S.;
Westerhausen, M.; Simchen, G. J. Organomet. Chem. 1997,
548, 131–137.
18. Concerning this observed difference of these two Lewis acids
derived from Tf2CH2 or Tf2CHMe, although detail is not clear,
we assume that acidic hydrogen of Tf2CHAlMe2 would act as
hydrogen bond donor to form complex D0 as shown in Scheme
2. In our previous work, we have proposed double coordination
manner of a,b-unsaturated lactones and esters to bidentate
Lewis acids, TfN[AlR1R2]2, to explain high activation of these
substrates by TfN[AlR1R2]2.9
19. In this paper, composition and catalyst loading of Lewis acid
was generally showed as ‘Tf2CH2+xMe3Al’ (y mol %), which
means the use of Lewis acid system derived from the reaction
of y mol % of Tf2CH2 and xy mol % of Me3Al.
Ferrando, F.; Font, J. Tetrahedron Lett. 1987, 28, 3405–
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obtained free of charge from The Cambridge Crystallographic
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