Ligand design for dual enantioselective control in Cu-catalyzed asymmetric conjugate addition of R2Zn to cyclic enone

Article abstract of DOI:10.1016/j.tet.2011.04.028

A new chiral N-heterocyclic carbene (NHC) ligand derived from a natural α-aminoester has been designed and synthesized. The coupling of N-methylbenzimidazole with an α-chloroacetamide derivative, which was prepared from chloroacetyl chloride and (S)-serin

Full text of DOI:10.1016/j.tet.2011.04.028

Tetrahedron 68 (2012) 3512e3518
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Ligand design for dual enantioselective control in Cu-catalyzed asymmetric
conjugate addition of R2Zn to cyclic enone
*
Misato Yoshimura, Naoatsu Shibata, Miaki Kawakami, Satoshi Sakaguchi
Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A new chiral N-heterocyclic carbene (NHC) ligand derived from a natural
designed and synthesized. The coupling of N-methylbenzimidazole with an
a
a
-aminoester has been
-chloroacetamide de-
Received 2 February 2011
Received in revised form 10 March 2011
Accepted 9 April 2011
rivative, which was prepared from chloroacetyl chloride and (S)-serine methyl ester, gave the corre-
sponding ester/amide-functionalized azolium compound 20. The reaction of 2-cyclohexen-1-one (17)
with Et2Zn in the presence of catalytic amounts of Cu(OTf)2 and 20 produced (R)-3-ethylcyclohexanone
(18) as a major product. In contrast, the enantioselective conjugate addition (ECA) reaction catalyzed by
Cu(OTf)2 under the influence of a hydroxy-amide-functionalized azolium compound 15, which was
derived from (S)-tert-leucinol, produced (S)-18 in preference to (R)-18. A series of azolium salts were
synthesized from (S)-serine esters, and the reaction conditions for the ECA reaction were optimized to
produce (R)-18 with 69% ee. The best results were obtained in the case of the reaction of 4,4-dimethyl-2-
cyclohexen-1-one (34) with Et2Zn catalyzed by Cu(OTf)2 in combination with azolium compounds. When
the reaction of 34 with Et2Zn was carried out in the presence of catalytic amounts of Cu(OTf)2 and 20, (S)-
3-ethyl-4,4-dimethylcyclohexanone (35) was obtained with 97% ee, whereas the ECA reaction under the
influence of hydroxy-amide-functionalized azolium 15 afforded (R)-35 with >99% ee. In this manner, the
reversal of enantioselectivity was achieved by controlling the structure of chiral ligands.
Available online 15 April 2011
Keywords:
Asymmetric catalysis
N-Heterocyclic carbene
Conjugate addition
Reversal of enantioselectivity
(S)-Serine ester
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
stereoselective formation of carbonecarbon bonds.3 Several chiral
N-heterocyclic carbene (NHC) ligands as effective alternatives to
The preparation of both enantiomers of a chiral compound is
increasingly important not only in life science, including medicine
and agricultural chemicals, but also in materials science. The most
effective approach for preparing optically active compounds in-
volves asymmetric catalysis using transition metal complexes
having appropriately designed chiral ligands. Despite the enormous
progress of the catalytic asymmetric syntheses, the efficient prep-
aration of both enantiomers still remains a significant challenge.1
The use of chiral ligands with opposite configurations in an
asymmetric catalysis is the most straightforward method. However,
the antipodes of the ligands are not always easily available when
the chiral ligands are prepared from chiral molecules of a natural
origin, such as amino acids. To overcome this disadvantage the
structural modification of the chiral ligands would provide a sig-
nificant breakthrough in switching the stereoselectivity of
a reaction.2
phosphine ligands have been prepared and applied to this re-
action.4 Initial studies on the NHCeCu-catalyzed ECA reaction in-
volved the utilization of a monodentate NHC ligand.5,6 However,
this reaction provided moderate enantioselectivity. In contrast,
polydentate NHC ligands exhibited better stabilities and selectiv-
ities. Arnold et al. reported a chiral anionic tethered bidentate NHC
ligand for Cu-catalyzed ECA reaction of 2-cyclohexen-1-one with
Et2Zn.7 Later, Mauduit et al. designed and applied chelating
hydroxy-alkyl-substituted NHC ligands for achieving high enan-
tioselectivities.8 Moreover, Hoveyda et al. developed chelating an-
ionic hydroxy-aryl-functionalized NHC ligands for the ECA
reaction.9,10
Recently, we developed hydroxy-amide-functionalized azolium
compounds derived from chiral b-amino alcohols to prepare tri-
dentate anionic amidate/NHCePd(II) as well as dianionic alkoxy/
amidate/NHCePd(II) complexes.11 The newly designed polydentate
ligand can lock the stereocontrol element in a fixed conformation
during the entire catalytic processes to afford higher enantiose-
lectivity. Thus, the Pd(II) complex catalyzes the asymmetric oxi-
dative Heck-type reaction of arylboronic acid with alkene with
excellent enantioselectivity. Encouraged by this success, we also
examined the Cu-catalyzed ECA reaction of cyclic enones with
The Cu-catalyzed enantioselective conjugate addition (ECA)
reaction has emerged as
a powerful synthetic tool for the
* Corresponding author. Tel.: þ81 6 6368 0867; fax: þ81 6 6339 4026; e-mail
address: satoshi@ipcku.kansai-u.ac.jp (S. Sakaguchi).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.04.028

M. Yoshimura et al. / Tetrahedron 68 (2012) 3512e3518
3513
dialkylzincs in the presence of the hydroxy-amide-functionalized
NHC ligand precursor.12 Surprisingly, the reversal of enantiose-
lectivity with the same ligand was achieved by changing the Cu
precatalyst from Cu(OTf)2 to Cu(acac)2 (Scheme 1).
O
Cl
O
N
R1
N
HN
O
HN
O
R1
OMe
+
N
1,4-dioxane, rf
OMe
N
Cl
R2
R2
O
cat. Cu(OTf)2
No.
1
2
3
4
5
6
7
t
i
i
i
R1 =
Me
Bu Ph Bn
Me Me Me Me Me Me Bn
53 97 71 90 55 58 60
Pr Bu
Bu
R2 =
O
R
n
O
N
Yield (%)
+ R2Zn
HN
R1
N
Cl
O
R2
n
HO
with the same ligand
O
N
O
Cl
N
R1
R1
HN
HN
O
N
+
cat. Cu(acac)2
N
Bn
Cl
1,4-dioxane, rf
OMe
R
n
Bn
O
OMe
Scheme 1. Reversal of enantioselectivity with the same ligand.
No.
R1 =
Yield (%)
8
9
10 11 12 13
t
As a part of our continuing efforts to design new catalyst sys-
tems, we examined the development of new functionalized NHC
i
i
Bu
Me Pr Bu
60 72 98 74 69 61
Ph Bn
ligands, which were derived from natural
a-aminoesters instead of
Scheme 3. Synthesis of various azolium salts.
b
-amino alcohols. In the previous paper, we briefly described an
ECA reaction catalyzed by Cu(OTf)2 in combination with a chiral
imidazolium salt having an ester/amide side chain, which was
prepared from (S)-leucine methyl ester.12b Interestingly, the abso-
lute configuration of the conjugate adduct obtained in the ECA
reaction using the ester/amide-functionalized azolium salt differs
from that obtained in the ECA reaction using the hydroxy-amide-
functionalized azolium salt (Scheme 2). Because both ligand pre-
Table 1
ECA reaction of 17 with Et2Zn catalyzed by Cu(OTf)2 combined with azolium salta
O
O
cat.
Cu(OTf)2 / Azolium salt
THF, r.t., 3 h
+ Et2Zn
cursors are prepared from natural a-amino acids, it is possible to
Et
17
18
achieve dual enantioselective control through the structural mod-
ification of chiral ligands. Herein, we wish to focus on the design
and development of various functionalized NHC ligands derived
Run
Azolium salt
Yieldb (%)
erb
S
R
from natural
a
-aminoesters for the Cu-catalyzed ECA reaction.
1
2
1
2
81
77
52.5
52
47.5
48
O
N
3
4
5
6
3
4
5
6
96
77
77
80
50
50
50.5
47.5
55
49.5
52.5
45
R1
O
HN
N
Cl
cat.
R2
Cu(OTf)2
Cu(OTf)2
HO
7
7
7
14
15
8
98
72
>99
>99
47
74
78
50
58
50.5
51.5
90.5
91
44
33
31
35
37
49.5
48.5
9.5
9
56
67
69
65
63
O
8c
9c
10c
11
12
13d
14
15
16
17
18
R
R
n
n
O
+R2Zn
N
O
HN
R1
OR3
N
n
Cl
cat.
9
9
R2
O
10
11
12
13
16
51
51
>99
44.5
43.5
82
55.5
56.5
18
Scheme 2. Strategy for switching of enantioselectivity.
a
Compound 17 (1 mmol), Et2Zn (3 mmol), Cu(OTf)2 (2 mol %), azolium salt (3 mol
%), THF (3 mL), rt, 3 h.
b
2. Results and discussion
Yield and enantiomer ratio (er) were determined by GLC analysis. Average of two
runs.
c
Cu(OTf)2 (6 mol %), azolium salt (4.5 mol %), THF (9 mL).
Cu(OTf)2 (6 mol %).
This study commenced with the synthesis of a series of azolium
chlorides derived from commercially available -aminoesters. The
coupling of N-alkylazoles with -chloroacetamide derivatives,
which were prepared independently from chloroacetyl chloride
and -aminoesters, afforded the corresponding ester/amide-func-
d
a
a
azolium salts 14e16, which were prepared from (S)-leucinol or (S)-
tert-leucinol, are also listed in Table 1. The treatment of 17 with
Et2Zn in THF in the presence of catalytic amounts of Cu(OTf)2 and
benzimidazolium salt 3, which was derived from (S)-leucine methyl
ester, produced 3-ethylcyclohexanone (18) in almost quantitative
yield (run 3). However, the reaction resulted in a racemic mixture,
and stereoselectivity could not be improved by the initial screening
of the chiral benzimidazolium salts 1e7 (runs 1e7). In contrast, the
Cu(OTf)2-catalyzed ECA reaction of 17 with Et2Zn in the presence of
hydroxy-amide-functionalized benzimidazolium salt 15 proceeded
efficiently to give (S)-18 in a 91:9 enantiomer ratio (er) (run 10). On
a
tionalized azolium compounds 1e13 (Scheme 3). Unlike hydroxy-
amide-functionalized azolium salts, which are stable in air,11,12
azolium chlorides 1e13 have a highly hydroscopic character.
Table 1 summarizes the conjugate addition of Et2Zn to 2-
cyclohexen-1-one (17) catalyzed by Cu(OTf)2 combined with 1e13.
To compare the relative abilities of azolium salts bearing ester/
amide functionality or hydroxy-amide functionality, the results of
the ECA reaction employing hydroxy-amide-functionalized

3514
M. Yoshimura et al. / Tetrahedron 68 (2012) 3512e3518
O
the other hand, the reaction under the influence of the imidazolium
salt 9 derived from (S)-valine methyl ester afforded (R)-18 in
preference to (S)-18 in a 31:69 er (run 13). These results suggest
that the reversal of enantioselectivity can be achieved. However,
attempts to increase enantioselectivity failed in the reaction of 17
with Et2Zn catalyzed by a Cu salt combined with 9 (see Table S1).
Br
Br
Et3N
19
(R3 = Me)
O
Br
O
N
N
HN
O
+
OH
OMe
HN
O
N
Me
OH
OMe
N
Me
Br
O
N
O
N
t
HN
HO
Bu
N
25 (55%)
24
R1
Cl
HN
HO
N
Bn
Cl
R2
14 (R1 = Bu, R2 = Bn)
O
i
16
O
N
N
15 (R1 = Bu, R2 = Bn)
t
MeI
OH
OMe
24
NH
HN
HN
O
N
Me
N
I
KOH
OH
OMe
N
O
Since the variation of the stereodirecting group (R1¼alkyl) on
the ester/amide-functionalized NHC ligands 1e13 was not effective
for achieving stereoselective reaction (Table 1), we next chose
a natural (S)-serine ester (19) as the origin of chiral induction. (S)-
26 (40%)
27 (75%)
Scheme 5. Synthesis of azolium bromide (25) and iodide (27).
Serine is an inexpensive
a-amino acid bearing a hydroxymethyl
substituent. A series of benzimidazolium chlorides, 20, 21, 22, and
23, were synthesized from (S)-serine methyl, ethyl, and benzyl
esters, respectively, by a route similar to that shown in Schemes 3
and 4. These compounds are air stable and easy to handle. In ad-
dition, we are interested in the influence of the counter ion of the
azolium ligand on the stereoselectivity of the Cu-catalyzed ECA
reaction. Therefore, the corresponding bromide 25 was synthesized
functionalized azolium salt, the replacement of the N-methyl by
an N-benzyl substituent at the azolium ring led to a significant
increase in enantioselectivity.12b However, the stereoselectivity of
the ECA reaction using an azolium salt 20 was comparable to that
obtained using 21 (runs 2 and 4). The use of the azolium chlorides,
22 and 23, which contained ethyl and benzyl esters, respectively,
only slightly reduced the enantioselectivity (runs 5 and 6).
Next, we screened Cu salts and solvents for the ECA reaction. By
using [Cu(OTf)]2(C6H6) and Cu(NO3)2, (R)-18 was obtained in 60% ee
and 62% ee, respectively, whereas the use of Cu(acac)2 and CuCl2
by a coupling reaction of N-methylbenzimidazole with an a-bro-
moacetamide derivative 24, which was prepared from bromoacetyl
bromide and (S)-serine methyl ester (Scheme 5). The treatment of
benzimidazole with 24 in the presence of KOH gave the corre-
sponding azole derivative 26. Subsequently, 26 was allowed to react
with methyl iodide to produce azolium iodide 27.
Table 2
ECA reaction of 17 with Et2Zn catalyzed by Cu salt combined with azolium salt
derived from serine ester to produce (R)-18a
Run
Cu salt
Azolium
Solvent
Yieldb (%)
eeb (%)
OH
O
1c
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(I) salte
Cu(NO)3
Cu(acac)2
CuCl2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
20
20
20
21
22
23
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
25
27
THF
THF
THF
THF
THF
THF
THF
THF
90
90
89
90
80
94
79
86
83
55
92
81
97
79
87
95
39
44
48
46
57
85
81
77
88
57
67
69
67
61
68
60
62
29
18
63
67
53
51
27
13
40
25
26
38
17
69
69
43
65
OR3
2d
3
Cl
H2N
Cl
O
4d
5d
6d
7
Et3N
19
O
Cl
O
N
N
8
9
HN
+
OH
OR3
HN
O
N
THF
THF
Cl
OH
OR3
N
R2
10
11
12
13
14
15
16
17
18
19
20
21
22h
23i
24
25
R2
O
2-MeeTHFf
DME
AcOEt
1,4-Dioxane
Et2O
No. 20 21 22 23
R2 =
Me
Me
Bn Me
Me Me Et Bn
85 51 78 62
R3 =
TBMEg
CH3CN
NMP
DMSO
DMF
DMA
THF
THF
THF
THF
Yield (%)
Scheme 4. Synthesis of azolium salts derived from serine ester.
The results for the Cu-catalyzed ECA reaction of 17 with Et2Zn in
the presence of an azolium salt derived from (S)-serine ester under
various reaction conditions are summarized in Table 2. Fortunately,
the reaction under the influence of azolium chloride 20 proceeded
smoothly to produce (R)-18, as desired (run 1). Under the reaction
condition that was optimized for the Cu(OTf)2-catalyzed ECA re-
action using the hydroxy-amide-functionalized benzimidazolium
salt 15 to afford (S)-18 with 82% ee, the ECA reaction catalyzed by
Cu(OTf)2 (6 mol %) combined with 20 (4.5 mol %) produced (R)-18 in
90% yield and 67% ee (Table 1 run 10 vs Table 2 run 2). Decreasing
the amount of Cu(OTf)2 from 6 mol % to 4.5 mol % slightly improved
the stereoselectivity of the reaction, producing (R)-18 with 69% ee
(run 3). In the ECA reaction using the hydroxy-amide-
a
Compound 17 (1 mmol), Et2Zn (3 mmol), Cu salt (4.5 mol %), azolium salt
(4.5 mol %), THF (9 mL), rt, 3 h.
b
See Table 1 b.
Cu(OTf)2 (2 mol %), 20 (3 mol %), THF (3mL).
Cu(OTf)2 (6 mol %).
[Cu(OTf)]2(C6H6).
c
d
e
f
2-Methyltetrahydrofuran.
g
tert-Butyl methyl ether.
h
Reaction was run at 10 ꢀC.
i
Reaction was run at ꢁ10 ꢀC.

M. Yoshimura et al. / Tetrahedron 68 (2012) 3512e3518
3515
resulted in poor enantioselectivity (runs 7e10). It should be noted
that no reversal of enantioselectivity was observed when the Cu
precatalyst was changed from Cu(OTf)2 to Cu(acac)2 (run 3 vs run
9). This observation is in contrast to the ECA reaction under the
influence of the hydroxy-amide-functionalized azolium salt
(Scheme 1), in which the reversal of enantioselectivity was ob-
served. The type of solvent used was also an important parameter
in the ECA reaction. The use of THF led to the best ee (69%), followed
by DME and 2-methyltetrahydrofuran (runs 3 and 11e21). De-
creasing the reaction temperature did not affect the enantiose-
lectivity (runs 22 and 23). The choice of the counter ion of the
azolium salt is also an important factor. The ECA reaction catalyzed
by Cu(OTf)2 combined with azolium iodide 27 proceeded in
a manner comparable to the reaction in which azolium chloride 20
was used, whereas the use of bromide 25 resulted in a somewhat
lower ee (runs 3, 24, and 25).
From a mechanical point of view, it seems likely that the present
ECA reaction was catalyzed by an NHCeCu species generated in situ
from an azolium compound and a Cu precatalyst under the influence
of Et2Zn. In fact, Hoveyda et al. reported the preparation of an
NHCeZn complex by allowing an azolium compound to react with
Et2Zn, where Et2Zn acts as a base to form the NHC species.13 In the
preceding papers, we showed that the treatment of a hydroxy-
amide-functionalized azolium salt with Ag2O formed the corre-
sponding NHCeAg complex, where Ag2O serves as a mild base and
reacts predominantly at the C2 position of the azolium salt without
causing the deprotonation of other acidic protons.11 Moreover,
Alexakis and Roland reported that the use of an NHCeAg complex
instead of an azolium salt carbene precursor in the Cu(OTf)2-cata-
lyzed ECA reaction of 17 with Et2Zn resulted in increased stereo-
selectivity.5c Therefore, we are interested in the ECA reaction
catalyzed by Cu(OTf)2 combined with an NHCeAg complex (Table 3).
First, an ECA reaction was preformed in the presence of the
hydroxy-amide-functionalized NHCeAg complex 28. The treatment
of 15 with 0.5 equiv of Ag2O in dichloromethane at room temperature
gave 28. Owing to the light-sensitive property of the silver complex,
28 was used without further purification for the ECA reaction. After
the resultant silver complex 28 was treated with Cu(OTf)2 in THF at
room temperature for 1 h, enone 17 and Et2Zn were subsequently
added tothe reactionvessel. Asexpected, this reactionafforded (S)-18
as a major product, and the enantiomer ratio (S/R¼91:9) obtained by
using 28 was very similar to that obtained by using 15 (runs 1 and 2).
These results stronglysuggest thata similarcatalytic copperspecies is
generated in both cases. On the other hand, (R)-18 was formed with
a 17:83 er by employing the NHCeAg complex 29, which was pre-
pared from 20 and Ag2O (run 4).
On the basis of these results, we finally investigated the scope of
the ECA reactions of different cyclic enones with dialkylzincs. The
results for the ECA reaction catalyzed by Cu(OTf)2 combined with
15 (or 28) or 20 (or 29) in THF at room temperature for 3 h are
summarized in Table 4. The present catalytic systems were found
suitable for the reaction of 2-cyclohepten-1-one (30) with Et2Zn.
The 1,4-addition of 30 with Et2Zn proceeded efficiently under the
influence of the Cu(OTf)2/15 system to afford (S)-3-ethyl-
cycloheptanone (31) in >99% yield with a 95.5:4.5 er, whereas (R)-
31 was obtained with a 7.5:92.5 er when the reaction was carried
out with the Cu(OTf)2/20 system (runs 1 and 3). Almost similar
results were obtained in the reactions by using the NHCeAg com-
plexes, 28 and 29 (runs 2 and 4). The reaction of 17 or 30 with Bu2Zn
gave the corresponding adduct in low yield probably due to steri-
cally reason (runs 6 and 8). Excellent ee values of >99% and 97%,
respectively, were obtained in the ECA reaction of 4,4-dimethyl-2-
cyclohexen-1-one (34) with Et2Zn (runs 9e11). It was found that
Table 4
Table 3
Switching of enantioselectivitya
ECA reaction of 17 with Et2Zn catalyzed by Cu(OTf)2 salt combined with NHC
precursora
Run
Substrates
Ligand
Yieldb (%)
erb
Yieldb (%)
erb
S
R
Run
NHC precursor
S
R
O
1c
2c
3
15
28
20
29
>99
96
85
95.5
96.5
7.5
9
4.5
3.5
92.5
91
O
O
N
+ Et2Zn
15
28
>99
91
91
9
HN
N
Bn
4
80
1c
Cl
30
HO
O
5c
6
15
20
>99
94
6
+ Bu2Zn
+ Bu2Zn
N
40
14
86
2c
>99
9
17
HN
N
Bn
Ag
Cl
O
HO
7c
8
15
20
>99
98
2
22
29
71
O
N
30
3
20
29
89
87
15.5
84.5
HN
N
OH
OMe
Cl
Me
9c
15
84
<0.5
>99.5
O
O
+ Et2Zn
10
20
20
21
42
58
83
98.5
97
97.5
1.5
3
2.5
O
N
11d
12
4
17
83
HN
N
34
OH
OMe
Ag
Me
a
Cl
Compound 17 (1 mmol), Et2Zn (3 mmol), Cu(OTf)2 (4.5 mol %), ligand (4.5 mol %),
THF (9 mL), rt, 3 h.
O
a
b
Compound 17 (1 mmol), Et2Zn (3 mmol), Cu(OTf)2 (4.5 mol %), NHC precursor
Isolated yield. Enantiomer ratio (er) was determined by GLC analysis. Average of
(4.5 mol %), THF (9 mL), rt, 3 h.
two runs.
b
c
See Table 1 b.
Cu(OTf)2 (6 mol %), ligand (4.5 mol %), THF (9 mL).
c
d
Cu(OTf)2 (6 mol %).
Et2Zn (5 mmol).

3516
M. Yoshimura et al. / Tetrahedron 68 (2012) 3512e3518
the yield of the conjugate adduct 35 increased when the reaction
was carried out in the presence of 21 instead of 20 (run 12).
4.2.4. Compound 4. 1H NMR (CDCl3):
J¼7.3 Hz, 1H), 8.05e8.03 (m, 1H), 7.66e7.64 (m, 3H), 5.89 (s, 2H),
4.21 (s, 1H), 4.19 (s, 3H), 3.62 (s, 3H), 1.10 (s, 9H); 13C NMR:
171.5,
d 10.80 (s, 1H), 9.46 (d,
d
3. Conclusion
165.3, 143.5, 132.0, 131.6, 127.3, 127.0, 114.5, 112.1, 62.4, 51.7, 49.5,
34.0, 33.6, 26.9. ½a D29
ꢁ5.4 (c 0.37 in CH3OH).
ꢂ
We developed a series of ester/amide-functionalized azolium
compounds derived from natural
a
-aminoesters for use as chiral
4.2.5. Compound 5. White solid; mp 188.9e189.2 ꢀC. 1H NMR
(CDCl3):
NHC precursors for a Cu-catalyzed ECA reaction. The reaction of
cyclic enones with dialkylzincs catalyzed by Cu(OTf)2 combined
with the appropriate chiral azolium salt 20 derived from an (S)-
serine ester gave the corresponding optically active conjugate ad-
ducts with moderate to excellent enantioselectivities (69e97% ee).
In contrast, the use of the hydroxy-amide-functionalized azolium
salt derived from
with opposite configurations in with 82% to >99% ee. Considering
that both the ligand precursors are prepared from natural -amino
d
10.67 (s, 1H), 10.10 (d, J¼7.3 Hz, 1H), 7.95e7.93 (m, 1H),
7.61e7.59 (m, 3H), 7.53e7.51 (m, 2H), 7.33e7.26 (m, 3H), 5.93 (d,
J¼16.1 Hz, 1H), 5.84 (d, J¼16.1 Hz, 1H), 5.47 (d, J¼7.3 Hz, 1H), 4.15 (s,
3H),3.58(s,3H);13CNMR((CD3)2SO):
d170.4,164.9,143.7,135.5,131.4,
131.3,128.8,128.5,127.8,126.6,126.4,113.6,113.4, 56.6, 52.4, 48.1, 33.3.
Anal. Calcd for C19H20ClN3O3$0.7H2O: C, 59.05; H, 5.58; N, 10.87.
b
-amino alcohol led to the formation of adducts
Found: C, 58.92; H, 5.48; N, 10.91%. ½a D30
ꢂ
þ5.0 (c 0.20 in CH3OH).
a
4.2.6. Compound 6. 1H NMR ((CD3)2SO):
d 9.82 (s, 1H), 9.70 (d,
acids, it can be said that the reversal of enantioselectivity by the
structural modification of chiral ligands was successfully achieved.
The applications of the chiral chelating polydentate NHC catalysts
for efficient catalytic enantioselective transformations including
the ECA reaction of acyclic enones are the subject of ongoing re-
search at our laboratory.
J¼7.8 Hz, 1H), 8.02e8.00 (m, 1H), 7.69e7.63 (m, 3H), 7.28e7.20 (m,
5H), 5.44 (d, J¼16.5 Hz, 1H), 5.38 (d, J¼16.5 Hz, 1H), 4.55e4.49 (m,
1H), 4.11 (s, 3H), 3.59 (s, 3H), 3.15e3.07 (m, 1H), 3.01e2.95 (m, 1H);
13C NMR:
d 171.3, 164.8, 143.6, 136.9, 131.4, 131.1, 129.2, 128.3, 126.6,
126.4, 113.6, 113.2, 54.0, 52.0, 48.1, 36.5, 33.3. ½a D32
ꢁ0.3 (c 0.90 in
ꢂ
CH3OH).
4. Experimental
4.2.7. Compound 8. Light yellow liquid. 1H NMR ((CD3)2SO):
d 9.30
(s, 1H), 9.08 (br, 1H), 7.81 (s, 1H), 7.71 (s, 1H), 7.41e7.38 (m, 5H), 5.47
(s, 2H), 5.09 (d, J¼16.9 Hz, 1H), 5.04 (d, J¼16.9 Hz, 1H), 4.36e4.28
4.1. General procedure for the preparation of azolium
compound
(m, 1H), 3.62 (s, 3H), 1.31 (d, J¼7.3 Hz, 3H); 13C NMR:
d 172.5, 164.8,
137.5, 134.8, 129.0, 128.2, 124.2, 121.8, 52.0, 51.8, 50.4, 47.9, 17.0. ½a D32
ꢂ
To 1,4-dioxane were added azole derivative (0.293 M) and
chloroacetamide derivative (0.267 M), which was prepared from
chloroacetyl chloride and -aminoester. After stirring the reaction
a
-
ꢁ5.1 (c 0.43 in CH3OH).
a
4.2.8. Compound 9. White solid. 1H NMR ((CD3)2SO):
d 9.26 (s, 1H),
mixture at 110 ꢀC for 16 h, the solvent was removed under reduced
pressure. The residue was dissolved in methanol, and then acti-
vated carbon was added. After 16 h, the activated carbon was re-
moved by filtration. The filtrate was concentrated under reduced
pressure to obtain a solid, which was purified by reprecipitation
using ethyl acetate and methanol to afford the corresponding
azolium compound. Because of the highly hydroscopic character,
elemental analyses of 1e4, 6e13, and 25 were not preformed.
Azolium salts 7, 10, and 14e16 were reported in the preceding
paper.12b Because of the light-sensitive character, elemental anal-
yses of 28 and 29 were not preformed.
8.86 (br,1H), 7.79 (s,1H), 7.72 (s,1H), 7.42e7.38 (m, 5H), 5.46 (s, 2H),
5.13 (d, J¼16.5 Hz, 1H), 5.07 (d, J¼16.5 Hz, 1H), 4.21 (t, J¼7.3 Hz, 1H),
3.64 (s, 3H), 2.09e2.01 (m, 1H), 0.89 (t, J¼6.9 Hz, 6H); 13C NMR:
d
171.5, 165.4, 137.5, 134.8, 129.0, 128.7, 128.2, 124.3, 121.8, 57.8, 51.8,
50.5, 30.1, 18.9, 18.1. ½a D32
ꢁ3.5 (c 0.63 in CH3OH).
ꢂ
4.2.9. Compound 10. White solid. 1H NMR ((CD3)2SO): 9.38 (s, 1H),
9.16 (d, J¼7.2 Hz, 1H), 7.84 (t, J¼1.6 Hz, 1H), 7.74 (t, J¼1.6 Hz, 1H),
7.43e7.39 (m, 5H), 5.50 (s, 2H), 5.15 (d, J¼16.4 Hz, 1H), 5.10 (d,
J¼16.4 Hz, 1H), 4.33e4.27 (m, 1H), 3.63 (s, 3H), 1.73e1.49 (m, 3H),
0.90 (d, J¼6.8 Hz, 3H), 0.85 (d, J¼6.4 Hz, 3H); 13C NMR:
d 172.4,
165.1, 137.5, 134.8, 129.0, 128.7, 128.2, 124.2, 121.8, 52.0, 51.8, 50.7,
4.2. Analytical data
50.4, 24.1, 22.6, 21.3. ½a D31
ꢁ3.3 (c 0.51 in CH3OH).
ꢂ
4.2.1. Compound 1. 1H NMR (CDCl3):
d
10.60 (s, 1H), 9.88 (d,
4.2.10. Compound 11. White solid. 1H NMR ((CD3)2SO):
d 9.36 (s,
J¼6.9 Hz, 1H), 8.00e7.98 (m, 1H), 7.69e7.58 (m, 3H), 5.80 (d,
1H), 8.93 (br, 1H), 7.82 (s,1H), 7.74 (s, 1H), 7.42e7.37 (m, 5H), 5.48 (s,
2H), 5.20 (d, J¼16.5 Hz,1H), 5.13 (d, J¼16.5 Hz,1H), 4.16 (d, J¼8.2 Hz,
J¼16.5 Hz, 1H), 5.76 (d, J¼16.5 Hz, 1H), 4.41e4.34 (m, 1H), 4.22 (s,
3H), 3.60 (s, 3H), 1.50 (d, J¼7.3 Hz, 3H); 13C NMR:
d
172.6, 164.7,
1H), 3.62 (s, 3H), 0.95 (s, 9H); 13C NMR:
d 170.9, 165.3, 137.5, 134.8,
143.5,131.6,131.4,127.2,126.9,114.1,112.1, 52.1, 49.2, 48.8, 33.6,16.7.
128.9, 128.7, 128.2, 124.2, 121.8, 60.9, 51.8, 51.5, 50.5, 33.8, 26.4. ½a D31
ꢂ
½
a 2D8
ꢂ
ꢁ5.1 (c 0.55 in CH3OH).
ꢁ3.2 (c 0.62 in CH3OH).
4.2.2. Compound 2. 1H NMR (CDCl3):
d
10.67 (s,1H), 9.67 (d, J¼7.3 Hz,
4.2.11. Compound 12. White solid. 1H NMR ((CD3)2SO):
d 9.53 (br,
1H), 8.04e8.02 (m, 1H), 7.68e7.60 (m, 3H), 5.94 (d, J¼16.5 Hz, 1H),
5.88 (d, J¼16.5 Hz, 1H), 4.29e4.26 (m, 1H), 4.22 (s, 3H), 3.61 (s, 3H),
2.32e2.24 (m, 1H), 1.07 (d, J¼6.9 Hz, 3H), 1.00 (d, J¼6.9 Hz, 3H); 13C
1H), 9.35 (s, 1H), 7.82 (s, 1H), 7.73 (s, 1H), 7.41e7.38 (m, 10H), 5.48 (s,
2H), 5.46 (d, J¼7.3 Hz,1H), 5.18 (d, J¼16.5 Hz, 1H), 5.12 (d, J¼16.5 Hz,
1H), 3.62 (s, 3H); 13C NMR:
d 170.5, 165.0, 137.5, 135.6, 134.8, 129.0,
NMR:
d
171.8, 165.2, 143.5, 131.9, 131.5, 127.4, 127.1, 114.5, 112.0, 59.0,
128.8, 128.7, 128.5, 128.2, 127.7, 124.3, 121.9, 56.4, 52.4, 51.8, 50.5.
51.9, 49.4, 33.6, 30.1, 19.1, 18.5. ½a D28
ꢂ
ꢁ3.8 (c 0.50 in CH3OH).
½ ꢂ þ3.2 (c 0.63 in CH3OH).
a 3D2
4.2.3. Compound 3. 1H NMR (CDCl3):
d
10.49 (s, 1H), 9.63 (d,
4.2.12. Compound 13. White solid. 1H NMR ((CD3)2SO):
d 9.24 (s,
J¼6.9 Hz, 1H), 7.96e7.94 (m, 1H), 7.64e7.62 (m, 3H), 5.80 (d,
J¼16.0 Hz, 1H), 5.71 (d, J¼16.0 Hz, 1H), 4.43e4.37 (m, 1H), 4.21 (s,
3H), 3.61 (s, 3H), 1.82e1.80 (m, 2H), 1.65e1.63 (m, 1H), 0.94 (d,
1H), 9.12 (br, 1H), 7.79 (s, 1H), 7.63 (s, 1H), 7.42e7.39 (m, 5H),
7.28e7.21 (m, 5H), 5.45 (s, 2H), 5.05 (d, J¼16.5 Hz, 1H), 5.00 (d,
J¼16.5 Hz, 1H), 4.54e4.49 (m, 1H), 3.59 (s, 3H), 3.07e3.02 (m, 1H),
J¼6.0 Hz, 3H), 0.88 (d, J¼6.0 Hz, 3H); 13C NMR:
d
173.0, 165.1, 143.6,
2.96e2.90 (m, 1H); 13C NMR:
d 171.4, 165.0, 137.5, 136.7, 134.8, 129.1,
131.8, 131.5, 127.2, 127.0, 114.3, 112.1, 52.1, 51.8, 49.4, 39.7, 33.6, 24.8,
129.0, 128.7, 128.3, 128.2, 126.7, 124.2, 121.8, 54.0, 53.2, 52.0, 50.4,
22.7, 21.5. ½a 2D8
ꢂ
ꢁ3.6 (c 0.50 in CH3OH).
17.3. ½a 3D2
þ0.7 (c 0.56 in CH3OH).
ꢂ

M. Yoshimura et al. / Tetrahedron 68 (2012) 3512e3518
3517
4.2.13. Compound 20. White solid; mp 165.0e165.3 ꢀC. 1H NMR
((CD3)2SO):
4.2.21. Compound 28. White solid. 1H NMR ((CD3)2SO):
d
8.19 (br,
d
9.78 (s, 1H), 9.28 (d, J¼7.3 Hz, 1H), 8.03e8.01 (m, 1H),
1H), 7.71e7.63 (m, 2H), 7.41e7.28 (m, 7H), 5.73 (s, 2H), 5.28 (d,
J¼15.9 Hz, 1H), 5.20 (d, J¼15.9 Hz, 1H), 4.58 (br, 1H), 3.63e3.58 (m,
7.91e7.88 (m, 1H), 7.71e7.67 (m, 2H), 5.42 (s, 2H), 5.32 (t, J¼6.0 Hz,
1H), 4.39e4.35 (m, 1H), 4.12 (s, 3H), 3.83e3.75 (m, 1H), 3.71e3.66
2H), 3.42e3.36 (m, 1H), 0.86 (s, 9H); 13C NMR:
d 166.1, 136.2, 134.0,
(m, 1H), 3.62 (s, 3H); 13C NMR:
d
170.4, 164.9, 143.7, 131.5, 131.3,
133.0, 128.7, 128.0, 127.3, 123.9, 123.9, 112.2, 60.4, 59.2, 51.7, 51.3,
33.6, 26.8, the carbene resonance was not observed.
126.7, 126.5, 113.6, 113.4, 61.0, 55.1, 52.0, 48.3, 33.3. Anal. Calcd for
C14H18ClN3O4$0.6H2O: C, 49.66; H, 5.72; N, 12.41. Found: C, 49.55;
H, 5.49; N, 12.33%. ½a D28
ꢂ
ꢁ3.2 (c 1.00 in CH3OH).
4.2.22. Compound 29. White solid. 1H NMR (CDCl3):
d 9.01 (br, 1H),
7.77e7.75 (m, 1H), 7.63e7.61 (m, 1H), 7.45e7.43 (m, 2H), 5.27 (br,
1H), 5.27 (s, 2H), 4.38e4.35 (m, 1H), 4.04 (s, 3H), 3.78e3.75 (m, 1H),
4.2.14. Compound 21. White solid; mp 213.0e213.3 ꢀC. 1H NMR
((CD3)2SO):
d
9.98 (s, 1H), 9.27 (d, J¼7.8 Hz, 1H), 7.99e7.97 (m, 1H),
3.69e3.65 (m, 1H), 3.63 (s, 3H); 13C NMR:
d 170.6,166.5, 133.7,133.7,
7.92e7.90 (m, 1H), 7.70e7.62 (m, 2H), 7.50e7.48 (m, 2H), 7.43e7.35
(m, 3H), 5.84 (s, 2H), 5.44 (s, 2H), 5.30 (t, J¼6.0 Hz, 1H), 4.41e4.37
(m, 1H), 3.81e3.76 (m, 1H), 3.71e3.66 (m, 1H), 3.63 (s, 3H); 13C
123.8, 123.8, 111.9, 111.8, 61.0, 54.8, 51.9, 50.6, 35.5, the carbene
resonance was not observed.
NMR:
d 170.3, 164.9, 143.6, 133.9, 131.6, 130.4, 129.0, 128.7, 128.1,
4.3. General procedure for the Cu(OTf)2-catalyzed ECA of
enone with R2Zn
126.8, 126.7, 113.8, 113.7, 61.0, 55.0, 52.0, 49.8, 48.4. Anal. Calcd for
C20H22ClN3O4: C, 59.48; H, 5.49; N, 10.40. Found: C, 59.39; H, 5.35;
N, 10.37%. ½a 2D9
ꢁ4.0 (c 0.10 in CH3OH).
ꢂ
To a solution of azolium salt (0.045 mmol) in THF (9 mL) were
added Cu(OTf)2 (0.045 mmol) and enone (1 mmol). After the
mixture was cooled to 0 ꢀC, Et2Zn (3 mmol, 1 mol/L in hexanes) was
added to the reaction vessel. The color immediately changed from
yellow to dark brown. After stirring at room temperature for 3 h,
the reaction was quenched with 10% HCl aq. The resulting mixture
was extracted with diisopropyl ether and dried over Na2SO4. The
product was purified by silica gel column chromatography (hexane/
EtOAc). The ee was measured by chiral GLC.
4.2.15. Compound 22. White solid; mp 171.0e171.2 ꢀC. 1H NMR
((CD3)2SO):
d
9.75 (s, 1H), 9.19 (d, J¼7.8 Hz, 1H), 8.04e8.02 (m, 1H),
7.91e7.88 (m, 1H), 7.72e7.67 (m, 2H), 5.41 (s, 2H), 5.28 (t, J¼6.0 Hz,
1H), 4.37e4.33 (m, 1H), 4.13 (s, 3H), 4.08 (q, J¼6.9 Hz, 2H),
3.80e3.75 (m, 1H), 3.71e3.65 (m, 1H), 1.15 (t, J¼6.9 Hz, 3H); 13C
NMR:
d 169.8, 164.9, 143.7, 131.5, 131.3, 126.6, 126.5, 113.6, 113.4,
61.0, 60.7, 55.2, 48.2, 33.3, 14.0. Anal. Calcd for
C15H20ClN3O4$0.6H2O: C, 51.09; H, 6.06; N, 11.92. Found: C, 51.10; H,
5.82; N, 11.85%. ½a D28
ꢁ2.8 (c 0.50 in CH3OH).
ꢂ
Acknowledgements
4.2.16. Compound 23. White solid; mp 176.8e177.1 ꢀC. 1H NMR
((CD3)2SO):
This work was financially supported by A-STEP (AS221Z00708D)
from Japan Science and Technology Agency (JST), the Sumitomo
Foundation (100631), a Grant-in-Aid for Scientific Research (C)
(20550103) from Japan Society for the Promotion of Science (JSPS),
and the Kansai University Grant-in-Aid for progress of research in
graduate course, 2010.
d
9.77 (s, 1H), 9.31 (d, J¼7.8 Hz, 1H), 8.03e8.01 (m, 1H),
7.88e7.86 (m, 1H), 7.71e7.62 (m, 2H), 7.35e7.33 (m, 5H), 5.43 (s,
2H), 5.36 (t, J¼6.0 Hz, 1H), 5.13 (s, 2H), 4.46e4.42 (m, 1H), 4.12 (s,
3H), 3.85e3.80 (m, 1H), 3.75e3.70 (m, 1H); 13C NMR:
d 169.8, 164.9,
143.7, 135.8, 131.4, 131.3, 128.3, 127.9, 127.6, 126.6, 126.4, 113.6, 113.3,
66.0, 61.0, 55.2, 48.2, 33.3. Anal. Calcd for C20H22ClN3O4$0.8H2O: C,
57.43; H, 5.69; N, 10.05. Found: C, 57.43; H, 5.46; N, 10.12%. ½a D28
ꢂ
Supplementary data
ꢁ2.2 (c 0.50 in CH3OH).
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2011.04.028.
4.2.17. Compound 24. Yellow solid. 1H NMR (CDCl3):
d 7.37 (br, 1H),
4.67e4.64 (m,1H), 4.06e4.03 (m,1H), 3.97e3.96 (m,1H), 3.93 (s, 2H),
3.82 (s, 3H), 2.34 (br,1H); 13C NMR:
d
170.3,166.1, 62.8, 55.1, 52.9, 28.5.
References and notes
4.2.18. Compound 25. Light yellow solid. 1H NMR ((CD3)2SO):
d 9.79
(s, 1H), 9.27 (d, J¼7.3 Hz, 1H), 8.04e8.02 (m, 1H), 7.90e7.87 (m, 1H),
7.70e7.68 (m, 2H), 5.43 (s, 2H), 5.39 (br,1H), 4.40e4.36 (m,1H), 4.13
(s, 3H), 3.80e3.76 (m,1H), 3.69e3.66 (m,1H), 3.62 (s, 3H); 13C NMR:
ꢀ
1. (a) Bartok, M. Chem. Rev. 2010, 110, 1663e1705; (b) Tanaka, T.; Hayashi, M.
Synthesis 2008, 3361e3376; (c) Zanoni, G.; Castronovo, F.; Franzini, M.; Vidari,
G.; Giannini, E. Chem. Soc. Rev. 2003, 32, 115e129; (d) Sibi, M. P.; Liu, M. Curr.
Org. Chem. 2001, 5, 719e755.
2. For selected recent examples: (a) Inagaki, T.; Ito, A.; Ito, J.-i.; Nishiyama, H.
Angew. Chem., Int. Ed. 2010, 49, 9384e9387; (b) Liu, Y.; Shang, D.; Zhou, X.; Zhu,
Y.; Lin, L.; Liu, X.; Feng, X. Org. Lett. 2010, 12, 180e183; (c) Nojiri, A.; Kumagai,
N.; Shibasaki, M. J. Am. Chem. Soc. 2009, 131, 3779e3784; (d) Kim, H. Y.; Shih, H.
J.; Knabe, W. E.; Oh, K. Angew. Chem., Int. Ed. 2009, 48, 7420e7423; (e) Kim, H.
Y.; Oh, K. Org. Lett. 2009, 11, 5682e5685; (f) Spangler, K. Y.; Wolf, C. Org. Lett.
2009, 11, 4724e4727; (g) Abermil, N.; Masson, G.; Zhu, J. P. Org. Lett. 2009, 11,
4648e4651; (h) Wu, W.-Q.; Peng, Q.; Dong, D.-X.; Hou, X.-L.; Wu, Y.-D. J. Am.
Chem. Soc. 2008, 130, 9717e9725.
3. For selected recent reviews: (a) Hawner, C.; Alexakis, A. Chem. Commun. 2010,
7295e7306; (b) Jerphagnon, T.; Pizzuti, M. G.; Minnaard, A. J.; Feringa, B. L.
Chem. Soc. Rev. 2009, 38, 1039e1075; (c) Alexakis, A.; Backvall, J. E.; Krause, N.;
Pamies, O.; Dieguez, M. Chem. Rev. 2008, 108, 2796e2823; (d) Alexakis, A.;
Benhaim, C. Eur. J. Org. Chem. 2002, 3221e3236.
4. For selected recent reviews: (a) Kuhl, O. Funtionalised N-Heterocyclic Carbene
d
170.4, 164.9, 143.6, 131.4, 131.3, 126.7, 126.4, 113.6, 113.4, 60.9, 55.1,
52.0, 48.2, 33.3. ½a D28
ꢁ1.1 (c 0.57 in CH3OH).
ꢂ
4.2.19. Compound 26. White solid. 1H NMR ((CD3)2SO):
d 8.83 (d,
J¼7.8 Hz, 1H), 8.15 (s, 1H), 7.65e7.63 (m, 1H), 7.45e7.44 (m, 1H),
7.25e7.17 (m, 2H), 5.18 (t, J¼6.4 Hz, 1H), 5.03 (s, 2H), 4.41e4.36 (m,
1H), 3.78e3.72 (m, 1H), 3.67e3.65 (m, 1H), 3.62 (s, 3H); 13C NMR:
d
170.7, 166.9, 144.8, 143.2, 134.1, 122.3, 121.4, 119.3, 110.2, 61.1, 54.7,
€
51.9, 46.5.
ꢁ
ꢀ
€
4.2.20. Compound 27. Light yellow solid; mp 169.5e169.8 ꢀC. 1H
ꢀ
Complexes; Wiley-VCH: Weinheim, 2010; (b) Díez-Gonzalez, S.; Marion, N.;
NMR ((CD3)2SO):
d
9.70 (s, 1H), 9.13 (d, J¼7.8 Hz, 1H), 8.05e8.01
Nolan, S. P. Chem. Rev. 2009, 109, 3612e3676; (c) Snead, D. R.; Seo, H.; Hong, S.
Curr. Org. Chem. 2008, 12, 1370e1387; (d) Hahn, F. E.; Jahnke, M. C. Angew.
Chem., Int. Ed. 2008, 47, 3122e3172; (e) N-Heterocyclic Carbenes in Transition
Metal Catalysis; Glorius, F., Ed.Topics in Organometallic Chemistry; Springer:
Berlin/Heidelberg, 2007; Vol. 21; (f) Douthwaite, R. E. Coord. Chem. Rev. 2007,
251, 702e717; (g) Nolan, S. P. N-Heterocyclic Carbenes in Synthesis; Wiley-VCH:
Weinheim, 2006; (h) Gade, L. H.; Bellemin-Laponnaz, S. Coord. Chem. Rev. 2007,
251, 718e725; (i) Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G. Angew. Chem., Int.
Ed. 2007, 46, 2768e2813; (j) Sigman, M. S.; Jensen, D. R. Acc. Chem. Res. 2006,
39, 21e229; (k) Peris, E.; Crabtree, R. H. Coord. Chem. Rev. 2004, 248,
(m, 1H), 7.88e7.84 (m, 1H), 7.72e7.68 (m, 2H), 5.42 (d, J¼16.5 Hz,
1H), 5.38 (d, J¼16.5 Hz, 1H), 5.29 (br, 1H), 4.42e4.38 (m, 1H), 4.12
(s, 3H), 3.81e3.76 (m, 1H), 3.69e3.65 (m, 1H), 3.63 (s, 3H); 13C
NMR:
d 170.4, 164.9, 143.6, 131.4, 131.3, 126.7, 126.5, 113.6, 113.3,
61.0, 54.9, 52.0, 48.2, 33.3. Anal. Calcd for C14H18IN3O4: C, 40.11; H,
4.33; N, 10.02. Found: C, 40.11; H, 4.26; N, 9.98%. ½a D27
ꢁ11.0 (c 0.10
ꢂ
in CH3OH).

3518
M. Yoshimura et al. / Tetrahedron 68 (2012) 3512e3518
ꢀ
2239e2246; (l) Cesar, V.; Bellemin-Laponnaz, S.; Gade, L. H. Chem. Soc. Rev.
2004, 33, 619e636; (m) Perry, M. C.; Burgess, K. Tetrahedron: Asymmetry 2003,
14, 951e961; (n) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290e1309.
5. (a) Guillen, F.; Winn, C. L.; Alexakis, A. Tetrahedron: Asymmetry 2001, 12,
2083e2086; (b) Pytkowicz, J.; Roland, S.; Mangeney, P. Tetrahedron: Asymmetry
2001, 12, 2087e2089; (c) Alexakis, A.; Winn, C. L.; Guillen, F.; Pytkowicz, J.;
Roland, S.; Mangeney, P. Adv. Synth. Catal. 2003, 345, 345e348.
9. (a) Brown, M. K.; Hoveyda, A. H. J. Am. Chem. Soc. 2008, 130, 12904e12906; (b)
May, T. L.; Brown, M. K.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2008, 47,
7358e7362; (c) Brown, M. K.; May, T. L.; Baxter, C. A.; Hoveyda, A. H. Angew.
Chem., Int. Ed. 2007, 46, 1097e1100; (d) Lee, K.-s.; Brown, M. K.; Hird, A. W.;
Hoveyda, A. H. J. Am. Chem. Soc. 2006, 128, 7182e7184.
10. Selected recent publications: (a) Shintani, R.; Takatsu, K.; Hayashi, T. Chem.
Commun. 2010, 6822e6824; (b) Uchida, T.; Katsuki, T. Tetrahedron Lett. 2009,
50, 4741e4743; (c) Matsumoto, Y.; Yamada, K.-i.; Tomioka, K. J. Org. Chem.
2008, 73, 4578e4581; (d) Moore, T.; Merzouk, M.; Williams, N. Synlett 2008,
21e24.
11. (a) Sakaguchi, S.; Yoo, K. S.; O’Neill, J.; Lee, J. H.; Stewart, T.; Jung, K. W. Angew.
Chem., Int. Ed. 2008, 47, 9326e9329; (b) Yoo, K. S.; O’Neill, J.; Sakaguchi, S.; Giles,
R.; Lee, J. H.; Jung, K. W. J. Org. Chem. 2010, 75, 95e101; (c) Sakaguchi, S.; Ka-
wakami, M.; O’Neill, J.; Yoo, K. S.; Jung, K. W. J. Organomet. Chem. 2010, 695,
195e200; (d) Kamisue, R.; Sakaguchi, S. J. Organomet. Chem. 2011, 696,
1910e1915.
6. (a) O’Brien, J. M.; Lee, K.-s.; Hoveyda, A. H. J. Am. Chem. Soc. 2010, 132,
10630e10633; (b) Lee, K.-s.; Hoveyda, A. H. J. Am. Chem. Soc. 2010, 132,
2898e2900; (c) Hirsch-Weil, D.; Abboud, K. A.; Hong, S. Chem. Commun. 2010,
7525e7527; (d) Lee, K.-s.; Hoveyda, A. H. J. Org. Chem. 2009, 74, 4455e4462.
7. Arnold, P. L.; Rodden, M.; Davis, K. M.; Scarisbrick, A. C.; Blake, A. J.; Wilson, C.
Chem. Commun. 2004, 1612e1613.
8. (a) Kehrli, S.; Martin, D.; Rix, D.; Mauduit, M.; Alexakis, A. Chem.dEur. J. 2010,
16, 9890e9904; (b) Rix, D.; Labat, S.; Toupet, L.; Crevisy, C.; Mauduit, M. Eur. J.
Org. Chem. 2009, 1989e1999; (c) Henon, H.; Mauduit, M.; Alexakis, A. Angew.
ꢀ
ꢀ
Chem., Int. Ed. 2008, 47, 9122e9124; (d) Martin, D.; Kehrli, S.; d’Augustin, M.;
Clavier, H.; Mauduit, M.; Alexakis, A. J. Am. Chem. Soc. 2006, 128, 8416e8417; (e)
Clavier, H.; Coutable, L.; Toupet, L.; Guillemin, J.-C.; Mauduit, M. J. Organomet.
Chem. 2005, 690, 5237e5254.
12. (a) Okamoto, M.; Yamamoto, Y.; Sakaguchi, S. Chem. Commun. 2009, 7363e7365;
(b) Shibata, N.; Okamoto, M.; Yamamoto, Y.; Sakaguchi, S. J. Org. Chem. 2010, 75,
5707e5715; (c) Harano, A.; Sakaguchi, S. J. Organomet. Chem. 2011, 696, 61e67.
13. Lee, Y.; Li, B.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 11625e11633.