Synthesis of new Schiff base-camphorsulfonyl amide ligands and in situ screening in the asymmetric additions of organozinc reagents to aldehydes

Article abstract of DOI:10.1016/j.tetasy.2008.10.017

We have designed and synthesized a new library of highly modular Schiff base-camphorsulfonyl amide ligands from readily available starting materials. These ligands have been used in the asymmetric addition of diethyl zinc to aldehydes in good yields (up to 91%) and high enantioselectivities (up to 93%). Moreover, when the ligands were used in the asymmetric addition of phenylacetylene to aldehydes, good yields and moderate to high ee values (up to 90%) were obtained. The introduction of the camphorsulfonyl moiety into the ligands is highly critical for the selectivities of the reactions.

Full text of DOI:10.1016/j.tetasy.2008.10.017

Tetrahedron: Asymmetry 19 (2008) 2451–2457
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Tetrahedron: Asymmetry
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Synthesis of new Schiff base-camphorsulfonyl amide ligands and in situ
screening in the asymmetric additions of organozinc reagents to aldehydes
Jiangtao Sun a, Xu Pan a, Zhenya Dai a, Chengjian Zhu a,b,
*
a School of Chemistry and Chemical Engineering, State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, PR China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, Shanghai 200032, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
We have designed and synthesized a new library of highly modular Schiff base-camphorsulfonyl amide
ligands from readily available starting materials. These ligands have been used in the asymmetric addi-
tion of diethyl zinc to aldehydes in good yields (up to 91%) and high enantioselectivities (up to 93%).
Moreover, when the ligands were used in the asymmetric addition of phenylacetylene to aldehydes, good
yields and moderate to high ee values (up to 90%) were obtained. The introduction of the camphorsulfo-
nyl moiety into the ligands is highly critical for the selectivities of the reactions.
Received 9 September 2008
Accepted 14 October 2008
Available online 29 November 2008
Published by Elsevier Ltd.
1. Introduction
asymmetric reaction is highly depended on the choice of a suitable
chiral ligand. However, there is no general ligand that is good for
To obtain enantiomerically pure organic compounds, asymmet-
ric catalysis is one of the most important methods. A successful
every reaction and every substrate.1 Therefore, exploring new
efficient ligands is always one of the key interests of synthetic
N
N
HO
HN
S
NH
SO2
O2
HO
t-Bu
t-Bu
OH
OH
t-Bu
t-Bu
Jacobsen's
Walsh's
2
1
R1
SO2
HN
N
O2
S
MeO
NH HN SO2
Me
R2
OH
OH
R2
Yus's
Gennari's
4
3
Figure 1.
* Corresponding author. Tel.: +86 25 83594886; fax: +86 25 83317761.
E-mail address: cjzhu@nju.edu.cn (C. Zhu).
0957-4166/$ - see front matter Published by Elsevier Ltd.
doi:10.1016/j.tetasy.2008.10.017

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J. Sun et al. / Tetrahedron: Asymmetry 19 (2008) 2451–2457
chemists. However, the synthetic procedures toward chiral ligands
are often lengthy and tedious. Moreover, expensive chiral starting
materials are often required. An efficient and flexible synthetic
strategy for a much simpler ligand structure from the readily avail-
able starting materials is strongly desired (Fig. 1).
ferent moieties, and the applications of this library in the asym-
metric addition of organozinc reagents to aldehydes.7,8
2. Results and discussion
Chiral Salen ligand 1 has been successfully used in various
asymmetric reactions with excellent results.2 Yus and Walsh inde-
pendently reported their applications of ligand 2 bearing a cam-
phor and cyclohexane backbone in various reactions with good
results.3 Recently, Gennari reported their discoveries of new effi-
cient ligands 3 for several reactions by the screening of a parallel
library.4 More recently, Yus reported the utilizations of ligands 4
in a series of asymmetric reactions.5 The excellent performances
of these types of ligands are due to the fact that these multi-
dentate donors favor the formation of organometallic complexes,
which possess well-organized spatial arrangements to give rise
to good asymmetric induction in the catalytic process.6 Moreover,
different chiral moieties of the ligand may play different roles in
the catalytic cycle, which results in a cooperation effect by activat-
ing the substrate, the nucleophile or the electrophile. Herein, we
report a rapid synthesis of a new library of ligands with three dif-
The synthesis of a new library of Schiff base-camphorsulfonyla-
mide ligands is straightforward (Scheme 1). They were synthesized
very efficiently in two or three steps from commercially available
chiral 1,2-cyclohexanediamine and chiral camphorsulfonyl
chloride. Firstly, treatment of chiral diamine (R,R)-5 with 1 equiv
of chiral (1S)-(+)-10-camphorsulfonyl chloride furnished the
single-substituted sulfonylamide. The reduction with sodium
borohydride under standard conditions produced a mixture of
two possible diastereomeric alcohols, the major exo-6 and the
minor endo-6 (in a ratio of 6:1). The crude products were recrystal-
lized from acetone/n-hexane to afford the desired exo-6 as a white
solid. Alternatively, the mixture of the two diastereomers can be
used directly for the next condensation reaction, and the Schiff
base-camphorsulfonylamide was obtained as a mixture of two
diastereomers. The minor one can be easily removed by a simple
recrystallization from a mixed solvent of acetone and n-hexane.
SO2
O
O
SO2
ii) salicylaldehyde,
Na2SO4
NH
i) (+)-camphorsulfonyl
chloride, Et3N, CH2Cl2
NH
H2N
NH2
N
OH
R1
NH2
5
R2
7a-h
ii) NaBH4, MeOH/THF
a: R1 = R2 = H
e: R1 = Cl, R2 = H
f : R1 = CH3, R2 = H
g: R1 = H, R2 = t-Bu
h: 2-naphthal
b: R1 = OCH3, R2 =H
c: R1 = R2 = t-Bu
d: R1 = R2 = Cl
OH
OH
SO2
NH
SO2
iii) salicylaldehyde,
Na2SO4
NH
N
OH
R1
NH2
6
8a-h
R2
a: R1 = R2 = H
e: R1 = Cl, R2 = H
f: R1 = CH3, R2 = H
g: R1 = H, R2 = t-Bu
h: 2-naphthal
b: R1 = OCH3, R2 =H
c: R1 = R2 = t-Bu
d: R1 = R2 = Cl
Scheme 1. Synthesis of chiral ligands.

J. Sun et al. / Tetrahedron: Asymmetry 19 (2008) 2451–2457
2453
Then, the pure target chiral ligands were obtained as yellow nee-
dles in a yield of 62–75% from (R,R)-5. Next, these ligands had been
tested in the asymmetric addition of organozinc reagents to
aldehydes.
Table 1 shows the results of the additions of diethyl zinc to
benzaldehyde in the presence of Schiff base-camphorsulfonyl-
amide ligands 7a–h and 8a–h. The reactions were carried out with
2 equiv of Et2Zn and 10 mol % of ligand in hexane at 0 °C for 24 h.
Over this period, the benzaldehyde was completely consumed, and
the ee values of the 1-phenyl-1-propranol were determined by chi-
ral HPLC in a range from 16% to 90%.
selectivity (Table 1, entry 9 vs entry 21). Although the substituents
on the phenyl ring of the salicyl part would significantly affect the
stereoselectivity, for un-substituted ligand, the stereoselectivity
was exclusively governed by the camphor portion. On the other
hand, for the matched cases, both the chirality of cyclohexanedi-
amine and camphor will be responsible for the high enantioselec-
tivity. For the mis-matched cases, the selectivity dropped sharply,
which may be due to the competitive effects between the two chi-
ral factors.
The results in Table 1 also showed that the efficiency of the cat-
alytic process strongly depended on the nature of the solvent.
Among all the four solvents investigated, hexane proved to be
the best choice in terms of reactivity and selectivity. Toluene or
CH2Cl2 gave good yields but moderate selectivities, while THF gave
both low yields and poor selectivities (Fig. 2).
Table 1
Asymmetric addition of ZnEt2 to benzaldehyde in the presence of Schiff base-
camphorsulfonylamide ligandsa
2 equiv. Et2Zn,
10 mol% ligand
O
OH
solvent, 0 oC, 24h
Ph
O
Ph
H
Entry
Ligand
Solvent
Yieldb (%)
eec (%)
N
HN
S
O
N
HN
S
O2
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
7a
7b
7c
7d
7e
7f
7g
7h
8a
8b
8c
8d
8e
8f
8g
8h
8a
8a
8a
9
Hexane
Hexane
Hexane
Hexane
Hexane
Hexane
Hexane
Hexane
Hexane
Hexane
Hexane
Hexane
Hexane
Hexane
Hexane
Hexane
Toluene
CH2Cl2
THF
62
55
47
64
46
62
66
51
88
80
87
92
91
68
81
82
86
75
56
52
76
42
46
57
35
54
36
49
61
90
33
85
47
62
45
64
71
70
65
43
22
<10
OH
OH
OH
10
9
Figure 2.
Under the optimized conditions, we examined the utility of
ligand 8a for the alkylation of a variety of aromatic and aliphatic
aldehydes. The results are summarized in Table 2. In all of the reac-
tions, the aldehydes were completely consumed after 24 h. In gen-
eral, the para- or ortho-substituted aromatic aldehydes with an
electron-withdrawing group furnished the products with a slight
higher ee values than those bearing electron-donating group (en-
tries 4–6 vs entries 2 and 3). In particular, 4-chloro benzaldehyde
gave the chiral alcohol in high yield (91%) and the highest ee value
(93%) (entry 4). And the aliphatic aldehydes gave both moderate
chemical yields and enantioselectivities (entries 9 and 10).
Hexane
Hexane
10
a
Unless otherwise noted, all reactions were carried out at 0 °C for 24 h. Molar
ratio: Et2Zn/aldehyde/ligand = 2:1:0.1.
Table 2
b
Asymmetric addition of ZnEt2 to aldehydes in the presence of ligand 8aa
The yields of isolated products.
c
Determined by HPLC with a Daicel Chiralcel OD column.
2 equiv. Et2Zn,
O
OH
10 mol% 8a
The results from Table 1 also indicate that the catalytic perfor-
mance of the ligands is highly affected by the sulfonylamide moi-
ety and the Schiff base part. In general, ligands 8a–h, which bear a
hydroxy group of the camphor backbone, gave better asymmetric
induction than those with the carbonyl group 7a–h (entries 9–16
vs entries 1–8). Namely, to obtain high enantioselectivity and good
reactivity in this reaction, the hydroxy group of the camphor moi-
ety is necessary. The different substituent at the aromatic ring of
the Schiff base moiety also affected both the reactivity and the
selectivity. The ortho- and para-substituted ligands gave lower
enantioselectivities than 8a. The ligands with an electron-donating
group at the phenyl ring displayed better asymmetric induction
than those bearing electron-withdrawing substitutes (entries 11
and 15 vs entries 12 and 13, Table 1). In particular, the best enantio-
selectivity was obtained when ligand 8a was employed. In addi-
tion, all of the products were obtained with (S)-configuration.
To determine whether there were cooperative effects between
the chiral 1,2-cyclohexanediamine and the chiral camphor moiety,
ligand 93l bearing an achiral tolyl sulfonylamide group and ligand
10 bearing (S,S)-1,2-cyclohexanediamine moiety had been pre-
pared and investigated in this reaction. However, they both affor-
ded poor reactivities and selectivities (Table 1, entries 20 and
21). Changing the (R,R)-diamine to the (S,S)-diamine furnished
the product in the same configuration but a sharply decreased
hexane, 0 oC, 24h
Ph
H
Ph
Entry
Aldehyde
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
Ph
88
84
82
91
84
89
78
91
76
82
90
88
82
93
89
90
65
79
76
82
p-CH3OC6H5
o-CH3OC6H5
p-ClC6H5
o-ClC6H5
p-BrC6H5
1-Naphthyl
2-Naphthyl
i-Bu
10
Cyclohexyl
a
Unless otherwise noted, all reactions were carried out in hexane at 0 °C for 24 h.
Molar ratio: Et2Zn/aldehyde/ligand = 2:1:0.1.
b
The yields of isolated products.
Determined by HPLC with a Daicel Chiralcel OD column.
c
Furthermore, ligands 7a–h and 8a–h were investigated in the
enantioselective addition of phenylacetylene to benzaldehyde. This
catalytic reaction was a two-step procedure. Firstly, deprotonation
of phenylacetylene with dimethylzinc yielded the corresponding
alkynyl zinc reagent. Secondly, the alkynyl zinc reagent reacted
with aldehyde in the presence of substoichiometric amounts of
chiral ligand and Ti(OiPr)4. The results are summarized in Table

2454
J. Sun et al. / Tetrahedron: Asymmetry 19 (2008) 2451–2457
Table 3
We also investigated the effect of the solvent in this reaction.
Among all the four solvents, toluene gave both good reactivity
and selectivity. THF displayed the best reactivity but poor selectiv-
ity (entry 7). Hexane gave both poor reactivity and selectivity
(entry 5). Also, CH2Cl2 afforded the product with moderate yield
but poor selectivity (entry 6). Increasing the catalyst loading
(15 mol % of 7a) gave a slightly higher enantioselectivity (89% ee)
but similar yield (entry 15). A lower catalyst loading gave a de-
crease in yield and poor selectivity (entry 16). Moreover, when
the reaction was carried out at 0 °C, moderate yields and moderate
ee values were observed (entry 17).
Under the aforementioned reaction conditions, we used 7a in
the asymmetric addition of phenylacetylene to a number of alde-
hydes. The results are summarized in Table 4. Moderate to high
chemical yields were obtained for all of the substrates. The aro-
matic aldehydes bearing an electron-withdrawing group at the
para-position gave products with higher enantioselectivity than
those with electron-donating group (entries 2–7). The aliphatic
aldehydes gave moderate chemical yields and moderate to high
enantioselectivities (entries 8 and 9). Increasing the ligand loading
to 15 mol % gave slightly higher ee values (entries 10–12).
Asymmetric addition of phenylacetylene to benzaldehyde in the presence of different
chiral ligandsa
30 mol% Ti(OiPr)4
OH
2 eq Me2Zn,
O
10 mol% 7a
Ph
solvent, rt, 24h
Ph
H
Ph
eec (%)
Entry
Ligand
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15d
16e
17f
7a
8a
9
Toluene
Toluene
Toluene
Toluene
Hexane
CH2Cl2
84
83
66
58
57
77
92
83
35
92
78
67
43
27
85
80
76
86
65
12
18
32
56
15
81
32
44
26
55
29
36
89
78
72
10
7a
7a
7a
7b
7c
7d
7e
7f
7g
7h
7a
7a
7a
THF
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
3. Conclusions
a
Unless otherwise noted, all reactions were carried out at room temperature for
In conclusion, we have prepared a new library of highly modu-
lar Schiff base-camphorsulfonyl amide ligands, and have applied
them to the enantioselective addition of organozinc reagents to
aldehydes, in which high yields and moderate to high enantio-
selectivities were obtained. This ligand library is very easily pre-
pared and only one simple recrystallization in the purification
procedure is needed. The results also showed that the cooperative
effects of the chiral 1,2-cyclohexanediamine and the chiral cam-
phor moiety are involved in our catalytic system. The matched chi-
rality of the two chiral parts of the ligand is essential for the high
enantioselectivity.
24 h. Molar ratio: phenylacetylene/Me2Zn/aldehyde/Ti(OiPr)4/ligand = 2:2:1:0.3:
0.1.
b
The yields of isolated products.
c
Determined by HPLC with a Daicel Chiralcel OD column.
d
Phenylacetylene/Me2Zn/aldehyde/Ti(OiPr)4/ligand = 2:2:1:0.3:0.15.
e
Phenylacetylene/Me2Zn/aldehyde/Ti(OiPr)4/ligand = 2:2:1:0.3:0.05.
f
This reaction was performed at 0 °C.
3. The best enantioselectivity was obtained when 7a was chosen as
the ligand. By comparing the reactivity and selectivity of 7a and 8a,
we chose 7a–h for further investigation. From the summarized
results, we can see that the substituted salicyl part had a large
influence on the reactivity and selectivity. The para- or ortho-
substituted ligands furnished chiral alcohols with lower enantio-
selectivity than 7a. However, there were no regular rules for the
reactivity. Ligands 9 and 10 also gave both low reactivities and
poor selectivities.
4. Experimental
4.1. General information
Elemental analyses were carried out on a Perkin–Elmer 240 C
elemental analyzer. 1H NMR data were recorded on a Bruker
AMX-300 spectra with chemical shifts referenced to SiMe4 as
internal standard. Electrospray ionization mass spectrums were
recorded on Finnigan LCQ Electrospray Mass Spectrometer. Optical
rotations were recorded on a Perkin–Elmer 241 Polarimeter. Ee
values were determined by a Perkin–Elmer 200 HPLC on a chiral
Chiralcel OD column with UV detection at 254 nm. All reagents
were obtained from commercial suppliers, and were used without
further purification unless otherwise stated. Toluene, hexane, and
THF were distilled from sodium/benzophenone. CH2Cl2 were dis-
tilled from CaH2. All reactions were carried out under an argon
atmosphere. All catalytic reactions were carried out in a Schlenk
tube.
Table 4
Asymmetric addition of phenylacetylene to aldehydes in the presence of ligand 7aa
30 mol% Ti(OiPr)4
OH
2 eq Me2Zn,
O
10 mol% 7a
R
toluene, rt, 24h
R
H
Ph
Entry
Aldehyde
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
Ph
84
82
78
91
76
83
54
73
74
85
80
82
86
84
81
72
73
85
78
82
68
89
87
90
p-ClC6H4
o-ClC6H4
o-MeOC6H4
p-MeOC6H4
p-BrC6H4
Piperonyl
n-Bu
i-Bu
Ph
p-ClC6H4
p-BrC6H4
4.2. Synthesis of chiral ligands
10d
11d
12d
4.2.1. Synthesis of intermediate 6
To a solution of (R,R)-1,2-diaminecyclohexane (1.7 g, 15 mmol)
in CH2Cl2 (40 mL) at 0 °C, was added dropwise (+)-camphor sulfo-
nyl chloride (2.0 g, 8 mmol) in CH2Cl2 (40 mL) over 60 min. After
the addition was completed, the mixture was allowed to warm
to room temperature. After being stirred overnight, the mixture
was washed with water. The organic phase was separated and
dried over anhydrous sodium sulfate. Then, the solvents were then
a
Unless otherwise noted, all reactions were carried out in toluene at room
temperature for 24 h. Molar ratio: phenylacetylene/Me2Zn/aldehyde/Ti(OiPr)4/
ligand = 2:2:1:0.3:0.1.
b
The yields of isolated products.
Determined by HPLC with a Daicel Chiralcel OD column. Absolute configuration
c
of the products was (S) by comparison of specific rotation reported in the literature.
d
Phenylacetylene/Me2Zn/aldehyde/Ti(OiPr)4/ligand = 2:2:1:0.3:0.15.

J. Sun et al. / Tetrahedron: Asymmetry 19 (2008) 2451–2457
2455
removed under reduced pressure. The following recrystallization
from acetone and n-hexane gave the single-substituted camp-
horsulfonyl amine (4.48 g, 91% yield) as a white solid. Mp 136–
138 °C; 1H NMR (300 MHz, CDCl3): d 3.42–3.37 (d, J = 15 Hz, 1H),
3.07–3.02 (d, J = 15 Hz, 1H), 3.42–1.18 (m, 8H), 1.04 (s, 3H), 0.92
(s, 3H) ppm; ESI (MS) m/z: 328.3 (M+); Anal. Calcd for C16H28N2O3S:
C, 58.50; H, 8.59; N, 8.53. Found: C, 58.62; H, 8.48; N, 8.41.
51.3, 48.8, 42.9, 35.4, 34.5, 33.8, 33.65, 31.9, 29.8, 27.2, 25.8,
24.6, 24.0, 20.1, 19.8 ppm; ESI (MS) m/z: 544.1 (M+); Anal. Calcd
for C31H48N2O4S: C, 68.34; H, 8.88; N, 5.14. Found: C, 68.51; H,
8.76; N, 5.27.
4.2.2.4. Compound 7d.
Yellow solid, mp 202–204 °C. ½a D26
¼
ꢁ
ꢂ60:2 (c 0.1, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 13.16 (s, 1H),
8.25 (s, 1H), 7.30 (m, 1H), 7.14 (m, 1H), 5.08 (m, 1H), 3.51 (m,
1H), 3.26–3.21 (d, J = 15 Hz, 1H), 3.03 (m, 1H), 2.76–2.72 (d,
J = 15 Hz, 1H), 2.20–1.19 (m, 15H), 0.90 (s, 3H), 0.74 (s, 3H) ppm;
13C NMR (75 MHz, CDCl3): d 217.1, 164.9, 160.7, 132.4, 131.2,
124.3, 120.1, 119.3, 73.0, 59.5, 58.1, 52.3, 48.3, 43.3, 34.9, 27.5,
26.6, 25.1, 24.1, 20.2, 19.5 ppm; ESI (MS) m/z: 500.6 (M+); Anal.
Calcd for C23H30Cl2N2O4S: C, 55.09; H, 6.03; N, 5.59. Found: C,
55.13; H, 55.16; N, 5.57.
In a 250 mL-three-necked flask equipped with a reflux con-
denser, the single-substituted camphorsulfonyl amine (4.3 g,
13.1 mmol) was dissolved in a mixed solvent (200 mL, MeOH/
THF = 1:1). Next, NaBH4 (1.89 g, 50 mmol) was added slowly. The
mixture was stirred for another 4 h. The reaction mixture was
quenched with saturated aqueous ammonium chloride, and the
solid was filtered. The filtrate was extracted with CH2Cl2
(3 ꢀ 50 mL). The organic phase was washed with water and was
dried over anhydrous sodium sulfate. The solvent was removed
under reduced pressure. The crude product was recrystallized from
acetone and n-hexane to give exo-6 (3.36 g, 78% yield) as a white
4.2.2.5. Compound 7e.
Yellow solid, mp 187–189 °C. ½a D26
¼
ꢁ
ꢂ71:4 (c 0.2, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 13.10 (s, 1H),
8.23 (s, 1H), 7.21–7.13 (m, 2H), 6.81 (m, 1H), 5.10 (m, 1H), 3.50
(m, 1H), 3.29–3.24 (d, J = 15 Hz, 1H), 3.0 (m, 1H), 2.74–2.69 (d,
J = 15 Hz, 1H), 2.20–1.19 (m, 15H), 0.84 (s, 3H), 0.70 (s, 3H) ppm;
13C NMR (75 MHz, CDCl3): d 216.5, 164.5, 160.0, 132.5, 131.0,
123.5, 119.8, 119.0, 72.8, 59.2, 57.5, 51.9, 48.8, 43.0, 33.7, 27.2,
26.3, 24.8, 24.0, 20.0, 19.7 ppm; ESI (MS) m/z: 466.4 (M+); Anal.
Calcd for C23H31ClN2O4S: C, 59.15; H, 6.69; N, 6.00. Found: C,
59.23; H, 6.65; N, 6.04.
solid. Mp 64–67 °C;
½
a 2D6
ꢁ
¼ ꢂ24:6 (c 0.1, CH2Cl2). 1H NMR
(300 MHz, CDCl3): d 3.57–3.53 (d, J = 13.5 Hz, 1H), 3.20–3.10 (m,
2H), 2.86–2.82 (d, J = 13.5 Hz, 2H), 2.07 (m, 2H), 1.66 (m, 6H),
1.45–1.26 (m, 6H), 1.0 (s, 3H), 0.85 (m, 1H), 0.77 (s, 3H) ppm; 13C
NMR (75 MHz, CDCl3): d 75.7, 62.4, 57.8, 53.5, 51.2, 48.3, 45.1,
39.4, 34.9, 34.1, 31.8, 28.2, 25.5, 24.6, 20.3, 19.7 ppm; ESI (MS)
m/z: 330.1 (M+); Anal. Calcd for C16H30N2O3S: C, 58.15; H, 9.15;
N, 8.48. Found: C, 58.32; H, 9.31; N, 8.56.
4.2.2. General procedure for synthesis of ligands 7a–h, 8a–h
To a solution of single-substituted sulfonyl amide (0.5 mmol) in
20 mL CH2Cl2 was added the aldehyde (0.5 mmol) at room temper-
ature. After being stirred overnight, the solid was filtered, and the
reaction mixture was washed with CH2Cl2. The filtrate was evapo-
rated under reduced pressure to give a crude yellow solid. Purifica-
tion of the crude solid by recrystallization from acetone and
n-hexane gave the ligand as a yellow solid in 75–93% yield.
4.2.2.6. Compound 7f.
Yellow solid, mp 172–174 °C. ½a D26
¼
ꢁ
ꢂ64:3 (c 0.1, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 13.27 (s, 1H),
8.26 (s, 1H), 7.10–7.04 (m, 2H), 6.76–6.69 (m, 1H), 4.88 (m, 1H),
3.50 (m, 1H), 3.34–3.29 (d, J = 15 Hz, 1H), 2.99 (m, 1H), 2.68–2.63
(d, J = 15 Hz, 1H), 2.20–2.18 (m, 2H), 2.15 (s, 3H), 1.91–1.14 (m,
12H), 0.80 (s, 3H), 0.65 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d
216.1, 165.8, 159.6, 133.8, 129.6, 126.3, 118.6, 72.6, 58.9, 57.5,
51.3, 48.8, 43.0, 33.8, 27.2, 25.9, 24.7, 24.0, 20.0, 19.7, 15.8 ppm;
ESI (MS) m/z: 446.0 (M+); Anal. Calcd for C24H34N2O4S: C, 64.54;
H, 7.67; N, 6.27. Found: C, 64.68; H, 7.77; N, 6.26.
4.2.2.1. Compound 7a.
Yellow solid, mp 150–152 °C. ½a D26
¼
ꢁ
ꢂ59:0 (c 0.1, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 13.1 (s, 1H),
8.36 (s, 1H), 7.33–7.28 (m, 2H), 6.95–6.86 (m, 2H), 4.79–4.76 (d,
J = 15 Hz, 1H), 3.57 (m, 1H), 3.42–3.37 (d, J = 15 Hz, 1H), 3.08 (m,
1H), 2.80–2.75 (d, J = 15 Hz, 1H), 2.30–1.47 (m, 15H), 0.9 (s, 3H),
0.76 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d 216.5, 165.5,
161.4, 132.8, 131.9, 119.0, 117.5, 72.9, 59.1, 57.4, 51.6, 48.9, 43.0,
33.7, 27.2, 26.7, 26.0, 24.7, 24.0, 20.0, 19.7 ppm; ESI (MS) m/z:
432.1 (M+); Anal. Calcd for C23H32N2O4S: C, 63.86; H, 7.46; N,
6.48. Found: C, 63.97; H, 7.61; N, 6.62.
4.2.2.7. Compound 7g.
Yellow solid, mp 163–166 °C. ½a D26
¼
ꢁ
ꢂ78:4 (c 0.2, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 13.54 (s, 1H),
8.27 (s, 1H), 7.24–7.22 (d, J = 6 Hz, 1H), 7.06–7.04 (d, J = 6 Hz,
1H), 6.75–6.69 (m, 1H), 4.98 (m, 1H), 3.50 (m, 1H), 3.32–3.27 (d,
J = 15 Hz, 1H), 3.0 (m, 1H), 2.74–2.69 (d, J = 15 Hz, 1H), 2.10–1.53
(m, 11H), 1.38 (s, 9H), 1.01 (m, 1H), 0.83 (s, 3H), 0.65 (s, 3H)
ppm; 13C NMR (75 MHz, CDCl3): d 216.4, 116.4, 160.7, 137.7,
130.3, 129.9, 118.9, 118.3, 72.6, 59.0, 57.3, 51.4, 48.8, 43.0, 35.2,
33.8, 29.8, 27.2, 25.9, 24.7, 24.0, 20.1, 19.7 ppm; ESI (MS) m/z:
487.8 (M+); Anal. Calcd for C27H40N2O4S: C, 66.36; H, 8.25; N,
5.73. Found: C, 66.48; H, 8.34; N, 5.89.
4.2.2.2. Compound 7b.
Yellow solid, mp 178–182 °C. ½a D26
¼
ꢁ
ꢂ66:0 (c 0.1, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 11.13 (s, 1H),
9.92 (s, 1H), 7.20–7.18 (d, J = 7.8 Hz, 1H), 7.14–7.11 (d, J = 7.8 Hz,
1H), 7.0–6.95 (m, 1H), 4.33–4.28 (d, J = 15 Hz, 1H), 3.92 (s, 3H),
3.76–3.71 (d, J = 15 Hz, 1H), 2.45 (m, 3H), 2.17–2.02 (m, 10H),
1.77 (m, 1H), 1.49 (m, 2H), 1.18 (s, 1H), 1.14 (s, 3H), 1.06 (s, 1H),
0.92 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d 213.2, 197.1,
151.9, 148.6, 124.9, 121.1, 120.0, 118.2, 64.6, 60.1, 56.6, 49.1,
48.6, 45.6, 43.1, 42.7, 27.2, 26.1, 25.7, 22.0, 21.4, 20.1, 20.0 ppm;
ESI (MS) m/z: 462.1 (M+); Anal. Calcd for C24H34N2O5S: C, 62.31;
H, 7.41; N, 6.06. Found: C, 62.48; H, 7.57; N, 6.16.
4.2.2.8. Compound 7h.
Yellow solid, mp 145–147 °C. ½a D26
¼
ꢁ
ꢂ28:5 (c 0.1, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 14.65 (s, 1H),
8.94 (s, 1H), 7.99–7.96 (d, J = 8.4 Hz, 1H), 7.68–7.62 (m, 2H),
7.48–7.43 (m, 1H), 7.26–7.24 (m, 1H), 6.99–6.96 (d, J = 9 Hz, 1H),
5.66–5.64 (d, J = 5.5 Hz, 1H), 5.54–5.51 (d, J = 7.8 Hz, 1H), 3.54–
3.49 (m, 2H), 3.39–3.34 (m, 2H), 2.83–1.54 (m, 9H), 1.12 (m, 1H),
1.04 (s, 2H), 0.9 (s, 2H), 0.84 (s, 3H), 0.69 (s, 3H) ppm; 13C NMR
(75 MHz, CDCl3): d 216.8, 173.6, 159.0, 136.9, 133.9, 129.4, 128.3,
126.8, 124.1, 123.2, 118.9, 107.4, 67.5, 59.1, 57.5, 51.6, 48.8, 43.0,
33.6, 32.9, 31.3, 27.2, 26.1, 24.5, 24.0, 19.9 ppm; ESI (MS) m/z:
482.0 (M+); Anal. Calcd for C27H34N2O4S: C, 67.19; H, 7.10; N,
5.80. Found: C, 67.31; H, 7.23; N, 5.95.
4.2.2.3. Compound 7c.
Yellow solid, mp 215–217 °C. ½a D26
¼
ꢁ
ꢂ44:8 (c 0.1, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 13.39 (s, 1H),
8.35 (s, 1H), 7.38 (s, 1H), 7.10 (s, 1H), 4.95 (s, 1H), 3.59 (m, 1H),
3.42–3.37 (d, J = 15 Hz, 1H), 3.08 (m, 1H), 2.82–2.77 (d, J = 15 Hz,
1H), 2.20–1.59 (m, 14H), 1.43 (s, 9H), 1.31 (s, 9H), 1.06 (s, 1H),
0.9 (s, 3H), 0.72 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d 216.5,
166.6, 158.4, 140.5, 137.1, 127.5, 126.5, 118.0, 72.7, 59.0, 57.3,
4.2.2.9. Compound 8a.
Yellow solid, mp 86–90 °C. ½a D26
¼
ꢁ
ꢂ61:5 (c 0.1, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 13.10 (s, 1H),
8.38 (s, 1H), 7.32–7.26 (m, 2H), 6.94–6.85 (m, 2H), 4.91–4.98 (d,

2456
J. Sun et al. / Tetrahedron: Asymmetry 19 (2008) 2451–2457
J = 8.1 Hz, 1H), 3.97 (m, 1H), 3.48 (m, 2H), 3.39–3.34 (d, J = 13.8 Hz,
1H), 3.0 (m, 1H), 2.45–2.41 (d, J = 13.8 Hz, 1H), 2.32–2.28 (m, 1H),
1.93–1.20 (m, 14H), 0.99 (s, 3H), 0.32 (s, 3H) ppm; 13C NMR
(75 MHz, CDCl3): d 166.1, 161.2, 133.0, 132.0, 119.2, 118.7, 117.7,
76.8, 73.1, 58.5, 53.7, 50.7, 49.0, 44.8, 39.2, 35.3, 34.3, 31.3, 27.7,
25.2, 24.3, 20.0, 19.6 ppm; ESI (MS) m/z: 433.8 (M+); Anal. Calcd
for C23H34N2O4S: C, 63.56; H, 7.89; N, 6.45. Found: C, 63.63; H,
7.94; N, 6.51.
4.2.2.15. Compound 8g.
Yellow solid, mp 95–97 °C. ½a D26
¼
ꢁ
ꢂ78:2 (c 0.2, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 13.36 (s, 1H),
8.31 (s, 1H), 7.26–7.24 (d, J = 7.8 Hz, 1H), 7.07–7.04 (d, J = 9 Hz,
1H), 6.77–6.72 (m, 1H), 4.62 (m, 1H), 3.91 (m, 1H), 3.40–3.32 (m,
1H), 3.33–3.28 (d, J = 13.2 Hz, 1H), 3.18 (m, 1H), 2.92 (m, 1H),
2.51–2.46 (d, J = 13.2 Hz, 1H), 2.29–2.27 (m, 1H), 1.98 (s, 1H),
1.87–1.38 (m, 10H), 1.34 (s, 9H), 1.23–1.17 (m, 2H), 0.82 (s, 3H),
0.33 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d 167.0, 160.6,
137.9, 130.3, 118.8, 118.6, 76.7, 72.8, 58.5, 53.8, 50.7, 48.9, 44.7,
39.2, 34.9, 34.4, 31.2, 29.9, 27.7, 24.3, 20.3, 20.3, 20.1 ppm; ESI
(MS) m/z: 490.4 (M+); Anal. Calcd for C27H42N2O4S: C, 66.09; H,
8.63; N, 5.71. Found: C, 66.12; H, 8.67; N, 5.68.
4.2.2.10. Compound 8b.
Yellow solid, mp 89–92 °C. ½a D26
¼
ꢁ
ꢂ42:2 (c 0.1, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 13.20 (s, 1H),
8.29 (s, 1H), 6.85–6.71 (m, 4H), 5.30 (s, 1H), 4.67 (m, 1H), 3.82 (s,
3H), 3.41–2.86 (m, 4H), 2.10–1.27 (m, 14H), 0.99 (s, 3H), 0.28 (s,
3H) ppm; 13C NMR (75 MHz, CDCl3): d 166.5, 152.6, 141.2, 135.1,
128.5, 127.1, 117.2, 74.1, 72.2, 57.5, 56.7, 54.2, 50.1, 49.2, 44.8,
39.7, 35.6, 35.4, 33.8, 32.1, 31.6, 29.8, 28.1, 25.6, 24.5, 19.8,
19.6 ppm; ESI (MS) m/z: 464.1 (M+); Anal. Calcd for C24H36N2O5S:
C, 62.04; H, 7.81; N, 6.03. Found: C, 62.21; H, 7.95; N, 6.17.
4.2.2.16. Compound 8h.
Yellow solid, mp 116–118 °C.
½
a 2D6
ꢁ
¼ ꢂ25:4 (c 0.1, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 14.72
(s, 1H), 9.0 (s, 1H), 8.0 (m, 1H), 7.74–7.66 (m, 3H), 7.48–7.46 (m,
1H), 7.32–7.28 (m, 1H), 7.02–6.99 (m, 1H), 5.28 (s, 1H), 3.85 (m,
1H), 3.50–3.22 (m, 4H), 1.85–1.31 (m, 13H), 0.93 (s, 3H), 0.68 (s,
1H), 0.34 (s, 1H), 0.28 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d
170.4, 160.0, 136.5, 133.5, 129.6, 128.4, 127.4, 123.5, 122.9,
119.0, 107.7, 76.6, 69.5, 58.7, 53.8, 50.7, 48.9, 44.7, 39.1, 35.4,
33.9, 31.0, 27.5, 24.5, 20.0, 19.7 ppm; ESI (MS) m/z: 484.2 (M+);
Anal. Calcd for C27H36N2O4S: C, 66.91; H, 7.49; N, 5.78. Found: C
66.91; H, 7.49; N, 5.78.
4.2.2.11. Compound 8c.
Yellow solid, mp 103–105 °C. ½a D26
¼
ꢁ
ꢂ49:0 (c 0.1, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 8.40 (s, 1H),
7.38 (s, 1H), 7.08 (s, 2H), 4.89–4.87 (d, J = 8.2 Hz, 1H), 3.98 (m,
1H), 3.37–3.33 (d, J = 13.8 Hz, 1H), 3.25 (m, 1H), 3.0 (m, 1H),
2.57–2.53 (d, J = 13.8 Hz, 1H), 2.34 (s, 1H), 2.17 (s, 4H), 2.07 (s,
1H), 2.05–1.50 (m, 9H), 1.42 (s, 9H), 1.29 (s, 9H), 0.96 (m, 1H),
0.85 (s, 3H), 0.35 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d 167.3,
158.3, 140.8, 137.2, 127.9, 126.3, 117.9, 76.7, 72.7, 58.5, 53.8,
50.6, 48.8, 44.6, 39.2, 35.4, 35.1, 34.5, 31.9, 31.1, 30.0, 27.7, 25.2,
24.3, 20.4, 20.1 ppm; ESI (MS) m/z: 546.2 (M+); Anal. Calcd for
C31H50N2O4S: C, 68.09; H, 9.22; N, 5.12. Found: C, 68.25; H, 9.42;
N, 5.24.
4.2.2.17. Compound 10.
Yellow solid, mp 53–55 °C. ½a D26
¼
ꢁ
ꢂ20:2 (c 0.1, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 13.13 (s, 1H),
8.42 (s, 1H), 7.36–7.30 (m, 2H), 7.04–6.95 (m, 2H), 5.01–4.96 (d,
J = 7.9 Hz, 1H), 4.02 (m, 1H), 3.51 (m, 2H), 3.43–3.38 (d,
J = 13.6 Hz, 1H), 3.11 (m, 1H), 2.52–2.46 (d, J = 13.6 Hz, 1H), 2.28–
2.26 (m, 1H), 1.90–1.22 (m, 14H), 1.02 (s, 3H), 0.36 (s, 3H) ppm;
13C NMR (75 MHz, CDCl3): d 167.2, 161.4, 133.3, 132.2, 119.6,
118.2, 117.3, 76.6, 73.3, 58.9, 54.2, 50.2, 48.3, 43.2, 38.7, 35.6,
34.7, 32.4, 28.2, 26.3, 25.7, 20.4, 19.4 ppm; ESI (MS) m/z: 433.8
(M+); Anal. Calcd for C23H34N2O4S: C, 63.56; H, 7.89; N, 6.45.
Found: C, 63.63; H, 7.94; N, 6.51.
4.2.2.12. Compound 8d.
Yellow solid, mp 130–132 °C. ½a D26
¼
ꢁ
ꢂ62:3 (c 0.2, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 14.06 (s, 1H),
8.23 (s, 1H), 7.32 (s, 1H), 7.12 (s, 1H), 5.06–5.0 (m, 1H), 3.87–
3.88 (m, 1H), 3.41 (m, 2H), 3.31–3.26 (d, J = 13.6 Hz, 1H), 2.98 (m,
1H), 2.39–2.34 (d, J = 13.6 Hz, 1H), 1.87–1.10 (m, 15H), 0.96 (s,
3H), 0.37 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d 164.6, 157.1,
132.9, 129.7, 123.6, 123.2, 119.5, 76.8, 72.0, 58.4, 53.8, 50.8, 49.0,
44.7, 39.3, 35.0, 34.0, 31.2, 27.7, 25.0, 24.1, 20.1, 19.8 ppm; ESI
(MS) m/z: 502.3 (M+); Anal. Calcd for C23H32Cl2N2O4S: C, 54.87;
H, 6.41; N, 5.56. Found: C, 58.86; H, 6.44; N, 5.58.
4.2.3. General procedure for the catalytic asymmetric addition
of diethylzinc to aldehydes
Under a dry argon atmosphere, a chiral ligand (10 mol %) in dry
n-hexane (2 mL) was cooled to 0 °C, and a solution of ZnEt2 (1.0 M
in hexanes, 3 mmol) was added slowly into the mixture. After
being stirred for an additional 1 h, freshly distilled aldehyde
(1 mmol) was added by a syringe. The resulting mixture was stir-
red at 0 °C for another 24 h. Next, the reaction mixture was
quenched with 2 M aqueous HCl. The aqueous phase was extracted
with ethyl acetate (3 ꢀ 10 mL). The combined organic phase was
dried over anhydrous sodium sulfate. Then, the solvent was re-
moved under reduced pressure. The residue was purified by flash
column chromatography on silica gel (petroleum ether/ethyl ace-
tate = 6:1) to give the product. The enantiomeric excess of the
product was determined by HPLC using a Daicel Chiralcel OD col-
umn. The absolute configurations of the products were assigned
by comparison to the literature values.
4.2.2.13. Compound 8e.
Yellow solid, mp 95–98 °C.
½
a 2D6
ꢁ
¼ ꢂ45:9 (c 0.2, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 13. 02
(s, 1H), 8.24 (s, 1H), 7.18–7.14 (m, 2H), 6.80–6.77 (d, J = 9 Hz,
1H), 4.95 (m, 1H), 3.88 (m, 1H), 3.40 (m, 1H), 3.30–3.26 (d,
J = 13.6 Hz, 1H), 2.92 (m, 1H), 2.36–2.32 (d, J = 13.6 Hz, 1H), 2.22–
2.20 (m, 1H), 1.80–1.14 (m, 14H), 0.91 (s, 3H), 0.32 (s, 3H) ppm;
13C NMR (75 MHz, CDCl3): d 165.1, 159.9, 132.8, 131.1, 123.8,
119.6, 119.2, 76.8, 72.9, 58.5, 53.8, 50.8, 49.0, 44.8, 39.2, 35.3,
34.3, 31.3, 27.7, 25.1, 24.2, 20.1, 19.7, 18.7 ppm; ESI (MS) m/z:
468.3 (M+); Anal. Calcd for C23H33ClN2O4S: C, 58.90; H, 7.09; N,
5.97. Found: C, 58.86; H, 7.13; N, 6.01.
4.2.2.14. Compound 8f.
Yellow solid, mp 97–99 °C. ½a D26
ꢁ
¼
4.2.4. General procedure for the catalytic asymmetric addition
of phenylacetylene to aldehydes
ꢂ64:3 (c 0.2, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 13.21 (s, 1H),
8.28 (s, 1H), 7.10–7.03 (m, 2H), 6.71–6.67 (m, 1H), 4.97–4.92 (m,
1H), 3.87 (m, 1H), 3.32–3.24 (m, 3H), 2.89 (m, 1H), 2.36–2.31 (d,
J = 13.6 Hz, 1H), 2.23–2.20 (m, 1H), 2.15 (s, 3H), 1.84–1.12 (m,
14H), 0.91 (s, 3H), 0.23 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d
166.4, 159.5, 134.1, 129.7, 126.5, 118.8, 118.0, 76.8, 72.9, 58.6,
53.6, 50.7, 48.9, 44.7, 39.2, 35.4, 34.5, 31.3, 27.7, 25.2, 24.3, 19.9,
19.7, 15.8 ppm; ESI (MS) m/z: 448.1 (M+); Anal. Calcd for
C24H36N2O4S: C, 64.25; H, 8.09; N, 6.24. Found: C, 64.28; H, 8.12;
N, 6.21.
Under a dry argon atmosphere, to a solution of chiral ligand
(10%, 0.1 mmol) in dry toluene (1 mL) was added Ti(OiPr)4
(0.3 mmol) at room temperature. Then, the above mixture was
introduced by a syringe into the system in which phenylacetylene
(2 mmol) and ZnMe2 (2 mmol) were premixed and stirred for 1 h at
room temperature. Then, the mixture was stirred for another
30 min, and aldehyde (1 mmol) was added. After being stirred for
24 h at the same temperature, the reaction mixture was quenched
with saturated aqueous ammonium chloride. The mixture was

J. Sun et al. / Tetrahedron: Asymmetry 19 (2008) 2451–2457
2457
Chem. Eur. J. 2008, 14, 944; (c) Mata, Y.; Pàmies, O.; Diéguez, M. Chem. Eur. J.
2007, 13, 3296; (d) Mata, Y.; Pàmies, O.; Diéguez, M.; Woodward, S. J. Org. Chem.
2006, 71, 8159; (e) Jagt, R. B. C.; Toullec, P. Y.; Schudde, E. P.; de Vries, J. G.;
Feringa, B. L.; Minnaard, A. J. J. Comb. Chem. 2007, 9, 407; (f) Richmond, M. L.;
Seto, C. T. J. Org. Chem. 2003, 68, 7505; (g) Sprout, C. M.; Richmond, M. L.; Seto, C.
T. J. Org. Chem. 2004, 69, 6666.
then extracted with diethyl ether (10 mL ꢀ 3). The organic phase
was washed with brine and was dried over anhydrous sodium sul-
fate. The solvent was removed under reduced pressure to give the
crude product. Purification of the residue by column chromatogra-
phy furnished the pure chiral alcohol. The enantiomeric excess was
determined by HPLC analysis using a Chiralcel column. The config-
uration was assigned by comparison with the sign of the specific
rotation of the known compounds.
7. Selected reports on the asymmetric addition of dialkyl zinc to aldehydes, see: (a)
Noyori, R.; Kitamura, M. Angew. Chem., Int. Ed. 1991, 30, 49; (b) Soai, K.; Niwa, S.
Chem. Rev. 1992, 92, 833; (c) Pu, L.; Yu, H.-B. Chem. Rev. 2001, 101, 757; (d)
Chelucci, G.; Conti, S.; Falorni, M.; Giacomelli, G. Tetrahedron 1991, 47, 8251; (e)
Kitamura, M.; Suga, S.; Kawai, K.; Noyori, R. J. Am. Chem. Soc. 1986, 108, 6071; (f)
Yang, X.; Shen, J.; Da, C.; Wang, R.; Choi, M. C. K.; Yang, L.; Wong, K. Tetrahedron:
Asymmetry 1999, 10, 133; (g) Huang, W. S.; Hu, Q. S.; Pu, L. J. Org. Chem. 1998, 63,
1364; (h) Huang, W. S.; Hu, Q. S.; Pu, L. J. Org. Chem. 1999, 64, 7940; (i) Pu, L.
Chem. Rev. 1998, 98, 2405; (j) Bringmann, G.; Walter, R.; Weirich, R. Angew.
Chem., Int. Ed. 1990, 29, 977; (k) Rheiner, P. B.; Seebach, D. Chem. Eur. J. 1999, 5,
3221; (l) Sellner, H.; Faber, C.; Rheiner, P. B.; Seebach, D. Chem. Eur. J. 2000, 6,
3692; (m) Yoshioka, M.; Kawakita, T.; Ohno, M. Tetrahedron Lett. 1989, 30, 1657;
(n) Lutz, C.; Graf, C. D.; Knochel, P. Tetrahedron 1998, 54, 10317; (o) Vidal-Ferran,
A.; Bampos, N.; Moyano, A.; Pericas, M. A.; Riera, A.; Sanders, J. K. M. J. Org. Chem.
1998, 63, 6309; (p) Brouwer, A. J.; Linden, H. J.; Liskamp, R. M. J. Org. Chem. 2000,
65, 1750; (q) Hui, A.; Zhang, J.; Fan, J.; Wang, Z. Tetrahedron: Asymmetry 2006, 17,
2101; (r) Yang, X.; Hirose, T.; Zhang, G. Tetrahedron: Asymmetry 2008, 19, 1670;
(s) Hatano, M.; Ishihara, K. Synthesis 2008, 1647; (t) Jammi, S.; Rout, L.;
Punniyamurthy, T. Tetrahedron: Asymmetry 2007, 18, 2016; (u) Bulut, A.; Aslan,
A.; Izgu, E. Q.; Dogan, O. Tetrahedron: Asymmetry 2007, 18, 1013.
Acknowledgments
We gratefully acknowledge the National Natural Science Foun-
dation of China (20672053, 20832001) and the National Basic Re-
search Program of China (2007CB925103) for their financial
support. The Program for New Century Excellent Talents in the
University of China (NCET-06-0425) is also acknowledged.
References
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4. (a) Chataigner, I.; Gennari, C.; Piarulli, U.; Ceccarelli, S. Angew. Chem., Int. Ed.
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5. (a) Forrat, V. J.; Ramón, D. J.; Yus, M. Tetrahedron: Asymmetry 2006, 17, 2054; (b)
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