Asymmetric addition of trimethylsilyl cyanide to ketones catalyzed by Al(salen)/triphenylphosphine oxide

Article abstract of DOI:10.1016/j.tet.2005.09.131

Trimethylsilyl cyanide asymmetrically adds to various ketones by catalysis of 1/triphenylphosphine oxide. This is a double activation where 1 acts as Lewis acid and Ph₃PO Lewis base. Various ketones were subjected to the enantioselective additi

Full text of DOI:10.1016/j.tet.2005.09.131

Tetrahedron 62 (2006) 49–53
Asymmetric addition of trimethylsilyl cyanide to ketones
catalyzed by Al(salen)/triphenylphosphine oxide
Sung Soo Kim and Ju Myung Kwak
*
Department of Chemistry, Inha University, Incheon 402-751, South Korea
Received 5 September 2005; revised 29 September 2005; accepted 29 September 2005
Available online 24 October 2005
Abstract—Trimethylsilyl cyanide asymmetrically adds to various ketones by catalysis of 1/triphenylphosphine oxide. This is a double
activation where 1 acts as Lewis acid and Ph
to 92% ee and O90% yield.
q 2005 Elsevier Ltd. All rights reserved.
3
PO Lewis base. Various ketones were subjected to the enantioselective addition so as to give up
1. Introduction
method used TMSCN and diphenylmethyl phosphine oxide
as co-reactants to generate Ph MePOTMS(N]C:) as a
2
Asymmetric addition of trimethylsilyl cyanide (TMSCN) to
carbonyl compounds and subsequent hydrolysis produces
reactive intermediate. The cyanosilylations of aldehydes
employing Al(salen)(1)/Ph PO and Mn(salen)/Ph PO,
respectively were developed by us. The former catalyst
gives better % ee than the latter. We would like to herein
report the cyanosilylation of ketones employing the same 1/
3
3
1
–3
15
chiral cyanohydrins . Such chiral compounds are useful
intermediates for synthesis of pharmaceutics. The two
functional groups (–OH and –CN) can be easily transformed
4
,5
,
into various homochiral ones including a-hydroxy acids
a-hydroxy aldehydes , a-hydroxy ketones , b-hydroxy
Ph PO as the catalysts.
3
6
6
5
amines and a-amino acid derivatives .
,6
7
A number of catalysts for the asymmetric addition of
TMSCN to ketones are known. Belokon and North used a
bimetallic titanium salen complex as a catalyst for the
8
asymmetric addition of TMSCN to ketones . Shibasaki has
reported enantioselective catalytic additions of TMSCN to
various ketones utilizing bifunctional ligand and Ti(OiPr)
or the lanthanide complexes . The concept of dual
4
9
activation has been pioneered by Shibasaki’s group. Deng
has first described method of cyanosilylation of ketones
employing chiral Lewis bases which are free of metal
1
0
2. Results and discussion
ions . Snapper and Hoveyda has described the addition of
TMSCN to ketones catalyzed by peptide chiral ligand and
Al(OiPr)3 . Feng and Jiang has employed chiral N-oxide/
1
1
p-Chlorophenyl methyl ketone was chosen as a test
substrate to find out the best conditions for the cyanosilyla-
tions. Amount of triphenylphosphine oxide was varied to
find out the optimal conditions (entries 1–4). No reaction
took place without triphenylphosphine oxide (entry 1).
1
2
titanium(IV) complex for the cyanosilylation of ketones .
Feng has utilized a catalytic double-activation method using
chiral salen-Ti(IV) complex and various achiral N-oxides
1
3
for the cyanosilylation of ketones . Recently, Corey has
shown that chiral oxazaborolidium salt is an excellent
catalyst for the cyanosilylation of methyl ketones . This
Entry 4 of 10 mol% Ph PO is shown to be the proper
3
1
4
quantity for the cyanosilylation reaction. Various solvents
were used for the cyanosilylations and CH Cl proved to be
2
2
the proper medium for the reactions (entries 4–7). The
substrate concentration of 1 M appears adequate (entries 4,
8 and 9). The reactions were run at four different
temperatures and rt offers the best outcome (entries 4, 10,
Keywords: Cyanohydrin; Ketone; Trimethylsilyl cyanide; Al(salen);
Asymmetric addition.
*
Corresponding author. Tel.: C82 32 864 4966; fax: C82 32 867 5604.;
e-mail: sungsoo@inha.ac.kr
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.131

50
S. S. Kim, J. M. Kwak / Tetrahedron 62 (2006) 49–53
cyanosilylation of isobutylphenone (entry 11) produces
excellent ee (92%). p-Methoxy phenyl acetone (entry
2), benzyl acetone (entry13) and 4-phenyl-3-buten-2-one
1
(
(
entry 14) take relatively short reaction time (3–4 h)
Table 2).
The % ee is quite good and % yield appears excellent that
9
–14
could be compared with other works.
temperature is milder (rt) than the previous cyanosilylations
The reaction
9
–11
9–14
(below K20 8C).
Cyanosilylations by others
usually
report quite longer reaction time. On the other hand
p-nitrophenyl methyl ketone underwent cyanosilylation
for only 2 h in our hand. The oxazaborolidium-catalyzed
Figure 1. Transition state involved in the enantioselective cyanosilylation
of ketones by double-activation catalysis.
14
cyanosilylation of ketones takes place at temperature of
25–40 8C that is higher than 0 8C at which similar reactions
of the aldehydes occur. Similar increase of reaction
1
6
1
1
1 and 12). The amount of 1 for the reactions should be
mol% that gives highest % yield and % ee(entries 4, 13, 14
1
5a
temperature from aldehydes (K40 to K50 8C) to ketones
rt)(present reactions) were also observed for our reactions.
(
and 15) (Table 1). The reactions appears to be catalyzed by
double activation process occurring through the catalysis of
both chiral Lewis acid and achiral Lewis base. Al(salen)
complex functions as a Lewis acid to activate the ketonic
oxygen and Ph PO acts as a Lewis base for activation of
3
TMSCN (Fig. 1).
Compared to aldehydes, ketonic structure maintains steric
hindrance so that TMSCN could add to the carbonyl at
elevated temperature. However the steric effects render
14
16
reaction time much longer for ketones than aldehydes.
15a
Such difference of reaction time between aldehydes and
ketones (present work) appears not significant in our
reactions.
o-Chlorophenyl methyl ketone appears susceptible to
steric effect compared to p-chloro- and m-chlorophenyl
methyl ketone so as to give the much longer reaction
time (23, 11 and 6 h) and lower % ee (62, 77 and
3. Conclusion
9
1%) although the % yield are nearly unaffected
entries 1, 2, 3 and 4). p-Chloro- and m-chloro group
shorten the reaction time from 19 to 11 and 6 h
(
A highly efficient double activation catalysis by 1/Ph PO
3
has been developed for the enantioselective cyanosilylations
of various ketones. The cyanosilylations take place under
comparatively mild conditions in terms of temperature and
reaction time. Several ketones with electron-withdrawing
groups in phenyl ring (entries 2, 3 and 5–7) exhibit quite
short reaction time that may indicate nucleophilic addition
(
(
entries 1, 2 and 3). Electron-withdrawing substituents
entries 2, 4, 5, 6 and 7) exert favorable influence for
the cyanosilylation in terms of reaction time (11, 6, 7,
and 2 h) to give excellent % yield and good % ee.
5
On the other hand, electron-donating substituents
indicate much longer reaction time (w20 h) and give
a little sluggish effect on reactions (entries 8 and 9).
The negative influence of longer reaction time is also
shown in entry 10(25 h) and entry 11(40 h). However
K
of CN group to carboxyl carbon as rate-determining
process. Some other ketones without methyl group (entries
12, 13 and 14) undergo cyanosilylation also for quite short
reaction time.
a
Table 1. Catalytic asymmetric cyanosilylation of methyl p-chlorophenyl ketone under various condition
Entry
Substrate
Solvent
Temperature
1 (mol%)
Time (h)
Yield (%)
ee (%)
M (mol/l)
b
1
CH
CH
CH
CH
CHCl
THF
2
2
2
2
Cl
Cl
Cl
Cl
2
2
2
2
rt
rt
rt
rt
rt
rt
rt
rt
1
1
1
1
1
1
1
1
1
1
1
1
3
5
10
40
20
10
11
12
16
20
21
7
34
72
200
9
—
80
98
98
92
97
67
96
96
97
93
10
97
99
98
—
74
75
77
68
72
69
75
73
76
77
81
68
72
57
1
1
1
1
1
1
1
0.5
2
1
c
2
d
3
4
5
6
7
8
9
3
Toluene
CH
CH
CH
CH
CH
CH
CH
CH
2
2
2
2
2
2
2
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
rt
0 8C
K10 8C
K40 8C
rt
10
11
12
13
14
15
1
1
1
1
rt
rt
3
3
1
a
b
c
d
1
3
0 mol% Ph PO has been used for all the cyanosilylation, except for otherwise stated.
0
5
2
mol% Ph
mol% Ph
3
PO has been used for the cyanosilylation.
PO has been used for the cyanosilylation.
3
3
0 mol% Ph PO has been used for the cyanosilylation.

S. S. Kim, J. M. Kwak / Tetrahedron 62 (2006) 49–53
51
a
Table 2. Catalytic Asymmetric Cyanosilylation of Ketones Catalyzed by 1/POPh
3
b
c
Entry
1
Substrate
Time (h)
19
Yield (%)
93
ee (%)
78
Config.
d
S
d
2
3
11
6
97
98
77
91
S
d
S
4
5
23
7
98
95
62
73
—
—
6
7
8
9
5
2
96
95
90
87
73
72
66
71
—
—
d
21
20
S
—
d
10
25
87
68
S
11
12
13
40
3
80
85
90
92
65
75
—
—
d
3
S
d
14
4
75
60
S
a
CH
2
Cl
2
is the solvent for the reactions. The reactions were run at rt 1 mol% 1 was used for all the cyanosilylations. 30 mol% of Ph
PO was employed for the reaction of entry 2.
3
PO has been used except
for entry 2. 10 mol% Ph
3
b
c
d
Substrate concentration is 1 M.
Determined by HPLC (see Refs. 9,11)
The specific rotations carry minus values while the reported ones indicate positive values with R configuration.
9a,11,17

52
S. S. Kim, J. M. Kwak / Tetrahedron 62 (2006) 49–53
4. Experimental
HRMS(MC) calcd for C H ClNOSi: 253.0690; found:
12 16
i
2
53.0692 HPLC (DAICEL CHIRALCEL OB-H, PrOH/
4
.1. General methods
hexaneZ1/99, flowZ0.25 mL/min) 14.6 and 17.4 min.
0
To a stirred CH Cl solution of 1 (1 mol%), POPh3
2
4.1.4. 2-Trimethylsilyloxy-2-(2 -chlorophenyl)propane-
nitrile (3d). H NMR (CDCl ) d 0.23 (s, 9H), 1.88 (s,
2
1
(
30 mol%) was added an aldehyde (2 mmol) and stirred
3
1
3H), 7.37–7.62 (m, 4H aromatic H) C NMR (CDCl ) d
1.0, 33.4, 70.9, 121.0, 122.7, 124.8, 128.8, 129.9, 134.6,
144.0 [a] K12.38 (c 1.58, CHCl3, 62% ee) HRMS(MC)
calcd for C H ClNOSi: 253.0691; found: 253.0687 HPLC
(DAICEL CHIRALCEL OD-H, PrOH/hexaneZ1/99,
flowZ0.25 mL/min) 24.2 and 25.0 min.
3
for 30 min at rt TMSCN (2.4 mmol) was added to the
reaction mixture using syringe pump and the mixture was
reacted at the same temperature for 2–25 h. The solvent was
evaporated. The crude product was futher purified by flash
chromatography (hexane: ethyl acetateZ9:1) to give a
cyanohydrin in more than 90% yield. The enantiomeric
excesses of some products were determined after conversion
to acetylester, ethylcarbonate, and t-butyl dimethylsilylether
3
2
4
D
1
2 16
i
0
nitrile (3e). H NMR (CDCl ) d 0.18 (s, 9H), 1.84 (s, 3H),
4.1.5. 2-Trimethylsilyloxy-2-(4 -fluorophenyl)propane-
1
1
by the known methods. The sample was identified by H,
C–MR, HRMS and ee % was determined by chiral HPLC
3
13
1
3
7.08 (m, 2H), 7.52 (m, 2H) C NMR (CDCl ) d 1.0, 33.5,
3
2
2
column (DAICEL CHIRALCEL OJ-H, DAICEL CHIR-
ALCEL OD-H and DAICEL CHIRALCEL OB-H). All
ketones and Al(salen) were purchased from Sigma-Aldrich.
71.0, 115.6, 121.4, 126.5, 138.0, 162.2 [a]D K17.38 (c 1.4,
CHCl3, 73% ee) HRMS(MC) calcd for C H FNOSi:
237.0985; found: 237.0981 HPLC (DAICEL CHIRALCEL
OB-H, PrOH/hexaneZ1/99, flowZ0.25 mL/min) 16.4 and
17.8 min.
12
16
1
13
i
H and C NMR were taken utilizing Varian Jemini 2000
200 MHz) or Varian Unity Inova 400 (400 MHz) NMR
(
spectrometer. Hewlett–Packard 5890A Gas Chromato-
graph/Jeol JMS-DX303 Mass Spectrometer was used for
HRMS data. Analytical high performance liquid chroma-
tography (HPLC) was performed on Gilson 305 series
HPLC using the indicated chiral column. All data was in
accordance with literature values. Absolute configurations
were determined by optical rotation, see: (a) Hamashima,
Y.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2000, 122,
0
nitrile (3f). H NMR (CDCl ) d 0.19 (s, 9H), 1.83 (s, 3H),
4.1.6. 2-Trimethylsilyloxy-2-(4 -bromophenyl)propane-
1
3
1
7.40–7.4 (m, 2H), 7.51–7.55 (m, 2H) C NMR (CDCl ) d
3
3
2
2
1.0, 33.4, 71.0, 121.1, 122.7, 126.3, 131.7, 141.2 [a]D
K14.68 (c 1.69, CHCl3, 73% ee) HRMS(MC) calcd for
C H BrNOSi: 297.0185; found: 297.0181 HPLC
1
2
16
i
(DAICEL CHIRALCEL OB-H, PrOH/hexaneZ1/99,
flowZ0.25 mL/min) 16.4 and 17.8 min.
7
412; (b) Hamashima, Y.; Kanai, M.; Shibasaki, M.
Tetrahedron Lett. 2001, 42, 691; (c) Yabu, K.; Masumoto,
S.; Yamasaki, S.; Hamashima, Y.; kanai, M.; Du, W.;
Curran, D.P.; Shibasaki, M. J. Am. Chem. Soc. 2001, 123,
0
nitrile (3g). H NMR (CDCl ) d 0.26 (s, 9H), 1.89 (s, 3H),
4.1.7. 2-Trimethylsilyloxy-2-(4 -nitrophenyl)propane-
1
3
1
3
9
908;. and references cited therein.;(c) Deng, H. -B.; Isler,
7.75 (d, 2H), 8.30 (d, 2H) C NMR (CDCl ) d 1.0, 33.5,
3
2
2
M. P.; Snapper, M. L.; Hoveyda, A. H. Angew. Chem. Int.
Ed. 2002, 41, 1009.
71.0, 115.6, 121.4, 126.5, 138.0, 162.2 [a]D K15.38 (c 1.65,
CHCl3, 72% ee) HRMS(MC) calcd for C H N O Si:
12
16 2 3
2
64.0930; found: 264.0933 HPLC (DAICEL CHIRALCEL
i
4
.1.1. 2-Trimethylsilyloxy-2-phenylpropanenitrile (3a).
H NMR (CDCl ) d 0.19 (s, 9H), 1.87 (s, 3H), 7.38–7.58
OJ-H, PrOH/hexaneZ1/99, flowZ0.25 mL/min) 51.38 and
54.61 min.
1
3
1
3
(
m,5H, aromatic H) C NMR (CDCl ) d 1.03, 33.5, 71.6,
3
2
4
0
nitrile (3h). H NMR (CDCl ) d 0.16 (s, 9H), 1.84 (s,
1
21.6, 128.6, 142.0 [a] K16.08 (c 1.18, CHCl 78% ee)
3,
4.1.8. 2-Trimethylsilyloxy-2-(4 -methylphenyl)propane-
D
2
0
1
[
lit. [a] C21.98 (c 1.18, CHCl , for R enantiomer with
3
D
3
9
3% ee)] HRMS(MC) calcd for C H NOSi: 219.1079;
a
13
3H), 2.36 (s, 3H), 7.21 (m, 2H), 7.43 (m, 2H) C NMR
9
found: 219.1082 HPLC (DAICEL CHIRALCEL OB-H,
1
2 17
(CDCl ) d 1.1, 20.8, 33.5, 71.8, 121.9, 124.9, 128.3, 138.4,
3
i
23
D
PrOH/hexaneZ1/99, flowZ0.25 mL/min) 14.9 and
139.8 [a]
K16.18 (c 1.65, CHCl3, 72% ee) [lit.
2
5
1
5.4 min.
[a] C21.38 (c 1.28, CHCl , for R enantiomer with 90%
D 3
ee)]9a HRMS(MC) calcd for C H NOSi: 233.1236;
1
3 19
0
nitrile (3b). H NMR (CDCl ) d 0.21 (s, 9H), 1.83 (s,
4
.1.2. 2-Trimethylsilyloxy-2-(4 -chlorophenyl)propane-
found: 233.1240 HPLC (DAICEL CHIRALCEL OJ-H,
1
i
PrOH/hexaneZ1/99, flowZ0.25 mL/min) 51.38 and
54.61 min.
3
1
H), 7.38 (m, 2H), 7.49 (m,2H) C NMR (CDCl ) d 1.05,
3
3
3
2
D
4
3
K17.38 (c 1.78, CHCl 77% ee) [lit. [a] C29.58 (c 1.04,
3.53, 71.06, 121.25, 126.07, 128.83, 134.60, 140.71 [a]
2
D
0
0
panenitrile (3i). H NMR (CDCl ) d 0.19(s, 9H), 1.87(s,
4.1.9. 2-Trimethylsilyloxy-2-(4 -methoxylphenyl)pro-
3
,
9
CHCl , for R enantiomer with 92% ee)] HRMS (MC)
a
1
3
3
1
3H), 3.85(s, 3H), 6.93(m, 2H), 7.49(m, 2H) C NMR
3
calcd for C H ClNOSi: 253.0690; found: 253.0687 HPLC
1
2 16
i
(
DAICEL CHIRALCEL OJ-H, PrOH/hexaneZ1/99,
(CDCl ) d 1.1, 33.41, 55.33, 71.28, 113.89, 121.81,
3
2
3
flowZ0.25 mL/min) 19.5 and 20.5 min.
126.06, 134.04, 159.80 [a]D K17.08 (c 1.44, CHCl3,
1% ee) HRMS(MC) calcd for C H NO Si: 249.1185;
found: 249.1182 HPLC (DAICEL CHIRALCEL OJ-H,
7
1
3
19
2
0
nitrile (3c). H NMR (CDCl ) d 0.22 (s, 9H), 1.86 (s,
4
.1.3. 2-Trimethylsilyloxy-2-(3 -chlorophenyl)propane-
1
i
PrOH/hexaneZ1/99, flowZ0.25 mL/min) 23.61 and
25.54 min.
3
1
H), 7.34–7.55 (m, 4H aromatic H) C NMR (CDCl ) d
3
3
1
1
3
.0, 33.4, 70.9, 121.0, 122.7, 124.8, 128.8, 129.9, 134.6,
44.0 [a] K19.38 (c 1.28, CHCl3, 91% ee) [lit. [a]D
2
D
4
26
4.1.10. 2-(Trimethylsilyloxy)indane-1-carbonitrile (3j).
H NMR (CDCl ) d 0.20 (s, 9H), 2.43–2.47 (m, 1H),
1
7
1
C7.18 (c 0.34, CHCl , for R enantiomer with 33% ee)]
3
3

S. S. Kim, J. M. Kwak / Tetrahedron 62 (2006) 49–53
53
2
7
.70–2.74 (m, 1H), 2.97–3.02 (m, 1H), 3.10–3.15 (m, 1H),
.28 (d, 1H), 7.31 (t, 1H), 7.36 (t, 1H), 7.55 (d, 1H)
Acknowledgements
1
3
C NMR (CDCl ) d 1.1, 29.4, 42.9, 76.8, 121.3, 124.5,
3
We warmly thank The Center for Biological Modulators for
the financial support.
2
3
1
CHCl3, 68% ee) [lit. [a]D C24.58 (c 2.18 CH Cl , for R
25.3, 127.8, 129.9, 142.7, 142.9 [a] K19.48 (c 1.4,
D
2
0
2
2
9
enantiomer with 65% ee)] HRMS(MC) calcd for
a
C H NOSi: 231.1079; found: 231.1082 HPLC (DAICEL
1
3 17
i
CHIRALCEL OD, PrOH/hexaneZ1/99, flowZ0.25 mL/
min) 3.27 and 3.64 min.
References and notes
1
2
. Gregory, R. J. H. Chem. Rev. 1999, 99, 3649.
. North, M. Tetrahedron: Asymmetry 2003, 14, 147.
4.1.11. 2-Trimethylsilyloxy-2-phenyl-3-methyl-butane-
nitrile (3k). H NMR (CDCl ) d 0.12 (s, 9H), d 1.03 (q,
1
3. Brunel, J.-M.; Holmes, I. P. Angew. Chem. Int. Ed. 2004, 43,
752.
3
2
4. Matthews, B. R.; Gountzos, H.; Jackson, W. R.; Watson, K. G.
Tetrahedron Lett. 1989, 30, 5157.
JZ7.4 Hz 6H), 1.97 (m, 1H), 7.38 (m, 3H), 7.50 (m, 2H)
2
0
[
C H NOSi: 247.1392; found: 247.1395 HPLC (DAICEL
a] K45.98 (c 4.1, CHCl 92% ee) HRMS(MC) calcd for
D 3,
1
4 21
5
. Ziegler, T.; Horsch, B.; Effenberger, F. Synthesis 1990, 575.
. Jackson, W. R.; Jacobs, H. A.; Jayatilake, G. S.; Matthews, B. R.;
Watson, K. G. Aust. J. Chem. 1990, 43, 2045. Jackson, W. R.;
Jacobs, H. A.; Matthews, B. R.; Jayatilake, G. S.; Watson, K. G.
Tetrahedron Lett. 1990, 31, 1447.
i
CHIRALCEL OD, PrOH/hexaneZ1/99, flowZ0.5 mL/
min) 6.36 and 6.84 min.
6
4
.1.12. 2-Trimethylsilyloxy-3-(4-methoxyphenyl)-2-
methyl-propanenitrile (3l). H NMR (CDCl ) d 0.1
1
7
. Effenberger, F.; Stelzer, U. Angew. Chem. Int. Ed. Engl. 1991,
3
3
0, 873.
(
s, 9H), d 1.73 (s, 1H), 2.71–2.93 (m, 2H), 3.75 (s, 3H),
2
.76–7.23 (m, 4H) [a]D K1.28 (c 4.1, CHCl3, 65% ee)
0
8
. (a) Belokon, Y. N.; Green, B.; Ikonnikov, N. S.; North, M.;
Tararov, V. I. Tetrahedron Lett. 1999, 40, 8147. (b)
Belokon, Y. N.; Green, B.; Ikonnikov, N. S.; North, M.;
Parsons, T.; Tararov, V. I. Tetrahedron 2001, 57, 771.
. (a) Hamashima, Y.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc.
6
HRMS(MC) calcd for C H NO Si: 263.1342;
1
4
21
2
found: 263.1345 HPLC (DAICEL CHIRALCEL OJ-H,
i
PrOH/hexaneZ1/99, flowZ0.25 mL/min) 24.72 and
9
2
7.38 min.
2
000, 122, 7412. (b) Hamashima, Y.; Kanai, M.; Shibasaki, M.
Tetrahedron Lett. 2001, 42, 691. (c) Yabu, K.; Masumoto, S.;
Yamasaki, S.; Hamashima, Y.; Kanai, M.; Du, W.;
Curran, D. P.; Shibasaki, M. J. Am. Chem. Soc. 2001, 123, 9908.
4.1.13. 2-Trimethylsilyloxy-2-methyl-4-phenylbutane-
nitrile (3m). H NMR (CDCl ) d 0.27 (s, 9H), d 1.61 (s, 3H),
1
3
2
7
6
.02 (m, 2H), 2.78(d, 2H) 2.87 (d, 2H), 7.19–7.22 (m, 3H),
10. (a) Tian, S. K.; Deng, L. J. Am. Chem. Soc. 2001, 123, 6195.
(b) Tian, S. K.; Hong, R.; Deng, L. J. Am. Chem. Soc. 2003,
125, 9900.
1
3
.28–7.3 (m, 2H) C NMR (CDCl ) d 1.3, 29.4, 30.7, 45.2,
3
2
0
9.4, 121.9, 126.1, 128.3, 128.5, 140.7 [a] K10.58 (c 4.8,
D
2
4
CHCl3, 75% ee) [lit. [a]D C13.38 (c 1.15, CHCl , for R
3
11. Deng, H. B.; Isler, M. P.; Snapper, M. L.; Hoveyda, A. H.
Angew. Chem. Int. Ed. 2002, 41, 1009.
9
enantiomer with 81% ee)] HRMS(MC) calcd for
a
C H NOSi: 247.1392; found: 247.1390 HPLC (DAICEL
4 21
CHIRALCEL OJ-H, PrOH/hexaneZ1/99, flowZ0 .5 mL/
min) 13.90 and 17.34 min.
12. (a) Shen, Y.; Feng, X.; Zhang, G.; Jiang, Y. Synlett 2002, 8,
1353. (b) Shen, Y.; Feng, X.; Li, Y.; Zhang, G.; Jiang, Y. Org
lett. 2003, 5, 949.
1
i
1
3. (a) Chen, F.; Feng, X.; Qin, B.; Zhang, G.; Jiang, Y. Org. Lett.
003, 5, 949. (b) Me, B.; Chen, F.; Chen, X.; Li, Y.; Feng, X.;
2
4.1.14. 2-Trimethylsilyloxy-2-methyl-4-phenyl-3-butene-
nitrile (3n). H NMR (CDCl ) d 0.29 (s, 9H), d 1.77 (s, 3H),
Zhang, G. Tetrahedron Lett. 2004, 45, 5465. (c) Me, B.;
Chen, F.; Chen, X.; Li, Y.; Feng, X.; Zhang, G. Eur. J. Org.
Chem. 2004, 4657. (d) Chen, F.; Chen, X.; Qin, B.; Feng, X.;
Zhang, G.; Jiang, Y. Tetrahedron 2004, 60, 10449.
1
3
6
.16 (d, 1H), 6.91(d, 1H) 7.31 (m, 1H), 7.39 (m, 2H), 7.44
1
3
(
m, 2H) C NMR (CDCl ) d 1.4, 30.8, 69.9, 120.6, 126.9,
3
2
0
1
CHCl3, 60% ee) [lit. [a]D C21.38 (c 1.34, CHCl , for R
28.6, 128.7, 129.5, 130.9, 135.1 [a] K17.58 (c 2.4,
D
14. Ryu, D. H.; Corey, E. J. J. Am. Chem. Soc. 2005, 127, 5384.
15. (a) Kim, S. S.; Song, D. H. Eur. J. Org. Chem. 2005, 1777. (b)
Kim, S. S.; Lee, S. H. Synth Comm. 2005, 35, 751.
16. Ryu, D. H.; Corey, E. J. J. Am. Chem. Soc. 2004, 126, 8106.
17. Shen, Y.; Feng, X.; Li, Y.; Zhang, G.; Jiang, Y. Eur. J. Org.
Chem. 2004, 129–137.
2
5
3
1
enantiomer with 91% ee)] HRMS(MC) calcd for
1
C H NOSi: 245.1236; found: 245.1233 HPLC (DAICEL
1
4 19
i
CHIRALCEL OJ-H, PrOH/hexaneZ1/99, flowZ0.5 mL/
min) 11.36 and 14.02 min.