Synthesis of chiral α-ethylphenylamine salts of tartaric acid and novel application to cyanosilylation of prochiral ketones

Article abstract of DOI:10.1007/s11164-010-0132-7

Chiral α-ethylphenylamine tartaric acid salts were synthesized from a-ethylphenylamine by direct reaction with chiral tartaric acid. The crystal structure of S-(-)-αethylphenylamine-( 2R,3R)-(-)-dihydroxybutanedioic acid was determined. The crystal is mon

Full text of DOI:10.1007/s11164-010-0132-7

Res Chem Intermed (2010) 36:227–236
DOI 10.1007/s11164-010-0132-7
Synthesis of chiral a-ethylphenylamine salts of tartaric
acid and novel application to cyanosilylation
of prochiral ketones
•
Luo Mei Sun Jie Jiang Ying
•
Received: 14 May 2009 / Accepted: 25 December 2009 / Published online: 11 March 2010
Ó Springer Science+Business Media B.V. 2010
Abstract Chiral a-ethylphenylamine tartaric acid salts were synthesized from a-ethyl-
phenylamine by direct reaction with chiral tartaric acid. The crystal structure of S-(-)-a-
ethylphenylamine-(2R,3R)-(-)-dihydroxybutanedioic acid was determined. The crystal
˚
˚
is monoclinic, of space group P21/n, with a = 6.331(5) A, b = 14.209(11) A, c =
´
˚
˚
7.495(6) A, a = 90.008, b = 107.000(13)8, c = 90.008, k = 0.7103 A, V = 644.7(9),
Z = 2, Dc = 1.397 g/cm3, Mr = 271.27 and F(000) = 288, R = 0.0477, and xR =
0.0838 for 1388 observed reflections with I [ 2r(I). We then used the chiral
a-ethylphenylamine tartaric acid salts as catalysts in the cyanosilylation of prochiral
ketones, and moderate conversions were obtained.
Keywords Chiral a-ethylphenylamine tartaric acid salts 1a–1d ꢀ Crystal structure ꢀ
Cyanosilylation of prochiral ketones ꢀ Cyanohydrin trimethylsily ethers
Introduction
Cyanosilylation reactions involving enantioselective addition of cyanotrimethylsi-
lane (TMSCN) to aldehydes have been studied by many groups, for example
Shibasaki [1–3], Deng, Jacobsen [4–6], Corey [7, 8], and Feng [9]. As novel
catalysts, they have high reaction activities and selectivities. Using this as a basis for
our work, we first employed the easily obtainable chiral a-ethylphenylamine tartaric
acid salts 1a–1d as catalysts in the cyanosilylation of prochiral ketones [10].
Electronic supplementary material The online version of this article (doi: 10.1007/s11164-010-0132-7)
contains supplementary material, which is available to authorized users.
L. Mei (&) ꢀ J. Ying
Department of Chemical Engineering, Hefei University of Technology, Hefei 230009, China
e-mail: luomei@pku.edu.cn; luomeihuahua@sohu.com
S. Jie
Shanghai Institute of Organic Chemistry, Shanghai 200032, China
123

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L. Mei et al.
As Bronsted acids, they were synthesized from R-(?)/S-(-)-a-ethylphenylamine
by reaction with (2S,3S)-(?)/(2R,3R)-(-)-dihydrobutanedioic acid in methanol
(Scheme 1). The salts were collected by filtration and recrystallized twice from
methanol to give single white crystals. The crystal structure of S-(-)-a-ethylphe-
nylamine-(2R,3R)-(-)-dihydroxybutanedioic acid was obtained from these crystals.
Experimental
General procedures
The course of all cyanosilylation reactions was monitored by thin-layer chroma-
tography using 0.25-mm E. Merck silica gel-coated glass plates (60F254), and
CH3
-
CH3
CO2
H
H
H
OH
H
+.
NH3
NH2
HO
+
COOH
OH
COOH
catalyst 1a
CH3
H
HO
H
+
-
CH3
CO2
H
H
COOH
H
OH
H
+.
NH3
NH2
HO
COOH
catalyst 1c
CH3
-
CH3
CO2
H
H
+.HO
H
H
NH3
NH2
OH
COOH
H
+
COOH
HO
H
catalyst 1b
CH3
OH
COOH
-
+
CO2
CH3
H
H
+. HO
H
H
NH3
NH2
OH
COOH
catalyst 1d
Catalyst 1a: R-(+)- α-Methylbenzylamine-(2R,3R)-(-)-2,3-dihydroxybutanedioic acid salt
Catalyst 1b: R-(+)- α-Methylbenzylamine-(2S,3S)-(+)-2,3-dihydroxybutanedioic acid salt
Catalyst 1c: S-(-)- α-Methylbenzylamine-(2R,3R)-(-)-2,3-dihydroxybutanedioic acid salt
Catalyst 1d: S-(-)- α-Methylbenzylamine-(2S,3S)-(+)-2,3-dihydroxybutanedioic acid salt
Scheme 1 Synthetic routes to catalysts 1a–1d
123

Synthesis of chiral a-ethylphenylamine tartaric acid salts
229
UV light for visualization. Flash column chromatography was performed using
E. Merck silica gel 60 (particle size 0.02–0.03 mm). Chemical conversion were
determined by 1H NMR and 13C NMR spectroscopy. 1H and 13C NMR spectra were
obtained using Bruker AM-300 and Bruker AM-400 spectrometers. The following
abbreviations were used to designate chemical shift multiplicities: s = singlet,
d = doublet, t = triplet, m = multiplet. Infrared spectra were recorded on a Mattson
Galaxy Series FTIR 3000 Spectrometer. High-resolution mass spectra were obtained
on Micro GCT-MS, Optical rotation was measured on WZZ-1 automatic polarimeter.
Enantiomeric excess (ee) was determined by HPLC analysis. HPLC was performed on
a Beijing Chuangxin tonghang system comprising a pump, UV detector, and Daicel
Chiralcel OD-H column with hexane as mobile phase. R-(?)/S-(-)-a-ethylphenyl-
amine and (2R,3R)-(-)/(2S,3S)-(?)-2,3-dihydroxybutanedioicacid were bought from
the Changzhou KeRuiDa Corporation, China. ee for R-(?)/S-(-) ethylphenylamine
and (2R,3R)-(-)/(2S,3S)-(?)-2,3-dihydroxybutanedioic acid were[99%.
Synthesis of catalysts 1a–1d
1a: preparation of R-(?)-a-ethylphenylamine-(2R,3R)-(-)-2,3-dihydroxybutanedioic
acid salt
(-)-Tartaric acid (6.3 g) was dissolved in 90 mL methanol and 5 g R-a-phenyleth-
ylamine was slowly added in a dry 250 mL cone bottle. The mixture was left motionless
for more than 24 h and the salts were collected by filtration and recrystallized twice from
methanol to give white single crystals (3.5 g). Melting point: 66–68 °C, [a]2D5 = -13.98
1
(c = 1.72, CH3OH); H NMR (300 MHz, CD3OD, 27 °C), d (ppm) = 7.38–7.48 (m,
5H), 4.89 (s, 5H), 4.43–4.48 (m, 1H), 4.40 (s, 2H), 1.62–1.64 (d, J = 5.16, 3H), 13CNMR:
20.80 (92), 52.27, 74.20, 127.69, 130.04, 130.24, 139.89, 177.07, I R: 3274, 3193, 2950,
2867, 2838, 1710, 1597, 1436, 1354, 1309, 1165, 1089, 996, 920, 898, 813, 754, 706, 669,
548, 577, 532; HRMS (EI): m/z (%): calcd for C14H26N2O: 271.1056; found: 271.1053.
1b: preparation of R-(?)-a-ethylphenylamine-(2S,3S)-(?)-2,3-dihydroxybutanedioic
acid salt
The procedure described for 1a was followed [a]2D5 = ?13.68 (c = 1.54, CH3OH).
1c: Preparation of S-(-)-a-ethylphenylamine-(2R,3R)-(-)-2,3-dihydroxybutanedioic
acid salt
The procedure described for 1a was followed. [a]2D5 = -13.58 (c = 1.62, CH3OH).
1d: Preparation of S-(-)-a-ethylphenylamine-(2S,3S)-(?)-2,3-dihydroxybutanedioic
acid salt
The procedure described for 1a was followed. [a]2D5 = ? 13.18 (c = 1.42, CH3OH).
Structure determination
A colorless block monoclinic crystal of the catalyst 1c with approximate size
0.51 mm 9 0.46 mm 9 0.35 mm was selected for data collection on a Bruker Smart
´
˚
diffractometer with graphite monochromatic MoKa radiation (k = 0.7103 A). A total of
3767 reflections were collected in the range 2.87 \h\27.00° by using the ‘‘phi and
omega’’ scan techniques at 293(2) K; of these, 1459 independent reflections were used in
123

230
L. Mei et al.
the succeeding refinements for 1388 observed reflections with I[2r(I). Rint = 0.0331
and Lp corrections were applied to the data.
The structure was solved by direct methods and different Fourier map techniques
by using the Bruker Smart software, and refinement on F2 was performed by full-
matrix least-squares methods with anisotropic displacement parameters for all non-
hydrogen atoms. All hydrogen atoms were found by difference Fourier map
techniques by using SHELXS-97 software and refined isotropically in the riding
mode with fixed thermal factors. The molecular graphics were drawn with the
Bruker SHELTXL software package [11–13].
Preparation of the cyanosilylation products
2-(Trimethylsilyloxy)-2-phenylpropanenitrile
1a 0.070 g (0.258 mmol) was dissolved in 1 mL CH2Cl2, acetophenone 0.1 mL
(0.857 mmol) and TMSCN (0.2 mL, 1.50 mmol) were successively added at room
temperature. After 0.5 h, the reaction was quenched. Further purification was
performed by silica gel column chromatography (petroleum–dichloromethane 4:1).
1
The title compound was obtained as a colorless oil, conversion = 45%, H NMR
(300 MHz, CDCl3): 7.44–7.47 (m, 3H), 7.24–7.32 (m, 2H), 1.76 (s, 3H), 0.079 (s,
9H). 13C NMR (75 MHz, CDCl3): 0.98 (93), 22.56, 33.51, 71.53, 121.54, 124.53
(92), 128.57 (92), 141.92. ee 5%; HPLC (Chiralcel OD-H), mobile phase hexane;
flow = 0.5 mL/min, tr(minor) = 16.579, tr(major) = 18.027.
2-(Trimethylsilyloxy)-2-(20-bromophenyl)propanenitrile
1
The title compound was obtained as a colorless oil, conversion = 29%, H NMR
(300 MHz, CDCl3): 7.73–7.76 (m, 2H), 7.22–7.24 (m, 2H), 1.27 (s, 3H), 0.24
(s,9H). 13C NMR (75 MHz, CDCl3): 1.16 (93), 29.8, 71.36, 120.08, 120.36, 127.24,
127.59, 130.08 135.17, 139.15; ee 1%, HPLC (Chiralcel OD-H), mobile phase
hexane; flow = 0.35 mL/min, tr(minor) = 49.469, tr(major) = 61.434.
2-(Trimethylsilyloxy)-2-(20-methylphenyl)propanenitrile
1
The title compound was obtained as a colorless oil, conversion = 60%, H NMR
(300 MHz, CDCl3): 7.53–7.58 (m, 1H), 7.18–7.27 (m, 3H), 2.55 (s, 3H), 1.94 (s, 3H),
0.077 (s, 9H). 13C NMR (75 MHz, CDCl3): 1.09 (93), 20.68, 30.51, 71.68, 121.62,
125.29, 125.97, 128.66, 132.64, 135.50, 138.41; ee 2%, HPLC (Chiralcel OD-H),
mobile phase hexane; flow = 0.35 mL/min, tr(minor) = 25.989, tr(major) =
28.390.
2-(Trimethylsilyloxy)-2-(40-methylphenyl)propanenitrile
1
The title compound was obtained as a colorless oil, conversion = 55%; H NMR
(300 MHz, CDCl3): 7.33–7.37 (m, 2H), d 7.09–7.17 (m, 2H), 2.28 (s, 3H), 1.18(s, 3H),
0.068 (s, 9H). 13C NMR (75 MHz, CDCL3): 1.00 (93), 20.98, 33.45, 71.44, 121.67,
123

Synthesis of chiral a-ethylphenylamine tartaric acid salts
231
124.51 (9), 129.19 (92), 138.43, 139.03. ee 2%; HPLC (Chiralcel OD-H), mobile
phase hexane; flow = 0.35 mL/min, tr(minor) = 22.778, tr(major) = 24.012.
2-(Trimethylsilyloxy)-2-(40-bromophenyl)propanenitrile
1
The title compound was obtained as a yellow solid, conversion = 91%; H NMR
(300 MHz, CDCl3): d 7.42–7.46 (d, J = 13.5 Hz, 2H), 7.31–7.35 (d, J = 12.6 Hz,
2H), 1.74 (s, 3H), -0.002(s, 9H). 13C NMR (75 MHz, CDCl3): 1.00 (9), 33.42,
71.02, 115.87, 121.07,122.66, 126.30 (92), 131.73 (92), 141.19; ee 3%; HPLC
(Chiralcel OD-H), mobile phase hexane; flow = 0.35 mL/min, tr(minor) = 25.358,
tr(major) = 27.717.
2-(Trimethylsilyloxy)-2-(40-chlorophenyl)propanenitrile
The title compound was obtained as a colorless oil, conversion = 89%; the physical
and spectral data were identical to those previously reported for this compound. 1H
NMR (300 MHz, CDCl3): d 8.13–8.16 (m, 2H), 7.61–7.64 (m, 2H), 7.33–7.36
(m, 2H), 1.75 (s, 3H), 0.12 (s, 9H). 13C NMR (75 MHz, CDCl3): 0.96 (93), 33.42,
70.96, 121.12, 126.00, 128.75 (92), 134.5 (92), 140.64. ee 2%; HPLC (Chiralcel
OD-H), mobile phase hexane; flow = 0.35 mL/min, tr(minor) = 29.850,
tr(major) = 32.291.
Results and discussion
The Bronsted acids were synthesized from R-(?)/S-(-)-a-ethylphenylamine by reaction
with (2S,3S)-(?)/(2R,3R)-(-)-dihydrobutanedioic acid in methanol (Scheme 1). The
salts were collected by filtration and recrystallized twice from methanol to give single
white crystals. The crystal structure of S-(-)-a-ethylphenylamine-(2R,3R)-(-)
-dihydrobutanedioic acid was obtained from these crystals.
The final atomic coordinates and equivalent isotropic displacement parameters are
listed in Table 1. Hydrogen bond lengths and angles are listed in Table 2. The selected
bond lengths and angles are shown in Tables 3 and 4 respectively. It can be seen from
Fig. 1 that a molecule of catalyst 1c was composed of S-(-)-a-ethylphenylamine and
(2R,3R)-(-)-2,3-dihydroxybutanedioic acid which together formed an ammonium
salt complex. The C(6), C(7), C(8), C(9), C(10), and C(11) atoms were coplanar
and the plane equation was found to be -2.8203(0.0059)x ? 12.7206(0.0117)y ?
´
˚
1.0243(0.0080)z = 7.0314(0.0071) with a maximum deviation of 0.0454 A for C(8).
´
˚
The C–C distances ranged from 1.372(4) to 1.393(3) with an average of 1.381 A. The
C–C bond angles ranged from 118.6(2)° to 120.8(2)°. The aromatic ring in the
molecule is in agreement with the literature without any unusual features. The
structure of the ammonium salt was pyramidal and the bond angles of N–C and N–H
were all nearly 109°. For example, the angle between C(5)–N(1)–H(1A) was
109.7(16)°, between C(5)–N(1)–H(2A) it was 109.7(19)°, between H(1A)–N(1)–
H(2A) it was 106(2)°, between C(5)–N(1)–H(3A) it was 111.7(19)°, and between
H(1A)–N(1)–H(3A) it was 104(2)°. (2R,3R)-(-)-2,3-dihydroxybutanedioic acid was
123

232
L. Mei et al.
4
2
Table 1 Atomic coordinates (910 ) and equivalent isotropic displacement parameters (A 9 103)
˚
x
y
z
U (eq)
O(1)
O(2)
O(3)
O(4)
O(5)
O(6)
N(1)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
C(10)
C(11)
C(12)
7079(2)
3493(1)
3491(1)
3917(1)
2190(1)
3018(1)
3934(1)
4182(1)
3578(1)
3835(2)
3099(1)
3391(1)
5239(2)
5690(1)
5571(2)
6004(2)
6558(2)
6680(2)
6252(2)
5536(2)
5162(2)
6531(2)
9830(2)
9044(2)
38(1)
40(1)
42(1)
45(1)
38(1)
43(1)
32(1)
28(1)
28(1)
30(1)
29(1)
36(1)
36(1)
44(1)
53(1)
60(1)
62(1)
48(1)
48(1)
10710(2)
10388(2)
7843(3)
7892(2)
5033(2)
2550(3)
8775(3)
8366(3)
6899(3)
6500(3)
2411(3)
3966(3)
3705(4)
5122(4)
6819(4)
7097(4)
5693(4)
25(3)
12232(2)
10809(2)
3752(2)
6548(2)
8401(2)
8937(2)
10774(2)
3607(3)
5329(3)
7081(3)
8626(4)
8433(4)
6696(5)
5148(4)
3278(4)
Table 2 Hydrogen bond lengths and angles for catalyst 1c
D–HꢀꢀꢀA
d(D–H)
d(HꢀꢀꢀA)
d(DꢀꢀꢀA)
\(DHA)
0.827(18)
0.827(18)
0.825(19)
0.870(19)
0.91(2)
2.03(2)
2.30(2)
2.05(3)
1.63(2)
1.94(3)
2.09(3)
2.03(3)
2.610(3)
2.815(3)
2.655(3)
2.491(3)
2.842(3)
2.882(3)
2.920(3)
127(2)
120(2)
130(4)
169(3)
175(2)
155(3)
177(3)
O3–H1ꢀꢀꢀO2
O3–H1ꢀꢀꢀO6
O4–H4ꢀꢀꢀO5
O5–H5ꢀꢀꢀO1
N1–H1AꢀꢀꢀO2
N1–H2AꢀꢀꢀO3
N1–H3AꢀꢀꢀO1
0.84(3)
0.89(3)
deprotonated. The C–O bond lengths of the carboxyl group were 1.263(2) [O(1)–
´
˚
C(1)], 1.235(2)[O(2)–C(1)] A. The amino group of S-(-)-a-ethylphenylamine was
protonated and the three bond lengths of N–H were nearly the same.
Catalyst 1c is further linked together to form a three-dimensional network
packing structure (Fig. 2). The hydrogen bond distances ranged from 0.827(18) to
´
˚
0.870(19) A between the O atoms of tartaric acid and the hydrogen atoms, from
´
´
˚
˚
0.84(3) A to 0.91(2) A between the N atom and the hydrogen atoms.
First, we compared the activities of catalysts 1a–1d under the same conditions. It
was found that 1a had relatively good activity and enantioselectivity. The solvent
effects were also optimized. The results are listed in Table 5. The conclusions about
123

Synthesis of chiral a-ethylphenylamine tartaric acid salts
233
´
˚
Table 3 Bond lengths [A] for
catalyst 1c
´
˚
´
˚
Length (A)
Length (A)
O(1)–C(1) 1.263(2)
O(2)–C(1) 1.235(2)
O(3)–C(2) 1.413(2)
O(3)–H(1) 0.827(18)
O(4)–C(3) 1.416(3)
O(4)–H(4) 0.825(19)
O(5)–C(4) 1.299(2)
O(5)–H(5) 0.870(19)
O(6)–C(4) 1.213(3)
N(1)–C(5) 1.505(3)
N(1)–H(1A) 0.91(2)
N(1)–H(2A) 0.84(3)
N(1)–H(3A) 0.89(3)
C(1)–C(2) 1.530(2)
C(2)–C(3) 1.528(3)
C(2)–H(2) 0.94(2)
C(3)–C(4) 1.528(3)
C(3)–H(3) 0.98(2)
C(5)–C(6) 1.517(3)
C(5)–C(12) 1.518(3)
C(5)–H(6) 1.00(2)
C(6)–C(7) 1.381(3)
C(6)–C(11) 1.393(3)
C(7)–C(8) 1.384(3)
C(7)–H(7) 0.9300
C(8)–C(9) 1.372(4)
C(8)–H(8) 0.9300
C(9)–C(10) 1.375(5)
C(9)–H(9) 0.9300
C(10)–C(11) 1.379(4)
C(10)–H(10) 0.9300
C(11)–H(11) 0.9300
C(12)–H(12A) 0.9600
C(12)–H(12B) 0.9600
Table 4 Bond angles [°] for catalyst 1c
Angle (°)
Angle (°)
C(2)–O(3)–H(1) 102.8(19)
C(3)–O(4)–H(4) 96(3)
N(1)–C(5)–H(6) 107.6(14)
C(6)–C(5)–H(6) 111.3(13)
C(12)–C(5)–H(6) 105.4(13)
C(7)–C(6)–C(11) 118.6(2)
C(7)–C(6)–C(5) 121.94(19)
C(11)–C(6)–C(5) 119.5(2)
C(6)–C(7)–C(8) 120.8(2)
C(6)–C(7)–H(7) 119.6
C(4)–O(5)–H(5) 107(2)
C(5)–N(1)–H(1A) 109.7(16)
C(5)–N(1)–H(2A) 109.7(19)
H(1A)–N(1)–H(2A) 106(2)
C(5)–N(1)–H(3A) 111.7(19)
H(1A)–N(1)–H(3A) 104(2)
H(2A)–N(1)–H(3A) 115(3)
O(2)–C(1)–O(1) 126.11(17)
O(2)–C(1)–C(2) 117.70(15)
O(1)–C(1)–C(2) 116.17(15)
O(3)–C(2)–C(3) 110.04(15)
O(3)–C(2)–C(1) 110.55(14)
C(3)–C(2)–C(1) 110.61(15)
O(3)–C(2)–H(2) 110.2(13)
C(3)–C(2)–H(2) 108.5(13)
C(1)–C(2)–H(2) 107.0(15)
O(4)–C(3)–C(2) 111.12(15)
C(2)–C(3)–H(3) 106.9(14)
C(4)–C(3)–H(3) 106.7(13)
C(8)–C(7)–H(7) 119.6
C(9)–C(8)–C(7) 120.2(3)
C(9)–C(8)–H(8) 119.9
C(7)–C(8)–H(8) 119.9
C(8)–C(9)–C(10) 119.5(2)
C(8)–C(9)–H(9) 120.2
C(10)–C(9)–H(9) 120.2
C(9)–C(10)–C(11) 120.8(2)
C(9)–C(10)–H(10) 119.6
C(11)–C(10)–H(10) 119.6
C(10)–C(11)–C(6) 120.1(3)
C(10)–C(11)–H(11) 119.9
C(6)–C(11)–H(11) 119.9
123

234
L. Mei et al.
Table 4 continued
Angle (°)
Angle (°)
O(6)–C(4)–O(5) 125.22(17)
O(6)–C(4)–C(3) 121.43(16)
O(5)–C(4)–C(3) 113.33(16)
N(1)–C(5)–C(6) 110.51(17)
N(1)–C(5)–C(12) 108.90(18)
C(6)–C(5)–C(12) 112.80(19)
C(5)–C(12)–H(12A) 109.5
C(5)–C(12)–H(12B) 109.5
H(12A)–C(12)–H(12B) 109.5
C(5)–C(12)–H(12C) 109.5
H(12A)–C(12)–H(12C) 109.5
H(12B)–C(12)–H(12C) 109.5
Fig. 1 Crystal structure of
catalyst 1c
Fig. 2 Packing structure of
catalyst 1c
123

Synthesis of chiral a-ethylphenylamine tartaric acid salts
235
Table 5 Effects of catalysts and solvents on the cyanosilylation of acetophenonea
O
OTMS
CH
30%mol catalyst 1a-1d
TMSCN
+
CH
3
3
Ph
Ph
°
solvents,10-20 C, 84h
CN
Catalyst
Solvent
Conv. (%)
1a
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
45
14
25
44
48
65
60
16
45
19
0
1b
1c
1d
1a
1a
Hexane
Ether
1a
1a
Isopropanol
Toluene
CH2Cl2
CH2Cl2
1a
1a
No catalyst
a
Conversion (%) was determined by use of 1H NMR (CDCl3)
Table 6 The cyanosilylation of acetophenone catalyzed by 1a
O
OTMS
30mol%,catalyst 1a
CH Cl ,
TMSCN
+
R2
R2
R1
R1
°
C, 84h
10-20
2
2
CN
Entry
R1
C6H5
R2
Conv. (%)a
1
2
3
4
5
6
a
CH3
CH3
CH3
CH3
CH3
CH3
45
29
60
55
91
89
2-BrC6H4
2-CH3C6H4
4-CH3C6H4
4-BrC6H4
4-ClC6H4
Conversion (%) was determined by use of 1H NMR (CDCl3)
the catalysts were as follows. The catalysts all had moderate activities in hexane,
ether, isopropanol, toluene, and dichloromethane. Hexane gave better reaction
activity than the other solvents, but lower enantioselectivity than ether. The
temperature also affected the reactivities. The lower the temperature, the better the
enantioselectivites.
Ranges of ketone activity were determined with 30 mol% catalyst 1a in hexane at
room temperature. The results are summarized in Table 6.
123

236
L. Mei et al.
Table 6 shows that the 2-position substitution substrates gave slightly higher
conversion than the 4-position substitution substrates.
A probable reaction mechanism that can be proposed is that the proton acid can
greatly activate the C=O bond, increasing the electrophilic reactivity of the carbon
atom, which can then accept nucleophilic attack of CN-.
Conclusions
In conclusion, novel chiral catalysts were synthesized and applied for the first time in
the cyanosilylation of ketones, with moderate yields. One X-ray structure character-
ization is also reported. Study of other applications of the catalysts in aldol reactions,
Henry reactions, and Baylis–Hillman reactions are all in progress. A complete
crystallographic information file for 1c has been deposited with the Cambridge
Crystallographic Data Center as supplementary publication CCDC 639907.
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