Asymmetric trimethylsilylcyanation of aldehydes catalyzed by chiral schiff base-Ti(OiPr)4 complex

Article abstract of DOI:10.1081/SCC-100105676

A new chiral Schiff base 4 was synthesized, which was found to be efficient catalyst for the enantioselective silylcyanation of aldehydes. The enantioselectivities of 25.1-72.7% were obtained by using the chiral Schiff base-Ti(OⁱPr)₄ complex.

Full text of DOI:10.1081/SCC-100105676

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ASYMMETRIC TRIMETHYLSILYL-CYANATION OF
ALDEHYDES CATALYZED BY CHIRAL SCHIFF BASE-
Ti(OiPr)4 COMPLEX
Zhuohong Yang a , Zhenghong Zhou a & Chuchi Tang b
a State Key Laboratory of Elemento-Organic Chemistry , Institute of Elemento-Organic
Chemistry, Nankai University , Tianjin, 300 071, P. R. China
b State Key Laboratory of Elemento-Organic Chemistry , Institute of Elemento-Organic
Chemistry, Nankai University , Tianjin, 300 071, P. R. China
Published online: 16 Aug 2006.
To cite this article: Zhuohong Yang , Zhenghong Zhou & Chuchi Tang (2001) ASYMMETRIC TRIMETHYLSILYL-CYANATION OF
ALDEHYDES CATALYZED BY CHIRAL SCHIFF BASE-Ti(OiPr)4 COMPLEX, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 31:19, 3031-3036, DOI: 10.1081/SCC-100105676
To link to this article: http://dx.doi.org/10.1081/SCC-100105676
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SYNTHETIC COMMUNICATIONS, 31(19), 3031–3036 (2001)
ASYMMETRIC TRIMETHYLSILYL-
CYANATION OF ALDEHYDES
CATALYZED BY CHIRAL SCHIFF
BASE-Ti(OiPr)4 COMPLEX
Zhuohong Yang,Zhenghong Zhou,and
Chuchi Tang*
State Key Laboratory of Elemento-Organic
Chemistry, Institute of Elemento-Organic Chemistry,
Nankai University, Tianjin 300 071, P. R. China
ABSTRACT
A new chiral Schiff base 4 was synthesized, which was found
to be efficient catalyst for the enantioselective silylcyanation
of aldehydes. The enantioselectivities of 25.1–72.7% were
obtained by using the chiral Schiff base-Ti(OiPr)4 complex.
Enantiomerically pure cyanohydrins are important synthetic inter-
mediates in the synthesis of other chiral compounds and can be prepared
by many biological and chemical methods.1–3 Recently, Oguni,4 Jiang
Yaozhong5 and North6 reported asymmetric trimethylsilylcyanation of alde-
hydes catalyzed by chiral Schiff base-titanium alkoxide complexes. The chiral
source compounds they used derived from chiral compounds 1, 2 and 3,
respectively. In their papers, the corresponding cyanohydrins have been
*Corresponding author.
3031
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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3032
YANG,ZHOU,AND TANG
obtained in good chemical yields with moderate to excellent enantio-
meric excesses, when 20 mol% chiral Schiff base and 20 mol% Ti(OiPr)4
were used.
Because D-camphor is easily obtained and has good stereogenic
center, chiral Schiff base 4 was synthesized from it and used in the trimethyl-
cyanation of aldehydes. The results are summarized in Table 1.
From the table, the enantioselectivity of the reaction was affected by
the reaction temperature and the amounts of catalyst. The highest enantios-
electivity of 66.1% was obtained, when the amounts of catalyst was
22 mol% and the Ti(OiPr)4 was 20 mol%. But when the amounts of catalyst
was increased up to 55 mol%, the enantioselectivity of cyanohydrin was
decreased, this was in accordance with Jiang’s results.7
Scheme 1.
At last, the trimethylsilylcyanation of several other aromatic aldehydes
proceeded smoothly in the amounts of 22 mol% of Schiff base 4 and
20 mol% of Ti(OiPr)4, in which the product 2-hydroxy-p-methoxylphenyl-
acetonitrile was obtained in 72.7% e.e. (Table 2, entry 1). Moreover, the
results showed that good enantiomeric excesses were obtained with electron-
rich aromatic aldehydes, while electron-deficient aromatic aldehyde gave
lower enantiomeric excesses. Further investigation to improve the enantio-
selectivity is still in progress.

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TRIMETHYLSILYLCYANATION OF ALDEHYDES
3033
Table 1. Enantioselective Addition of Trimethylsilylcyano to Benzaldehyde in
Presence of 4
Cat.
Entry (mol%) (mol%)
Ti(OiPr)4
Temp.
(ꢀC)
C.Y.
(%)a
Ee
[a]D
Ee
(%)b (c 1, CHCl3) (%)c
1
2
3
4
5
6
7
8
11
11
5.5
11
22
55
20
22
10
10
5
10
20
50
10
20
20
0
100
97
94
97
97
94
94
þ11.3
þ20.5
þ13.7
þ24.9
þ31.4
þ19.5
þ25.9
–
25.1
45.6
30.4
55.4
70
43.4
57.4
–
À35 ꢁ À45
À35 ꢁ À45
À35 ꢁ À45
À35 ꢁ À45
À35 ꢁ À45
À78
66.1
47.8
No reaction
–
aIsolated yield; bDetermined by chiral GC after derivation with acetic acid anhy-
c
20
D
dride; Determined by the comparison of specific rotation values ½aŠ ¼ þ45 (c 1,
CHCl3)8.
Table 2. Enantioselective Addition of Trimethylsilylcyano to Aromatic Aldehydes
in Presence of 4
Temp.
(ꢀC)
C.Y.
(%)a
Ee
(%)
[a]D
(c 1, CHCl3)
Ee
(%)c
Entry
Compd.
1
2
3
4
p-CH3OPhCHO
p-ClPhCHO
p-CH3PhCHO
o-CH3OPhCHO
À35 ꢁ À45
À35 ꢁ À45
À35 ꢁ À45
À35 ꢁ À45
89
92.5
92
þ36
72.7d
32.8e
65f
30.0b
þ13.5
þ33.3
þ19.4
92
71.7g
aIsolated yield; bDetermined by chiral GC after derivation with acetic acid anhy-
c
d
25
D
dride. Determined by the comparison of specific rotation values; ½aŠ ¼ þ49 (c 1,
e
25
D
CHCl3) with e.e. > 99%;8 ½aŠ ¼ þ27.2 (c 1.487, CHCl3) with e.e. ¼ 66%;9
f
25
D
g
20
D
½aŠ ¼ þ47.4 (c 1.822, CHCl3) with e.e. ¼ 92%;9 ½aŠ ¼ À21.0 (c 1.25, CHCl3)
with e.e. ¼ 77%.1
EXPERIMENTAL
1H NMR were recorded in CDCl3 as solvent on AC-P200 instruments
using TMS as internal standard. Elemental analyses were conducted on
MF-3 automatic analyzer. Melting points were determined on MP-500 mel-
ting point apparatus. Optical rotations were measured on a Perkin–Elmer
241MC polarimeter. All temperatures were uncorrected.

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YANG,ZHOU,AND TANG
Preparation of (Q)-Cis-1,2,2-trimethyl-1,3-cyclopentane-
dicarboxylic Acid 610
A mixture of D-camphor 19.00 g (0.125 mol), FeSO4ꢂ7H2O 1.00 g
(0.0036 mol), 85 mL H2O and 180 mL HNO3 (65–68%) was refluxed at
100–105ꢀC for 30 h, then the resulting solution was cooled to room tem-
perature.Thewhitesoliddepositedwasfiltered,washingwithH2O(2 ꢃ 10 mL),
afforded the desired product 6 12.24 g, yield: 48.9%, m.p. 202–205ꢀC,
½aŠ ¼ þ44.5(c ¼ 10, EtOH). (Lit.: Yield: 53.5%, m.p.: 204–205ꢀC).
25
D
Preparation of (Q)-Cis-1,2,2-trimethyl-1,3-diamino-
cyclopentane 511
A mixture of 6 20.30 g (0.1 mol), CHCl3 (200 mL) and H2SO4 (60 mL)
was stirred at 55–60ꢀC with NaN3 18.60 g (0.286 mol) added at intervals,
reacting until no gas formed. The resulting solution was cooled to room
temperature and adjusted to pH >14 with saturated NaOH. The solution
was deposited overnight and filtered, washing with CHCl3 (2 ꢃ 30 mL). The
organic layer was separated and the aqueous layer was extracted with
CHCl3 (2 ꢃ 30 mL). The combined organic layer was dried over anhydrous
sodium sulfate, then the solvent was removed in vacuo to give the crude
product 5 12.23 g. Yield: 86.13%. Because the crude product 5 is difficult to
purify, it was used straightly in the next step.
Preparation of Catalyst 4
A mixture of toluene (40 mL), 2-hydroxylbenzaldehyde (2.44 g,
20 mmol), 5 (1.42 g, 10 mmol), p-toluenesulfonic acid (0.01 g) was refluxed
for 2 h. After evaporation yellow solid was recrystallized from ethyl acetate
25
to give 4 2.80 g. Yield: 80%. m.p. 159–161ꢀC; ½aŠ ¼ þ34.0 (c ¼ 2, CHCl3);
D
1H NMR (d, ppm): 0.95 (s, 3H), 0.97 (s, 3H), 1.36 (s, 3H), 2.15 (m, 4H), 3.71
(t, 1H), 7.11 (m, 8H), 8.45 (s, 2H). Anal. calcd. for C22H26N2O2: C, 75.36; H,
7.49; N, 7.99. Found: C, 75.15; H, 7.50; N, 7.88.
Typical Procedure for the Trimethylsilylcyanation of Aldehydes
To a solution of Schiff base 4 (154 mg, 0.44 mmol) in CH2Cl2 (5 mL)
was added Ti(OiPr)4 (114 mg, 0.4 mmol) and stirred for 1 h at room tem-
perature. The reaction mixture was cooled to À35 ꢁ À45ꢀC, then freshly

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TRIMETHYLSILYLCYANATION OF ALDEHYDES
3035
distilled benzaldehyde (212 mg, 2 mmol) and trimethylsilyl cyanide (400 mg,
4 mmol) were added. After stirring for 12 h at this temperature, the mixture
was poured into a mixture of 1 N HCl (30 mL) and ethyl acetate (60 mL) and
stirred for 4 h at room temperature, washing the organic layer with distilled
water and saturated NaHCO3 (each 20 mL), drying with anhydrous sodium
sulfate and concentrating the reaction mixture followed by column chroma-
tography (eluent: petroleum ether/ethyl acetate: 5/1) yielded the expected
(S)-cyanohydrin (260 mg, 97.7%). After measuring the optical rotation of
the pure cyanohydrin, the compound was converted directly into the corre-
sponding acetates by reaction with two equivalents of acetic acid anhydride
and pyridine in CH2Cl2 (20 mL) at room temperature for 12 h, washing the
organic layer with 5% H2SO4, distilled water and saturated NaHCO3 (each
20 mL), drying with anhydrous sodium sulfate and concentrating the reac-
tion mixture followed by column chromatography (eluent: petroleum ether/
ethyl acetate: 5/1) yielded the acetylated cyanohydrin, which was used for
further analysis.
ACKNOWLEDGMENT
We are grateful to the National Science Foundation (No. 29872016)
for generous financial support.
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YANG,ZHOU,AND TANG
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Received in the Netherlands October 12, 2000

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