ZnI2-Catalyzed Cyanation of Acyl Chlorides with TMS-CN
Letters in Organic Chemistry, 2009, Vol. 6, No. 8
641
Na2SO4, and concentrated to give crude mandelonitrile (4ea).
The crude mandelonitrile is treated with Ac2O (100 μL) and
pyridine (50 μL) in CH2Cl2 (5 mL) at room temperature for 1
h. It is quenched with 5 mL water. The organic layer is
separated, washed with H2O and brine, dried over anhydrous
Na2SO4, and concentrated under reduced pressure. The crude
product is purified by silica gel flash chromatography
(petroleum ether/ethyl acetate = 20:1, v/v) to yield the O-
acetyl mandelonitrile 4eb (39.2 mg, 98%) as colorless oil. 1H
NMR (400 MHz, CDCl3) ꢀH: 7.45-7.47 (m, 3H), 7.51-7.54
(m, 2H), 6.41 (s, 1H), 2.17 (s, 3H).
Tamio Hayashi at Kyoto University is gratefully
acknowledged for discussion.
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The two enantiomers are resoluted by chiral HPLC on a
Daicel OD-H, n-hexane/2-propanol = 99:1, flow rate = 1.0
mL/min, tS = 6.64 min (49.9%), tR = 7.09 min (50.1%). The
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Preparation of (R)-4ea
To a dry Schlenk tube under argon is added a solution of
benzoyl cyanide (20 mg, 0.15 mmol) in of anhydrous CH2Cl2
(0.5 mL). The solution is added (S)-CBS (30 μL, 1.0 M in
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stirring another 0.5 h, the reaction mixture is separated into
layers. The aqueous layer is extracted with CH2Cl2 (3x). The
combined organic layers are dried over Na2SO4,
concentrated, and the residue is subjected to silica gel
column (petroleum ether/EtOAc = 10/1, V/V) to give the
mandelonitrile (4ea) as a pale yellow oil, 82% yield
([ꢀ]D30 = 8.89 (0.09, CH2Cl2, 24% ee)) [lit. [ꢀ]D23 = +45.3
(0.2, CHCl3, 95% ee)] [19]. The absolute configuration of
4ea is R by comparing to the sign of the optical rotation
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After derived to its acetyl ester (R)-4eb the ee value of
the cyanohydrins is determined to be 24% ee by chiral HPLC
analysis. HPLC condition: OD-H (Daicel 4.6 mm*25 cm),
hexane/i-propanol = 99: 1 (V/V), wavelength = 254 nm,
rate = 1 mL/min, sample = 5μL, tS (minor) = 6.65 min
(38%), tR (major) = 7.10 min (62%).
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ACKNOWLEDGEMENTS
The authors thank NSFC (20502019) and Beijing
Institute of Technology for financial support. Professor