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Synlett 2002(5): 0793-0795
DOI: 10.1055/s-2002-25370
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Mild and Efficient Cyanosilylation of Ketones Using In Situ Generated N-oxides-Ti(iPrO)4 Complexes as Catalysts

Yongcun Shenb, Xiaoming Feng*a, Yan Lia, Guolin Zhangc, Yaozhong Jiang*b
a Sichuan Key Laboratory of Green Chemistry and Technology, The Faculty of Chemistry, Sichuan University, Chengdu 610064, China
Fax: +86(28)5412907; e-Mail: xmfeng@pridns.scn.edu.cn;
b Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China
c Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China
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Publication History

Received 12 February 2002
Publication Date:
07 February 2007 (online)

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Abstract

The addition of TMSCN to ketones catalyzed by complex of racemic N-(2′-pyridylmethyl)-2-diphenylhydroxymethyl-pyrrolidine N-oxide (rac-1) or N-benzyl-N,N-dihydroxyethylamine N-oxide and Ti(iPrO)4 affords the racemic O-TMS cyanohydrins in good to excellent isolated yields (up to 97%) under mild reaction conditions.

Key words

catalysis - cyanosilylation - ketones - N-oxides - complex

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N-(3’-Pyridylmethyl), N-(2¢-methoxyphenylmethyl) and N-phenylmethyl-2- diphenylhydroxymethyl-pyrrolidine N-oxides were screened.

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With 20 mol% rac-1-Ti(iPrO)4 (1:1.2 ratio) complex used as catalyst, acetophenone gave O-TMS cyanohydrin in 0% ee, but with 20 mol% (S)-1-Ti(iPrO)4 (1:1.2 ratio) complex used as catalyst, acetophenone gave O-TMS cyanohydrin in 53.3% ee {GC [Varian, Chirasil DEX CB (0.25 mm × 25 m), Column temperature = 100 °C(isothermal), Injector temperature = 200 °C, Detector temperature = 250 °C, tR(minor) = 26.3 min, tR(major) = 27.8 min]}.

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A series of solvents were examined including toluene, THF, Et2O, CH2Cl2 and CH3CN.

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A representative procedure: To a solution of rac-1 (12.2 mg, 0.034 mmol) in CH2Cl2 (1 mL) was added Ti(iPrO)4 (1 M in toluene, 17 mL, 0.017 mmol) at room temperature, and the mixture was stirred for 1 h, CH2Cl2 was evaporated under reduced pressure. The resulting residue was further dried in vacuo for 30 min. The residue was dissolved in CH2Cl2 (0.5 mL). To this solution, the ketone (0.17 mmol) was added under ice-water bath, followed by the addition of TMSCN (45 mL, 0.34 mmol) as shown in Table [1] . The reaction was monitored by TLC, and after the reaction period described in Table [1] , the solution was concentrated, usual work up and purification by silica gel chromatography gave the product.

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N-oxide 2:
White crystals; mp 135-137 °C; 1H NMR (CDCl3, 200 MHz): δ = 3.46-3.47(t, J = 1.6 Hz, 4 H), 4.12(m, 4 H), 4.61(S, 2 H), 5.15(br, 2 H), 7.37-7.46(m, 5 H); MS m/z: 212(M+ + H, 81%).

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Manuscript in preparation.