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

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.

catalysis - cyanosilylation - ketones - N-oxides - complex

References

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7

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

8

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, t_R(minor) = 26.3 min, t_R(major) = 27.8 min]}.

9

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

10

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.

11

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%).

12 Kobayashi S. Tsuchiya Y. Mukaiyama T. Chem. Lett.  1991,  537 

13

Manuscript in preparation.