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(i PrO)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.
8 With 20 mol% rac -1 -Ti(i PrO)4 (1:1.2 ratio) complex used as catalyst, acetophenone gave O-TMS cyanohydrin in 0% ee, but with 20 mol% (S )-1 -Ti(i PrO)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]}.
9 A series of solvents were examined including toluene, THF, Et2 O, CH2 Cl2 and CH3 CN.
10
A representative procedure : To a solution of rac -1 (12.2 mg, 0.034 mmol) in CH2 Cl2 (1 mL) was added Ti(i PrO)4 (1 M in toluene, 17 mL, 0.017 mmol) at room temperature, and the mixture was stirred for 1 h, CH2 Cl2 was evaporated under reduced pressure. The resulting residue was further dried in vacuo for 30 min. The residue was dissolved in CH2 Cl2 (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; 1 H 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.
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13 Manuscript in preparation.