Asymmetric cyanosilylation of ketones catalyzed by recyclable polymer-supported copper(II) salen complexes

Various ketones have undergone asymmetric trimethylsilylcyanation at room temperature with (CH3)3SiCN (TMSCN) in the presence of a chiral-supported Cu(salen) complex and Ph3PO as the catalyst. Aromatic, aliphatic, and heterocyclic ketones have been converted into the corresponding cyanohydrin trimethylsilyl ethers in 83−96% yields with 52−84% ee. Several factors concerning the reactivity and enantioselectivity have been discussed. A double activation where Cu(salen) plays the role of Lewis acid and Ph3PO acts as a Lewis base is reported. Poly(ethylene glycol) monomethyl ether (MeO-PEG) has been used as a soluble support while JandaJel (JJ) and Merrifield (MF) resins served as insoluble supports. Each polymer is linked to the salen catalyst through a glutarate spacer. The soluble catalysts were recovered by precipitation with a suitable solvent while the insoluble catalysts were simply filtered from the reaction mixture. The JandaJel-attached Cu(salen) catalyst could be used for five cycles with the retention of efficiency and the Merrifield-bound Cu(salen) catalyst was found to loose activity with each use.

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(S)-2-Trimethylsilyloxy-2-phenylpropanenitrileC12H17NOSiEe = 84%[α]D24=-15.1 (c 1.18, CHCl3)Absolute configuration: (S)Source of chirality: Asymmetric catalysis

(S)-2-Trimethylsilyloxy-2-(4′-chlorophenyl)propanenitrileC12H16ClNOSiEe = 67%[α]D24=-16.4 (c 1.78, CHCl3)Absolute configuration: (S)Source of chirality: Asymmetric catalysis

(R)-2-Trimethylsilyloxy-2-(2′-chlorophenyl)propanenitrileC12H16ClNOSiEe = 60%[α]D24=+11.4 (c 1.20, CHCl3)Absolute configuration: (R)Source of chirality: Asymmetric catalysis

(R)-2-Trimethylsilyloxy-2-(4′-fluorophenyl)propanenitrileC12H16FNOSiEe = 70%[α]D24=+16.4 (c 1.3, CHCl3)Absolute configuration: (R)Source of chirality: Asymmetric catalysis

(S)-2-Trimethylsilyloxy-2-(4′-bromophenyl)propanenitrileC12H16BrNOSiEe = 71%[α]D22=-14.8 (c 1.50, CHCl3)Absolute configuration: (S)Source of chirality: Asymmetric catalysis

(S)-2-Trimethylsilyloxy-2-(4′-nitrophenyl)propanenitrileC12H16N2O3SiEe = 61%[α]D22=-14.4 (c 1.60, CHCl3)Absolute configuration: (S)Source of chirality: Asymmetric catalysis

(S)-2-Trimethylsilyloxy-2-(4′-methylphenyl)propanenitrileC13H19NOSiEe = 65%[α]D24=-15.2 (c 1.50, CHCl3)Absolute configuration: (S)Source of chirality: Asymmetric catalysis

(S)-2-Trimethylsilyloxy-2-(4′-methoxyphenyl)propanenitrileC13H19NO2SiEe = 82%[α]D24=-18.1 (c 1.65, CHCl3)Absolute configuration: (S)Source of chirality: Asymmetric catalysis

(S)-2-Trimethylsilyloxy-2-phenyl-3-methyl-butanenitrile.C14H21NOSiEe = 92%[α]D24=-46.0 (c 4.1, CHCl3)Absolute configuration: (S)Source of chirality: Asymmetric catalysis

(S)-2-Trimethylsilyloxy-2-methyl-4-phenyl-3-butenenitrileC14H19NOSiEe = 60%[α]D24=-16.9 (c 2.1, CHCl3)Absolute configuration: (S)Source of chirality: Asymmetric catalysis