Catalytic Asymmetric Synthesis of Bioactive Molecules

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As our continuing studies toward enantioselective reactions of organolithiums based on an external chiral ligand, we have developed the catalytic asymmetric addition of thiophenol to enoates using lithium thiophenolate as a catalytic nucleophile which has higher reactivity than thiophenol activated by amine. The 2-substituent of thiophenol exerts profound effects on reactivity and enantioselectivity in the asymmetric addition reaction with enoates catalyzed by lithium thiophenolate and a chiral ligand. The bulky substituent gave the higher reactivity and enantioselectivity. The asymmetric reaction of 2-trimethylsilylthiophenol with methyl enoates was catalyzed by the combination of 0.08 eq of lithium 2-trimethylsilylthiophenolate and 0.1 eq of the chiral ligand, (1R,2R)-1-dimethylamino-2-(2-methoxyphenoxy)-1,2-diphenylethane, in toluene-hexane (1 : 1) to afford the corresponding methyl 3-(2-trimethylsilylphenylthio) carboxylates in excellently high ees. The chiral ligand was recovered quantitatively for reuse without racemization. The 2-trimethylsilyl group was protodesilylated by treatment with triflic acid to give the corresponding 3-phenylthiocarboxylates in excellently high yield without racemization. The kinetic control is operative in the asymmetric addition reaction.