Asymmetric syntheses using new chiral indoline derivatives

Abstract

The new chiral auxiliaries for the stereoselective reactions were synthesized from (S)-indoline-2-carboxylic acid. These derivatives provided high stereo-selectivities in various asymmetric reactions. Diastereoselective addition of organometal reagents to new chiral a-ketoamides having (S)-2-methoxy-methylindoline resulted in a-hydroxyamides with extremely high diastereo-selectivities (up to 99% de). The reactions of organolithiums with chiral hydrazones derived from (S)-indoline-2-carboxylic acid afforded chiral hydrazines with high diastere-oselectivity (up to 99% de). As an application of the present method, (-)-coniine natural product was synthesized in high optical purity (94% ee). Diasteroselective addition of trimethylsilylcyanide to aldehyde (S)-1-amino-2-methoxymethyl-indoline hydrazones at -78℃ in $CH_2Cl_2$ in the presence of diethylaluminium- chloride gave chiral α-hydrazinonitriles in high optical yields (up to 96% de). During the course of sturdy on the cleavage of N-N bond of chiral hydrazines it has been found that α-hydrazinonitriles were smoothly dehydrogenated with palladium charcoal catalyst under mild conditions in the presence of cyclopentene to hydrazonoyl cyanides in good yields. Diastereoselective addition of aryllithium to chiral trifluoropyruvic aldehyde hydrazones gave the corresponding tertiary alcohols in good optical yield (up to 72% de), which may be used for the enantio-selective synthesis of Mosher reagent ((S) or (R)-α-methoxy-α-(trifluoro-methyl) phenyl acetic acid).