New asymmetric reactions using (S)-indoline derivatives

Abstract

The new chiral auxiliaries for the stereoselective reactions were synthesized from (S)-indoline-2-carboxylic acid. Chiral hydrazones derived from (S)-indoline reacted with organolithiums at -78℃ in short reaction time within 10 minutes to afford arylated or alkylated chiral hydrazines with extremely high diastereoselectivity (up to ＞ 99% de) and high chemical yields (90-99%). The hydrazines are readily converted to chiral amino alcohols. Lithiated methoxyallene was added to chiral α-keto amides derived from (S)-indoline to give the hydroxyalkylated allenes with high diastereoselectivity (up to ＞ 99% de). The crude reaction products could either be transformed to enones by hydrolysis with HCl or converted into 2,5-dihyro-3-methoxyfuran derivatives, which were hydrolyzed to give 3(2H)-dihydrofuranones. The diastereoselectivity was not changed in transformation to the dihydrofuran derivative. Chiral α-keto amides reacted with lithiated acetylene to afford the quaternary propargylic alcohols with very high diastereoselectivity (up to ＞ 99% de). α-Bromoacrylamides reacted with aldehydes or ketones in the presence of $SmI_2$ to produce Baylis-Hillman reaction type``s products through anionic process in good yields (52-89%). This reaction system could be applied to functionalize at 5-position of pyrimidines. 2-Bromoacrlamides bearing (S)-indoline chiral auxiliary reacted with aldehydes in the presence of $SmI_2$ to give the α-hydroxyalkylacrylamides in good yields but with low diastereoselectivity. The asymmetric reductive homocoupling reaction at the 3-position of α, β -unsaturated amides derived from (S)-indoline with $SmI_2$ resulted in (3R,4R)-dialkyladipamide derivatives with extremely high diastereoselectivities (up to ＞ 99%). When the chiral auxiliary was changed from (S)-indoline derivative to (2S,3aS,7aS)-octahydroindoline derivatives, which were obtained by reduction of benzene ring of indoline to cyclohexane ring, the opposite configuration, (3S,4S)-diethyl...