New asymmetric syntheses utilizing (S)-2-indoline derivatives

Abstract

New chiral auxiliaries and catalysts have been synthesized from (S)-indoline-2-carboxylic acid and found to provide high stereoselectivities in various asymmetric reactions. Diastereoselective pinacol coupling reaction of the (-ketoamides in the presence of samarium (Ⅱ) diiodide gave the outstanding results of (S,S)-threo-pinacols up to > 99% de. The pinacol coupled diol (S-indoline-(S,S)-threo-pinacol) was hydrolyzed to (2S,3S)-dialkylsubstituted tartaric acid as the almost optically pure form ( ＞ 99% de). S-2-Alkoxymethylindoline was recovered in ca. 90% yield. The absolute configuration was determined by X-ray crystallography and CD spectroscopy. While, octahydro (2S, 3aS, 7aS)-N-pyruvoyl-2-(t-butyldiphenylsilyloxy)-indoline, which was obtained by reduction of benzene ring of indoline to cyclohexane ring afforded the opposite configuration (R,R)-threo-pinacol (97% de). The absolute configuration of (R,R)-threo-pinacol (97% de) was determined by measuring [(]D of (S,S)-2,3-dimethyltartaric acid which was obtained from hydrolysis of (S,S)-threo-pinacol and by comparing it with the known one. It is the first to obtain optically pure 2,3-disubstituted tartaric acids. The asymmetric reductive homocoupling reaction at the 3-position of α,β-unsaturated amides with samarium (Ⅱ) diiodide which is a strong one electron donor resulted in 3,4-dialkyladipiamide derivatives with extremely high diastereoselectivities (up to ＞ 99% de) with (3S,4S) configuration. The absolute configuration was determined by X-ray crystallography. The conjugate additions of dibenzyllithium amide to α,β-unsaturated amides of indoline derivatives proceeded rapidly to result in extremely high diastereoselectivities. The procedure can be readily carried out under atmospheric pressure, and the chiral auxiliary is recovered in high yield (up to 98 % de).