Highly enantioselective addition of methyl propiolate to aldehydes catalyzed by a titanium(IV) complex of a β-hydroxy amide

Three chiral β-hydroxy amide ligands were prepared by the reaction of benzyl chloride with amino alcohols derived from l-tyrosine. The titanium(IV) complex of chiral ligand 4a was found to be an effective catalyst for the asymmetric addition of methyl propiolate to aliphatic and aromatic aldehydes. The γ-hydroxy-α,β-acetylenic esters were obtained in excellent enantiomeric excesses (up to 94% ee) under optimized conditions.

Graphical abstractThe optically active γ-hydroxy-α,β-acetylenic esters were obtained in highly enantiomeric excesses (up to 94% ee) catalyzed by titanium(IV) complex of ligand 4a.Figure optionsDownload full-size imageDownload as PowerPoint slide

N-((S)-1-(4-(Benzyloxy)phenyl)-3-ethyl-3-hydroxypentan-2-yl)benzamideC27H31NO3[α]D20=139 (c 1.00, acetone)Source of chirality: (S)-tyrosineAbsolute configuration: (S)

N-((S)-1-(4-(4-Methoxybenzyloxy)phenyl)-3-ethyl-3-hydroxypentan-2-yl)benzamideC28H33NO4[α]D20=128 (c 1.00, acetone)Source of chirality: (S)-tyrosineAbsolute configuration: (S)

N-((S)-1-(4-(Benzyloxy)phenyl)-3-ethyl-3-hydroxypentan-2-yl)-2-methoxybenzamideC28H33NO4[α]D20=115 (c 1.00, acetone)Source of chirality: (S)-tyrosineAbsolute configuration: (S)