Highly enantioselective addition of phenylacetylene to aldehydes catalyzed by titanium(IV) complexes of β-hydroxy amides

A series of chiral β-hydroxy amide ligands was synthesized via the reaction of benzoyl chloride and chiral amino alcohols derived from l-amino acid. Titanium(IV) complexes of these new β-hydroxy amide ligands were used for catalyzing the enantioselective addition of phenylacetylene to aldehydes. We found that the enantioselectivity of the reaction was strongly affected by the amount of titanium tetraisopropoxide and the solvent used. Chiral ligand 2b synthesized from 2-amino-3-ethyl-1-phenylpentan-3-ol was effective for the asymmetric alkynylation of aldehydes and the propargyl alcohols were obtained in high yields (up to 96%) and high enantiomeric excesses (up to 97%) under optimized conditions. A practical solution for preparing the chiral propargylic alcohol was described.

Graphical abstractA series of chiral β-hydroxy amide ligands were synthesized from l-amino acids by facile approaches. The enantioselective addition of phenylacetylene to aldehydes catalyzed by titanium(IV) complexes of these new chiral ligands were investigated. Excellent enantioselectivities were obtained for the desired propargyl alcohols with enantiomeric excesses values up to 97%. Figure optionsDownload full-size imageDownload as PowerPoint slide