Enantioselective addition of alkynylzinc to arylaldehydes catalyzed by azetidino amino alcohols bearing an additional stereogenic center

Chiral azetidino amino alcohol ligands bearing an additional stereogenic center were readily prepared and used as catalysts for the asymmetric addition of alkynylzinc to aromatic aldehydes with enantioselectivities of up to 87% ee. The relationship between the reaction enantioselectivity and the structure of the chiral ligands was also evaluated in this reaction. The experimental results showed that the enantioselectivity level of the reaction was greatly influenced by the second stereogenic center attached to azetidine ring, but the stereochemical sense was only determined by the configuration of the azetidine ring. A possible transition structure for the catalytic asymmetric addition was also proposed.

Figure optionsDownload as PowerPoint slide

Diphenyl-(l-((1R)-phenylethyl)azetidin-(2S)-yl)-methanolC24H25NO[α]D20=+63.6 (c 1.00, CHCl3)Source of chirality: (R)-phenylethylamineAbsolute configuration: (R,2S)

Diphenyl-(l-((1R)-phenylethyl)azetidin-(2R)-yl)-methanolC24H25NO[α]D20=+22.4 (c 1.00, CHCl3)Source of chirality: (R)-phenylethylamineAbsolute configuration: (R,2R)