3-Aminoquinazolinones as chiral ligands in catalytic enantioselective diethylzinc and phenylacetylene addition to aldehydes

A series of readily known enantiomerically pure 3-aminoquinazolinones 1a–d were synthesised from easily accessible chiral pool α-hydroxy acids and α-amino acids in only four steps without any requirement of chromatography. These quinazolinones were examined as chiral ligands for catalytic enantioselective diethylzinc and phenylacetylene additions to aldehydes. For enantioselective alkylations, the effects of temperature, solvent, diethylzinc and ligand criteria were analysed, and the desired chiral alcohols were obtained in up to 86% ee. 3-Aminoquinazolinones 1a–d were also shown to be very useful ligands in enantioselective alkynylations of aldehydes. Based upon the optimised conditions, the corresponding propargylic alcohols were obtained in up to 94% ee.

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(S)-3-Amino-2-(1-hydroxyethyl)quinazolin-4(3H)-oneC10H11N3O2[α]D25 = −29.8 (c 1.0, CHCl3)Source of chirality: l-Lactic acidAbsolute configuration: (S)

(S)-3-Amino-2-(1-hydroxy-2-methylpropyl)quinazolin-4(3H)-oneC12H15N3O2[α]D25 = −23.5 (c 1.26, CHCl3)Source of chirality: l-ValineAbsolute configuration: (S)

(S)-3-Amino-2-(1-hydroxy-2,2-dimethylpropyl)quinazolin-4(3H)-oneC13H17N3O2[α]D25 = +21.5 (c 1.07, CHCl3)Source of chirality: l-t-LeucineAbsolute configuration: (S)

(S)-3-Amino-2-(hydroxy(phenyl)methyl)quinazolin-4(3H)-oneC15H13N3O2[α]D25 = +4.1 (c 1.22, CHCl3)Source of chirality: l-Mandelic acidAbsolute configuration: (S)