Isoxazole-embedded allylic zinc reagent for the diastereoselective preparation of highly functionalized aldol-type derivatives bearing a stereocontrolled quaternary center

Abstract

Highly functionalized aldol-type products bearing a β-quaternary center and a stereoselectively controlled γ-hydroxy function are readily prepared by the diastereoselective addition of an allylic zinc reagent embedded in an isoxazole ring to various aromatic and heteroaromatic aldehydes, in the presence of Lewis acids, such as MgCl2 or LaCl3⋅2 LiCl. After reductive cleavage of the N-O bond by using Fe, NH4Cl, aldol-type products bearing a stereocontrolled β-quaternary center and a γ-hydroxy group were observed. The benzylic reactivity of the isoxazolylmethylzinc reagent towards other electrophiles, such as acid chlorides, aryl and allylic halides, as well as aldehydes in the presence of BF3⋅OEt2 are also described.

Keywords: Lewis acids; isoxazoles; magnesium; quaternary centre; zinc.