Diastereoselective Synthesis of Nonplanar 3-Amino-1,2,4-oxadiazine Scaffold: Structure Revision of Alchornedine.

Herein, we report the diastereoselective synthesis of a 3-amino-1,2,4-oxadiazine (AOXD) scaffold. The presence of a N-O bond in the ring prevents the planar geometry of the aromatic system and induces a strong decrease in the basicity of the guanidine moiety. While DIBAL-H appeared to be the most efficient reducing agent because it exhibited high diastereoselectivity, we observed various behaviors of the Mitsunobu reaction on the resulting β-aminoalcohol, leading to either inversion or retention of the configuration depending on the steric hindrance in the vicinity of the hydroxy group. The physicochemical properties (p