Regio- and Stereoselective Synthesis of Bicyclic Limonene-Based Chiral Aminodiols and Spirooxazolidines

A library of monoterpene-based aminodiols was synthesized and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. The reduction of a bicyclic alpha-methylene ketone, derived from natural (-)-limonene followed by epoxidation, gave the key epoxy alcohol intermediate. Ring opening of the oxirane ring with primary amines induced by lithium perchlorate afforded the required aminodiols. Substituent-dependent ring closure of the secondary aminodiols with formaldehyde resulted in both spirooxazolidines and a fused 1,3-oxazine. Cyclization reactions of the studied aminodiols, resulting in spirocyclic oxazolidines and an isomeric perhydro-1,3-oxazine-fused compound along with the possible iminium intermediates, were analyzed by a systematic series of comparative DFT models performed at the B3LYP/6-31+G(d,p) level of theory.