Synthesis of aza-macrocycles by palladium-catalyzed dehydrative allylation

Abstract

Nitrogen-heterocycles are of great interest in the pharmaceutical industry because they are found in many biologically active compounds. The study of small rings with Nitrogen-heteroatoms is relatively well known because of the stability of this structure, but the study of macrocyclic molecules with Nitrogen-heteroatoms is still a big challenge. In this dissertation, a dehydrative substitution study of allyl alcohol and nitrogen heteromolecules by palladium-briphos catalyst was carried out. Through this allylation, aza-macrocycles could be well synthesized. Briphos ligands, which have very good π-electron acceptor properties, form complexes with palladium, and show very good reactivity to dehydrative allyl substitution reactions. The hydroxyl group was taken as a leaving group to enable double substitution using 1,4-dihydroxy-2-butene, which was conceived from allyl alcohol leaving the water. Furthermore, macrocyclic molecules having hetero atoms could be synthesized using a product made by replacing 1,4-dihydroxy-2-butene twice at the end of a nucleophile.