Direct Intramolecular Coupling of Primary/Secondary Alcohols with Secondary Alcohols for Macrocyclic Alkenylation Using Ni-Zeolite Catalyst Under Continuous-Flow Conditions

Abstract

Herein, we report the direct intramolecular coupling of primary and secondary alcohols for the selective synthesis of macrocyclic olefins in the presence of Ni-zeolite catalyst under continuous flow. This reaction proceeds via dehydration of secondary alcohols to alkenes, which subsequently undergo intramolecular dehydrative coupling reaction with a primary alcohol to obtain moderate yields of macrocyclic olefins. This reaction is also effective for the coupling of secondary-secondary alcohols and alkene-alcohols to produce diverse macrocyclic olefin products. This unique approach has various advantages including step-economy, no additives and pre-functionalization required, inexpensive and reusable catalyst, and exemplification with 23 macrocycles in different ring sizes. The continuous flow macrocyclisation afforded higher productivity and space-time yield than the batch reaction conditions.