Continuous Flow Z-Stereoselective Olefin Metathesis: Development and Applications in the Synthesis of Pheromones and Macrocyclic Odorant Molecules*

Abstract

The first continuous flow Z-selective olefin metathesis process is reported. Key to realizing this process was the adequate choice of stereoselective catalysts combined with the design of an appropriate continuous reactor setup. The designed continuous process permits various self-, cross- and macro-ring-closing-metathesis reactions, delivering products in high selectivity and short residence times. This technique is exemplified by direct application to the preparation of a range of pheromones and macrocyclic odorant molecules and culminates in a telescoped Z-selective cross-metathesis/ Dieckmann cyclisation sequence to access (Z)-Civetone, incorporating a serial array of continually stirred tank reactors.

Keywords: (Z)-Civetone; Z-selectivity; continuous flow; olefin metathesis; pheromones.