Selectivity in Olefin-Intervened Macrocyclic Ring-Closing Metathesis

Abstract

The ring-closing metathesis (RCM) of α,m,ω-triene was employed for the syntheses of four slightly different EE, EZ, ZE, and ZZ isomers of macrocycles with two greatly separated type I olefins. Kinetic control of the RCM reaction using G1 was achieved, in which secondary metathesis of the initially formed RCM product that usually afforded the thermodynamically favored product was inhibited, and a reliable model was built to differentiate the kinetic or thermodynamic control in the RCM reaction. Kinetic studies of olefin metathesis using the kinetically controlled Z-selective catalyst Cat-Z were conducted to determine its thermodynamic capability to convert (Z)-olefin to (E)-olefin. Finally, the ring size selectivity of α,ω- vs α,m-/m,ω-products in the RCM reaction of α,m,ω-triene revealed that all types of isomeric α,ω-products are favored for the 18-membered ring and above, and α,m-/m,ω-products are predominant for the rings with 14-members and less. For the 15-, 16-, and 17-membered rings, each of the E/Z-selective RCM reactions of starting (mE)- and (mZ)-trienes has a different performance under the optimized conditions. These studies provide insights into the applications of RCM on the synthesis of macrocycles with two separate type I olefins.