Methods for preparing macrocyclic products by ring-closing diyne metathessis

Abstract

The present invention relates to methods for preparing macrocyclic products having 9 or more ring atoms by ring-closing diyne metathesis of suitable diyne substrates. The diyne substrates can be converted into cycloalkynes or into cycloalkadiynes by cyclodimerization, depending on the particular reaction conditions. Any alkyne metathesis catalyst can be used as the catalyst, regardless of whether said catalysts are heterogeneously or homogeneously present in the reaction medium. The preferred catalysts or pre-catalysts are transition metal alkylidyne complexes, transition metal compounds which form alkylidyne complexes under the reaction conditions, and transition metal compounds with metal-metal triple bonds. The method can be carried out with numerous functional groups, solvents, and additives. Using known methods, the formed macrocyclic cycloalkynes or cycloalkadiynes can be converted into numerous secondary products, especially macrocyclic cycloalkenes with a uniform configuration of the double bond, and used, e.g., for the synthesis of epothilone or epothilone analogues.