Ring-closing metathesis in the synthesis of large and medium-sized oxacycles. Application to the synthesis of polyoxygenated macrocycles

Ring-closing olefin metathesis (RCM) catalyzed by Grubbs's ruthenium benzyl idene complex 1 is applied to the synthesis of unsaturated rings ranging in size from seven to thirteen members in trans-fused polyether systems. Reac tion occurs with great efficiency in the cyclization of oxepene and oxocene rings, but as ring size increases, yields drop. The influence of the final double bond position is also studied. Better yields and milder reaction co nditions are observed when an additional oxygen atom is introduced on the d iene. This feature has promoted the application of this reaction to the syn thesis of polyoxygenated macrocycles (with sizes ranging from 15 to 21 memb ers), with excellent results.