Development of a general, sequential, ring-closing metathesis/intramolecular cross-coupling reaction for the synthesis of polyunsaturated macrolactones.

ABSTRACT: A general strategy for the construction of macrocyclic lactones containing conjugated Z,Z-1,3-diene subunits is described. The centerpiece of the strategy is a sequential ring-closing metathesis (RCM) that forms an unsaturated siloxane ring, followed by an intramolecular cross-coupling reaction with a pendant alkenyl iodide. A highly modular assembly of the various precursors allowed the preparation of unsaturated macrolactones containing 11-, 12-, 13-, and 14-membered rings. Although the RCM process proceeded uneventfully, the intramolecular cross-coupling required extensive optimization of palladium source, solvent, fluoride source, and particularly fluoride hydration level. Under the optimal conditions (including syringe pump high dilution), the macrolactones were produced in 53-78% yie

SUBMITTER: Denmark SE 

PROVIDER: S-EPMC2923678 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature