Ring-closing Olefin Metathesis for Organic Synthesis

Abstract

With the commercial availability of well-defined ruthenium metathesis catalysts which combine high stability and broad functional group compatibility with undiminished activity, metathesis has firmly established itself in the toolbox of target-oriented chemists. Ring-closing metathesis (RCM) is now routinely integrated in the retrosynthetic planning of natural product syntheses. The availability of metathesis catalysts with different activity, and hence chemoselectivity, allows increasingly to influence regio- and stereoselectivity of metathesis events. Thus, ring sizes of practically any kind from five onward may be formed. The presence of heteroatoms such as oxygen and nitrogen is unimportant. Ring strain and the presence of other double bonds may be overcome by judicious selection of the conditions. An increasing number of uniquely short and atom-economical natural product syntheses feature sequences of several metathesis events by combining ring-opening metathesis (ROM) with RCM to transform one ring into a thermodynamically more stable one. The remaining drawback of macrocyclic RCM is the lack of control over the stereochemistry of the newly formed double bond. A solution for this problem is provided by diene–ene RCM, which furnishes (E)-olefins selectively. Another issue is the execution of RCM on solid supports, in particular for the preparation of combinatorial libraries.