The Joy and Challenge of Small Rings Metathesis

Abstract

Recent decades have seen a burgeoning of interest in olefin metathesis, as witnessed by a rapidly growing number of elegant applications. Using this tool, chemists can now efficiently synthesize an impressive range of molecules that only a decade ago required significantly longer and tedious routes.[1] Several types of olefin metathesis have been identified so far, among them ring-closing metathesis (RCM) and cross-metathesis (CM) being widely and successfully applied in the synthesis of biologically active complex compounds (Scheme 1). Ring closing metathesis occurs when a diene undergoes intramolecular metathesis affording a cyclic olefin. Analogous intramolecular reaction of an enyne is sometimes called enyne cycloisomerisation or enyne RCM.[2] Ring-closing metathesis reactions of dienes and enynes represent an attractive and powerful tool for formation of medium and large cycles (≥5 members). However, it is generally acknowledged that small rings (threeand four-membered) and strained cannot be formed by RCM.[3] In such cases, the ring opening process can be far more thermodynamically favourable than ring closing. Indeed, various strained molecules, such as norbornene derivatives, are well known substrates for ring-opening metathesis polymerization (ROMP) reactions (Scheme 1).[4]