Although the efficient preparation of cyclooctanoids has remained a long-standing objective, a real breakthrough was possible only relatively recently with the development of more specific reagents and by the development of new reactions. The direct construction of carbocyclic eight-membered rings from acyclic precursors is still a challenge, mainly because of unfavorable entropic and enthalpic factors that preclude ring formation. This Minireview describes the utilization of ring-closing metathesis (RCM) as a new approach to synthesize cyclooctanoids.

Bei der Synthese von Cyclooctanoiden kam es in jüngster Zeit zu bemerkenswerten Fortschrittten dank der Entwicklung von hochspezifisch wirkenden Reagentien und der Entdeckung neuartiger Reaktionen. Trotzdem bleibt der direkte Aufbau achtgliedriger Carbocyclen aus acyclischen Vorstufen eine Herausforderung, da entropische und enthalpische Faktoren für die Bildung von Ringen dieser Größe nachteilig sind. Dieser Kurzaufsatz beschreibt die Anwendung der Ringschlussmetathese (RCM) als eine neue Methode zur Synthese von Cyclooctanoiden.

[reaction: see text] A new versatile methodology, resulting in a formal three-carbon ring expansion of cyclopentanones, for the efficient assembly of functionalized cyclooctanoids is described. The approach is based on the chemo-, regio-, and stereoselective alpha,gamma-difunctionalization of beta-ketoesters followed by ring-closing metathesis to form functionalized bicyclo[4.2.1]nonanes, precursors of the corresponding cyclooctanes, by selective ring cleavage of the one-carbon-atom bridge.

A series of cis-α,γ-difunctionalized five-membered cyclic β-oxo esters have been chemo-, regio-and diastereoselectively prepared through an efficient domino anionic ring-cleavage/ ring-reconstitution/alkylation sequence including a 1,3-shift of the ester group. These unsaturated substrates were successfully engaged in various ring-closing metatheses to pro-