Application of Sequential Ring‐Opening, and Ring‐Closing Metathesis or Ring‐Rearrangement Metathesis to Design Oxacycles and Azacycles

Abstract

We report a concise and simple synthetic approach to oxacycles, azacycles and aza‐propellanes starting with endo/exo‐nadic anhydride via olefin metathesis as a key step. This methodology relies on the usage of Lewis acid mediated allylation of the hydroxy derivatives followed by ring‐opening metathesis (ROM) and ring‐closing metathesis (RCM) to assemble fused oxacycles and azacycles. Moreover, this methodology generates diverse skeletons such as propellanes, highly fused azacycles. Interestingly, some of these heterocyclic frames constitute the basic core of biologically active natural products.

Selectivity: A Goal for Synthetic Economy

“…By treating compound 188 with catalyst G-II at room temperature, the expected aza-propellane 189 was obtained in 73% yield (Scheme 41). 55 10 Separation as a Parameter for Selectivity 1,7-Diallyl-substituted cage compound 190 successfully underwent RCM to yield the desired ring-closure product 191. However, with the reduced derivative 192, devoid of one C-C bond-containing 1,7-allyl substitution, the ringclosure product was not obtained (Scheme 42).…”