Ring-closing metathesis: development of a cyclisation–cleavage strategy for the solid-phase synthesis of cyclic sulfonamides

Abstract

A series of novel 7-membered cyclic sulfonamides have been synthesised using a solid-phase cyclisation–cleavage RCM strategy. Model solution studies indicated the sulfonamides were suitable substrates for RCM using the Grubbs' catalyst 2. Starting from either 2-carboxyethyl polystyrene (21) or Merrifield resin, various seven-membered sulfonamides were prepared in good to excellent yields at low catalyst loadings (2.5–5 mol%) using a flexible spacer between the polymer and the substrate. In addition, a novel double-armed linker was shown to allow efficient RCM cleavage of sulfonamides with as little as 1 mol% of the ruthenium alkylidene complex 2.