Optimized Synthesis of Hydrogen-Bond Surrogate Helices: Surprising Effects of Microwave Heating on the Activity of Grubbs Catalysts

Abstract
This manuscript discusses microwave-assisted solid-phase synthesis of hydrogen-bond surrogate based α-helices and analogues by ring-closing metathesis (RCM). Microwave-mediated RCM allows access to a greater variety of amino acid residues in the macrocycles in shorter reaction times and higher yields compared to conventional heating. Surprisingly, we discovered that the Grubbs II catalyst is highly active under the influence of microwaves but catalytically dead under oil-bath conditions for the metathesis of these peptide bisolefins.