Hydrocarbon stapling as a strategy to stabilize secondary structures of peptides, while introduced by Miller, Blackwell and Grubbs in the mid 1990s, really grew to the forefront with seminal work by Schaffmeister and Verdine in early 2000s.  Protocols have been developed that enable this post-synthesis modification while the peptide is still on resin, but often these metathesis reactions are performed manually, and at room temperature.

In today's post, I'll compare several different sets of reaction conditions using microwave heating with the goal of expediting the olefin metathesis reaction, without compromising reaction efficiency, and towards automating the entire synthesis.