Following notable cases of remarkable potency increases in methylated analogues of lead compounds, this review documents the state-of-the-art in C–H methylation technology.

In this work an approach for the synthesis of furanocembranoid natural products containing the C-7,8-diol moiety is disclosed. This culminated in the first total synthesis of the natural product molestin E, together with entsinulacembranolide A and ent-sinumaximol A as well as a thorough exploration of their chemistry. Late-stage ringclosure of the C-7,8-diols to the corresponding epoxides was also demonstrated. Key features of this synthetic strategy include a stereoselective Baylis-Hillman reaction, ring-closing metathesis and Shiina macrolactonisation. Chiral-pool materials were deployed to ensure the desired absolute stereochemistry which was confirmed by late-stage single crystal Xray diffraction.

The use of benzylic and allylic alcohols in HFIP solvent together with Ti(OiPr)4 has been shown to trigger a highly stereoselective polyene cyclisation cascade. Three new carbon‐carbon bonds are made during the process and complete stereocontrol of up to five new stereogenic centers is observed. The reaction is efficient, has high functional group tolerance and is atom‐economic generating water as a stoichiometric by‐product. A new polyene substrate‐class is employed, and subsequent mechanistic studies indicate a stereoconvergent mechanism. The products of this reaction can be used to synthesize steroid‐analogues in a single step.