Synthesis of (+)-N-Methylwelwitindolinone D Isonitrile

Key words

welwitindolinone D - isotope effect - nitrene insertion - C–H functionalization - aerobic oxidation

Significance

The welwitindolinones display interesting biological properties such as antifungal ­activity and microtubule depolymerization in human carcinoma cells. The challenging architecture of the target compound features an oxidized bicyclo­[4.3.1]decane motif. The additional tetra­hydrofuran ring was efficiently introduced by a double functionalization using air.

Comment

A was converted into deuterium-­containing indolinone C. As described earlier by the authors, exploitation of the isotope effect during nitrene insertion afforded E in good yield. Oxidation to F was affected using tetra-n-butylammonium fluoride (TBAF) and air. Since hydrolysis of F led to decomposition, H was prepared by a reduction–hydrolysis–oxidation sequence. Formylation and dehydration yielded the target.