Styduhar ED, Huters AD, Weires NA, Garg NK * University of California, Los Angeles, USA
Enantiospecific Total Synthesis of
N-Methylwelwitindolinone D Isonitrile.
Angew. Chem. Int. Ed. 2013;
52: 12422-12425
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.
