A strategy for regiochemical reversal of reductive macrocyclisations of aldehydes and terminal alkynes has been developed by US researchers. Using an advanced synthetic intermediate directed towards the methymycin/neomethymycin class of macrolides, selective endocyclisation provides the natural twelve-membered ring series, whereas ligand alteration enables selective exocyclisation to provide access to the unnatural eleven-membered ring series. The twelve-membered ring adduct was converted to 10- deoxymethynolide, completing an efficient total synthesis of this natural product.
Reference:
Nickel-Catalyzed Regiodivergent Approach to Macrolide Motifs
A-R Shareef, D H Sherman and J Montgomery, Chem. Sci., 2012
DOI: 10.1039/c2sc00866a
