Exo-Selective Reductive Macrocyclization of Ynals

A general
protocol for the highly exo-selective macrocyclization
of ynals using a nickel/N-heterocyclic carbene catalyst
system has been developed. A series of 10- to 21-membered macrocycles
bearing an exomethylene substituent was synthesized in good yields
with excellent regioselectivity (exo/endo >95:5). Very high levels
of long-range diastereocontrol can also be achieved for some classes
of macrocycles. Complementary to previously reported endo-selective
macrocyclizations, this method provides accesses to exoalkylidene
macrocycles from simple ynals in high selectivity.