Total syntheses of isodomoic acids G and H: an exercise in tetrasubstituted alkene synthesis.

A unified approach to the pyrrolidine triacid natural products isodomoic acids G and H has been developed. Total syntheses of both natural products were completed, and determination of the correct stereostructure of isodomoic acid G was established by comparing 5'-(R) and 5'-(S) isomers to a sample of authentic material. A nickel-catalyzed cyclization constructs the pyrrolidine ring while simultaneously establishing either the E or Z stereochemistry of an exocyclic tetrasubstituted alkene. Stereoselective assembly of both the E- and Z-alkenes of the natural products is made possible by a predictable strategy that alters the timing of substituent introduction to control alkene stereochemistry.