Synthesis of Amphidinolide T1 via Catalytic, Stereoselective Macrocyclization

Journal of the American Chemical Society 126(4), 998-999, DOI: 10.1021/ja039716v

Two nickel-catalyzed reductive coupling reactions of alkynes were instrumental in a modular, stereoselective synthesis of amphidinolide T1 (1). The C13−C21 fragment was prepared from two simple starting materials that were joined in a catalytic alkyne−epoxide fragment coupling operation, whereas an intramolecular aldehyde−alkyne reductive coupling simultaneously formed the final carbon−carbon bond of the macrocycle and established the C13 carbinol configuration with complete selectivity in the desired fashion.