Palladium-assisted macrocyclization approach to cytochalasins: A synthesis of antibiotic A26771B

Article abstract of DOI:10.1021/ja00341a043

A synthetic strategy to macrocycles possessing a gamma -oxo delta -hydroxy-, gamma , delta -dihydroxy- and gamma -hydroxy- alpha , beta -unsaturated carbonyl system derives from a palladium-catalyzed C-C bond-forming reaction. In this approach, the macrocyclization employs a beta -keto sulfone as an electrofugal group and a 2-ethoxyallyl acetate as a nucleofugal group mediated by a phosphine-palladium (0) complex. In addition to facilitating anion formation and nucleophilic attack on the ( pi -allyl) palladium intermediate, the benzenesulfonyl group serves as a stereochemical control element which permits relay of stereochemical information between remote centers. The total synthesis of antibiotic A26771B is completed in 12 steps from 10-undecenal to illustrate the applicability of this methodology. Refs.