Biomimetic total synthesis of (--)-SNF4435 C and (+)-SNF4435 D.

摘要

The biomimetic total synthesis of the natural products (-)-SNF4435 C and (+)-SNF4435 D is described. We forwarded a biosynthetic hypothesis in which both molecules are created from a single reactive tetraene precursor. Synthetic validation of this hypothesis involves the palladium catalyzed cross-coupling of two diene fragments to form the tetraene. Once formed, an 8pi-6pi electrocyclization cascade produces the natural products in the approximate ratio found in nature.; The synthesis involves development and exploration of stereoselective methods for creating conjugated trisubstituted alkenes. Of particular relevance in this synthesis are the use of Wittig-type olefination reactions and the Claisen rearrangement. At the outset of this project, relatively little was known regarding the synthesis of conjugated alkenes of this type.; In the context of the synthesis of the SNF compounds, we discovered novel intramolecular Diels-Alder reactions of isomeric 5-vinyl-1,3-hexadienes displaying unusual rates. Such reactions had not been systematically examined. Through investigations of scope, kinetic measurements, and density functional theory calculations, we were able to explain the factors contributing to the peculiar rates.