Collect. Czech. Chem. Commun. 2000, 65, 490-510

Studies Toward an Asymmetric Synthesis of CP-263,114 and CP-225,917

Jean-Fran├žois Devaux, Steven V. O'Neil, Nathalie Guillo and Leo A. Paquette*

Evans Chemical Laboratories, The Ohio State University, Columbus, OH 43210, U.S.A


An enantioselective approach to construction of the complex framework of the CP compounds is presented. The synthesis relies on initial elaboration of the two sidechains. The "upper" appendage was asymmetrically dihydroxylated with both AD-mix reagents in order to lend flexibility to the scheme and provide the necessary handle for evolving the additional stereogenic centers. These fragments were linked to benzoic acid via Birch reduction-alkylation and subsequent cuprate addition. A series of functionalization reactions including dissolving metal reduction, Claisen rearrangement, iodolactonization, regioselective epoxide cleavage-oxidation, and intramolecular Wadsworth-Emmons cyclization took advantage of highly efficient stereocontrol. However, this flexibility was thwarted when deprotonation of a penultimate intermediate failed to be regioselective in the proper direction.

Keywords: Dihydroxylation; Birch reduction; Allylic oxidation; Iodolactonization; Claisen rearrangement; CP compounds; Total synthesis.

References: 58 live references.