Diastereoselective Pd(II)-Catalyzed sp(3) C-H Arylation Followed by Ring Opening of Cyclopropanecarboxamides: Construction of anti beta-Acyloxy Carboxamide Derivatives

摘要

The diastereoselective Pd(OAc)(2)-catalyzed, bidentate ligand-directed sp(3) C-H activation/arylation followed by ring opening of cyclopropanecarboxamides, which were assembled from cyclopropanecarbonyl chlorides and bidentate ligands (e.g., 8-aminoquinoline and 2-(methylthio)aniline), has been investigated. The treatment of various cyclopropanecarboxamides with excess amounts of aryl iodides in the presence of the Pd(OAc)(2) catalyst, AgOAc and AcOH directly afforded the corresponding multiple beta-C-H arylated open-chain carboxamides (anti beta-acyloxy amides). This method has led to the construction of several anti beta-acyloxy amides that possess vicinal stereocenters with a high degree of stereocontrol with the formation of a new C-O bond and three new C-C bonds. A plausible mechanism for the formation of multiple beta-C-H arylated open-chain carboxamides from the Pd-catalyzed, bidentate ligand-directed beta-C-H arylation and the ring opening of cyclopropanecarboxamides is proposed based on several control experiments. The observed diastereoselectivity and anti stereochemistry of the beta-acyloxy amides were ascertained based on X-ray structural analysis of representative beta-acyloxy amides.