Additive Effects in the Palladium-Catalyzed Carboiodination of Chiral N-Allyl Carboxamides

• Published in: Angewandte Chemie International Edition 2014-07, Vol.53 (30), p.7908-7912
• Main Authors: Petrone, David A., Yoon, Hyung, Weinstabl, Harald, Lautens, Mark
• Format: Article
• Language: English
• Subjects: Additives; Amines; Asymmetry; carboiodination; Catalysis; Catalysts; heterocycles; Ligands; Palladium; phosphine ligands; Synthesis; Troubleshooting
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201404007

The use of Pd catalysis as a means to synthesize organic halides has recently received increased attention. Among the reported methods is the Pd‐catalyzed carboiodination, which uses extremely bulky ligands to facilitate carbon–halogen reductive elimination from PdII as the key catalytic step. When approaching substrates exhibiting low stereoselectivity, catalyst troubleshooting becomes difficult as there are few ligands known to promote the key reductive elimination. Herein, we present our finding that tertiary amines act as weakly coordinating ligands which significantly enhance diastereoselectivity in the Pd/QPhos‐catalyzed carboiodination of chiral N‐allyl carboxamides. This methodology allows efficient access to enantioenriched and densely functionalized dihydroisoquinolinones, and has been applied toward the asymmetric formal synthesis of (+)‐corynoline. A‐mean combination: A general and efficient synthesis of chiral dihydroisoquinolinones by a highly diastereoselective Pd0‐catalyzed carboiodination is reported. As an additive, the bulky tertiary amine base PMP (1,2,2,6,6‐pentamethylpiperidine) is presumed to act as a weakly coordinating ligand, leading to a significant and general increase in diastereoselectivity. The utility of the method was applied to the asymmetric formal synthesis of (+)‐corynoline.