The Development of Palladium - Catalysts for Organic Synthesis

Chapter 1. Suzuki-Miyaura coupling reactions of aryl and heteroaryl halides with aryl-, heteroaryl and vinyl boronic acids proceed in very good to excellent yield with the use of 2-(2',6'-dimethoxybiphenyl)dicyclohexylphosphine, SPhos. Additionally, a comparison of the reactions with SPhos and with 2(2',4',6'-triisoprocpylbiphenyl)-diphenylphosphine is presented that is informative in determining the relative importance of ligand bulk and electron-donating ability in the high activity of catalysts derived from ligands of this type. Further, when the aryl bromide becomes too hindered, an interesting C-H bond functionalization-cross-coupling sequence intervenes to provide product in high yield. Chapter 2. The direct transformation of aryl bromides into the corresponding Weinreb amides via Pdcatalyzed aminocarbonylation at atmospheric pressure is described. Electron-deficient, -neutral and -rich aryl bromides were all efficiently transformed to product. Furthermore, the process tolerates a wide variety of functional groups, is mild, and is operationally simple. Chapter 3. A general, functional group tolerant, and mild system for the Pd-catalyzed Heck carbonylation of aryl chlorides into the corresponding benzamides has been developed. This catalyst operates at one atmosphere of carbon monoxide using an inexpensive, air-stable and commercially available ligand. A variety of aryl chlorides were all successfully transformed to the corresponding amides using primary, abranched primary, cyclic secondary, acyclic secondary, or aryl amines. Additionally, the mechanism of this reaction was studied using in situ IR spectroscopy and revealed the unique effect of sodium phenoxide in this reaction. Chapter 4. Pressurized microreactor systems greatly expand the range of reaction conditions and accelerate gas-liquid mass transfer. Heck aminocarbonylation reactions exemplify the potential for quickly and safely scanning of reagents and reaction conditions (1 to 15 bar and 100 160'C). The results reveal a general trend of increased yield of amide with temperature and selectivity for a-ketoamide production at lower temperature and higher pressure. Thesis Supervisor: Stephen L. Buchwald Title: Camile Dreyfus Professor of Chemistry