Part I Catalytic asymmetric arylation of esters for profen synthesis Part II Fast Suzuki coupling of heteroaryl chlorides

Abstract

Transition metal-catalyzed cross-coupling reaction has become a useful methodology for the formation of CC bond. This thesis describes two new improved methods of the CC bond formation catalyzed by palladium catalyst. Chapter one reports a general method of palladium-catalyzed coupling of ester to produce tertiary carbon centers with high yield and exellent ee. It offers a general method for the synthesis of profen drugs. Aryl triflates carrying para-elctron-withdrawing and electron-donating groups are tolerated. Vinyl triflates can also be converted to the corresponding vinyl ester with excellent ee. The use of a new biarylphosphine improved stereoselectivity as compared to the previously reported catalyst. The two CF 3 groups on the benzyl side chain of the ligand may acidify the benylic CH bonds. This probably makes the C-H bond better hydrogen donors in the interaction with Pd-bound enolate, which is responsible for excellent stereoinduction and ligand design. Chapter two describes a new catalytic system for Suzuki-Miyaura coupling of heteroaryl chlorides and heteroayl boronic acids. Most of the major families of heteroaryl chlorides can reached full conversion within minutes to hours at room temperature. The relative reactivity of coupling partners is also studied in this part. Firstly, for heteroaryl chloride, the more electron-rich ones reacted more slowly than electron-deficient ones because of the slower oxidative addition. Secondly, for the heteroarylboronic acids, the more electron-deficient ones reacted more slowly.