Abstracts Biological Sciences

Transition metal catalysis for organic synthesis:

by Stephen Spinella

Transition metal-catalyzed reactions are one of the most powerful and direct approaches for the synthesis of organic molecules. During the past several decades, phosphorus containing ligands have been extensively used in transition metal catalyzed C-C and C-H bond forming reactions. Development of new phosphine ligands for palladium cross coupling and also methodology for C-H activation strategies will be the focus of this dissertation. A variety of triazole containing monophosphine ligands have been prepared via efficient 1,3-dipolar cycloaddition of readily available azides and acetylenes. Their palladium complexes provided excellent yields in the amination reactions (up to 98% yield) and Suzuki-Miyaura coupling reactions (up to 99% yield) of unactivated aryl chlorides. A CAChe model for one of the Pd-complexes shows that the likelihood of a Pd-arene interaction might be a rationale for its high catalytic reactivity. A main goal for Organic chemists is to develop and utilize efficient and atom-economical methods for the elaboration of complex structures from simple and readily available starting materials. C-H bonds are the most fundamental linkage in organic chemistry and recently tremendous strides have been have been made in the functionalization of C-H bonds. A central goal in the development of any new methodology is synthetic utility, which has been difficult to achieve with C-H activation strategies because of the inherent stability of C-H bond. Aryl carboxylic acid derivatives are very prevalent in industrial and pharmaceuticals and thus a direct C-H activation approach would be very desirable. A general protocol for the rhodium-catalyzed oxidative carbonylation of arenes to form esters has been developed. A broad substrate scope has been demonstrated allowing carbonylation of electron rich, electron-poor, and heterocyclic arenes, and the reaction shows wide functional group tolerance and excellent regioselectivities. Up to 96% yield of ortho-substituted aryl or heteroaryl carboxylic esters were obtained with this methodology. The possible mechanism for the rhodium-catalyzed oxidative carbonylation reaction was proposed in this article. Studies show that Oxone play an important role in the transformation. We have developed a new C2-symmetric monophosphine ligand based upon a C3* tunephos backbone. The ligand was available in several steps from commercially available starting materials. In future studies this ligand was be tested for its use in chiral cross coupling reactions.