טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentSuez Gal
SubjectCatalysis with Metal-Free Molecules and by Non-Covalent
Bonds
DepartmentDepartment of Chemistry
Supervisor Professor Mark Gandelman
Full Thesis textFull thesis text - English Version


Abstract

Organocatalysis has emerged as one of the leading strategies in the synthesis of asymmetric molecules in the last few years. Several classes of small organic molecules acting as metal-free catalysts have been developed and reported in the literature. These employ a few kinds of activation mechanisms including covalent and non-covalent bonding. Undoubtedly, progress in the field relies on the discovery and design of both new modes of activation and new catalyst architectures. One goal of this study was the development of a new hydrogen bonding organocatalyst by rational design, and demonstration of the catalytic activity of the newly designed catalyst in a model reaction. Another aim of the research was the application of halogen bonding phenomenon as a new activation mode for catalysis.

The design, preparation and studies of a family of new organic hydrogen bonding catalysts are presented. The design of these catalysts is inspired by the phenomenon of DNA nucleobases pairing to form a precise and specific set of hydrogen bonds. It has been shown that this phenomenon can be used to create useful organic catalysts which demonstrate similar recognition patterns with common organic substrates. Selected bifunctional catalysts based on a guanine structure has proved able to catalyze the conjugate addition of 1,3-dicarbonyl compounds to nitroalkenes, providing products in good yields and enantioselectivities. The results demonstrate proof of concepts and potential usefulness of the catalysts in further challenging applications.

In the second part of this research we have demonstrated that the halogen bonding phenomenon can be a useful tool for activation of substrates with the designed catalysts. Phosphine oxides were used as Lewis bases in the activation of N-halogen compounds in halogen transfer reactions. A new concept was described towards the desymmetrization of a bis(aryl) system by halogenation. Excellent regioselectivities were obtained in bromination experiments. Importantly, thermodynamic parameters of studied halogen bonds were quantified. Namely, binding constants of various phosphine oxides with series of N-bromo- and N-chloro-based acceptors were determined in solution for the first time. A correlation between catalytic activity of the phosphine oxides and the binding strength of the latter to halogenating compounds was obsereved. Additionally, X-ray structures of several N-halogen compounds co-crystallized with phosphine oxides exhibited well-defined halogen bonding between the investigated molecules.   

Further research is directed to apply halogen bonding activation phenomenon to the asymmetric catalytic synthesis of chiral materials. To this end, chiral phosphine oxides derivatives are prepared.