Pyrido 1,4,2,5-diazadiborinine : from EDA induced preparation to diboron biradical in-situ generation, reactivity; stereo-selectivity and BNCT toolbox

Abstract

The thesis consists of three chapters with aim to develop a pyridine derived 1,4,2,5-diazadiborinine system through borylation of pyridines followed by a ligand exchange strategy, the resulting diborane was then transferred to active biradical spices in-situ and applied in 4+2 reactions and drug modification. Chapter one outlines the background and phtotochemical synthesis of 2-borylated pyridine, in- duced by electron donor-acceptor complexes. The study of borylation of pyridine ensured a robust, scalable production of 2-borylated pyridines, which serve as precursor for pyrido 1,4,2,5-diazadiborinine. Including detailed experimental procedures and compound characteri- zations. It also describes mechanistic studies, including the identification of EDA complexes, on and off experiments, quantum yield determination. Chapter two describes the synthetic procedure for our 1,4,2,5-diazadiborinine, including lig- and abstraction methods through free borane coordination, and thermal ligand exchange exper- imentations towards the 1,4,2,5-diazadiborinine. The simple and straightforward methodology ensured gram - scale preparation of the diborane intermediate. Including detailed experimental procedures and compound characterizations. Chapter three mainly focus on the generation of biradical spices using thermal controlled in- situ dehydrogenation process, and the synthetic application of our pyrido 1,4,2,5-diazadiborinine, including 4 + 2 addition reactions with alkenes, alkynes and drug molecules. The wide trials exhibited great potential towards a robust borylation toolbox, which can be applied onto existing drugs and modify them into BNCT therapeutics. Including detailed experimental procedures and compound characterizations. The mechanistic studies for generation and reactivity of the active biradical spices and the detection and characterization of hydrogen gas generation are also included in the chapter. The original copies of ¹H, ¹¹B, ¹⁹F and ¹³C NMR spectra are provided in the Appendix section of this thesis.

Date of Award	2023
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Yangjian QUAN (Supervisor)