A number of palladacycles containing chiral chelating auxiliaries have been utilized as efficient catalysts for asymmetric hydrophosphination reactions. In all cases, the chiral auxiliaries remained coordinated to the palladium centres...

Enantioenriched phosphine azoles were synthesized in high yields via palladium-catalyzed asymmetric hydrophosphination with excellent yields and enantioselectivities under mild reaction conditions. One of the phosphine azoles was methylated and complexed to palladium(II) cleanly to give a chiral phosphine−NHC palladium(II) complex with excellent overall conversion.

A series of activated vinyl azoles was hydrophosphinated in the presence of a chiral palladacycle catalyst under mild conditions to give enantioenriched phosphine azoles with moderate enantioselectivities and yields. The racemic phosphine azoles were transformed into eleven novel chelating phosphine–N-heterocyclic carbene (NHC) platinum complexes. The drug efficacies of nine selected phosphine–NHC platinum­(II) chlorides in two cancer cell lines (MKN74 and MCF7) were evaluated, and two were found to exhibit activities comparable to that of cisplatin.

Chiral hybrid phosphine-N-heterocyclic carbenes form a unique class of bidentate ligands which finds extensive uses as privileged ligands in homogeneous transition metal catalysis.The current methodologies associated with their syntheses suffer from significant drawbacks and the diversity of the structural backbones of these ligands has hence been limited. Catalytic asymmetric hydrophosphination was contrived as a solution to address the abovementioned problem as it is arguably one of the most efficient methods of generating chiral phosphines with high enantiopurities and simultaneously, offering additional advantages such as a 100% atom economy, mild reaction conditions and a diverse substrate scope. Catalytic asymmetric hydrophosphination was employed in the syntheses of novel chiral phosphine-N-heterocyclic carbene precursors and these precursors were subsequently transformed into chiral novel phosphine-N-heterocyclic carbene metal complexes. The structures of the complexes were elucidated via X-ray crystallography and their catalytic and biological applications were explored.I would like to express my sincere gratitude to my supervisor, Prof. Leung Pak-Hing, whose passion for Chemistry has motivated me in numerous ways during the course of my project; for his encouragement that made challenging situations seem simpler; for the freedom he has given me to pursue my own directions; and for his trust and support he has placed in me.My gratitude also extends to my co-supervisor, Dr. Sumod A. Pullarkat, for his unwavering support and guidance provided to me way before I began my postgraduate journey. I would also like to thank Prof. Andrew Tan and Prof. Leong Weng Kee for being my academic mentors over the years and providing valuable insights which proved to be greatly helpful in my research. In addition, I would like to thank Jeannie from the Lee Kong Chian School of Medicine for her contributions towards the biological applications of the novel platinum complexes on cancer cells. Special appreciation goes to my lab mates and friends Ronald, Shafiq, Ce Qing, Jeremy, Jia Sheng, Po Kai, Sadeer, Wee Shan and Wen Qian for being my lunch buddies and rendering help unconditionally whenever I needed. I would also like to thank my parents for their constant encouragement, confidence and trust placed in me for the past 29 years.Lastly, I would also like to acknowledge the kind assistance provided by Dr. Li