The work presented in this thesis is mainly focused on the development of iridium- or rhodium-catalyzed asymmetric hydrogenation featuring a number of practical concepts including cascade reaction, kinetic resolution, desymmetrization, and dearomatization. The protocols rely on gaining control of the reactivity among different olefins or olefin precursor as well as maintaining chemo- and stereo-selectivity in the hydrogenation. Furthermore, the application of the developed methodologies into the asymmetric synthesis of some bioactive natural products is also described.

In the first part of this work (Chapter 2), we have developed a tandem Peterson olefination and asymmetric hydrogenation of β-hydroxy silanes that provides an efficient access to stereogenic carbons bearing benzyl-methyl substituents. This strategy is based upon the controllable chemoselectivity of hydrogenating either the β-hydroxy silane or an olefin in the same reaction system. A two-step asymmetric total synthesis of natural product (S)-(+)-Curcumene further illustrates the usefulness of this methodology.

The second part of the thesis (Chapter 3) is focused on the development of two discriminative hydrogenations: kinetic resolution and desymmetrization. The developed methods exhibit excellent selectivity towards reaction of one enantiomer in a racemic mixture or a mono-hydrogenation of one enantiotopic group in a meso compound. A broad range of allylic alcohols or amides bearing one or two contiguous stereogenic centers could be obtained in high enantiomeric purity by using these discriminative hydrogenations. DFT calculations and kinetic modelling were applied to give insights into the origin of selectivity and the kinetics for the desymmetrization process. Based on the usefulness of these reactions, the third part of the thesis (Chapter 4) is focused on their applications into the asymmetric synthesis of key intermediates for the total synthesis of natural products including Pumiliotoxin A, Inthomycins (A and B), Zaragozic acid A and Invictolide.

The last chapter (Chapter 5) describes the merging of homogenous and heterogeneous rhodium catalysis for the asymmetric hydrogenation of benzene derivatives, which is a long-standing challenge in the field. Based on the discovery that the commonly used rhodium precursors (such as [Rh(COD)]BF₄) could undergo in situ formation of rhodium nanoparticles, we have expanded the application of well-established Rh/diphosphine catalytic system into efficient dearomative asymmetric hydrogenations.