Photoinduced Enantioselective Functionalization of C(sp³)−H Bonds

The construction of enantioenriched chiral compounds is critical for diverse fields, such as pharmaceuticals, agrochemicals, and functional materials. To this end, direct enantioselective functionalization of C(sp³)−H bonds is arguably an ideal approach in terms of step economy and starting material availability. Furthermore, enantioselective late-stage C−H functionalization of pharmaceutical candidates and complex bioactive molecules is highly advantageous for drug development. Thus, research in the field of enantioselective C(sp³)−H functionalization is of vital importance to the pharmaceutical industry in particular and the society in general. As an alternative to transition-metal-catalyzed C−H activation and metallonitrene/metallocarbene insertion, we focus on a strategy that combines enantioselective transition-metal catalysis and hydrogen atom transfer reagents, which convert C(sp³)−H bonds into carbon-centered radical intermediates that are directly trapped by chiral transition-metal catalysts.
Photocatalysis is an emerging and powerful tool in organic synthesis that offers a unique approach for easy access to carbon-centered radical intermediates from C−H substrates through diverse activation processes under mild reaction conditions. Recently, the combination of C−H-derived radical formation by photocatalysis with functionalization of these reactive radical species by transition-metal catalysis has been demonstrated as a transformative platform for the enantioselective construction of challenging chemical bonds.
In this thesis, our efforts toward the development of new methods that can enable enantioselective conversion of C(sp3)−H bonds into diverse functionalities by the means of photocatalysis and transition-metal catalysis will be presented. The main focus is C(sp3)−H amination and oxidation through the enantioselective C−N and C−O bond construction, respectively.