Transition metal-catalyzed reactions of arylmetal reagents and alkynes involving remote C-H activation
Date of Issue2018
School of Physical and Mathematical Sciences
Selective C–H bond activation is a highly demanding task due to the presence of multiple C–H bonds of strong and similar bond strength in a complex molecule. Over the last three decades, a variety of approaches based on transition metal catalysis have been developed to enable efficient and selective C–H activation. Among them, one of the most successful approaches capitalizes on the use of a heteroatom-containing directing group, which allows transition metal catalysts to activate the proximal C–H bond. While the "directed C–H activation" uses dative bond (coordination) to achieve site-selectivity, analogous approach, termed remote C–H activation/metal migration, employs metal–carbon covalent bond as a steppingstone. Thus, an organotransition metal species may undergo activation of the proximal C–H bond in an intramolecular fashion, which may result in formation of a metalacycle and/or complete migration of the transition metal center. In this context, noble metals (Pd, Rh) have been extensively employed to enable numerous reactions involving 1,4-metal migration, while the use of base metals remains underdeveloped. This thesis research aimed at development of new base metal-catalyzed transformations involving remote C–H activation/metal migration. In particular, the present research was focused on transition metal-catalyzed reactions between arylmetal reagents and alkynes. Chapter 2 describes a cascade arylative cyclization reaction between ester- or ketone-tethered alkynes and arylzinc reagents that involves 1,4-cobalt migration as a key step. The reaction was achieved by a cobalt catalyst bearing an appropriately chosen biaryl-diphosphine ligand, which displayed unique reactivity in comparison with previously reported rhodium and iridium catalysts. Chapter 3 reports on the discovery of 1,4-chromium migration. Investigation into a chromium-catalyzed alkyne arylmagnesiation reaction unexpectedly indicated the feasibility of 1,4-chromium migration and allowed us to establish effective chromium catalyst systems for “migratory” arylmagnesiation of alkynes to afford ortho-alkenylaryl Grignard reagent. Stimulated by this discovery, we further developed a chromium-catalyzed [4+2] benzannulation reaction between 2-biaryl Grignard reagents and internal alkynes to afford phenanthrene derivatives, which is described in Chapter 4.