Studies on copper-catalyzed aerobic molecular transformation with heteroatom radicals
Tnay, Ya Lin
Date of Issue2016-05-27
School of Physical and Mathematical Sciences
Copper-catalyzed oxidation chemistry using oxygen as the oxidant has been widely studied and employed in various types of powerful molecular transformations. Not only does oxygen maintain catalytic turnover of copper catalyst, but also allow oxygenation of organic substrates. In this thesis, three types of molecular transformations involving heteroatom radicals generated from Af-H-imines, organohydroperoxides and A-hydroxyphthalimide under copper- catalyzed aerobic reaction conditions have been developed. In the first transformation, azaspirocyclohexadienones were synthesized via intramolecular i^>so-spirocyclization of iminyl radicals derived from biaryl-A-H imines with the benzene rings under copper-catalyzed aerobic reaction conditions (Scheme la). Under similar reaction conditions, an unexpected oxospirocyclohexadienone formation from biaryl-2-methane carbonitriles via P-carbon fragmentation of the corresponding iminyl radicals was also discovered (Scheme lb). In the second transformation, organohydroperoxides were exploited for the generation of alkoxy-radical species under copper-catalyzed aerobic conditions to perform l,5-H radical shift on aliphatic C-H bonds. The resulting carbon radical was successfully oxygenated by molecular oxygen, affording l,4-diols via aliphatic C-H bond oxygenation (Scheme 2). With the utility of iV-hydroxyphthalimide (NHPI), a similar strategy was applied to the direct 1,4-dioxygenation of alkanes. The third transformation in this thesis involved the investigation of aerobic copper- catalyzed NHPI-mediated synthesis of lactones from the corresponding lactols through radical- mediated C-C bond cleavage. During this process, NHPI was oxidized to phthalimide N-oxy radicals under copper-catalyzed aerobic reaction conditions, which was found to be responsible for the unsaturation and methyl group cleavage.