Photoinduced Pyridine N-Oxide Catalyzed Functionalization of Unactivated Olefins and Alkylboronic Acids

Abstract

Primary alcohols are fundamental substrates in organic synthesis, and widely used in pharmaceutical, agrochemical, and bulk/fine chemical industries. Chapter one describes the current practices in industry and discoveries in academia for primary aliphatic alcohol synthesis. The methods discussed in chapter one include hydroboration-oxidation, the Ziegler process, hydroformylation/hydrogenation, transition metal-catalyzed hydrogenation of epoxides. Catalytic methods are described as well, both in transition metal catalysis and photoredox catalysis. Chapter two introduces a photoinduced pyridine N-oxide-catalyzed method for carbohydroxylation of unactivated olefins. The extensive reaction optimization process is shown, including the screening of different pyridine N-oxides, photocatalysts, and solvents. In this chapter, the applicability of the method is confirmed for a broad scope of unactivated olefins, both mono- and di-substituted. The regioselectivity of the transformation is confirmed by X-ray crystallography. Chapter three offers mechanistic insights regarding the carbohydroxylation of unactivated olefins. The proposed mechanism is corroborated through different experiments. Cyclic voltammetry and Stern-Volmer fluorescence quenching analysis, revealed that the photocatalyst directly oxidized pyridine N- oxide but does not oxidize the olefin substrate. The substitution step that ultimately affords the primary alcohol is confirmed with the use of different oxygen nucleophiles, that generate the corresponding carbo-oxygenated products. The 18O labeling experiments provide solid evidence that the oxygen source is not the pyridine N-oxide, rather it is the added nucleophile. Radical trapping experiments confirm the existence of the carbon radical generated, after pyridine N-oxy radical addition to the olefin. Chapter four delves in the development of a protocol for the generation of alkyl carbon radicals from alkylboronic acids, wherein photoexcited 4-nitropyridine N-oxide biradical features a catalyst to promote the nucleo-homolytic substitution of boronic acids. With a wide range of readily available aliphatic boronic acids, including methyl boronic acid, the developed catalytic system demonstrates broad applicability for alkylation, amination, and cyanation.