Studies on development of radical-mediated carbon-carbon and carbon-heteroatom bond formation reaction

Abstract

Part 1. Development of Pyrylium-Catalyzed C−O Bond Formation Reaction for The Construction of Cyclic Ethers and Lactones The regioselective reaction for the construction of cyclic ethers and lactones was developed using 2,4,6-triphenylpyrylium tetrafluoroborate (TPT), which selectively activates benzylic position through the generation of aryl radical cation. This powerful strategy can achieve regioselectivity by preventing a competing 1,5-hydrogen abstraction or decarboxylative pathway. Detailed mechanistic studies containing DFT calculation suggest that molecular oxygen is used to trap the benzylic radical intermediate to form benzyl alcohol, which can be activated by catalytic iodine to afford intramolecular cyclization. This new approach serves as a meaningful platform by providing efficient access to valuable 5- and 6-membered cyclic ethers and lactones with a unified protocol.

Part 2. Development of N-Heterocyclic Carbene-Catalyzed Deaminative Acylation and Three Component Reaction with Katritzky Pyridinium Salts With the catalytic generation of Breslow intermediate by N-heterocyclic carbene (NHC) catalyst, we developed a new catalytic single electron transfer system without the necessity of visible light and additional thermal energy that enables deaminative acylation and three component alkyl acylation reaction with Katritzky pyridinium salts. The Katritzky pyridinium salts behave as single-electron oxidants for the enolates form of Breslow intermediate following generation of persistent radical intermediate. The resultant alkyl radical from Katritzky pyridinium salts undergoes radical-radical coupling efficiently with persistent radical cation or three component coupling selectively in the presence of styrene derivatives. The mild and transition metal-free reaction conditions tolerate a broad range of functional groups, and its utility has been further demonstrated by the modification of a series of peptide feedstocks and application to the three-component dicarbofunctionalization of olefins.

Part 3. Development of Visible-Light-Induced Umpolung Aminopyridylation Reaction of Ketones via One-Pot Strategy The unprecedented ortho-selective aminopyridylation of ketones containing umpolung reactivity was developed in a one-pot procedure. This novel strategy for manipulation of alpha and carbonyl position of ketone derivatives could be enabled by the potential, with modified pyridine N–N ylides. The ortho migration of alkyl radical to electrophilic pyridinium cation, which is the key step in the mechanism, could occur in intramolecular type through the reaction between silyl enol ether and nitrogen-centered radical cation, generated by single-electron oxidation of pyridine N–N ylide. Finally, the desired polarity-inverse aminopyridylated alcohol product was afforded within a deprotection step in one-pot. This significant reaction could also demonstrate its utility with a broad range of scope with high regioselectivity to 2 and 6 positions of pyridine, and by its application to the formation of ortho-selective pyridylated diamine species.