Oxidative Dearomative Coupling of Electron-Deficient Arenols Using Hypohalite Catalysis.

We developed performant in situ hypohalite, especially hypobromite, catalysis for the oxidative dearomatization of low-reactivity electron-deficient arenols. The reaction scope encompasses inter- and intramolecular oxidative dearomative C-O, C-N, and C-C coupling reactions. Notably, using a chiral ammonium countercation, we achieved enantioselective hypobromite catalysis for oxidative dearomative coupling reactions.

Catalytic enantioselective nucleophilic desymmetrization of phosphonate esters.

Molecules that contain a stereogenic phosphorus atom are crucial to medicine, agrochemistry and catalysis. While methods are available for the selective construction of various chiral organophosphorus compounds, catalytic enantioselective approaches for their synthesis are far less common. Given the vastness of possible substituent combinations around a phosphorus atom, protocols for their preparation should also be divergent, providing facile access not only to one but to many classes of phosphorus compounds.

Development of a Manufacturing Process toward the Convergent Synthesis of the COVID-19 Antiviral Ensitrelvir.

We describe the development of the practical manufacturing of Ensitrelvir, which was discovered as a SARS-CoV-2 antiviral candidate. Scalable synthetic methods of indazole, 1,2,4-triazole and 1,3,5-triazinone structures were established, and convergent couplings of these fragments enabled the development of a concise and efficient scale-up process to Ensitrelvir. In this process, introducing a -cresolyl moiety successfully enhanced the stability of intermediates.

Chemo- and Enantioselective Oxidative α-Azidation of Carbonyl Compounds.

We report high-performance I /H O catalysis for the oxidative or decarboxylative oxidative α-azidation of carbonyl compounds by using sodium azide under biphasic neutral phase-transfer conditions. To induce higher reactivity especially for the α-azidation of 1,3-dicarbonyl compounds, we designed a structurally compact isoindoline-derived quaternary ammonium iodide catalyst bearing electron-withdrawing groups. The nonproductive decomposition pathways of I /H O catalysis could be suppressed by the use of a catalytic amount of a radical-trapping agent.

Chemoselective Oxidative Spiroetherification and Spiroamination of Arenols Using I/Oxone Catalysis.

We developed a chemoselective oxidative dearomative spiroetherification and spiroamination of arenols using I/oxone catalysis. The intramolecular dearomative C-O and C-N couplings proceeded much more efficiently under slightly acidic conditions to give the corresponding spiro adducts in higher yields compared with previous methods using transition metal or hypervalent iodine catalysts. Control experiments suggested that both hypoiodous acid and iodine might be active species for these reactions.