Eisuke Ota

We report a general protocol for the light-driven isomerization of cyclic aliphatic alcohols to linear carbonyl compounds. These reactions proceed via proton-coupled electron-transfer activation of alcohol O-H bonds followed by subsequent C-C β-scission of the resulting alkoxy radical intermediates. In many cases, these redox-neutral isomerizations proceed in opposition to a significant energetic gradient, yielding products that are less thermodynamically stable than the starting materials. A me

The reductive ring opening of epoxides is a powerful transformation to convert readily accessible epoxides into a diverse array of valuable alcohols, including pharmaceuticals, agrochemicals, and functional polymers. Although significant progress has been made, the established methods were limited to titanocene-catalyzed reactions. Herein, we report an unprecedented zirconocene-catalyzed ring opening of epoxide enabled by photoredox catalysis. Compared with the conventional ring-opening methods,

Photoaffinity labeling (PAL) is an important tool in chemical biology research, but application of α-ketoamides for PAL has been hampered by their photoinstability. Here, we show that 2-thienyl-substituted α-ketoamide is a superior photoreactive group for PAL. Studies with a series of synthetic mannose-conjugated α-ketoamides revealed that 2-thienyl substitution of α-ketoamide decreased the electrophilicity of the keto group and reduced the rate of photodegradation. Mannose-conjugated thienyl α-

Alkyl chlorides are robust precursors to carbon radicals; however, their relative inertness has hampered their practical use. Although modern photochemical strategies have greatly enhanced the utility of alkyl chlorides as radical precursors, these methods often depend on strongly reducing conditions leading to unproductive side reactions. Here, we report a catalytic radical generation from 1°, 2°, and 3° unactivated alkyl chlorides with zirconocene and photoredox catalysis, which enables both h

The bibenzyl skeleton is prevalent in numerous natural products and other biologically active compounds. Radical homocoupling provides a straightforward approach for synthesizing bibenzyls in a single step with the reductive homocoupling of benzyl halides undergoing extensive development. Unlike benzyl bromides and other tailored precursors used in visible-light-mediated homocoupling, benzyl chlorides offer greater abundance and chemical stability. Nevertheless, achieving chemoselective cleavage

Abstract Oxetanes are frequently utilized in organic synthesis, both as target products and as fairly reactive intermediates. Whereas ring cleavage of oxetanes through polar mechanisms has been extensively investigated, their radical-based counterparts remain underexplored. We used zirconocene and photoredox catalysis to open an oxetane ring in a radical manner. In our protocol, the reaction selectively delivers the more-substituted alcohols via putative less-stable radicals. This method not onl

Abstract With recent advances in photoredox chemistry, a variety of methods for generating carbon radicals have emerged. This review highlights recent approaches for radical generation utilizing zirconocene(III), a species infrequently employed in organic syntheses. Of particular interest are methods employing visible light irradiation, which induce C–Zr bond homolysis of alkyl zirconium species or activate a photoredox catalyst to reduce zirconocene(IV).

Abstract In recent years, the deconstructive transformation of unstrained cyclic amines via C−N bond cleavage has emerged as a powerful strategy for expanding chemical space and facilitating the synthesis of structurally diverse molecules. Notably, advancements in the C−N bond cleavage of pyrrolidine and other unstrained cyclic amines have highlighted the significant potential of this approach in modern organic synthesis. This concept reviews recent developments in the C−N bond cleavage reaction

We have developed a catalytic protocol for the selective cleavage of C–O bonds at benzylic positions using zirconocene and photoredox catalysis. This catalytic system enables the reductive cleavage of C–O bonds in both benzyl ethers and benzyl alcohols. Additionally, aromatic carbonyl compounds undergo deoxygenation to afford the corresponding hydrogenated products. Mechanistic studies support that ZrIII is the catalytically active species responsible for the C–O bond cleavage, driven by the for

Abstract Cyclic amines represent ubiquitous structural motifs in organic chemistry, prominently featured in natural products and pharmaceuticals. The development of synthetic methodologies targeting cyclic amines has attracted considerable interest, given their significance in medicinal chemistry. These transformations can be broadly categorized into two main types: (1) peripheral modification and (2) skeletal remodeling. Recent advancements in late-stage C–H functionalization have showcased the

Abstract The reductive ring opening of cyclic amines is a powerful strategy for transforming cyclic structures into entirely different molecular frameworks, with significant potential application in synthetic and medicinal chemistry. Previously reported methods have been primarily limited to highly strained substrates such as aziridines and azetidines. In this study, we report a novel approach for generating carbon-centered radicals upon ring opening from less strained cyclic amines, particularl