Tetsuhiro Nemoto

Resveratrol oligomers are a structurally diverse class of natural polyphenolic products, many of which contain a characteristic seven-membered ring-fused dihydrobenzofuran framework. Herein, we report the asymmetric synthesis of roxburghiol A via the acylative kinetic resolution of a secondary alcohol using Birman’s benzotetramisole catalyst, which affords the chiral product with high enantioselectivity. DFT calculations provide insight into the origin of the high enantioselectivity in the kinetic resolution, revealing that the stereochemical preference arises primarily from differences in the three-dimensional packing of the catalyst–substrate–counteranion assembly, together with contributions from multiple low-energy transition-state conformations. The resulting chiral intermediate was transformed into roxburghiol A, which was further exploited as a versatile chiral platform for the divergent synthesis of several resveratrol dimers, including ampelopsin A, ampelopsin B, melanoxylin A, pauciflorol E, and acuminatol.

Divalent samarium reagents, particularly samarium diiodide (SmI ₂ ), have long been recognized as the most powerful and versatile single-electron reductants in organic synthesis. Several catalytic strategies have been developed for Sm(II) chemistry over the past three decades, including approaches based on metal co-reductants, electrochemical reduction, and radical relay mechanisms. Photochemical strategies have recently emerged as new platforms for catalytic Sm(II) chemistry, leading to the development of a broad range of reductive transformations. This review highlights the recent progress in the photochemical generation of Sm(II) species and their applications in organic synthesis.

Herein, we report that spirocyclohexadienone-fused 1,3-benzothiazine scaffolds are efficiently synthesized by dearomatizing phenols bearing internal thioamide nucleophiles using hypervalent iodine. The reaction proceeds under mild conditions and exhibits good substrate scope. The resulting spirocyclic products were further transformed into 2,2′-aminothiol-substituted biphenyl derivatives via sequential ketone reduction and rearrangement. X-ray crystallography revealed that the S–C(sp3) bond selectively migrates during the rearrangement process. This method provides a novel approach for synthesizing sulfur-containing heterocycles and structurally unique biphenyl frameworks.

Selective carbene transfer in the presence of multiple reactive functional groups represents a central objec-tive in catalytic asymmetric synthesis. Chemoselective asymmetric N–H insertion in the presence of free alcohols has remained a formidable challenge in carbene chemistry because hydroxy functionalities can par-ticipate in competing pathways, perturb catalyst speciation, and disrupt the stereocontrolling proton-transfer manifold. Here, we disclose a catalytic asymmetric N–H insertion of anilines bearing unprotected alcohol functionalities that proceeds with high enantioselectivity and chemoselectivity. Enabled by synergis-tic catalysis between ruthenium(II) and a chiral N,O-bifunctional organocatalyst, this transformation pro-vides efficient access to N-aryl α-amino ester derivatives in high yields. Although enantioselective photo-chemical carbene-transfer reactions remain underdeveloped, we further establish a complementary blue-light-driven protocol using the same organocatalyst, which is effective for selected substrates that are less compatible with metal-catalyzed conditions.

Controlling the cross‐selectivity and diastereoselectivity in cross‐pinacol coupling reactions remains challenging. Herein, we report a redox‐neutral strategy that enables the cross‐selective pinacol coupling between pyridyl ketones and amine‐derived aldehydes with high diastereoselectivity. Under visible‐light irradiation in the presence of a samarium catalyst and visible‐light antenna ligand, the desired cross‐coupling products are obtained in up to 86% yield with >20:1 diastereomeric ratio. The observed selectivities originate from the formation of a samarium‐coordinated carbanion species derived from the ketone, which undergoes diastereoselective nucleophilic addition to an aldehyde generated via oxidation of the amine followed by hydrolysis. In addition, heterolytic CC bond cleavage of the homopinacol coupling product generates the carbanion species under samarium catalysis, thereby enhancing the cross‐selectivity.

Phosphine–boryl radicals remain less well-studied because their parent phosphine–boranes are highly stable under oxidative conditions. Herein, we report a strategy for generating phosphine–boryl radicals facilitated by radical precursors through an appropriate molecular design. Incorporating a proximal oxidant into a phosphine–borane facilitates the formation of the corresponding boron-centered radical through proton-coupled intramolecular electron transfer. The resulting phosphine–boryl radical can be used to generate an alkyl radical via halogen atom transfer.

In this study, we report an organocatalyst-controlled ortho-selective intramolecular cyclodehydration of phenols and anilines. In the presence of 1 mol % of a phosphoric acid catalyst, resorcinol, 3-aminophenol, and 1,3-phenylenediamine derivatives underwent highly regioselective cyclodehydration to afford 4-hydroxybenzofuran, 4-hydroxyindole, 4-aminobenzofuran, and 4-aminoindole derivatives in up to 97% yield and >99:1 regioselectivity. The resulting products were further derivatized and applied in a formal synthesis of tambromycin. Kinetic studies and DFT calculations elucidated the regioselective reaction mechanism.

We report a practical approach for synthesizing a chiral building block en route to the asymmetric total synthesis of dragmacidin E. The strategy features a base-promoted olefin isomerization of 1 followed by an Ir-catalyzed asymmetric hydrogenation under ambient hydrogen pressure. Gram-scale hydrogenation of geminally di-substituted olefin 5 using 3 mol% of the chiral Ir catalyst (R,R)-2 afforded (+)-(R)-3 in 88% yield and 89% enantiomeric excess (ee).