The reactions of reductive amination are of paramount importance as tools of synthetic organic chemistry. Recently, the applicability of sodium hypophosphite as a promising reductant for such reaction...

Aldolases, especially 2-deoxyribose-5-phosphate aldolase (DERA) enzymes, have been widely employed to access key chiral precursors for various active pharmaceutical ingredients (APIs). This has been e...

The standard protocol for Alloc group removal during peptide synthesis still presents limitations, including low reaction yields, N-allylated byproducts, and the use of air-sensitive Pd(PPh3)4. We addressed these challenges by developing a novel protocol using the air-stable Pd(PPh3)2Cl2 catalyst, Meldrum’s acid (MA), and triethylsilane (TES-H). This combination ensured high yields, eliminated N-allylated byproducts, and is compatible with automated synthesis. This cost-effective and efficient method shows promise for widespread use in peptide chemistry applications and beyond.

The generation, interconversion, and reactivity of electrophilic species generated upon activation of nitroalkanes with protic acids (the Nef and Meyer reactions) were investigated by quantum-chemical calculations. N,N-Bis(hydroxy)iminium (R2C═N+(OH)2) and N-oxoiminium (R2C═N+═O) cations were shown to be produced independently from aci-nitroalkanes, while N-hydroxynitrilium cations (RC≡N+–OH) were formed via nearly barrierless C–H bond cleavage in N-oxoiminium cations. The N-oxoiminium and N-hydroxynitrilium cations whose formation is favored under highly acidic anhydrous conditions are strong electrophiles capable of reacting even with nonactivated arenes under ambient conditions. The N-oxoiminium cations R2C═N+═O are highly unusual ambident species containing three contiguous electrophilic centers (C, N, and O atoms). Nucleophilic addition at the oxygen atom is less preferred than the C- and N-attack yet possible in an intramolecular variant. These computational results shed light on some key aspects of the mechanisms of the Nef and Meyer reactions and predict the possibility of numerous interrupted versions of these reactions.

We report a practical 5 g scale stereoselective synthesis of the valuable iminosugar DMDP from d-fructose in only 7 synthetic steps and in a 70% overall yield, which doubles previously reported yields. This process requires only two chromatographic purification steps, taking advantage of a regioselective Appel reaction. The regioselective reaction has also been applied on a similar scale to prepare the C-2 diastereomer of DMDP, DGDP, from l-sorbose in 7 steps (two purifications) and 56% overall yield, albeit with diminished diastereomeric purity (d.r. 90:10). The C-5 regioselectivity has also been illustrated on d-psicose and d-tagatose, making this an attractive method for preparing pyrrolidine iminosugars or 5-thiosugars from ketopyranoses.

This Special Issue will celebrate the chemistry and biology of peptides, from synthesis, to structure and modifications, to biology and applications, and finally to degradation. Submit your manuscript...

A pyridinium ylide-alkylation strategy has been developed for selectively accessing N,N-disubstituted pyridinium salts from monosubstituted pyridinium salts possessing ambident nucleophiles. The metho...

l-Guluronic acid is integral to the structures of alginates and to the pathogenesis of Pseudomonas aeruginosa. The exploitation of this hexose in both existing and new contexts is, however, limited by its prohibitively high commercial cost. We report on a short and efficient synthetic route to an l-GulA building block from a simple d-mannose thioglycoside. In this synthesis, the fluorine-directing effect is exploited to achieve a stereoselective C-5 epimerization. DFT calculations illuminate the substituent effects, which operate to confer this selectivity.

A one-step synthetic method to access medicinally essential anthraquinones has been developed by reacting Kobayashi’s aryne precursors with 3-sulfonylphthalides following [4 + 2] Hauser–Kraus annulation reaction. The developed method has been implemented for the total synthesis of bioactive natural products, chrysophanol, danthron, and physcion in 30, 20, and 36% overall yields, respectively, from known compounds.

The newly discovered cyclo[13]carbon, the first artificially synthesized odd-numbered carbon ring, is an intriguing carbon isomer that provides a valuable subject for studying low-symmetry carbon materials. In this work, we employed first-principles calculations to explore the geometric structure and electronic properties of cyclo[13]carbon through various techniques such as vibrational mode analysis, bond order analysis, spin density analysis, electron localization analysis, electrostatic potential and van der Waals potential analysis, visualization of weak interactions, and energy decomposition analysis. We investigated the interaction characteristics of cyclo[13]carbon with small molecules and examined its dimer formation mechanism and dynamics features using ab initio molecular dynamics. Our study reveals the unique physicochemical properties of this novel carbon ring system. The antiaromaticity of the low-symmetry cyclo[13]carbon sets it apart from previously synthesized even-numbered carbon rings, with van der Waals interactions playing a crucial role in its binding with small molecules and in the formation of C13 dimers. This research provides theoretical insights that complement experimental observations and theoretical studies, aiding further investigation into the diverse properties of fresh carbon material isomers and promoting the synthesis and application of novel molecular materials in molecular electronics and nanotechnology.

A quantitative and predictive understanding of how attractive noncovalent interactions (NCIs) influence functional outcomes is a long-standing goal in mechanistic chemistry. In that context, better comprehension of how substituent effects influence NCI strengths, and the origin of those effects, is still needed. We sought to build a resource capable of elucidating fundamental origins of substituent effects in NCIs and diagnosing NCIs in chemical systems. To accomplish this, a library of 893 NCI energies was calculated encompassing cation−π, anion−π, CH−π, and π–π interactions across 60 different arenes and heteroarenes. The interaction energies (IEs) were calculated using symmetry-adapted perturbation theory (SAPT), which identifies electrostatic, inductive, exchange-repulsive, and dispersive contributions to total IE. This descriptor library provides a comprehensive platform for evaluating substituent effect trends beyond traditional molecular descriptors such as Hammett values, frontier molecular orbital energies, and electrostatic potential, thereby expanding the tools available to analyze modern chemical processes that involve NCIs. To demonstrate the application of this library, three case studies in asymmetric catalysis and supramolecular chemistry are presented. These case studies informed the development of an automated NCI analysis tool, which employs statistical analyses to diagnose a particular NCI in a chemical system of interest.

A zinc iodide-mediated [3 + 2] cyclization between donor–acceptor cyclopropanes and ammonium thiocyanate has been developed to afford 2-imino-tetrahydrothiophene derivatives under mild conditions. Sub...

Indanones are key structural motifs in pharmaceuticals and bioactive natural products, making their efficient synthesis a subject of continued interest. Conventional methods typically rely on transiti...

This Special Issue will celebrate the chemistry and biology of peptides, from synthesis, to structure and modifications, to biology and applications, and finally to degradation. Submit your manuscript...

This Special Issue will showcase the breadth of modern Physical Organic Chemistry and will set the stage for future innovation. Submit your manuscript by April 1, 2025.

Polymer-supported selenium has been reported as a heterogeneous catalyst that is easily separated from the reaction system, thereby making the recovery and reuse of the catalyst more convenient. However, the utilization of polymer-supported selenium in the preparation of catalysts is not restricted to the aforementioned technical advantages. Recent studies have shown that polymer-supported selenium and small-molecule organoselenium catalysts have significant performance differences, leading to distinct reaction mechanisms, which offer more opportunities for the development of new organic reactions.

In this work, we present a photoredox three-component reaction that enables the synthesis of medicinally relevant β-trifluoromethyl β-amino ketones from a N-trifluoroethylhydroxylamine derivative, styrenes and DMSO. Remarkably, fluoromethyl, difluoromethyl and pentafluoroethyl analogues are also accessed using the same reaction conditions. The mechanistic investigations, including radical trapping experiments, cyclic voltammetry, Stern–Volmer quenching studies and isotope labelling experiments support the photoinduced radical/polar crossover and Kornblum-type oxidation mechanisms. Finally, the applicability of the accessed organic skeletons is showcased by notable derivatization reactions.