Beauty Katebe Chabuka

A divergent synthesis of substituted hexahydropyridazin-3-ones and 1-aminopyrrolidin-2-ones has been achieved through domino ring opening/ring closure reactions of donor–acceptor cyclopropanes with ambident, unsymmetrically substituted hydrazines, affording target products in good yields under mild conditions. The selectivity of this process depends strongly on the nature of substituents in hydrazine. Aryl hydrazines bearing electron-rich and electron-neutral aromatic groups form six-membered rings by attacking the cyclopropane via the NH group, while the NH2 group reacts in hydrazines equipped with electron-withdrawing aromatic substituents, acyl hydrazines, and carbazates. In both scenarios, the initial products of nucleophilic ring opening undergo in situ Lewis acid-induced cyclization, providing important azaheterocyclic systems in a single synthetic step; further transformations enable access to other valuable products. The proposed mechanism of the title process and the observed chemoselectivity switch have been explained by both experimental and computational studies.

Substituted hydrazines were successfully applied as ambident partners to prepare pyridazin-3-ones via 6-ring closure with arylhydrazines and 1-aminopyrrolidin-2-ones by 5-membered ring formation with hydrazines bearing electron-withdrawing groups.

Nearly 70 years after its discovery, the fundamental origin of the anomeric effect remains debated, attributing it to stereoelectronic, electrostatic, or steric influences. In this study, we combine computational modeling and statistical analysis to quantitatively assess these explanations. A data set of 49 2-substituted tetrahydropyrans was analyzed using 15 distinct molecular descriptors, encompassing stereoelectronic effects (via NBO analysis), electrostatics (dipole moments), sterics (Sterimol parameters), pyramidalization at the anomeric carbon, and dispersion (molecular surface area). The diversity of the substituent set ensured that no single factor could dominate across all cases. Linear regression modeling in three environments (gas phase, water, and toluene) revealed that conformational preferences arise from a combination of influences. Four parameters consistently emerged as statistically significant: (1) stereoelectronic interactions, notably, hyperconjugation between the oxygen lone pair and the exocyclic σ* acceptor orbital, (2) pyramidalization at the anomeric carbon, (3) steric effects, and (4) changes in total molecular surface area associated with dispersion forces. While the choice of statistical method can shift the relative weighting of secondary contributors, the multifactorial nature of the effect remains clear. These findings suggest that efforts to attribute the anomeric effect to a single dominant cause may have oversimplified a fundamentally complex and nuanced phenomenon.

2025 H. H. Uhlig Research Fellowship – Summary Report: Electron and Hole Upconversion as a New Design Paradigm for Combining Photochromism with Electrochromism

This work investigates the fundamental role of electron transfer (ET) chemistry in enhancing the performance of photochromic organic compounds, with specific focus on 1,3,5-hexatriene-based molecular systems. Computational analysis using DFT methods shows that electron catalysis can be activated in pericyclic reactions of 6π-electron systems through redox upconversion mechanisms: photochromic reactions intrinsically fulfill the energetic requirements for redox catalysis in at least one reaction direction, establishing electrochromism as an inherent feature of photochromic systems. Such redox upconversion processes provide the key to using electrons as true catalysts for chemical transformations because they allow for chain propagation through electron transfer with potential of using substoichiometric amounts of redox agents. This work provides a theoretical framework for precise control over selectivity and directionality in reversible molecular switches.

A methodology for the synthesis of substituted furans via an "ylide dance" sequence has been developed. The reaction involves phenacyl sulfonium salts and alkenyl- or propargyl sulfonium salts under basic conditions. The key feature is a stepwise evolution where a primary sulfur ylide, generated from phenacyl sulfonium salt and base, transforms into another ylide, which then undergoes conversion into yet another, a "third generation" ylide, culminating in the formation of the target furan.

Radical anions are well known to react with proton donors, yet their reactivity with hydrides remains largely unexplored. Here, we investigate the reactions of five stable radical anions with B-H and Si-H hydrides (pinacolborane, diphenylsilane, and triphenylsilane) and uncover a new class of chemical reactions. Ketyl radical anions react with main-group hydrides, forming C-E and O-H bonds (E = B, Si) through a process in which the radical anion acts both as a Lewis base and as a H atom acceptor. The resulting radical anions of the hydroelementation products are substantially stronger reductants than the original radical anions, with an estimated increase of ∼1.1 V, bringing their overall reducing power into the range of alkali metals (∼3 V). This allows electron transfer from the product radical anion to neutral substrate molecules, propagating a single-electron-transfer chain and achieving efficient electron catalysis with turnover numbers exceeding 300. These reactions are scalable and do not require conventional catalysts: Either electric current or substoichiometric chemical reductants are sufficient as the source of catalytic electrons. Analogous electron-catalyzed silylation and borylation are also demonstrated with quinone radical anions and inorganic radical anions such as superoxide. This work highlights a new reactivity mode of radical anions, broadens the scope of electron upconversion, and establishes a versatile platform for catalytic single-electron transformations.

Sulfur ylides enable a stereoelectronically-assisted C–C bond insertion followed by Corey–Chaykovsky cyclopropanation or epoxidation, allowing for dual CH ₂ transfer to alkenes and aldehydes.

Here, we present a new approach for the activation of donor-acceptor cyclopropanes in ring-opening reactions, which does not require the use of a Lewis or Brønsted acid as a catalyst. Donor-acceptor cyclopropanes containing a phenolic group as the donor undergo deprotonation and isomerization to form the corresponding quinone methides. This innovative strategy was applied to achieve (4 + 1)-annulation of cyclopropanes with sulfur ylides, affording functionalized dihydrobenzofurans. Additionally, the generated ortho- and para-(aza)quinone methides can be trapped by various CH-acids.

Here, we present a new approach for activation of donor-acceptor cyclopropane systems in ring-opening reactions, which does not require the use of Lewis or Brønsted acid as a catalyst. Under treatment with a base, donor-acceptor cyclopropanes containing a phenolic group as the donor undergo deprotonation and fast isomerisation to the corresponding quinone methides. This innovative strategy was applied to realise [4+1] annulation of 2-(2-hydroxyaryl)-substituted DA cyclopropanes with sulfur ylides, affording functionalised dihydrobenzofurans. A plausible mechanism of this process has been proposed based on theoretical calculations. Additionally, the generated ortho- and para-quinone methides as well as their aza-analogues can be trapped by deprotonated CH-acids as nucleophiles providing a simple path toward acyclic polyfunctional compounds as promising building blocks for the synthesis of more complexed and biologically interesting cyclic structures.