-BuNI/KSO mediated C-N coupling between aldehydes and amides is reported. A strong electronic effect is observed on the aromatic aldehyde substrates. The transformylation from aldehyde to amide takes place exclusively when an aromatic aldehyde bears electron-donating groups at either the or position of the formyl group, while the cross-dehydrogenative coupling dominates in the absence of these groups. Both the density functional theory (DFT) thermochemistry calculations and experimental data support the proposed single electron transfer mechanism with the formation of an acyl radical intermediate in the cross-dehydrogenative coupling. The -BuNI/KSO mediated oxidative cyclization between 2-aminobenzamide and aldehydes is also reported, with four quinazolin-4(3)-ones prepared in 65-99% yields.

Compared to ubiquitous functional groups such as alcohols, carboxylic acids, amines, and amides, which serve as central "actors" in most organic reactions, sulfamates, phosphoramidates, and di--butyl silanols have historically been viewed as "extras". Largely considered functional group curiosities rather than launch-points of vital reactivity, the chemistry of these moieties is under-developed. Our research program has uncovered new facets of reactivity of each of these functional groups, and we are optimistic that the chemistry of these fascinating molecules can be developed into truly general transformations, useful for chemists across multiple disciplines. In the ensuing sections, I will describe our efforts to develop new reactions with these "unusual" functional groups, namely sulfamates, phosphoramidates, and di--butyl silanols.

We herein report a two-step approach for the enantioselective synthesis of novel chiral δ-lactams. By using a cooperative chiral ITU/achiral Pd-catalyst system, this protocol proceeds via an asymmetric α-allylation of activated aryl esters first, followed by an acid-mediated lactam formation. A variety of differently substituted products could be obtained with usually high levels of enantioselectivities and in reasonable yields (16 examples, up to 98 : 2 er and 73 % yield over two steps). In addition, further utilizations of the products via transformations of the exocyclic double bond were successfully carried out as well.

Distinct aggregated proteins are correlated with numerous neurodegenerative diseases and the development of ligands that selectively detect these pathological hallmarks is vital. Recently, the synthesis of thiophene-based optical ligands, denoted bi-thiophene-vinyl-benzothiazoles (bTVBTs), that could be utilized for selective assignment of tau pathology in brain tissue with Alzheime's disease (AD) pathology, was reported. Herein, we investigate the ability of these ligands to selectively distinguish tau deposits from aggregated amyloid-β (Aβ), the second AD associated pathological hallmark, when replacing the terminal thiophene moiety with other heterocyclic motifs. The selectivity for tau pathology was reduced when introducing specific heterocyclic motifs, verifying that specific molecular interactions between the ligands and the aggregates are necessary for selective detection of tau deposits. In addition, ligands having certain heterocyclic moieties attached to the central thiophene-vinylene building block displayed selectivity to aggregated Aβ pathology. Our findings provide chemical insights for the development of ligands that can distinguish between aggregated proteinaceous species consisting of different proteins and might also aid in creating novel agents for clinical imaging of tau pathology in AD.

We herein report a two-step protocol for the asymmetric synthesis of novel chiral benzofused ϵ-lactones starting from O-protected hydroxymethyl-para-quinone methides and activated aryl esters. By using chiral isothiourea Lewis base catalysts a broad variety of differently substituted products could be obtained in yields of around 50 % over both steps with high levels of enantioselectivities, albeit low diastereoselectivities only.

Lycorane is a pentacyclic core presented in alkaloids isolated from the family of herbaceous flowering plants. Members of this class of natural products have shown to display important biological properties including analgesic, antiviral, and antiproliferative activities. This review presents the known synthetic routes toward α-, β-, γ-, and δ-lycoranes. α-(19 routes), β-(10 routes), γ-(38 routes), and δ-(6 routes).

Fluorinated carbohydrates are valuable tools for enzymological studies due to their increased metabolic stability compared to their non-fluorinated analogues. Replacing different hydroxyl groups within the same monosaccharide by fluorine allows to influence a wide range of sugar-receptor interactions and enzymatic transformations. In the past, this principle was frequently used to study the metabolism of highly abundant carbohydrates, while the metabolic fate of rare sugars is still poorly studied. Rare sugars, however, are key intermediates of many metabolic routes, such as the pentose phosphate pathway (PPP). Here we present the design and purely chemical synthesis of a set of three deoxyfluorinated analogues of the rare sugars d-xylulose and d-ribulose: 1-deoxy-1-fluoro-d-ribulose (), 3-deoxy-3-fluoro-d-ribulose () and 3-deoxy-3-fluoro-d-xylulose (). Together with a designed set of potential late-stage radio-fluorination precursors, they have the potential to become useful tools for studies on the complex equilibria of the non-oxidative PPP.

YM-254890 and FR900359 are potent and selective inhibitors of the Gq/11-signaling pathway. As such, they have been attractive targets for both synthesis and biological studies. Yet in spite of this effort, a versatile synthetic approach to the molecules that allows for the rapid construction of a variety of non-natural and labelled analogs and an increase in the amount of those analogs available remains elusive. We report here a convergent building block approach to the molecules that can solve this challenge.

Herein we report, a rhodium-catalyzed Fujiwara-Moritani-type reaction of unactivated terminal alkenes and benzoic acid derivatives bearing electron donating residues under mild conditions. The acid functionality acts as a traceless directing group delivering products alkenylated in -position to the electron donating substituent in contrast to the usually obtained - and -substitution in Friedel-Crafts-type reactions. Remarkably, the new C-C bond is formed to the C2 of the terminal olefin, in contrast to similar reported transformations. Initially formed mixtures of - and -double bond isomers can be efficiently isomerized to the more stable -products.

Asymmetric organocatalysis has experienced a long and spectacular way since the early reports over a century ago by von Liebig, Knoevenagel and Bredig, showing that small (chiral) organic molecules can catalyze (asymmetric) reactions. This was followed by impressive first highly enantioselective reports in the second half of the last century, until the hype initiated in 2000 by the milestone publications of MacMillan and List, which finally culminated in the 2021 Nobel Prize in Chemistry. This short Perspective aims at providing a brief introduction to the field by first looking on the historical development and the more classical methods and concepts, followed by discussing selected advanced recent examples that opened new directions and diversity within this still growing field.

An expedient method for the synthesis of cyclic carbonates from homoallylic carbonic acid esters by means of photo-aerobic selenium-π-acid multicatalysis is reported. Until now, conceptually related methods commonly relied either on the stoichiometric addition of electrophiles onto the substrate's alkene moiety or the presence of pre-installed leaving groups in allylic position of said alkene to - in part, catalytically - initiate an intramolecular attack by an adjacent carbonic acid ester group. In sharp contrast, the current study shows that the C-C double bond of homoallylic carbonic acid esters can be directly activated by the catalytic interplay of a pyrylium dye and a diselane using ambient air as the sole oxidant and visible light as an energy source.

Cyclopropanation reactions between C and different malonates decorated with monosaccharides and steroids using the Bingel-Hirsch methodology have allowed the obtention of a new family of hybrid compounds in good yields. A complete set of instrumental techniques has allowed us to fully characterize the hybrid derivatives and to determine the chemical structure of monocycloadducts. Besides, the proposed structures were investigated by cyclic voltammetry, which evidenced the exclusive reductive pattern of fullerene Bingel-type monoadducts. Theoretical calculations at the DFT-D3(BJ)/PBE 6-311G(d,p) level of the synthesized conjugates predict the most stable conformation and determine the factors that control the hybrid molecules' geometry. Some parameters such as polarity, lipophilicity, polar surface area, hydrophilicity index, and solvent-accessible surface area were also estimated, predicting its potential permeability and capability as cell membrane penetrators. Additionally, a molecular docking simulation has been carried out using the main protease of SARS-CoV-2 (Mpro) as the receptor, thus paving the way to study the potential application of these hybrids in biomedicine.

is a Gram-negative bacteria associated with drug resistance and infection in healthcare settings. An understanding of both the biological roles and antigenicity of surface molecules of this organism may provide an important step in the prevention and treatment of infection through vaccination or the development of monoclonal antibodies. With this in mind, we have performed the multistep synthesis of a conjugation-ready pentasaccharide -glycan from with a longest linear synthetic sequence of 19 steps. This target is particularly relevant due to its role in both fitness and virulence across an apparently broad range of clinically relevant strains. Synthetic challenges include formulating an effective protecting group scheme as well as the installation of a particularly difficult glycosidic linkage between the anomeric position of a 2,3-diacetamido-2,3-dideoxy-D-glucuronic acid and the 4-position of D-galactose.

The development of novel and effective metal-free catalytic systems, which can drive value-added organic transformations in environmentally benign solvents (for instance, water), is highly desirable. Moreover, these new catalysts need to be harmless, easy-to-prepare, and potentially recyclable. In this context, amine-rich carbon dots (CDs) have recently emerged as promising nano-catalytic platforms. These nitrogen-doped nanoparticles, which show dimensions smaller than 10 nm, generally consist of carbon cores that are surrounded by shells containing numerous amino groups. In recent years, organic chemists have used these surface amines to guide the design of several synthetic methodologies under mild operative conditions. This Concept highlights the recent advances in the synthesis of amine-rich carbon dots and their applications in organic catalysis, including forward-looking opportunities within this research field.

Two templates used in -directed C-H functionalisation under metal catalysis do not direct -C-H borylation under electrophilic borylation conditions. Using BCl only Lewis adduct formation with Lewis basic sites in the template is observed. While combining BBr and the template containing an amide linker only led to amide directed C-H borylation, with no pyridyl directed borylation. The amide directed borylation is selective for the borylation of the aniline derived unit in the template, with no borylation of the phenylacetyl ring - which would also form a six membered boracycle - observed. In the absence of other aromatics amide directed borylation on to phenylacetyl rings can be achieved. The absence of -borylation using two templates indicates a higher barrier to pyridyl directed borylation relative to amide directed borylation and suggests that bespoke templates for enabling -directed electrophilic borylation may be required.

H-bonded counterion-directed catalysis (HCDC) is a strategy wherein a chiral anion that is hydrogen-bonded to the achiral ligand of a metal complex is responsible for enantioinduction. In this article we present the application of H-bonded counterion-directed catalysis to the Au(I)-catalyzed enantioselective tandem cycloisomerization-addition reaction of 2-alkynyl enones. Following the addition of C-, N- or O-centered nucleophiles, bicyclic furans were obtained in moderate to excellent yield and enantioselectivity (28 examples, 59-96 % yield, 62 : 38 to 95 : 5 er). The optimal catalytic system, comprising a phosphinosquaramide Au(I) chloride complex and a BINOL-derived phosphoramidate Ag(I) salt, was selected in a combinatorial fashion from a larger library with the help of high-throughput screening. An enantioselectivity switch of ca. 120 Δee% was observed upon addition of the achiral Au(I) component to the Ag(I) salt.

Macrocyclic metal porphyrin complexes can act as shape-selective catalysts mimicking the action of enzymes. To achieve enzyme-like reactivity, a mechanistic understanding of the reaction at the molecular level is needed. We report a mechanistic study of alkene epoxidation by the oxidant iodosylbenzene, mediated by an achiral and a chiral manganese(V)oxo porphyrin cage complex. Both complexes convert a great variety of alkenes into epoxides in yields varying between 20-88 %. We monitored the process of the formation of the manganese(V)oxo complexes by oxygen transfer from iodosylbenzene to manganese(III) complexes and their reactivity by ion mobility mass spectrometry. The results show that in the case of the achiral cage complex the initial iodosylbenzene adduct is formed on the inside of the cage and in the case of the chiral one on the outside of the cage. Its decomposition leads to a manganese complex with the oxo ligand on either the inside or outside of the cage. These experimental results are confirmed by DFT calculations. The oxo ligand on the outside of the cage reacts faster with a substrate molecule than the oxo ligand on the inside. The results indicate how the catalytic activity of the macrocyclic porphyrin complex can be tuned and explain why the chiral porphyrin complex does not catalyze the enantioselective epoxidation of alkenes.

The possibility of performing designed transition-metal catalyzed reactions in biological and living contexts can open unprecedented opportunities to interrogate and interfere with biology. However, the task is far from obvious, in part because of the presumed incompatibly between organometallic chemistry and complex aqueous environments. Nonetheless, in the past decade there has been a steady progress in this research area, and several transition-metal (TM)-catalyzed bioorthogonal and biocompatible reactions have been developed. These reactions encompass a wide range of mechanistic profiles, which are very different from those used by natural metalloenzymes. Herein we present a summary of the latest progress in the field of TM-catalyzed bioorthogonal reactions, with a special focus on those triggered by activation of multiple carbon-carbon bonds.

While studying indolylthio glycosides, previously we determined their activation profile that required large excess of activators. This drawback was partially addressed in the present study of N-alkylated SInR derivatives. The activation process was studied by NMR and the increased understanding of the mechanism led to a discovery of different activation pathways taking place with SIn versus SInR derivatives. Also investigated was orthogonality of the SInR leaving groups versus thioglycosides and selective activation of thioimidates over SInR glycosides.

The influence on glycosyl selectivity of substituting oxygen for sulfur at the 3-position of 4,6--benzylidene-protected mannopyranosyl thioglycosides is reported and varies considerably according to the protecting group employed at the 3-position. The substitution of a thioether at the 3-position for the more usual 3--benzyl ether results in a significant loss of selectivity. The installation of a 3--picolinyl thioether results in a complex reaction mixture, from which a stable seven-membered bridged bicyclic pyridinium ion is isolated, while the corresponding 3--picolinyl ether affords a highly α-selective coupling reaction. A 3--picolyl ester provides excellent β-selectivity, while the analogous 3--picolyl thioester gives a highly α-selective reaction. The best β-selectivity is seen with a 3-deoxy-3-(2-pyridinyldisulfanyl) system. These observations are discussed in terms of the influence of the various substituents on the central glycosyl triflate - ion pair equilibrium.

Herein, a new scaffold for anion recognition based on a tripodal tris(pyrrolamide) motif is presented. The receptors were able to bind to a variety of anions with high affinity. Using density functional theory methods, the three-dimensional geometry of the receptor-anion complex was calculated. These calculations show that the receptors bind anions via a preorganized cavity of amide and pyrrole hydrogen bond donor groups. Based on these findings, homochiral tris(pyrrolamide) receptors were prepared, which produced as much as a 1.6-fold greater affinity for ()-(+)-mandelate over ()-(-)-mandelate, demonstrating the ability to differentiate between these enantiomeric anions. The interaction of ()-(+)-mandelate and ()-(-)-mandelate within the homochiral receptor was examined by solution NMR spectroscopy and density functional theory calculations. These findings indicate that the preorganized positioning of the pyrrole groups and subsequent sterics allows to differentiate between the stereoisomeric anions.