The cover picture illustrates symbolically the critical step in π-acid catalysis as a bullfighting scene: a metal catalyst (the toreador) binds an alkyne and activates it for an attack by a nucleophile (the bull). Cover image by Dr. Igor Armiach.
The Annual Wolf Prize Symposia of the Israel Chemical Society (ICS) have become a significant component of the scientific landscape of the State of Israel. These highly attended events occur annually in late May or early June as part of the Wolf Prize week, usually one day before the award ceremony in the Knesset. This account covers the one-day symposium at the Weizmann Institute of Science on June 14, 2023, the Wolf Prize ceremony in the Knesset on June 15, and several other events in Israel that week, all honoring Chuan He, Jeffrey W. Kelly, and Hiroaki Suga.
A one-pot synthesis of 2-acylidene-3-oxindole and azaaurone derivatives starting from O-alkynylanilines and alkynes is presented. By means of oxidative gold catalysis the two starting materials are transferred to reactive intermediates that in situ form the target products. This double oxidation strategy enables a protecting group-free step-economic strategy towards these valuable substrate classes.
![5-Sulfurated Imidazo[1,5-a]Pyridin-3-ylidenes: Ligands for π-Acidic Catalysts](https://onlinelibrary.wiley.com/cms/asset/429c16e8-b220-49de-a29f-c8afc637cd54/ijch202200038-toc-0001-m.png)
A series of 5-sulfurated imidazo[1,5-a]pyridin-3-ylidenes (Imidazo[1,5-a]pyridine carbenes: IPCs) and their Cu and Pd complexes were synthesized. Theoretical investigations of the free carbenes and Cu complexes implied that the IPCs were good π-acceptors. Particularly, Cu complexes of 5-arylsulfonyl IPC were strong π-acids. These complexes were tested as π-acidic catalysts in the Cu-catalyzed hydroboration of an internal alkyne with diboron and the Mizoroki-Heck reaction. As a result, the trend in reactivity corresponded with the theoretical considerations.
Recent years have witnessed a renaissance of organic electrochemistry since the cheap, safe, sustainable electron could be employed as a traceless redox agent to facilitate redox conversions. Additionally, divergent selectivity could be achieved by tuning the potential or current of the electrochemical reaction. Compared to electrooxidation or electroreduction reactions, paired electrolysis represents a more practical and energy-efficient strategy that delivers the products by making use of both anodic and cathodic reactions simultaneously. This mini-review summarized the breakthroughs and recent advances in this fascinating field and mainly is divided into three parts: parallel, sequential, and convergent paired electrolysis.
The merger of rhodium catalysis and electrochemical synthesis enabled the exclusive access to the C7−H electro-alkenylation of indoles.
Indole derivatives are fundamental structural units in many bioactive compounds and molecular materials. The site-selective C7-functionalization of these moieties has been proven to be extremely challenging due to the inherent reactivity of the C2- and C3-positions. Herein, we report the first electro-C7-alkenylation of indoles. This novel and sustainable methodology provides highly exclusive access to the C7-position devoid of often toxic and expensive chemical oxidants. Moreover, an array of substrates was successfully alkenylated at the C7-position, and versatile product diversification was achieved.
Truncated mucin-type O-glycans, such as Tn-associated antigens, are aberrantly expressed biomarkers of cancer, but remain challenging to target. Reactive antibodies to these antigens either lack high affinity or are prone to antigen escape. Here, we have developed a robust chemoenzymatic strategy for the global labeling of Tn-associated antigens, i. e. Tn (GalNAcα-O-Ser/Thr), Thomsen-Friedenreich (Galβ1-3GalNAcα-O-Ser/Thr, TF) and STF (Neu5Acα2-3Galβ1-3GalNAcα-O-Ser/Thr, STF) antigens, in human whole blood with high efficiency and selectivity. This method relies on the use of the O-glycan sialyltransferase ST6GalNAc1 to transfer a sialic acid-functionalized adaptor to the GalNAc residue of these antigens. By tagging, the adaptor functionalized antigens can be easily targeted by customized strategies such as, but not limited to, chimeric antigen receptor T-Cells (CAR-T). We expect this tagging system to find broad applications in cancer diagnostics and targeting in combination with established strategies.
Herein, we report a minimalistic protocol for the solvent-free, mechanochemical difluoromethylation of (thio)phenols and N-heteroarenes using non-ozone depleting chlorodifluoromethyl phenyl sulfone as a difluorocarbene source. This mechanochemical difluoromethylation features a short reaction time, excellent functional group tolerance, and compatibility with complex biologically active scaffolds.
There is an urgent need to develop new antibacterial agents against multidrug resistant bacteria. Herein we report our investigation of antimicrobial peptide dendrimers (AMPDs) active against Gram-negative bacteria, whose sequences were designed using a genetic algorithm optimizing molecular similarity to the previously reported AMPD T7 with sequence (KL)8(KKL)4(KKLL)2 KKKL. Our computational approach selected analogues unlikely to emerge from a systematic study, including AMPD X66 with a non-conservative Leu→Glu mutation at the dendrimer core which proved compatible with antibacterial effects. Circular dichroism showed that this AMPD is α-helical. Molecular dynamics suggest that its α-helical structure is stabilized by an intramolecular salt bridge involving the core glutamate side chain and a lysine side chain in the dendrimer branches. More substantial variations at the dendrimer core were also tolerated such as the installation of the dianionic pegylated fatty acid side chain of the drug semaglutide potentially useful for in vivo studies.