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A metal-free and redox-neutral method for Beckmann rearrangement employing inexpensive and readily available SO 2 F 2 gas is described. The reported transformation proceeds at ambient temperature and is compatible with a wide range of sterically and electronically diverse aromatic, heteroaromatic, aliphatic and lignin-like oximes providing amides in good to excellent yields. The reaction proceeds through the formation of an imidoyl fluoride intermediate that can also be used for the synthesis of amidines., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Acetylcholinesterase (AChE), an enzyme that degrades the neurotransmitter acetylcholine, when covalently inhibited by organophosphorus compounds (OPs), such as nerve agents and pesticides, can be reactivated by oximes. However, tabun remains among the most dangerous nerve agents due to the low reactivation efficacy of standard pyridinium aldoxime antidotes. Therefore, finding an optimal reactivator for prophylaxis against tabun toxicity and for post-exposure treatment is a continued challenge. In this study, we analyzed the reactivation potency of 111 novel nucleophilic oximes mostly synthesized using the CuAAC triazole ligation between alkyne and azide building blocks. We identified several oximes with significantly improved in vitro reactivating potential for tabun-inhibited human AChE, and in vivo antidotal efficacies in tabun-exposed mice. Our findings offer a significantly improved platform for further development of antidotes and scavengers directed against tabun and related phosphoramidate exposures, such as the Novichok compounds., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aliphatic, aromatic, and heteroaromatic aldehydes were readily converted to corresponding nitriles in a one-pot reaction sequence with hydroxylamine and sulfuryl fluoride. The reaction proceeds at room temperature, does not require metal catalysts and special precautions, and produces nitriles in excellent yields. It is compatible with a variety of functional groups, can be performed in aqueous and organic solvents, and is readily scalable to multigram quantities. Mild conditions and high selectivity of the reaction enabled the construction of polyfunctional probes containing nitrile, alkyne, azide, and fluorosulfate groups for further orthogonal derivatization., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

High-molecular-weight polysulfates are readily formed from aromatic bis(silyl ethers) and bis(fluorosulfates) in the presence of a base catalyst. The reaction is fast and proceeds well under neat conditions or in solvents, such as dimethyl formamide or N-methylpyrrolidone, to provide the desired polymers in nearly quantitative yield. These polymers are more resistant to chemical degradation than their polycarbonate analogues and exhibit excellent mechanical, optical, and oxygen-barrier properties., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

(Cyclopentadienyl)(cyclooctadiene) ruthenium(II) chloride [CpRuCl(cod)] catalyzes the reaction between nitrile oxides and electronically deficient 1-choro-, 1-bromo-, and 1-iodoalkynes leading to 4-haloisoxazoles. Organic azides are also suitable 1,3-dipoles, resulting in 5-halo-1,2,3-triazoles. These air-tolerant reactions can be performed at room temperature with 1.25 equivalents of the respective 1,3-dipole relative to the alkyne component. Reactive 1-haloalkynes include propiolic amides, esters, ketones, and phosphonates. Post-functionalization of the halogenated azole products can be accomplished by using palladium-catalyzed cross-coupling reactions and by manipulation of reactive amide groups. The lack of catalysis observed with [Cp*RuCl(cod)] (Cp* = pentamethylcyclopentadienyl) is attributed to steric demands of the Cp* (η(5)-C5Me5) ligand in comparison to the parent Cp (η(5)-C5H5). This hypothesis is supported by the poor reactivity of [(η(5)-C5Me4CF3)RuCl(cod)], which serves as a an isosteric mimic of Cp* and as an isoelectronic analogue of Cp., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A convenient one-pot asymmetric synthesis of 2,3-dihydropyrroles from in situ generated triflated triazoles and olefins is described that further expands the utility of azavinyl carbene chemistry and provides access to an important class of cyclic enamides. Mechanistic investigations support the involvement of triflated cyclopropylaldimine intermediates in the formation of 2,3-dihydropyrrole. To the best of our knowledge, this is the first example of a chiral Brønsted acid catalyzed rearrangement of cyclopropylimines into enantioenriched 2,3-dihydropyrroles.

Fully loaded: Readily accessible and shelf-stable 1-bismuth(III) acetylides react rapidly and regiospecifically with organic azides in the presence of a copper(I) catalyst. The reaction tolerates many functional groups and gives excellent yields of the previously unreported 5-bismuth triazolides. This uniquely reactive intermediate is functionalized under mild reaction conditions to give fully substituted 1,2,3-triazoles., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Room for expansion: an efficient, regioselective, and convergent method for the ring expansion and rearrangement of 1-sulfonyl-1,2,3-triazoles under rhodium(II)-catalyzed conditions is described. These denitrogenative reactions form substituted enaminone and olefin-based products. The enaminone products can be further functionalized to give various heterocycles and ketone derivatives, thus rendering the sulfonyl triazole traceless., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Click 'n' chips: Azide and alkyne-bearing sialic acids (purple diamond; see picture) were subjected to high-throughput click chemistry to generate a library of sialic acid analogues. Microarray printing of the library and screening with the siglec family of sialic-acid-binding proteins, led to the identification of high-affinity ligands for siglec-9 and siglec-10., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Special agents for protein capture: Iterative in situ click chemistry (see scheme for the tertiary ligand screen) and the one-bead-one-compound method for the creation of a peptide library enable the fragment-based assembly of selective high-affinity protein-capture agents. The resulting ligands are water-soluble and stable chemically, biochemically, and thermally. They can be produced in gram quantities through copper(I)-catalyzed cycloaddition.