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In diesem Aufsatz sind die jüngsten Fortschritte beim Verständnis und Design von N‐funktionalisierten Pyridiniumsalzen als redoxaktivierte Einelektronentransfer‐Reagenzien zur Übertragung funktioneller Gruppen zusammengefasst. Anhand einer Auswahl an repräsentativen Methoden werden Reaktivität und grundlegende Fortschritte in diesem sich rasch entwickelnden Bereich diskutiert. Diese Reagenzien weisen zwei grundsätzlich divergierende Reaktionspfade auf: homolytische Fragmentierung zur Freisetzung des N‐gebundenen Substituenten als entsprechendes Radikal oder eine alternative, heterolytische Fragmentierung zur Freisetzung eines radikalischen Pyridiniumkations. Die elementaren Schritte der durch Einelektronentransfer induzierten Fragmentierung werden kritisch diskutiert. [ABSTRACT FROM AUTHOR]

In this Review, we highlight recent advances in the understanding and design of N‐functionalized pyridinium scaffolds as redox‐active, single‐electron, functional group transfer reagents. We provide a selection of representative methods that demonstrate reactivity and fundamental advances in this emerging field. The reactivity of these reagents can be divided into two divergent pathways: homolytic fragmentation to liberate the N‐bound substituent as the corresponding radical or an alternative heterolytic fragmentation that liberates an N‐centered pyridinium radical. A short description of the elementary steps involved in fragmentation induced by single‐electron transfer is also critically discussed to guide readers towards fundamental processes thought to occur under these conditions. [ABSTRACT FROM AUTHOR]

We leverage the slow liberation of nitrogen dioxide from a newly discovered, inexpensive succinimide‐derived reagent to allow for the C−H diversification of alkenes and alkynes. Beyond furnishing a library of aryl β‐nitroalkenes, this reagent provides unparalleled access to β‐nitrohydrins and β‐nitroethers. Detailed mechanistic studies strongly suggest that a mesolytic N−N bond fragmentation liberates a nitryl radical. Using in situ photo‐sensitized, electron paramagnetic resonance spectroscopy, we observed direct evidence of a nitryl radical in solution by nitrone spin‐trapping. To further exhibit versatility of N‐nitrosuccinimide under photoredox conditions, the late‐stage diversification of an extensive number of C−H partners to prepare isoxazolines and isoxazoles is presented. This approach allows for the formation of an in situ nitrile oxide from a ketone partner, the presence of which is detected by the formation of the corresponding furoxan when conducted in the absence of a dipolarophile. This 1,3‐dipolar cycloaddition with nitrile oxides and alkenes or alkynes proceeds in a single‐operational step using a mild, regioselective, and general protocol with broad chemoselectivity. [ABSTRACT FROM AUTHOR]

Electron‐transfer photocatalysis provides access to the elusive and unprecedented N‐pyridyl radical cation from selected N‐substituted pyridinium reagents. The resulting C(sp2)−H functionalization of (hetero)arenes furnishes versatile intermediates for the development of valuable aminated aryl scaffolds. Mechanistic studies that include the first spectroscopic evidence of a spin‐trapped N‐pyridyl radical adduct implicate SET‐triggered, pseudo‐mesolytic cleavage of the N−X pyridinium reagents mediated by visible light. [ABSTRACT FROM AUTHOR]

Electron‐transfer photocatalysis provides access to the elusive and unprecedented N‐pyridyl radical cation from selected N‐substituted pyridinium reagents. The resulting C(sp2)−H functionalization of (hetero)arenes furnishes versatile intermediates for the development of valuable aminated aryl scaffolds. Mechanistic studies that include the first spectroscopic evidence of a spin‐trapped N‐pyridyl radical adduct implicate SET‐triggered, pseudo‐mesolytic cleavage of the N−X pyridinium reagents mediated by visible light. The road less travelled: Select pyridinium reagents undergo an unprecedented heterolytic fragmentation upon single electron reduction to afford a synthetically viable N‐pyridyl radical cation. This reactive species was leveraged for the C−H amination of (hetero)arenes to furnish N‐aryl pyridinium products, which enable access to diverse nitrogen scaffolds. [ABSTRACT FROM AUTHOR]

Eine einfache Methode für die Trifluormethoxylierung nicht funktionalisierter C‐H‐Bindungen bietet Zugang zu aromatischen Trifluoromethylethern. Die lichtgetriebene Reaktion unterscheidet sich von herkömmlichen Prozessen, indem das OCF3‐Radikal durch eine photoredoxkatalytische N‐O‐Bindungsfragmentierung generiert wird. Das entsprechende Pyridinium‐basierte Reagenz ist stabil und ermöglicht einen einfachen Zugang zu verschiedenen Verbindungen der oben genannten Klasse. Die Bestie freilassen: Ein stabiles Pyridinium‐Reagenz transferiert das schwer fassbare Trifluormethoxyradikal zu verschiedenen Arenen, inklusive biologisch aktiver Moleküle. Das Reagenz überwindet die Nachteile der bekannten OCF3‐Quellen und zeichnet sich durch sein einzigartiges Verhalten aus. Die beschriebene Methode erlaubt eine direkte C‐H‐Funktionalisierung in späten Syntheseschritten. [ABSTRACT FROM AUTHOR]

A simple trifluoromethoxylation method enables non‐directed functionalization of C−H bonds on a range of substrates, providing access to aryl trifluoromethyl ethers. This light‐driven process is distinctly different from conventional procedures and occurs through an OCF3 radical mechanism mediated by a photoredox catalyst, which triggers an N−O bond fragmentation. The pyridinium‐based trifluoromethoxylation reagent is bench‐stable and provides access to synthetic diversity in lead compounds in an operationally simple manner. N‐O problem: A bench‐stable pyridinium reagent transfers the elusive trifluoromethoxyl radical to a variety of arenes, including a selection of biorelevant compounds. By sidestepping limitations of traditional OCF3 sources, this approach enables late‐stage diversification by direct C−H functionalization in a mechanistically unique fashion. [ABSTRACT FROM AUTHOR]

Abstract: Fluorchemie nimmt eine zentrale Rolle bei der Entdeckung chemischer Reaktionen, in der Wirkstoffentwicklung und in der Chemischen Biologie ein. NMR‐Spektroskopie, die wohl meistbenutzte und wichtigste analytische Methode für fluorierte Verbindungen, weist weitverbreitete Missstände auf, die durch inkonsistentes Referenzieren chemischer Verschiebungen zustande kommen und Abweichungen von über 1 ppm verursachen können. In dieser Zuschrift beschreiben wir neuartige, eindeutige Belege, die zeigen, wie es – unbeabsichtigt – zur weitverbreiteten Streuung von 19F‐NMR‐chemischen‐Verschiebungen gekommen ist. Dies betrifft sowohl die Konzipierung der Spektrometer als auch das gegenwärtige Unified Scale System, das typischerweise als Grundlage für die Kalibrierung von heteronuklearen NMR‐Spektren dient. Wir zeigen, dass internes Referenzieren als robuste, pragmatische und reproduzierbare Methode die Abweichung chemischer Verschiebungen, die an mehreren verschiedenen Instituten gemessen wurden, auf weniger als 30 ppb minimiert. Schließlich wird eine umfassende Tabelle mit entsprechend kalibrierten Referenzverbindungen zur Verfügung gestellt, die es Nutzern ermöglicht, 19F‐NMR‐Spektren künftig korrekt zu kalibrieren. [ABSTRACT FROM AUTHOR]

Abstract: Fluorine chemistry has taken a pivotal role in chemical reaction discovery, drug development, and chemical biology. NMR spectroscopy, arguably the most important technique for the characterization of fluorinated compounds, is rife with highly inconsistent referencing of fluorine NMR chemical shifts, producing deviations larger than 1 ppm. Herein, we provide unprecedented evidence that both spectrometer design and the current unified scale system underpinning the calibration of heteronuclear NMR spectra have unintentionally led to widespread variation in the standardization of 19F NMR spectral data. We demonstrate that internal referencing provides the most robust, practical, and reproducible method whereby chemical shifts can be consistently measured and confirmed between institutions to less than 30 ppb deviation. Finally, we provide a comprehensive table of appropriately calibrated chemical shifts of reference compounds that will serve to calibrate 19F spectra correctly. [ABSTRACT FROM AUTHOR]

Hydrofluoroethers are shown to alkylate tertiary amines readily under solvent-free conditions, affording valuable tetraalkylammonium perfluoroalkoxides bearing α-fluorines. The reaction of RFCF2OCH3 (RF=CF2CF3, CF2CF2CF3, and CF(CF3)2) with NR1R2R3 produces twenty new α-perfluoroalkoxides, [(CH3)NR1R2R3][RFCF2O] under mild conditions. These α-perfluoroalkoxides are easy to handle, thermally stable, and can be used for the perfluoroalkoxylation of benzyl bromides. [ABSTRACT FROM AUTHOR]

Hydrofluoroethers are shown to alkylate tertiary amines readily under solvent-free conditions, affording valuable tetraalkylammonium perfluoroalkoxides bearing α-fluorines. The reaction of RFCF2OCH3 (RF=CF2CF3, CF2CF2CF3, and CF(CF3)2) with NR1R2R3 produces twenty new α-perfluoroalkoxides, [(CH3)NR1R2R3][RFCF2O] under mild conditions. These α-perfluoroalkoxides are easy to handle, thermally stable, and can be used for the perfluoroalkoxylation of benzyl bromides. [ABSTRACT FROM AUTHOR]

Highlights: [•] The smallest PFPAE nanoemulsions ever reported with droplet size of 85nm. [•] The first report of PFPAE aromatic conjugates formulated with PFPEs as nanoemulsions. [•] Triphasic (organic/fluorous/water) nanoemulsions prepared with two distinct oils in the organic phase (olive oil and synthetic lipid oil). [•] Nanoemulsions showed remarkable stability upon storage at elevated temperatures and when exposed to stress. [ABSTRACT FROM AUTHOR]

Highlights: [•] We deprotonate a hydrophosphorane using LiTMP. [•] The lithium phosphoranide is isolated in high yield and features a P(III) atom. [•] However on coordination to Ni, the species returns to P(V). [•] The Ni(II) structure features tetrahedral distortion and a Ni-O close approach. [•] We provide further evidence M→P pi-donation in a metalated phosphorane structure. [Copyright &y& Elsevier]

Keywords: alkenes; C-H nitration; photoredox; radicals; reaction mechanisms Furthermore, using in situ photo-sensitized, electron paramagnetic resonance spectroscopy, clear evidence for a nitryl radical in solution by nitrone spin-trapping was obtained. Alkenes, C-H nitration, photoredox, radicals, reaction mechanisms. [Extracted from the article]

A synthetic method for the palladium‐catalyzed cyanation of aryl boronic acids using bench stable and non‐toxic N‐cyanosuccinimide has been developed. High‐throughput experimentation facilitated the screen of 90 different ligands and the resultant statistical data analysis identified that ligand σ‐donation, π‐acidity and sterics are key drivers that govern yield. Categorization into three ligand groups – monophosphines, bisphosphines and miscellaneous – was performed before the analysis. For the monophosphines, the yield of the reaction increases for strong σ‐donating, weak π‐accepting ligands, with flexible pendant substituents. For the bisphosphines, the yield predominantly correlates with ligand lability. The applicability of the designed reaction to a wider substrate scope was investigated, showing good functional group tolerance in particular with boronic acids bearing electron‐withdrawing substituents. This work outlines the development of a novel reaction, coupled with a fast and efficient workflow to gain understanding of the optimal ligand properties for the design of improved palladium cross‐coupling catalysts. [ABSTRACT FROM AUTHOR]

A perfluoroisopropenyl ether terminated oligo(hexafluoropropylene oxide), a perfluoropolyalkyl ether macromonomer for radical copolymerization, has been prepared. The synthesis was achieved through a carefully controlled defluorination of a highly unstable lithium perfluorocarbanion intermediate. Several undesired pathways were also observed by GC/MS and we report conditions for generating the desired product in 82% yield. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl methyl ether acts as methylating reagent on tertiary aliphatic amines. [ABSTRACT FROM AUTHOR]

Replacement of the iodine atom in an iodine (III) CF3‐transfer reagent with a Te‐aryl moiety was accomplished in a three‐step synthetic sequence. Three compounds of this type have been prepared, two of which were characterized by X‐ray diffraction. Single crystal structures were also obtained for three related Te(IV) compounds unreported so far (4a, 4b, 6b). Comparison with the iodine (III) analogues indicate a large degree of structural similarity, however these species display an interesting decomposition pathway under thermal conditions. In addition to the expected Te−CF3 bond cleavage, C−F bond cleavage is also observed, unlike in the case of iodine (III) compounds. [ABSTRACT FROM AUTHOR]

The hydrophosphorane HP(OC 6 H 4 NMe) 2 was used to prepare the diastereotopic complexes [MCl 2 {P(OC 6 H 4 NMe)OC 6 H 4 NHMe}] (M = Pd, Pt) by reaction with [MCl 2 (PhCN) 2 ], and [RhCl(PPh 3 ){P(OC 6 H 4 NMe)OC 6 H 4 NHMe}] by reaction with [RhCl(PPh 3 ) 3 ]. To form these complexes, the phosphorane undergoes ring-opening, whereby it is coordinated as the tautomeric neutral phosphoramidite-amino chelating ligand. The crystal structure of [RhCl(PPh 3 ){P(OC 6 H 4 NMe)OC 6 H 4 NHMe}] was determined and the geometry about the Rh(I) atom is square-planar with cis-disposed phosphorus-donor ligands. The Rh–P distance is shortened (2.1056(6) Å) due to Rh( d ) → P π-backbonding. In addition, [RhCl(PPh 3 ){P(OC 6 H 4 NMe)OC 6 H 4 NHMe}] was shown to be an effective regio- and stereoselective catalyst for the hydrosilylation of 1-octene and 1-hexyne. [ABSTRACT FROM AUTHOR]

The crystal structure of the spirobicyclic phosphorane 3,3′-dimethyl-2λ-2,2′(3 H,3′ H)-spirobi[1,3,2-benzoxazaphosphole], [HP(OCHNCH)] ( 1) has been determined. Crystals of CHNOP are monoclinic, a = 8.483(2), b = 7.616(2), c = 19.805(6) Å, Z = 4, space group P2(1)/c. Compound 1 was also characterized by C{H} and H NMR. The crystal structure along with DFT B3LYP (6-311++G(2df,2p)) calculations, both suggest significant π-overlap between the equatorial nitrogen atoms and the phosphorus center. Graphical Abstract: The crystal structure and DFT B3LYP (6-311++G(2df,2p)) calculations of the spirobicyclic phosphorane 3,3′-dimethyl-2λ-2,2′(3 H,3′ H)-spirobi[1,3,2-benzoxazaphosphole], [HP(OCHNCH)] is reported.[Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]