LongLarf

Publication date: 12 August 2021

Source: Chem, Volume 7, Issue 8

Author(s): Jianbo Liu, Matthew F.L. Parker, Sinan Wang, Robert R. Flavell, F. Dean Toste, David M. Wilson

A Wittig reaction within a dearomatized pyridine ring system results in 4-alkylated pyridines, a valuable motif in the pharmaceutical and agrochemical sciences. N-Triazinyl salts are key to this strategy, and a range of substituted pyridines and aldehydes are amenable. Late-stage methylation is also feasible using a formaldehyde surrogate.

Abstract

Methods to synthesize alkylated pyridines are valuable because these structures are prevalent in pharmaceuticals and agrochemicals. We have developed a distinct approach to construct 4-alkylpyridines using dearomatized pyridylphosphonium ylide intermediates in a Wittig olefination-rearomatization sequence. Pyridine N-activation is key to this strategy, and N-triazinylpyridinium salts enable coupling between a wide variety of substituted pyridines and aldehydes. The alkylation protocol is viable for late-stage functionalization, including methylation of pyridine-containing drugs. This approach represents an alternative to metal-catalyzed sp ²-sp ³ cross-coupling reactions and Minisci-type processes.

Nature Catalysis, Published online: 02 August 2021; doi:10.1038/s41929-021-00661-7

Common native functional groups would be appealing as handles to enable C–H annulation with diverse aromatic rings. Now, this is achieved using ketones as unconventional alkyl radical precursors providing a practical method to synthesize biologically important fused-ring systems.

Nature Chemistry, Published online: 02 August 2021; doi:10.1038/s41557-021-00757-4

Metathesis reactions involving carbon–carbon double bonds have been well established, but direct metathesis of carbon–carbon single bonds is extremely rare. Now, a ruthenium-catalysed carbon–carbon single-bond metathesis reaction has been developed with unstrained homo-biaryl substrates. The reaction shows wide functional group tolerance and operates via an ‘olefin-metathesis-like’ mechanism.

Synlett
DOI: 10.1055/s-0037-1610780

The reaction of 1,3-bis(silyloxy)-1,3-butadienes with functionalized and nonfunctionalized acid chlorides and bis(acid chlorides) gives rise to the formation of a great variety of 1,3,5-tri- and 1,3,5,7-tetracarbonyl compounds and cyclic products derived from them. Examples include functionalized and nonfunctionalized 3,5-dioxopentanoates, 3,5-dioxopimelates, 3-alkylidene-3H-isobenzofuran-1-ones, salicylates, 3(2H)furanones, and 3-oxo-4-sulfonylesters. Methylation and cyclopropanation reactions of 1,3,5-tri- and 1,3,5,7-tetracarbonyl compounds do not provide access to the expected permethylated and cyclopropanated polycarbonyl compounds. However, the latter could be prepared by stepwise protocols. The reaction of 1,3,5-tri- and 1,3,5,7-tetracarbonyl compounds with dinucleophiles resulted in cyclization reactions to give a variety of heterocyclic structures.1 Introduction2 Reactions of 1,3-Bis(silyloxy)-1,3-butadienes with Acid Chlorides3 Reactions of 1,3,5-Tri- and 1,3,5,7-Tetracarbonyl Compounds4 Conclusion
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

Nature Chemistry, Published online: 30 July 2021; doi:10.1038/s41557-021-00768-1

A diverse group of people with a range of skills is required to be successful in academia, just as it is in team sports, argues Bruce C. Gibb.

Escape from flatland. Increased saturation (fraction of sp³) is more likely to be successful when moving compounds through the drug development pipeline. Bridged nitrogen heterocycles have a huge potential in drug discovery, although long synthetic sequences are typically required. New step-economic and selective organic syntheses are therefore highly sought after. Bert U. W. Maes et al. describe in their Research Article on page 21988 the synthesis of the normorphan skeleton through challenging tandem catalysis. Cover design by Joris Snaet.

Synthesis
DOI: 10.1055/s-0040-1719822

Enantioselective diamination of alkenes represents one of the most straightforward methods to access enantioenriched, vicinal diamines, which are not only frequently encountered in biologically active compounds, but also have broad applications in asymmetric synthesis. Although the analogous dihydroxylation of olefins is well-established, the development of enantioselective olefin diamination lags far behind. Nevertheless, several successful methods have been developed that operate by different reaction mechanisms, including a cycloaddition pathway, a two-electron redox pathway, and a radical pathway. This short review summarizes recent advances and identifies limitations, with the aim of inspiring further developments in this area.1 Introduction2 Cycloaddition Pathway3 Two-Electron Redox Pathway3.1 Pd(0)/Pd(II) Diamination3.2 Pd(II)/Pd(IV) Diamination3.3 I(I)/I(III) Diamination3.4 Se(II)/Se(IV) Diamination4 One-Electron Radical Pathway4.1 Cu-Catalyzed Diamination4.2 Fe-Catalyzed Diamination5 Summary and Outlook
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

The reactions of K[N(SiMe₃)₂] with ¹³CO affords K¹³CN and O(SiMe₃)₂ under mild conditions. DFT calculations affirmed this reaction proceeds via an isocyanide intermediate. This was confirmed experimentally as the alkali metal amides, M[N(SiR₃)R′] (M=Li, K; R=Ph, Me; R′=alkyl, aryl) are shown to provide a facile route to the 19 ¹³C labeled isocyanide RN¹³C and MOSiR₃ generally in high yields.

Abstract

The reaction of K[N(SiMe₃)₂] with ¹³CO proceeds in C₆D₆ or THF affording K¹³CN and O(SiMe₃)₂ under mild conditions as confirmed by crystallographic characterization of K(18-crown-6)CN. Similarly reaction of the alkali metal amides, M[N(SiR₃)R′] (M=Li, K; R=Ph, Me; R′=alkyl, aryl) provides the corresponding ¹³C labeled isocyanide RN¹³C and MOSiR₃, generally in high yields. In some instances, the use of the sterically bulky Ph₃Si-substituent is required to preclude 1,2-silyl migration affording the silylcarbamoyl salt M[Me₃SiC(O)NR′]. These reactions have been used to obtain 19 examples of ¹³C labelled isocyanides, and several examples of gram scale reactions are reported. The mechanism of the reactions is probed via reliable DFT calculations.

A mild glycosylation protocol is developed by using glycosyl 1-methylimidazole-2-carboxylates as donors. Such a glycosylation can be promoted by a series of metal triflates and triflimides, especially Cu(OTf)₂.

Abstract

A mild glycosylation protocol is developed by using glycosyl 1-methylimidazole-2-carboxylates. Such a glycosylation can be promoted by a series of metal triflates and triflimides, especially Cu(OTf)₂. The reaction is initiated by activation of the glycosyl ester donor via coordination with the metal cation assisted by the adjacent 1-methylimidazole chelating group.

Nature Catalysis, Published online: 22 July 2021; doi:10.1038/s41929-021-00662-6

Research projects are often developed by multiple groups worldwide, either in collaboration or in a form of genuine competition. In this Editorial, we discuss our approach to dealing with situations where multiple related manuscripts are submitted or published, in our journal or elsewhere, within a short period of time.

Nature Catalysis, Published online: 22 July 2021; doi:10.1038/s41929-021-00648-4

Plastics are invaluable materials for modern society, although they result in the generation of large amounts of litter at the end of their life cycle. This Review explores the challenges and opportunities associated with the catalytic transformation of waste plastics, looking at both chemical and biological approaches to transforming such spent materials into a resource.

Donorfreie, kinetisch-stabilisierte Diarylphosphenium- und Arsenium-Ionen wurden durch die Kombination sterisch anspruchsvoller starrer Aryl-Substituenten und schwach koordinierender Anionen erhalten.

Abstract

Chemiker waren schon immer begeistert von Carbenen und ihren Homologen, von ihrer faszinierenden Reaktivität und ihrem ambiphilen Charakter, der aus der besonderen elektronischen Struktur herrührt. Phosphenium- und Arsenium-Ionen sind extrem reaktive kationische Spezies, deren Stabilisierung in kondensierter Phase bislang nur dadurch erreicht werden könnte, indem die positive Ladung durch elektromere Konjugation über mindestens einen elektronenreichen Substituenten (häufig eine Amidogruppe) delokalisiert wurde. Obwohl sie in der Gasphase beobachtet wurden, entzogen sich dikoordinierte Phosphenium- und Arsenium-Ionen ohne stabilisierende Liganden für viele Jahrzehnte ihrer Isolierung. Hier zeigen wir, dass durch die geeignete Wahl aromatischer Substituenten dikoordinierte, donorfreie, Lewis supersaure Phosphenium- und Arsenium-Ionen kinetisch stabilisiert werden können. Diese zeichnen sich durch einen elektronischen Singulett-Grundzustand aus und weisen ein nicht-besetztes p-Orbital sowie ein freies Elektronenpaar mit dominierendem s-Charakter auf.