LongLarf

Abstract

α-Indol-3-yl α,β-unsaturated carbonyl compounds are synthesized from 3-propargyl indoles, obtained by direct propargylation of indoles, via a gold-catalyzed tandem oxidation-1,2-indole migration reaction in the presence of pyridine N-oxides. Fine-tuning of the catalyst and oxidant enables the reaction of 3-propargyl indoles bearing different substituents. The order of oxidation and indole migration is determined by the terminal or internal nature of the alkyne moiety. In addition, the process can be coupled with additional reactions, allowing an increase in molecular complexity or the design of more elaborated tandem reactions. In this sense, indole derivatives bearing an alkenyl substituent at the alkyne position evolve through a gold-catalyzed tandem oxidation-1,2-indole migration-Nazarov cyclization producing α-indolyl cyclopentenones.

Abstract

A method for the radical functionalization of 1,2,4-oxadiazoles using alkyl halides as precursors of radicals is described. The reaction efficiency is determined by potassium tetrafluoropyridinyl thiolate additive, which plays dual role. First, the thiolate converts alkyl halides into more reactive fluorinated aryl sulfides, which undergo photoredox activation of the C−S bond. Second, the thiolate decreases the unproductive loss of alkyl radicals by converting them back to the sulfides.

Nature, Published online: 28 March 2024; doi:10.1038/s41586-024-07341-z

Copper-catalyzed dehydrogenation or lactonization of C(sp³)−H bonds

Nature Synthesis, Published online: 28 March 2024; doi:10.1038/s44160-024-00507-7

Methods for enzymatic C–F bond formation are rare. Now an enzymatic method for enantioselective C(sp3)–F bond formation is reported, through reprogramming non-haem iron enzyme (S)-2-hydroxypropylphosphonate epoxidase. Mechanistic studies reveal that the process proceeds through an iron-mediated radical fluorine transfer process.

Proteins and enzymes can be repurposed by the introduction of artificial cofactors or non-canonical amino acids (ncAAs). These artificial biocatalytic constructs turned into valuable tools to perform new-to-nature reactions with biocatalysts increasing their scope. This perspective focuses on the limitations and future application for in vivo biosynthetic pathways.

Abstract

Astonishing progress has been achieved in unlocking new-to-nature biocatalysis in the past decades. The progress in protein engineering enabled research to efficiently incorporate artificial structural elements into enzyme design. Recent trends include cofactor mimetics, artificial metalloenzymes and non-canonical amino acids. In this perspective article, we present the state-of-the-art, discuss recent examples and our view on what we call artificial biocatalysis. Although these artificial systems undoubtedly increase the scope of biocatalysis, their applicability remains challenging. Fundamental questions regarding the impact of this research field are addressed in this perspective.

Publication date: 13 June 2024

Source: Chem, Volume 10, Issue 6

Author(s): Qiang Wang, Haifeng Qi, Yujing Ren, Zhusong Cao, Kathrin Junge, Rajenahally V. Jagadeesh, Matthias Beller

Science, Volume 383, Issue 6689, Page 1312-1317, March 2024.

Science, Volume 383, Issue 6689, March 2024.

A novel nitroreductase from Bacillus tequilensis, named BtNR, enabled the synthesis of arylamines from bulky nitroarenes with good conversions and isolated yields. These enzymatically prepared arylamines are valuable synthons for the production of pharmaceutically active compounds, such as the antibiotic linezolid and the anticancer drugs vismodegib and sonidegib.

Abstract

Arylamines are essential building blocks for the manufacture of valuable pharmaceuticals, pigments and dyes. However, their current industrial production involves the use of chemocatalytic procedures with a significant environmental impact. As a result, flavin-dependent nitroreductases (NRs) have received increasing attention as sustainable catalysts for more ecofriendly synthesis of arylamines. In this study, we assessed a novel NR from Bacillus tequilensis, named BtNR, for the synthesis of pharmaceutically relevant arylamines, including valuable synthons used in the manufacture of blockbuster drugs such as vismodegib, sonidegib, linezolid and sildenafil. After optimizing the enzymatic reaction conditions, high conversion of nitroaromatics to arylamines (up to 97 %) and good product yields (up to 56 %) were achieved. Our results indicate that BtNR has a broad substrate scope, including bulky nitro benzenes, nitro pyrazoles and nitro pyridines. Hence, BtNR is an interesting biocatalyst for the synthesis of pharmaceutically relevant amine-functionalized aromatics, providing an attractive alternative to traditional chemical synthesis methodologies.

Nature Chemistry, Published online: 01 March 2024; doi:10.1038/s41557-024-01472-6

Although generally perceived as an old-fashioned and unselective tool to build molecules, the photochemistry community is now re-discovering the power of UV light and is using key mechanistic information to develop new catalytic processes driven by visible light. This Perspective discusses the progress and impact of UV light in organic synthesis.

Flat, tri-coordinate boron rears its had, becomes tetra-coordinate and chiral! When treated in an appropriate manner, it forms enantiomers that are configurationally stable. Only since recently, boron-stereogenic complexes are accessible by catalytic enantioselective syntheses. What makes this particularly exciting is that tetra-coordinate boron compounds are considered promising light-emitting materials.

Abstract

Boron-based enantiomerism is fragile due to the inherent tendency of a dissociation of a ligand from tetra-coordinate chiral boron complexes under formation of the achiral tri-coordinate species. This review will present the different approaches in overcoming the inherent tendency of racemization in boron-stereogenic compounds. When embedded in an environment of chiral ligands or substituents, configurationally stable boron stereogenic centers can form in a diastereoselective manner. Compounds incorporating boron as the exclusive stereogenic center are obtained by resolution of the racemic mixtures. The recently developed – much more efficient – methods of a catalytic, enantioselective creation of boron stereogenic compounds are highlighted in this review. Finally the chiroptical properties of enantiomerically pure boron complexes that makes them promising materials or devices are addressed.