With an ever-growing emphasis on sustainable synthesis, aerobic C-H activation (the use of oxygen in air to activate C-H bonds) represents a highly attractive conduit for the development of novel synthetic methodologies. Herein, we report the air mediated functionalisation of various saturated heterocycles and ethers aerobically generated radical intermediates to form new C-C bonds using acetylenic and vinyl triflones as radical acceptors. This enables access to a variety of acetylenic and vinyl substituted saturated heterocycles that are rich in synthetic value. Mechanistic studies and control reactions support an aerobic radical-based C-H activation mechanism.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337743 | PMC |
| http://dx.doi.org/10.1039/d2sc01626e | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Novel antimalarial 3-substituted quinolones isosteres with improved pharmacokinetic properties.
Eur J Med Chem
December 2024
School of Pharmacy and Food Engineering, Wuyi University, 529020, Jiangmen, China; Department of Chemistry, University of Liverpool, L69 7ZD, Liverpool, UK. Electronic address:
Aryl quinolone derivatives can target the cytochrome bc complex of Plasmodium falciparum, exhibiting excellent in vitro and in vivo antimalarial activity. However, their clinical development has been hindered due to their poor aqueous solubility profiles. In this study, a series of bioisosteres containing saturated heterocycles fused to a 4-pyridone ring were designed to replace the inherently poorly soluble quinolone core in antimalarial quinolones with the aim to reduce π-π stacking interactions in the crystal packing solid state, and a synthetic route was developed to prepare these alternative core derivatives.
View Article and Find Full Text PDFInterrogation of Enantioselectivity in the Photomediated Ring Contractions of Saturated Heterocycles.
J Am Chem Soc
January 2025
Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, United States.
We recently reported a chiral phosphoric acid (CPA) catalyzed enantioselective photomediated ring contraction of piperidines and other saturated heterocycles. By extruding a single heteroatom from a ring, this transformation builds desirable C(sp)-C(sp) bonds in the ring contracted products; however, the origins of enantioselectivity remain poorly understood. In this work, enantioselectivity of the ring contraction has been explored across an expanded structurally diverse substrate scope, revealing a wide range of enantioselectivities (0-99%) using two distinct CPA catalysts.
View Article and Find Full Text PDFStructure-guided engineering an (R)-transaminase from Mycobacterium neoaurum for efficient synthesis of chiral N-heterocyclic amines.
Int J Biol Macromol
December 2024
School of Life Sciences and Biopharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe, Shenyang 110016, People's Republic of China. Electronic address:
(R)-selective amine transaminases (R-ATAs) show considerable potential for the asymmetric synthesis of chiral drug intermediates. However, the low catalytic efficiency of natural R-ATAs toward bulky ketone substrates, such as N-heterocyclic compounds, severely limits its industrial application. In this study, five putative (R)-ATAs were mined from NCBI database, among which MnTA showed the highest activity for N-Boc-3-pyrrolidinone (1a) and N-Boc-3-piperidone (2a), and its crystal structure was performed.
View Article and Find Full Text PDFPhysicochemical and Biological Evaluation of gem-Difluorinated Saturated Oxygen Heterocycles as Bioisosteres for Drug Discovery.
Chemistry
December 2024
Enamine Ltd., Winston Churchill Street 78, 02094, Kyїv, Ukraine.
A comprehensive study on the physicochemical properties of gem-fluorinated O-heterocyclic substituents is reported. Systematic additive effects of introducing O- and gem-CF group introduction on acidic properties (pK) of the corresponding carboxylic acids/protonated primary amines were demonstrated. The impact of the O/CF moieties on lipophilicity (LogP) was found to be complex; significant mutual influence of the corresponding polar moieties governed the compound's overall properties in this case.
View Article and Find Full Text PDFTailored chiral phosphoramidites support highly enantioselective Pd catalysts for asymmetric aminoalkylative amination.
Nat Commun
December 2024
Key Laboratory of Precision and Intelligent Chemistry and Department of Chemistry, University of Science and Technology of China, 230026, Hefei, P. R. China.
Even though tuning electronic effect of chiral ligands has proven to be a promising method for designing efficient catalysts, the potential to achieve highly selective reactions by this strategy remains largely unexplored. Here, we report a palladium-catalyzed enantioselective ring-closing aminoalkylative amination of aminoenynes enabled by rationally tuning the remote electronic property of 1,1'-binaphthol-derived phosphoramidites. With a tailored 6,6'-CN-substituted 1,1'-binaphthol-derived phosphoramidite as a ligand, a broad range of aromatic amines are compatible with this reaction, allowing the efficient synthesis of a series of enantioenriched exocyclic allenylamines bearing saturated N-heterocycles with up to >99% enantiomeric excess.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!