Organic chemistry frontiers : an international journal of organic chemistry最新文献

We describe a catalyst-free visible-light mediated akynylperfluoroalkylation of unactive alkenes with perfluoroalkyl iodides, which provides a series of α-perfluoroalkyl-β-alkynyl ketone derivatives. This new synthetic protocol is enabled by a charge-transfer complex, which is a compound of a 1,4-enynol anion and an enolate ion of acetone as the electron donor and perfluoroalkyl iodides as the electron acceptor. Excellent functional group compatibility and chemoselectivity render this method suitable for fluoroalkylation of pharmaceutically relevant molecules, featuring a broad substrate scope, scalability and significant characteristics of green chemistry, further demonstrating the flexibility and potential for the synthesis of the mentioned compounds.

Macrocyclic arenes have been widely used due to their special structures, ease of modification, and outstanding properties. However, macrocyclic arenes with well-defined cavities are still rare. Recently, Quan, Jiang and co-workers constructed a novel class of macrocyclic arenes with well-defined cavities, namely methylene-bridged naphthotubes, which used rigid and curved alkoxy-substituted bisnaphthalene clefts as building blocks. Compared with structurally similar but flexible macrocycles, methylene-bridged naphthotubes possessed stronger binding affinities to organic cations and showed more outstanding molecular recognition capabilities. Moreover, methylene-bridged naphthotubes could serve as chiral sensors for chiral organic cations through different chiral transfer mechanisms. Herein, we highlight this ground-breaking work, which opens up great prospects for the unlimited application of macrocyclic arenes with well-defined cavities in supramolecular chemistry.

Herein, we report an efficient and practical protocol for dehalocarboxylation of C(sp²)-halides with formate by the engagement of a CO₂ radical anion in a nickel-mediated bond-forming process. A wide variety of aryl iodides, aryl bromides, and alkenyl bromides bearing a diverse set of functional groups underwent the reaction smoothly through visible-light photoredox nickel dual catalysis. The synthesis of several ¹³C-labeled drug intermediates and the gram-scale synthesis of commercial drugs highlight the synthetic value of the approach in drug discovery settings.

This work reports SnCl₂/Me₂SnCl₂-catalyzed site-selective carbamoylation of carbohydrates with a broad substrate scope, associated with mild reaction conditions, good selectivity and high isolated yields (using a flash column). In particular, the selectivity of carbamoylation resulting from the SnCl₂ method is complementary to that resulting from the Me₂SnCl₂ method in many cases. For several glycoside substrates containing cis-diol, their axial hydroxyl groups are selectively carbamoylated in the presence of the SnCl₂ catalyst, while their equatorial hydroxyl groups are selectively carbamoylated in the presence of the Me₂SnCl₂ catalyst. The substrate scope for the SnCl₂ method also includes glycosides containing 1,3-diol, but excludes glycosides containing trans-diol. The substrate scope for the Me₂SnCl₂ method can include glycosides containing trans-diol.

The challenging direct α-alkylation of sulfoxonium ylides is demonstrated after a deep study with several electrophiles. Twenty-five alkylated ester sulfoxonium ylides could be prepared in 12–67% isolated yields, employing Michael acceptors as electrophiles. Interestingly, no product arising from the classical cyclopropanation reaction, commonly observed for the reaction between sulfur ylides and Michael acceptors, was observed. To demonstrate the applicability of these unprecedented and more decorated sulfoxonium ylides, new and medicinal-chemistry important sulfur heterocycles, such as 2-mercaptobenzothiazoles, 1,4-benzothiazin-3-ones, and coumarin derivatives, were prepared.

A transition metal and external fluorine anion-free method has been developed for the efficient trifluoromethylation of sulfoxonium ylides with BrCF₂CO₂Et to afford α-trifluoromethyl ketones. Mechanistic investigation revealed that taking advantage of the dual role of BrCF₂CO₂Et, which concurrently acts as a CF₂ and F source, is key to realizing this reaction. This method is applicable to the late-stage modification of biologically active compounds and can be readily scaled up.

We present herein a palladium-catalyzed decarboxylation [2 + 2 + 2] annulation with 3-iodochromones, bridged olefins, and o-bromobenzoic acids to give various exo-chromone-containing polycyclic compounds (49 examples, up to 92% yield), in which o-bromobenzoic acids were employed as the electrophilic aryl units. Gram-scale experiments, late-stage modification of estrone, and further transformations of products show a great potential of this palladium-catalyzed Heck coupling/C(sp²)–H activation/decarboxylation cascade for drug discovery and development.

Allenes are a unique type of powerful synthon used for the construction of various carbocycles and heterocycles, but their annulation reactions with N–N triple bond electrophiles have not been disclosed. Here we report an efficient silver-catalysed boronate-directed [3 + 2] annulation reaction of aryl diazonium salts with allenylboronates. This transformation offers unprecedented access to a wide scope of N¹-aryl-1H-pyrazoles with high regioselectivities under mild conditions. Preliminary experimental and computational studies support a transmetalation/stepwise cycloaddition/pyrazolyl silver hydrolysis pathway involving propargyl silver species as the key intermediate in enabling reactivity and controlling regioselectivity.

We describe a ligand-enabled Cu(ii)-catalyzed approach for highly selective synthesis of 2E-alkenylfurans 2 from ynenones under an air atmosphere. In this reaction, the amide group on our designed 1,10-phenanthroline framework had a key role in promoting the α-H internal 1,2-migration to Cu(ii) carbene species and stabilizing the in situ-generated carbocation. This approach prevented the external oxygen participating to oxidize α-furyl copper carbene rapidly to 2-acylfuran. With the bifunctional ligand L1, the Cu(ii) catalyst became highly efficient at catalyzing ynenones selective to 2E-alkenylfurans 2 under an air atmosphere at room temperature in excellent yields. Moreover, the ligand could lower the Cu(ii) catalyst loading dramatically to ppm-level at a higher temperature and concentration, with turnover numbers of the Cu(ii) catalyst up to 9300. This economical and practical approach with good application was mild and environmentally friendly.