Synlett

In this study, the development of an improved process for the synthesis of a key cannabidiol intermediate, methyl olivetolate, is described. The process involves an improvement of the iodine-catalyzed aromatization of cyclohexanone using potassium persulfate as an oxidant. This approach enabled for the efficient synthesis of methyl olivetolate with a 90% yield and 99.84% HPLC purity on a 5 kg scale. Additionally, a total of 19 cyclohexanone substrates afforded higher yields (71–92%) of m-diphenol compounds compared to the established methods.

Sulfur-containing heterocycles, where the S(R) moiety is located within the cyclic structure, have found tremendous applications in the fields of chemical, pharmaceutical, and materials sciences due to their unique chemical, biological and pharmaceutical activities. Recent years have witnessed increasing interest in sulfur-containing heterocycles, and new methods for their synthesis have been reported by adopting modern methodologies and technologies through insertion of sulfur dioxide. The main objective of this Account is to overview the latest major developments on the synthesis of sulfur-containing heterocyclic systems, mainly covering thermo-, photo- and electron-induced cyclization through the insertion of sulfur dioxide (SO2). We aim to provide the readership with a comprehensive understanding of this topic and offer a positive outlook on the promising future of this field.1 Introduction2 Thermal-Induced Cyclization3 Photoinduced Radical Cyclization4 Electron-Induced Radical Cyclization5 Conclusion

We report an investigation of the microwave-assisted catalytic transfer hydrogenation (TH) of carbonyl and nitro compounds by employing Ru(II) complexes: bimetallic [(p-cymene)2(RuCl)2L1]2X (X = BF4 (Cat2); X = PF6 (Cat3)) and mononuclear [(p-cymene)(RuCl)L2]BF4 (Cat4) (where L1 = N,N′-(3,3′,5,5′-tetraisopropyl-[1,1′-biphenyl]-4,4′-diyl)bis(1-(pyridin-2-yl)methanimine) and L2 = N-(2,6-diisopropylphenyl)-1-(pyridin-2-yl)methanimine). At a low catalyst loading of 0.01 mol% (Cat2/Cat3), a broad range of substrates, comprising aromatic as well as aliphatic ketones and aldehydes, undergo the TH reaction in a short reaction time of just 10 minutes. Additionally, chemoselective hydrogenation of nitroaromatic compounds is achieved under microwave irradiation in the presence of Cat2 within 5 minutes. Control experiments demonstrate that microwave heating conditions outperform conventional heating in terms of improved catalytic activity and reaction efficiency. The bimetallic catalyst Cat2 is used at a very low loading of 0.001 mol% to achieve high TONs and TOFs of 7.7 × 104 and 2.3 × 105 h–1, respectively, for the TH reaction. Spectrometry experiments involving trapping of intermediates are used to propose a mechanism for the TH of the carbonyl compounds.

Lipopolysaccharides (LPSs) are major virulence determinants in Gram-negative bacteria and are responsible for many pathophysiological processes during bacterial infections. However, the accessibility of LPS-associated oligosaccharides for infectious mechanism study and vaccine development remains challenging. We report an efficient stereocontrolled approach for the synthesis of a common inner-core trisaccharide containing difficult-to-access, rare, higher-carbon sugars: a heptose (Hep) and 3-deoxy-α-d-manno-oct-2-ulosonic acid (Kdo). Key features include comprehensive elaboration of a practical synthesis of versatile Hep and Kdo building blocks, and stereoselective assembly of an inner-core trisaccharide from multiple pathogenic bacteria.

(Trifluoromethyl)sulfanylamides are an important class of organic compounds that are common among natural products and drug molecules. Here, we report a (trifluoromethyl)sulfanylation reaction using silver(I) (trifluoromethyl)sulfide as a free-radical (trifluoromethyl)sulfanylation reagent for β-amide compounds. This reaction does not require stoichiometric oxidants or additional transition-metal catalysts, and can be achieved by adding common organic acids. This method has excellent applicability and can accommodate several functional groups, including ester groups, acyl groups, and even bromo or iodo groups. Heterocyclic α,β-amides can also be readily converted into the corresponding products. This reaction also provides a new method for the synthesis of deuterated (trifluoromethyl)sulfanylamides.

Herein, we report the novel strategy for the synthesis of 4-enamino-5-phenyl-2,3-dihydroisothiazole 1-oxides (in other words α-phenyl β-enamino γ-sultims) based on the CSIC reaction. Particularly, readily available α-amino nitriles (the Strecker products) reacted with benzyl sulfinyl chloride to give the corresponding sulfinamides, which upon treatment with excess of LiHMDS converted into the target α-phenyl β-enamino γ-sultims. The method works well and tolerates strained 3- and 4-membered spirocyclic substituents. A preliminary in silico study indicated that the γ-sultim scaffold can be considered a promising pharmacophore template.

Two novel copper-catalyzed cyclization reactions involving a remote propargylic substitution/cyclization/isomerization cascade are disclosed. Derivatives of the seldomly studied heterocycles thieno[2,3-c]pyrrole and thieno[2,3-d]pyridazine are conveniently synthesized in moderate to good yields from primary amines or arylhydrazines through [4+1] and [4+2] reactions, respectively. Preliminary mechanistic experiments corroborated the occurrence of the designed cascade reactions.

A visible-light-catalyzed arylcarboxylation of allenes with CO2 was developed using [Ir(ppy)2(dtbbpy)]PF6 (ppy = 2-phenylpyridine; dtbbpy = 4,4′-di-tert-butyl-2,2′-bipyridine) as a photocatalyst to synthesis β-aryl β,γ-unsaturated carboxylic acids. This multicomponent protocol proceeds in an atom-economical way with exclusive regioselectivity. Preliminary mechanistic experiments suggested that allylic carbanion species are the key intermediates.

Synlett 2024; 35: 832-832DOI: 10.1055/s-0043-1763761Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, GermanyArticle in Thieme eJournals:Table of contents  |  Full text

Synlett 2024; 35: V-DOI: 10.1055/s-0043-1763762Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, GermanyArticle in Thieme eJournals:Table of contents