Helvetica Chimica Acta最新文献

The generation of benzylic radicals through hydrogen atom abstraction (HAT) has been a recent research focus and various C(sp³)−H bond functionalization protocols have been developed relying on this elementary step. We report herein copper- and iron-catalyzed C(sp³)−H benzylic azidation reactions using mCPBA and NFSI as oxidant, respectively, and TMSN₃ as azide source. The reaction is thought to be initiated via intermolecular abstraction of benzylic hydrogen by the in situ generated heteroatom-centered radicals. The Fe(OTf)₃-catalyzed azidation protocol displays good chemoselectivity as it takes place preferentially at the secondary and tertiary benzylic C(sp³)−H bonds over the primary benzylic and tertiary aliphatic carbons. Efforts on the development of catalytic enantioselective processes are also documented.

We describe herein the design and synthesis of a new class of dialkylarylphosphine ligands incorporating a Lewis-basic urea subunit. The ligand synthesis consisted of six linear steps and was enabled by the discovery of a new N-to-N alkyl migration reaction. This new series of dialkylarylphosphine urea ligands were applied in common palladium-catalyzed cross-coupling reactions for the formation of carbon-carbon and carbon-nitrogen bonds in moderate to high yields.

Functionalized cubanes are attractive scaffolds for medicinal chemists as they are bioisosteres of benzene rings. The replacement of a benzene ring by a cubane, in a bioactive compound, can have a beneficial effect on the biological activity of such compound. Thus, the design of new molecular cubyl building blocks is of importance. In this review, we will focus on the functionalization of cubanes by creating C−C, C−heteroatom bonds e. g. C−N, C−O, C−B, C−P and C−S bonds. Different methods are reported involving organometallics, radicals, and ionic species. Mechanisms are included when relevant.

The title triarylamine N,N-bis(9,9-dimethyl-9H-fluoren-2-yl)-3′,3′,4′,7′-tetramethyl-2′,3′-dihydrospiro[fluorene-9,1′-indene]-2-amine is a new hole transport material for organic solar cells. After investigating different discovery approaches (Schemes 1 + 2), a multi gram-scale synthetic sequence was developed (Scheme 4). The key intermediate 2-bromo-9-(2,5-dimethylphenyl)-9H-fluorene was accessible from 2-bromo-9-fluorenone by either the sequence Grignard reaction, Et₃SiH/BF₃ reduction or by direct arylation of the corresponding 2-bromo-9-fluorenol. Alkylation at C(9) of 2-bromo-9-(2,5-dimethylphenyl)-9H-fluorene with methallyl chloride and cyclization by an intramolecular Friedel-Crafts alkylation led to the key building block 2-bromo-3′,3′,4′,7′-tetramethyl-2′,3′-dihydrospiro[fluorene-9,1′-indene] (Scheme 4). A Buchwald-Hartwig coupling was employed (Scheme 3 + 4) for the assembly of the final triarylamines. The developed gram-scale synthesis of the title compound is scalable and chromatography-free with an overall yield >25 % over 5 steps.

Guaiane sesquiterpenes are an important class of biologically active natural products. Several oxygenated bicyclic but also tricyclic derivatives show unprecedented olfactory activity with great importance in perfumery. Their in vivo syntheses are largely controlled by the intrinsic selectivities of terpene synthases and only a few rearrangements of their hydroazulene skeletons were reported, mostly resulting into terpenoids with decalin motives. Using α-guaiene and bulnesene, complex rearrangements into novel tri and tetracyclic terpenoids are described herein. The cationic rearrangement mechanisms of their formation based on subsequent 1,2-H and alkyl shifts promoted by substoichiometric amounts of ethylaluminum dichloride.

Umifenovir is a broad-spectrum antiviral agent used to treat influenza in China and Russia, and it has been studied as an antiviral agent for the treatment of coronavirus disease 2019 (COVID-19). We have previously reported the synthesis of novel umifenovir analogues and their biological evaluation with a focus on their inhibitory activity against the binding of the spike glycoprotein (S-protein) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the angiotensin-converting enzyme 2 (ACE2) receptor; however, no strong inhibitory activity was observed from these analogues. In the present study, an additional set of umifenovir analogues was synthesized with replacement of the substituents at the 2-, 3-, and 4-positions of the indole, and a cell-based assay using SARS-CoV-2 (B.1.1) was performed to examine the antiviral activity of the analogues. We found that one of the newly synthesized umifenovir analogues exhibited antiviral activity and reduced the viral load to 0.06 % as compared to the control when it was assessed in the presence of nafamostat and marimastat, which inhibit cell-surface viral entry. In contrast, when this analogue was evaluated without the addition of nafamostat or marimastat, it exhibited less antiviral activity, suggesting that the umifenovir analogue would exert antiviral activity mainly by inhibiting endosome-mediated viral entry.

Advancing the use of alkali-metal alkoxides as additives to activate organometallic reagents, here we report the synthesis and characterization of a novel potassium zincate [{(PMDETA)KZn(OtBu)Et₂}₂] obtained by co-complexation of equimolar amounts of potassium tert-butoxide, diethyl zinc and the tridentate donor PMDETA (N,N,N’,N’’,N’’-pentamethyldiethylenetriamine). Demonstrating its ability to activate both of the Et groups towards alkyne C−H metalation, this zincate reacts at room temperature with 2 equivalents of phenylacetylene to furnish [(THF)₂KZn(CCPh)₂(OtBu)}₂], whereas, for the homometallic [ZnEt₂(TMEDA)] (TMEDA=N,N,N’,N’-tetramethylethylendiamine) only one Et group is reactive towards the same substrate under the same conditions. Investigations on the reactivity of these complexes to undergo N−H amine metalation using 2, 6-diisopropylphenylamine (NH₂Dipp) and 1,2,3,4-tetrahydroquinoline (THQ(H)) as model substrates revealed that while homometallic [ZnEt₂(TMEDA)] is completely inert towards these amines, heterobimetallic [{(PMDETA)KZn(OtBu)Et₂}₂] reacts through one of its Et groups to form [(THF)₂KZn(OtBu)(Et)(NHDipp)] as well as [(THF)₄K₂Zn(THQ)₄]. The latter is obtained as a side product of ligand redistribution of a putative [(THF)_nKZn(OtBu)(Et)(THQ)] intermediate. An alternative method to access mixed amide/alkoxide potassium zincates is also described by assessing the co-complexation of KOtBu with Zn(HMDS)₂ in the presence of PMDETA which gave [(PMDETA)KZn(HMDS)₂(OtBu)].

The development of water-soluble hosts for the selective recognition of aromatic amino acids is highly desirable and may serve as a tool to facilitate drug discovery and enable fabrication of sensors for point-of-care monitoring in the context of phenylketonuria disease. This paper presents the synthesis and characterization of a water-soluble molecular cleft which is demonstrated to selectively bind aromatic amino acid guests over other amino acids in aqueous medium, favoring ʟ-Trp over ʟ-Phe and ʟ-Tyr by a factor of approximately five. Host/guest-interaction forces were studied by ¹H-NMR titrations complemented by fluorescence titrations and isothermal titration calorimetry. The here presented results provide a starting point for future optimizations in our efforts to selectively identify and quantify individual aromatic amino acids in aqueous medium.

The preparations, photophysical and electrochemical properties of a series of fac-[Re(CO)₃(diimine)Br] complexes are presented. The bipyridine (bpy) based diimine ligands feature symmetrical and asymmetrical 3,3’-diamino-2,2’-bipyridine substitution patterns. Photophysical and electrochemical properties of these complexes are tunable, depending on their organic diimine framework. Introduction of a distal urea bridge via the 3,3’-substitution pattern led to prolonged phosphorescence lifetimes without a significant change in absorbance and phosphorescence emission wavelengths. Reversible electrochemical bipyridine reduction remained largely unchanged by this derivatization.