Control over Anion Coordination on Pd(II), Cu(I), and Ag(I) with Regioisomeric Phosphine-Carboxylate Ligands.

The coordination of anionic donors is involved at various stages of catalytic cycles in transition-metal catalysis, but control over the spatial positioning of anions around a metal center is a challenge in coordination chemistry. Here we show that regioisomeric phosphine-carboxylate ligands provide spatial anion control on palladium(II) centers by favoring either κ2, cis-κ1, or trans-κ1 coordination of the carboxylate donor. Additionally, the palladium(II) carboxylates, which contain a methyl donor, upon protonation, deliver metal-alkyl complexes that feature a coordinated carboxylic acid. Such complexes can be considered as models for the minima that follow the concerted metalation-deprotonation transition state for C-H activation. The predictability of the coordination modes is further demonstrated on silver(I) and copper(I) centers, for which less common structures of mononuclear and dinuclear complexes can be obtained by using spatial anion control. Our results demonstrate the potential for spatial control over carboxylate anions in coordination chemistry.

Directional Ionic Bonds.

Covalent and ionic bonds represent two fundamental forms of bonding between atoms. In contrast to bonds with significant covalent character, ionic bonds are of limited use for the spatial structuring of matter because of the lack of directionality of the electric field around simple ions. We describe a predictable directional orientation of ionic bonds that contain concave nonpolar shields around the charged sites. Such directional ionic bonds offer an alternative to hydrogen bonds and other directional noncovalent interactions for the structuring of organic molecules and materials.

Azatriseptanes: Strained Framework Analogs of [7,7,7]Circulenes.

Invited for the cover of this issue is the group of Michel Rickhaus at the University of Zurich. The image depicts the "unearthing" of the highly contorted azatriseptane, a carbon framework consisting of three fused seven-membered rings surrounding a central nitrogen. Read the full text of the article at 10.1002/chem.202203954.

Azatriseptanes: Strained Framework Analogs of [7,7,7]Circulenes.

The synthesis and characterization of heptagon-embedded polycyclic aromatic compounds are essential for understanding the effect of negative curvature on carbon allotropes such as fullerenes and graphenes that have applications in functional organic materials. However, owing to the synthetic difficulties in functionalizing and embedding seven-membered rings, these strain-challenged structures are relatively unexplored. We report here the synthesis, characterization, and properties of a triarylamine core bridged with ethano chains at the 2,2'-positions. In doing so, we provide access to the first heterocycle containing three fused heptagon rings with a nitrogen at its core (BATA-NHAc). X-ray crystallographic analysis and DFT calculations revealed a remarkably strained structure wherein two of the bridged aryl units approach coplanarity, while the third ring is twisted out of plane at 70°. UV-vis and emission spectroscopies identify red-shifted absorption and concentration-dependent emission profiles, respectively, as a result of the unique conformation and self-assembly properties of BATA-NHAc. Furthermore, cyclic voltammetry shows a decrease in the oxidation potential for BATA-NHAc in comparison to the non-bridged analog. This study opens new avenues in understanding the structure-property relationships of curved π-aromatics and the construction of π-frameworks of increasing complexity.

Stereochemical Stability of Planar-Chiral Benzazepine Tricyclics: Inversion Energies of P- and S-Alkene Ligands.

Inversion barriers ΔG‡ for planar chiral phosphine-alkene and sulfonamide-alkene hybrid ligands based on phenyl-dibenz[b,f]azepine have been determined by density-functional theory calculations. Analysis of the structural and electronic characteristics of the minima and transition states explains the magnitudes of ΔG‡ and the geometrical changes during the inversion process. The steric repulsion caused by bulky substituents attached to the azepine nitrogen atom has a pronounced effect on the ΔG‡ value, explaining, inter alia, the stereochemical stability of the P- and S-alkene ligands when compared to the fluxional parent compound where X = H.

HNODThia: A Promising Chelator for the Development of 64Cu Radiopharmaceuticals.

Herein, we present the synthesis and coordination chemistry of copper(II) and zinc(II) complexes of two novel heterocyclic triazacyclononane (tacn)-based chelators (HNODThia and NODThia-AcNHEt). The chelator HNODThia was further derivatized to obtain a novel PSMA-based bioconjugate (NODThia-PSMA) and a bifunctional photoactivatable azamacrocyclic analogue, NODThia-PEG3-ArN3, for the development of copper-64 radiopharmaceuticals. 64Cu radiolabeling experiments were performed on the different metal-binding chelates, whereby quantitative radiochemical conversion (RCC) was obtained in less than 10 min at room temperature. The in vitro stability of NODThia-PSMA in human plasma was assessed by ligand-challenge and copper-exchange experiments. Next, we investigated the viability of the photoactivatable analog (NODThia-PEG3-ArN3) for the light-induced photoradiosynthesis of radiolabeled proteins. One-pot photoconjugation reactions to human serum albumin (HSA) as a model protein and the clinically relevant monoclonal antibody formulation MetMAb were performed. [64Cu]Cu-7-azepin-HSA and [64Cu]Cu-7-azepin-onartuzumab were prepared in less than 15 min by irradiation at 395 nm, with radiochemical purities (RCP) of >95% and radiochemical yields (RCYs) of 42.7 ± 5.3 and 49.6%, respectively. Together, the results obtained here open the way for the development of highly stable 64Cu-radiopharmaceuticals by using aza-heterocyclic tacn-based chelators, and the method can easily be extended to the development of 67Cu radiopharmaceuticals for future applications in molecularly targeted radio(immuno)therapy.

Xanthones and Xanthone O-ß-D-Glucosides from the Roots of Polygala azizsancarii Dönmez.

Nine xanthone derivatives (1-9) were isolated from the roots of Polygala azizsancarii, which is a narrow endemic species for the flora of Türkiye. Based on all of the evidence, the structures of 1-9 were established as two previously undescribed xanthone O-glucosides, 3-O-ß-D-glucopyranosyloxy-1,6-dihydroxy-2,5,7-trimethoxyxanthone (1), 3-O-ß-D-glucopyranosyloxy-1,6-dihydroxy-2,7-dimethoxyxanthone (2), and seven previously described xanthones, 1,3,6-trihydroxy-2,5,7-trimethoxyxanthone (3), 1,3,6-trihydroxy-2,7-dimethoxyxanthone (4), 1,2,3,4,7-pentamethoxyxanthone (5), 1,3-dihydroxy-2,5,6,7-tetramethoxyxanthone (6), 1,3-dihydroxy-4,7-dimethoxyxanthone (7), 1,7-dihydroxy-3-methoxyxanthone (8), and 1,7-dihydroxy-2,3-methylenedioxyxanthone (9). The structures of the compounds were determined by spectroscopic methods, including 1D-NMR (1 H-NMR, 13 C-NMR, DEPT-135), 2D-NMR (COSY, NOESY, HSQC, HMBC, INADEQUATE), and HR-MS. The solid-state structures of 1-4, including the absolute configurations of the stereogenic carbons of the sugar moiety in 1 and 2, were established by X-ray crystal-structure analyses. For the newly described compounds, the trivial names sancarosides A (1) and B (2) are proposed.

Site-Selective C-H Arylation of Diverse Arenes Ortho to Small Alkyl Groups.

Catalytic systems for direct C-H activation of arenes commonly show preference for electronically activated and sterically exposed C-H sites. Here we show that a range of functionally rich and pharmaceutically relevant arene classes can undergo site-selective C-H arylation ortho to small alkyl substituents, preferably endocyclic methylene groups. The C-H activation is experimentally supported as being the selectivity-determining step, while computational studies of the transition state models indicate the relevance of non-covalent interactions between the catalyst and the methylene group of the substrate. Our results suggest that preference for C(sp2 )-H activation next to alkyl groups could be a general selectivity mode, distinct from common steric and electronic factors.

Boron Trifluoride-Mediated Cycloaddition of 3-Bromotetrazine and Silyl Enol Ethers: Synthesis of 3-Bromo-pyridazines.

Pyridazines are important scaffolds for medicinal chemistry or crop protection agents, yet the selective preparation of 3-bromo-pyridazines with high regiocontrol remains difficult. We achieved the Lewis acid-mediated inverse electron demand Diels-Alder reaction between 3-monosubstituted s-tetrazine and silyl enol ethers and obtained functionalized pyridazines. In the case of 1-monosubstituted silyl enol ethers, exclusive regioselectivity was observed. Downstream functionalization of the resulting 3-bromo-pyridazines was demonstrated utilizing several cross-coupling protocols to synthesize 3,4-disubstituted pyridazines with excellent control over the substitution pattern.

Synthesis and Characterization of Bidentate (P

A new family of cationic, bidentate (P^N)gold(III) fluoride complexes has been prepared and a detailed characterization of the gold-fluoride bond has been carried out. Our results correlate with the observed reactivity of the fluoro ligand, which undergoes facile exchange with both cyano and acetylene nucleophiles. The resulting (P^N)arylgold(III)C(sp) complexes have enabled the first study of reductive elimination on (P^N)gold(III) systems, which demonstrated that C(sp2 )-C(sp) bond formation occurs at higher rates than those reported for analogous phosphine-based monodentate systems.

Spatial Anion Control on Palladium for Mild C-H Arylation of Arenes.

C-H arylation of arenes without the use of directing groups is a challenge, even for simple molecules, such as benzene. We describe spatial anion control as a concept for the design of catalytic sites for C-H bond activation, thereby enabling nondirected C-H arylation of arenes at ambient temperature. The mild conditions enable late-stage structural diversification of biologically relevant small molecules, and site-selectivity complementary to that obtained with other methods of arene functionalization can be achieved. These results reveal the potential of spatial anion control in transition-metal catalysis for the functionalization of C-H bonds under mild conditions.

Synthesis and Solid State Conformation of Tetrapeptide Amides Containing two Aib and two (αMe)Phe Residues - Use of Enantiomerically Pure 2-Benzyl-2-methyl-2H-azirin-3-amines as (αMe)Phe-Synthons.

A series of tetrapeptide amides containing two aminoisobutyric acids (Aib) and two α-methylphenylalanine ((αMe)Phe) units were prepared through the 'azirine/oxazolone method'. New 2-benzyl-2-methyl-2H-azirin-3-amines have been used for the selective introduction of (S)- and (R)-(αMe)Phe, respectively. The solid-state conformations of five tetrapeptide amides were determined by X-ray crystallography. In all cases, two ß-turns stabilize 310 -helical conformations and it was confirmed that, in contrast to proteinogenic amino acids, the configuration of (αMe)Phe does not determine the screw sense of the helix.

Metal-Free Regioselective Chloroazidation of Internal Alkynes.

A metal-free, room temperature protocol for the regioselective chloroazidation of internal alkynes is disclosed. The reactions of internal alkynes with trimethylsilyl azide (TMSN3 ) in the presence of 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) afforded the corresponding chloroazidoalkenes in good yields. This reaction has good functional group tolerance and is operationally simple.

The Furan Shuffling Hypothesis: A Biogenetic Proposal for Eremophilane Sesquiterpenoids.

Based on the structural similarities of the recently isolated eremophilane-type sesquiterpenoids microsphaeropsisin B and C and the iso-eremophilane periconianone C, a revised biogenetic hypothesis for C8-C11-connected iso-eremophilanes is presented and corroborated by strong experimental evidence. The first enantioselective total syntheses of microsphaeropsisin B and C were achieved starting from a known intermediate, whose synthesis was elaborated previously in the total synthesis of periconianone A, and in a total of 15 steps starting from γ-hydroxy carvone. Mild reaction conditions for the subsequent α-ketol rearrangement not only resulted in the herein proposed conversion of microsphaeropsisin B into periconianone C, but also in the conversion of microsphaeropsisin C into 4-epi-periconianone C.

Chiral Atropisomeric Indenocorannulene Bowls: Critique of the Cahn-Ingold-Prelog Conception of Molecular Chirality.

Chiral corannulenes abound, but suffer generally from configurational lability associated with bowl-to-bowl inversion, thus obviating questions of stereogenicity and stereoelement construction. In contrast, peri-annulated corannulenes show greatly increased barriers for bowl-to-bowl inversion; specifically indenocorannulenes invert on a time scale too slow to observe by normal NMR methods and raise the possibility of creating chiral atropisomeric bowl-shaped aromatics. Two methods for preparing indenocorannulene from simple 2-haloarylcorannulenes-silyl cation C-F activation, and Pd-mediated C-Cl activation[5] -enable the synthesis of an array of such chiral atropisomeric indenocorannulenes. Resolution of the enantiomers by high-performance liquid chromatography over chiral support phases motivates the study of chiroptical properties, the assignment of absolute "Cartesian" configuration, and the assessment of configurational stability. These studies bring into question any systematic assignment of nontrivial stereoelements (i.e. not the molecule in its entirety) and refute any assertion of congruence between "Cahn-Ingold-Prelog elements" and the physical or "Cartesian" basis of chirality.

First thia-Diels-Alder reactions of thiochalcones with 1,4-quinones.

Aryl and hetaryl thiochalcones react smoothly with 1,4-quinones in THF solution at 60 °C yielding the corresponding fused 4H-thiopyrans after spontaneous dehydrogenation of the initially formed [4 + 2] cycloadducts. In general, the yields of the isolated products were high. With 5-chloro-10-hydroxy-1,4-anthraquinone, the thia-Diels-Alder reaction occurred with complete regioselectivity. In the case of the reaction of vitamin K3 (menadione) with diphenylthiochalcone, the initial cycloadduct was isolated in 37% yield.

Total Synthesis of the Sesquiterpenoid Periconianone A Based on a Postulated Biogenesis.

The first enantioselective total synthesis of the complex tricarbocyclic sesquiterpenoid periconianone A based on a postulated biogenesis is reported. Key elements of the synthetic route include the use of an isopropenyl group as a removable directing group for stereoselective synthesis, a sequence featuring a Rh-mediated O-H insertion/[3,3]-sigmatropic rearrangement and subsequent α-ketol rearrangement, and a late stage aldol reaction to furnish the complex cage-like framework.

Synthesis and Characterization of 0D-3D Copper-Containing Tungstobismuthates Obtained from the Lacunary Precursor Na9[B-α-BiW9O33].

The reaction of the lacunary polyoxometalate precursor Na9[B-α-BiW9O33]·19.5H2O with Cu(II) ions was explored in search of new economic ways to copper tungstobismuthates as interesting prototypes for water oxidation and reduction catalysts. The emerging series of new 0D-3D polyoxometalate architectures with distinct copper cores was structurally characterized. Na6Rb6[Cu3(H2O)3(BiW9O33)2] (Cu-4) and 3D-K6.56Cu0.43H2.20[(Cu3Cl)(K2.62Cu0.38(H2O)3)(B-α-BiW9O33)2]·13H2O (Cu-5) display a Cu3(H2O)3 core. The 2D representatives Na12[Cu2(H2O)4Cl2(BiW10O35)2] (Cu-1a), Na10[Cu2(H2O)6(BiW10O35)2] (Cu-1b), 2D-Na7K3Cu0.5Cl[Cu2(H2O)4(BiW10O35)2] (Cu-2), and 2D-Na5.5K2.5Cu[Cu2(H2O)4(BiW10O35)2] (Cu-3) contain Cu2(H2O)nW2O4 cores. Interestingly, the bismuth-free 1D paratungstate B Na4K4Cu[H2W12O42] (Cu-6) is formed through reassembly of the precursor. Cu-5 displays a disordered transition metal core, implying the presence of the polyanions [Cu4(H2O)4(BiW9O33)2]10- and [Cu5(H2O)5(BiW9O33)2]8-. The magnetic properties of Cu-5 as well as its activity as visible-light-driven H2 and O2 evolution catalyst were evaluated.

The First Gold(III) Formate: Evidence for ß-Hydride Elimination.

The first stable gold(III) formate and experimental evidence for its ß-hydride elimination are described. A catalytic dehydrogenation of formic acid together with mechanistic studies shed light on potential pathways operating in fundamental gold-catalyzed transformations.

Evidence for Direct Transmetalation of AuIII-F with Boronic Acids.

The underlying reactivity of AuIII-F species with aryl boronic acids has been studied in detail taking advantage of four novel, stable difluoro-[(C^N)AuF2], arylmonofluoro-[(C^N)AuArF], and alkylmonofluoro-[(C^N)AuAlkF] gold(III) complexes, prepared and isolated in monomeric form. We provide the first experimental evidence for a direct AuIII-F/B transmetalation preceding the Csp2-Csp2 or Csp3-Csp2 bond formation.