Diastereoselective Dearomatizing Cyclizations of 5-Arylpentan-2-ones by Samarium Diiodide - A Computational Analysis.

This study analyzes the samarium diiodide-promoted cyclizations of 5-arylpentan-2-ones to dearomatized bicyclic products utilizing density functional theory. The reaction involves a single electron transfer to the carbonyl group, which occurs synchronously with the rate determining cyclization event, and a second subsequent proton-coupled electron transfer. These redox reactions are accurately computed employing small core pseudo potentials explicitly involving all f-electrons of samarium.

One-pot nucleophilic substitution-double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives.

The nucleophilic substitution of benzylic bromides with sodium azide was combined with a subsequent copper-catalyzed (3 + 2) cycloaddition with terminal alkynes. This one-pot process was developed with a simple model alkyne, but then applied to more complex alkynes bearing enantiopure 1,2-oxazinyl substituents. Hence, the precursor compounds 1,2-, 1,3- or 1,4-bis(bromomethyl)benzene furnished geometrically differing bis(1,2,3-triazole) derivatives.

Spin State in Homoleptic Iron(II) Terpyridine Complexes Influences Mixed Valency and Electrocatalytic CO Reduction.

Two homoleptic Fe(II) complexes in different spin states bearing superbasic terpyridine derivatives as ligands are investigated to determine the relationship between spin state and electrochemical/spectroscopic behavior. Antiferromagnetic coupling between a ligand-centered radical and the high-spin metal center leads to an anodic shift of the first reduction potential and results in a species that shows mixed valency with a moderately intense intervalence-charge-transfer band. The differences afforded by the different spin states extend to the electrochemical reactivity of the complexes: while the low-spin species is a precatalyst for electrocatalytic CO reduction and leads to the preferential formation of CO with a Faradaic efficiency of 37%, the high-spin species only catalyzes proton reduction at a modest Faradaic efficiency of approximately 20%.

The Boekelheide Rearrangement of Pyrimidine N-oxides as a Case Study of Closed or Open Shell Reactions - Experimental and Computational Evidence for the Participation of Radical Intermediates.

In a case study, the acetic anhydride-promoted reaction of a model pyrimidine N-oxide to the corresponding 4-acetoxymethyl-substituted pyrimidine derivative (Boekelheide rearrangement) was investigated in detail by experiment and quantum chemical calculations. The reaction conditions were varied and several side products formed in low to moderate yields were identified. These experiments indicate that a (pyrimidin-4-yl)methyl radical is one of the key species of the rearrangement.

-Diels-Alder Reactions of In Situ-Generated Azoalkenes with Thioketones; Experimental and Theoretical Studies.

The -Diels-Alder reactions of in situ-generated azoalkenes with thioketones were shown to offer a straightforward method for an efficient and regioselective synthesis of scarcely known N-substituted 1,3,4-thiadiazine derivatives. The scope of the method was fairly broad, allowing the use of a series of aryl-, ferrocenyl-, and alkyl-substituted thioketones. However, in the case of N-tosyl-substituted cycloadducts derived from 1-thioxo-2,2,4,4-tetramethylcyclobutan-3-one and the structurally analogous 1,3-dithione, a more complicated pathway was observed.

A Homage to Siegfried Hünig and His Research.

Examples from different research areas of Siegfried Hünig are displayed to remind us that organic chemistry owes much more than Hünig's base to this exceptionally versatile and creative chemist. The main research lines dealing with the synthesis and physical characterization of new dyes, multistage redox systems, and organic metals will be presented as well as his contributions to enamine chemistry, the discovery of diimine as a hydrogenation agent, and nucleophilic acylation with trimethylsilyl cyanide, which are less well-known nowadays. In addition, exotic compounds with parallel C=C and N=N bonds were systematically studied in Hünig's group.

Rolf Huisgen (1920-2020).

Rolf Huisgen would have celebrated his 100th birthday this year. Three of his academic progeny look back on Huisgen as a person, teacher, and scientist. They underline his leading role in rebuilding the chemistry department in Munich after the Second World War and the enduring importance of the 1,3-dipolar cycloaddition (Huisgen reaction).

The Huisgen Reaction: Milestones of the 1,3-Dipolar Cycloaddition.

The concept of 1,3-dipolar cycloadditions was presented by Rolf Huisgen 60 years ago. Previously unknown reactive intermediates, for example azomethine ylides, were introduced to organic chemistry and the (3+2) cycloadditions of 1,3-dipoles to multiple-bond systems (Huisgen reaction) developed into one of the most versatile synthetic methods in heterocyclic chemistry. In this Review, we present the history of this research area, highlight important older reports, and describe the evolution and further development of the concept.

The [4+2]-Cycloaddition of α-Nitrosoalkenes with Thiochalcones as a Prototype of Periselective Hetero-Diels-Alder Reactions-Experimental and Computational Studies.

The [4+2]-cycloadditions of α-nitrosoalkenes with thiochalcones occur with high selectivity at the thioketone moiety of the dienophile providing styryl-substituted 4H-1,5,2-oxathiazines in moderate to good yields. Of the eight conceivable hetero-Diels-Alder adducts only this isomer was observed, thus a prototype of a highly periselective and regioselective cycloaddition has been identified. Analysis of crude product mixtures revealed that the α-nitrosoalkene also adds competitively to the thioketone moiety of the thiochalcone dimer affording bis-heterocyclic [4+2]-cycloadducts.

Adsorption of Mono- and Divalent 4-(Dimethylamino)pyridines on Gold Surfaces: Studies by Surface-Enhanced Raman Scattering and Density Functional Theory.

The adsorption thermodynamics of 4-(dimethylamino)pyridine (DMAP) and its five divalent derivatives di-DMAP- n (2 ≤ n ≤ 6) with gradually increasing methylene-spacer lengths n binding to planar gold surfaces has been studied by surface-enhanced Raman spectroscopy (SERS) and density functional theory (DFT). SERS intensities of the totally symmetrical breathing mode of the pyridine ring at approximately 1007 cm are used to monitor the surface coverage of the DMAP and di-DMAP- n ligands on gold surfaces at different concentrations. The equilibrium constant as a measure of the binding affinity is obtained from these measurements by using a modified Langmuir isotherm.

New Dyes Based on Extended Fulvene Motifs: Synthesis through Redox Reactions of Naphthoquinones with Donor-Acceptor Cyclopropanes and Their Spectroelectrochemical Behavior.

Novel dyes based on extended fulvene motifs are reported. The carbon skeleton was generated by a catalyzed addition of donor-acceptor cyclopropanes to naphthoquinone. The hydroxy group at the central ring of the tricyclic fulvene motif was converted into the triflate, which reacted efficiently with a wide range of nucleophiles, resulting in substitution and thereby providing new derivatives.

Stereoselective Cascade Cyclizations with Samarium Diiodide to Tetracyclic Indolines: Precursors of Fluorostrychnines and Brucine.

A series of γ-indolylketones with fluorine, cyano or alkoxy substituents at the benzene moiety was prepared and subjected to samarium diiodide-promoted cyclization reactions. The desired dearomatizing ketyl cascade reaction forming two new rings proceeded in all cases with high diastereoselectivity, but with differing product distribution. In most cases, the desired annulated tetracyclic compounds were obtained in moderate to good yields, but as second product tetracyclic spirolactones were isolated in up to 29 % yield.

The LANCA three-component reaction to highly substituted β-ketoenamides - versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives.

The LANCA three-component reaction of lithiated alkoxyallenes , nitriles and carboxylic acids leads to β-ketoenamides in good to excellent yields. The scope of this reaction is very broad and almost all types of nitriles and carboxylic acids have successfully been used. The alkoxy group introduced via the allene component is also variable and hence the subsequent transformation of this substituent into a hydroxy group can be performed under different conditions.

Efficient Syntheses of New Super Lewis Basic Tris(dialkylamino)-Substituted Terpyridines and Comparison of Their Methyl Cation Affinities.

Syntheses of very electron-rich dialkylamino-substituted 2,2':6',2''-terpyridines (TPYs) were adapted to moderate scale preparation without tedious purification of intermediates. The key 4'-bromo-6,6''-dimethyl-2,2':6',2''-terpyridine-4,4''-diyl bisnonaflate is now available in gram quantities. Its nucleophilic aromatic substitution with dimethylamine provided mixtures of 4'-bromo-substituted 4,4''-bis(dimethylamino)-TPY and the tris(dimethylamino)-TPY.

Alkoxyallene-based syntheses of preussin and its analogs and their cytotoxicity.

Short syntheses of oxa-preussin, racemic preussin and (-)-preussin are reported. Starting from a racemic 3-nonyl-substituted methoxyallene derivative, its lithiation and addition to phenylethanal provided the corresponding allenyl alcohol that was converted into two diastereomeric dihydrofuran derivatives by silver nitrate-catalyzed 5-endo-trig cyclization. The acid hydrolysis of the enol ether moiety gave heterocyclic ketones and subsequent highly stereoselective reductions with l-selectride furnished 2-benzyl-5-nonylfuran-3-ol derivatives in good overall yield.

To Anion-π or not to Anion-π: The Case of Anion-Binding to Divalent Fluorinated Pyridines in the Gas Phase.

A series of mono- and divalent fluorinated pyridine derivatives is investigated by electrospray ionization (tandem) mass spectrometry and quantum chemical calculations with respect to their capability to bind anions in the gas phase. The pyridine derivatives differ not only in valency, but also with regard to the degree of fluorination of the pyridine rings, the positions of the fluorine atoms, the rigidity of the spacers connecting the two pyridines in the divalent compounds, and the relative configuration. While the monovalent compounds did not form anion complexes, the divalent analogues exhibit anion binding even to weakly coordinating anions such as tetrafluoroborate.

A computational study of samarium diiodide-induced cyclizations of N-oxoalkyl-substituted methyl indole-3-carboxylates-A rationale of the diastereoselectivity.

A detailed model for the reaction mechanism of the samarium diiodide (SmI ) mediated reductive coupling of N-oxoalkyl-substituted methyl indole-3-carboxylates is developed in this study by determining the Gibbs energies for the intermediates of possible reaction pathways. The Gibbs energies at ambient temperature are calculated with dispersion corrected density functional theory in combination with implicit (D-COSMO-RS) and explicit solvent description. Temperature dependent ro-vibrational contributions are considered with the help of statistical thermodynamics.

Novel Alkoxy-Substituted Dipyrrins and Near-IR BODIPY Dyes-Preparation and Photophysical Properties.

Starting from 3-alkoxy-2-aryl-substituted pyrroles and aromatic aldehydes, a collection of new dipyrrins was prepared. Under the standard conditions of Treibs, these were converted into the corresponding boron dipyrrins (BODIPYs). Compounds of this type with alkoxy groups at C-3 position of both pyrrole subunits are new and hence the photophysical properties of this collection of novel dipyrrins and BODIPY dyes were investigated.

Ruthenium Complexes with Strongly Electron-Donating Terpyridine Ligands: Effect of the Working Electrode on Electrochemical and Spectroelectrochemical Properties.

The combination of 2,2':6',2''-terpyridines (tpy) and Ru is known to deliver molecular and supramolecular assemblies with remarkable properties. Here new Ru complexes, with modified tpy ligands substituted with varying numbers of dimethlyamino groups, are presented. Electrochemistry shows that the incorporation of the strongly electron-donating groups on the tpy ligands leads to a negative shift of the Ru oxidation potential by close to 1 V.

Alkoxyallene-Based Stereodivergent Syntheses of (-)-Hyacinthacine B and of Putative Hyacinthacine C Epimers: Proposal of Hyacinthacine C Structure.

Hyacinthacines are members of the class of polyhydroxylated pyrrolizidines exhibiting outstanding biological activity as glycosidases inhibitors. Their structural complexity is embodied in the densely functionalized core, possessing a series of contiguous stereogenic centers. In this synthetic study we report a route to the more complex congeners of this class of alkaloids exploiting the diastereoselective addition of an axially chiral lithiated alkoxyallene to an enantiopure cyclic nitrone.

Synthesis, Characterization, and DFT Analysis of Bis-Terpyridyl-Based Molecular Cobalt Complexes.

Terpyridine ligands are widely used in chemistry and material sciences owing to their ability to form stable molecular complexes with a large variety of metal ions. In that context, variations of the substituents on the terpyridine ligand allow modulation of the material properties. Applying the Stille cross-coupling reaction, we prepared with good yields a new series of terpyridine ligands possessing quinoline-type moieties in ortho, meta, and para positions and dimethylamino substituents at central or distal positions.

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions.

Iodination of carbohydrate-derived 3,6-dihydro-2-1,2-oxazines of type using iodine and pyridine in DMF furnished 5-iodo-substituted 1,2-oxazine derivatives with high efficacy. The alkenyl iodide moiety of 1,2-oxazine derivatives - and - was subsequently exploited for the introduction of new functionalities at the C-5 position by applying palladium-catalyzed carbon-carbon bond-forming reactions such as Sonogashira, Heck, or Suzuki coupling reactions as well as a cyanation reaction. These cross-coupling reactions led to a series of 5-alkynyl-, 5-alkenyl-, 5-aryl- and 5-cyano-substituted 1,2-oxazine derivatives being of considerable interest for further synthetic elaborations.

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups.

Starting from γ-ketoesters with an o-iodobenzyl group we studied a palladium-catalyzed cyclization process that stereoselectively led to bi- and tricyclic compounds in moderate to excellent yields. Four X-ray crystal structure analyses unequivocally defined the structure of crucial cyclization products. The relative configuration of the precursor compounds is essentially transferred to that of the products and the formed hydroxy group in the newly generated cyclohexane ring is consistently in trans-arrangement with respect to the methoxycarbonyl group.

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides - scope and limitations.

The scope of a flexible route to unsymmetrically functionalized bipyridines is described. Starting from 1,3-diketones 1a-e, the corresponding β-ketoenamines 2a-e were converted into different β-ketoenamides 3a-g by N-acylation with 2-pyridinecarboxylic acid derivatives. These β-ketoenamides were treated with a mixture of TMSOTf and Hünig's base to promote the cyclocondensation to 4-hydroxypyridine derivatives.

Nucleophilic Aromatic Substitution on Pentafluorophenyl-Substituted Dipyrranes and Tetrapyrroles as a Route to Multifunctionalized Chromophores for Potential Application in Photodynamic Therapy.

The application of porphyrinoids in biomedical fields, such as photodynamic therapy (PDT), requires the introduction of functional groups to tune their solubility for the biological environment and to allow a coupling to other active moieties or carrier systems. A valuable motif in this regard is the pentafluorophenyl (PFP) substituent, which can easily undergo a regiospecific nucleophilic replacement (S Ar) of its para-fluorine atom by a number of nucleophiles. Here, it is shown that, instead of amino-substitution on the final porphyrinoid or BODIPY (boron dipyrromethene), the precursor 5-(PFP)-dipyrrane can be modified with amines (or alcohols).