Synthesis of Prenyl‐ and Geranyl‐Substituted Carbazole Alkaloids by DIBAL‐H Promoted Reductive Pyran Ring Opening of Dialkylpyrano[3,2‐a]carbazoles

The DIBAL‐H promoted reductive pyran ring opening of dialkylpyrano[3,2‐a]carbazoles provides a direct access to a broad range of prenyl‐ and geranyl‐substituted carbazoles. Formation of a pyran ring followed by reductive ring opening represents a new method for the introduction of prenyl and geranyl groups. In the course of the present work, we achieved the first total syntheses of the following eight carbazole alkaloids: clauraila‐E, 7‐hydroxyheptaphylline, 7‐methoxyheptaphylline, mukoenine‐B (clausenatine‐A), mukoenine‐A (girinimbilol), mahanimbinol (mahanimbilol), euchrestine‐A, and isomurrayafoline‐B.     

Oligotriarylamines with a Pyrene Core: A Multicenter Strategy for Enhancing Radical Cation and Dication Stability and Tuning Spin Distribution

Monoamine 1 , diamines 2 – 4 , triamine 5 , and tetraamine 6 have been synthesized by substituting dianisylamino groups at the 1‐, 3‐, 6‐, and/or 8‐positions of pyrene. Diamines 2 – 4 differ in the positions of the amine substituents. No pyrene–pyrene interactions are evident in the single‐crystal packing of 3 , 4 , and 6 . With increasing numbers of amine substituents, the first oxidation potential decreases progressively from the mono‐ to the tetraamine. These compounds show intense charge‐transfer (CT) emission in CH₂Cl₂ at around 530 nm with quantum yields of 48–68 %. Upon stepwise oxidation by electrolysis or chemical oxidation, these compounds were transformed into radical cations 1 ^?+– 6 ^?+ and dications 2 ²⁺– 6 ²⁺, which feature strong visible and near‐infrared absorptions. Time‐dependent density functional theory studies suggested the presence of localized transitions from the pyrene radical cation and aminium radical cation, intervalence CT, and CT between the pyrene and amine moieties. Spectroscopic studies indicated that these radical cations and dications have good stability. Triamine 5 and tetraamine 6 formed efficient CT complexes with tetracyanoquinodimethane in solution. The results of EPR spectroscopy and density functional theory calculations suggested that the dications 2 ²⁺– 4 ²⁺ have a triplet ground state, whereas 5 ²⁺ and 6 ²⁺ have a singlet ground state. The dication of 1,3‐disubstituted diamine 4 exhibits a strong EPR signal.     

An Unusual Triphenylphosphine Oxide Catalyzed Stereoselective 1,3‐Dichlorination of Unsaturated Ketoesters

An unusual Ph₃PO‐catalyzed stereoselective 1,3‐dicholorination of an unsaturated ketoester has been developed. The novel activation mode involved in this cascade reaction can promote consecutively elusive transformations. The products were obtained with good yields and excellent stereoselectivities. This reaction makes important complementation to the limitations associated with the field of dichlorination.     

Luminescent Mechanochromic Porous Coordination Polymers

Three 2D luminescent isomeric porous coordination polymers are synthesized and characterized. Their luminescence properties can be modified by grinding and they can act as mechanochromic materials and their properties are probably related to the weak interactions of cuprophilicity and π–π interactions.     

A Deadly Organometallic Luminescent Probe: Anticancer Activity of a ReI Bisquinoline Complex

The photophysical properties of [Re(CO)₃(L ‐N₃)]Br (L ‐N₃=2‐azido‐N,N‐bis[(quinolin‐2‐yl)methyl]ethanamine), which could not be localized in cancer cells by fluorescence microscopy, have been revisited in order to evaluate its use as a luminescent probe in a biological environment. The Re^I complex displays concentration‐dependent residual fluorescence besides the expected phosphorescence, and the nature of the emitting excited states have been evaluated by DFT and time‐dependent (TD) DFT methods. The results show that fluorescence occurs from a ¹LC/MLCT state, whereas phosphorescence mainly stems from a ³LC state, in contrast to previous assignments. We found that our luminescent probe, [Re(CO)₃(L ‐N₃)]Br, exhibits an interesting cytotoxic activity in the low micromolar range in various cancer cell lines. Several biochemical assays were performed to unveil the cytotoxic mechanism of the organometallic Re^I bisquinoline complex. [Re(CO)₃(L ‐N₃)]Br was found to be stable in human plasma indicating that [Re(CO)₃(L ‐N₃)]Br itself and not a decomposition product is responsible for the observed cytotoxicity. Addition of [Re(CO)₃(L ‐N₃)]Br to MCF‐7 breast cancer cells grown on a biosensor chip micro‐bioreactor immediately led to reduced cellular respiration and increased glycolysis, indicating a large shift in cellular metabolism and inhibition of mitochondrial activity. Further analysis of respiration of isolated mitochondria clearly showed that mitochondrial respiratory activity was a direct target of [Re(CO)₃(L ‐N₃)]Br and involved two modes of action, namely increased respiration at lower concentrations, potentially through increased proton transport through the inner mitochondrial membrane, and efficient blocking of respiration at higher concentrations. Thus, we believe that the direct targeting of mitochondria in cells by [Re(CO)₃(L ‐N₃)]Br is responsible for the anticancer activity.     

Alkene Isomerisation Catalysed by a Ruthenium PNN Pincer Complex

The [Ru(CO)H(PNN)] pincer complex based on a dearomatised PNN ligand (PNN: 2‐di‐tert‐butylphosphinomethyl‐6‐diethylaminomethylpyridine) was examined for its ability to isomerise alkenes. The isomerisation reaction proceeded under mild conditions after activation of the complex with alcohols. Variable‐temperature (VT) NMR experiments to investigate the role of the alcohol in the mechanism lend credence to the hypothesis that the first step involves the formation of a rearomatised alkoxide complex. In this complex, the hemilabile diethylamino side‐arm can dissociate, allowing alkene binding cis to the hydride, enabling insertion of the alkene into the metal–hydride bond, whereas in the parent complex only trans binding is possible. During this study, a new uncommon Ru⁰ coordination complex was also characterised. The scope of the alkene isomerisation reaction was examined.     

Aryl‐Copper(III)‐Acetylides as Key Intermediates in CCsp Model Couplings under Mild Conditions

The mechanism of copper‐mediated Sonogashira couplings (so‐called Stephens–Castro and Miura couplings) is not well understood and lacks clear comprehension. In this work, the reactivity of a well‐defined aryl‐Cu^III species ( 1 ) with p‐R‐phenylacetylenes (R=NO₂, CF₃, H) is reported and it is found that facile reductive elimination from a putative aryl‐Cu^III‐acetylide species occurs at room temperature to afford the C_aryl?C_sp coupling species ( I_R ), which in turn undergo an intramolecular reorganisation to afford final heterocyclic products containing 2H‐isoindole ( P , P , P_Ha ) or 1,2‐dihydroisoquinoline ( P_Hb ) substructures. Density Functional Theory (DFT) studies support the postulated reductive elimination pathway that leads to the formation of C?C_sp bonds and provide the clue to understand the divergent intramolecular reorganisation when p‐H‐phenylacetylene is used. Mechanistic insights and the very mild experimental conditions to effect C_aryl?C_sp coupling in these model systems provide important insights for developing milder copper‐catalysed C_aryl?C_sp coupling reactions with standard substrates in the future.     

Highly Curved Bowl‐Shaped Fragments of Fullerenes: Synthesis,Structural Analysis,and Physical Properties

Highly curved buckybowls 3 , 4 , and 5 were synthesized from planar precursors, fluoranthenes 8 , benzo[k]fluoranthenes 10 and naphtho[1,2‐k]‐cyclopenta[cd]fluoranthenes 12 , respectively, using straightforward palladium‐catalyzed cyclization reactions. These fluoranthene‐based starting materials were easily prepared from 1,8‐bis(arylethynyl)naphthalenes 6 . Both buckybowls 3 and 4 are fragments of C₆₀, whereas 5 is a unique subunit of C₇₀. The curved structures were identified by X‐ray crystallography, and they are deep bowls. The maximum π‐orbital axis vector (POAV) pyramidalization angle in both 3 and 4 is 12.8°. Such a high curvature is very rarely obtained. Buckybowls 5 are less curved than the others because they have a lower density of five‐membered rings, analogous to the tube portion of C₇₀. Cyclopentaannulation increases the bowl depths of 3 and 4 , but not the maximum POAV pyramidalization angle. Among the eight buckybowls studied herein, five form polar crystals. The bowl‐to‐bowl inversion dynamics of these buckybowls can be classified into two types; one has a planar transition structure, whereas the other has an S‐shaped transition structure. A larger longitudinal length of these buckybowls corresponds to a stronger preference for the latter. The photophysical properties of these buckybowls were examined and compared with those of C₆₀ and C₇₀. Buckybowls 5 have absorption bands at wavelengths greater than 450 nm, which are similar to those of C₇₀. The chiral resolution of the mono‐substituted buckybowl 4 ac was also studied by using HPLC with a chiral column.     

Uncatalyzed Hydroamination of Electrophilic Organometallic Alkynes: Fundamental,Theoretical, and Applied Aspects

Simple reactions of the most used functional groups allowing two molecular fragments to link under mild, sustainable conditions are among the crucial tools of molecular chemistry with multiple applications in materials science, nanomedicine, and organic synthesis as already exemplified by peptide synthesis and “click” chemistry. We are concerned with redox organometallic compounds that can potentially be used as biosensors and redox catalysts and report an uncatalyzed reaction between primary and secondary amines with organometallic electrophilic alkynes that is free of side products and fully “green”. A strategy is first proposed to synthesize alkynyl organometallic precursors upon addition of electrophilic aromatic ligands of cationic complexes followed by endo hydride abstraction. Electrophilic alkynylated cyclopentadienyl or arene ligands of Fe, Ru, and Co complexes subsequently react with amines to yield trans‐enamines that are conjugated with the organometallic group. The difference in reactivities of the various complexes is rationalized from the two‐step reaction mechanism that was elucidated through DFT calculations. Applications are illustrated by the facile reaction of ethynylcobalticenium hexafluorophosphate with aminated silica nanoparticles. Spectroscopic, nonlinear‐optical and electrochemical data, as well as DFT and TDDFT calculations, indicate a strong push–pull conjugation in these cobalticenium– and Fe– and Ru–arene–enamine complexes due to planarity or near‐planarity between the organometallic and trans‐enamine groups involving fulvalene iminium and cyclohexadienylidene iminium mesomeric forms.     

Synthesis and Antiviral Properties of Spirocyclic [1,2,3]‐Triazolooxazine Nucleosides

An efficient synthesis of spirocyclic triazolooxazine nucleosides is described. This was achieved by the conversion of β‐D ‐psicofuranose to the corresponding azido‐derivative, followed by alkylation of the primary alcohol with a range of propargyl bromides, obtained by Sonogashira chemistry. The products of these reactions underwent 1,3‐dipolar addition smoothly to generate the protected spirocyclic adducts. These were easily deprotected to give the corresponding ribose nucleosides. The library of compounds obtained was investigated for its antiviral activity using MHV (mouse hepatitis virus) as a model wherein derivative 3 f showed the most promising activity and tolerability.