Radical Cyclisation of α‐Halo Aluminium Acetals: A Mechanistic Study

α‐Bromo aluminium acetals are suitable substrates for Ueno–Stork‐like radical cyclisations affording γ‐lactols and acid‐sensitive methylene‐γ‐lactols in high yields. The mechanistic study herein sets the scope and limitation of this reaction. The influence of the halide (or chalcogenide) atom X (X=Cl, Br, I, SPh, SePh) in the precursors α‐haloesters, as well as influence of the solvent and temperature was studied. The structure of the aluminium acetal intermediates resulting from the reduction of the corresponding α‐haloesters has been investigated by low‐temperature ¹³C‐INEPT diffusion‐ordered NMR spectroscopy (DOSY) experiments and quantum calculations, providing new insights into the structures of these thermally labile intermediates. Oxygen‐bridged dimeric structures with a planar Al₂O₂ ring are proposed for the least hindered aluminium acetals, while monomeric structures seem to prevail for the most hindered species. A comparison against the radical cyclisation of aluminium acetals derived from allyl and propargyl alcohols with the parent Ueno–Stork has been made at the BHandHLYP/6‐311++G(d,p) level of theory, highlighting mechanistic similarities and differences.     

Prefolded Synthetic G‐Quartets Display Enhanced Bioinspired Properties

A water‐soluble template‐assembled synthetic G‐quartet (TASQ) based on the use of a macrocyclodecapeptide scaffold was designed to display stable intramolecular folds alone in solution. The preformation of the guanine quartet, demonstrated by NMR and CD investigations, results in enhanced peroxidase‐type biocatalytic activities and improved quadruplex‐interacting properties. Comparison of its DNAzyme‐boosting properties with the ones of previously published TASQ revealed that, nowadays, it is the best DNAzyme‐boosting agent.     

Nickel-Catalyzed Electrochemical Synthesis of (Hetero)Aryl Trifluoromethyl Selenides

A convenient and efficient approach for the construction of aryl trifluoromethyl selenoethers from aryl iodides under mild conditions is reported. Electrochemical activation of stable and inexpensive NiBr₂bipy (bipy – bipyridine) complex instead of labile Ni(COD)₂ (COD – cyclooctadiene) catalyst. [NMe₄][SeCF₃] is employed as shelf-stable source of SeCF₃ fragment. The reaction tolerates a wide range of substrates, including modification of drug-like molecules. Cyclic voltammetry studies allow insight into the reaction mechanism.     

Development of Effective Skin Cancer Treatment and Prevention in Xeroderma Pigmentosum

Xeroderma pigmentosum (XP) is a rare, recessively transmitted genetic disease characterized by increasingly marked dyspigmentation and xerosis (dryness) of sun‐exposed tissues, especially skin. Skin cancers characteristically develop in sun‐exposed sites at very much earlier ages than in the general population; these are often multiple and hundreds or even thousands may develop. Eight complementation groups have been identified. Seven groups, XP‐A…G, are associated with defective genes encoding proteins involved in the nucleotide excision DNA repair (NER) pathway that recognizes and excises mutagenic changes induced in DNA by sunlight; the eighth group, XP‐V, is associated with defective translesion synthesis (TLS) bypassing such alterations. The dyspigmentation, xerosis and eventually carcinogenesis in XP patients appear to be due to their cells’ failure to respond properly to these mutagenic DNA alterations, leading to mutations in skin cells. A subset of cases, especially those in some complementation groups, may develop neurological degeneration, which may be severe. However, in most XP patients, in the past the multiple skin cancers have led to death at an early age due to either metastases or sepsis. Using either topical 5‐fluorouracil or imiquimod, we have developed a protocol that effectively prevents most skin cancer development in XP patients.     

Cationic Polymerization of Cyclic Sulfides

Abstract

The mechanism of the cationic polymerization of several thietanes and of propylene sulfide under the influence of triethyloxonium tetrafluoroborate in methylene chloride is described. The thietane polymerizations stop at limited conversions because of a termination reaction occurring between the reactive chain ends (cyclic sulfonium salts) and the sulfur atoms of the polymer chain. The maximum conversions obtained under identical conditions differ markedly for the different monomers. Ratios of rate constants of propagation (k_p) to rate constants of termination (k_t) have been calculated. The differences in k _p/k_t. values for the different monomers are explained in terms of differences in basicity and differences in steric hindrance of the monomers compared to the corresponding polymers. In the case of propylene sulfide it is proposed that the main termination reaction is the formation of 12-membered ring sulfonium salts by an intramolecular reaction of the third sulfur of the growing polymer chain with the reactive chain end (three-membered ring sulfonium salt). This terminated polymer is able to reinitiate the polymerization, for example, by reaction of a monomer molecule at the exocyclic carbon atom of the sulfonium salt function. The cyclic tetramer of propylene sulfide is formed in this reaction. After complete polymerization, formation of cyclic tetramer continues, probably via a backbiting mechanism. In methylene chloride as solvent, the absolute value of the rate constant of propagation for 3,3-dimethylthietane changes with changing concentration of initiator and by adding different amounts of indifferent electrolyte to the reaction mixture. From these changes, and assuming that the value of the dissociation constant of the growing chain-ends is close to values of dissociation constants of low molecular weight sulfonium salts, separate rate constants for propagation via free ions and ion-pairs were calculated. The propagation constant of free ions is about 70 times higher than that of ion pairs in methylene chloride at 20°C. Free ions and ion pairs are nearly equally reactive in nitrobenzene.     

Synthesis,Electronic Properties and WOLED Devices of Planar Phosphorus‐Containing Polycyclic Aromatic Hydrocarbons

We describe the synthesis and the physical properties of polyaromatic hydrocarbons (PAHs) containing a phosphorus atom at the edge. In particular, the impact of the successive addition of aromatic rings on the electronic properties was investigated by experimental (UV/Vis absorption, fluorescence, cyclic voltammetry) and theoretical studies (DFT). The physical properties recorded in solution and in the solid state showed that the P‐containing PAHs exhibit properties expected for an emitter in white organic light‐emitting diodes (WOLEDs).     

Aromatic CC Bonds as Dipolarophiles: Facile Reactions of Uncomplexed Electron‐Deficient Benzene Derivatives and Other Aromatic Rings with a Non‐Stabilized Azomethine Ylide

Non‐stabilized azomethine ylide 4 a reacts smoothly at room temperature with a variety of uncomplexed aromatic heterocycles and carbocycles on the condition that the ring contains at least one or two electron‐withdrawing substituents, respectively. Aromatic substrates, including pyridine and benzene derivatives, participate as 2 π components in [3+2] cycloaddition reactions and interact with one, two, or three equivalent(s) of the ylide, depending on their structure and substitution pattern. Thus, this process affords highly functionalized polycyclic structures that contain between one and three pyrrolidinyl ring(s) in useful yields. These results indicate that the site selectivity of the cycloaddition reactions strongly depends on both the nature and the positions of the substituents. In most cases, the second 1,3‐dipolar reaction occurs on the opposite face to the one that contains the first pyrrolidinyl ring. DFT calculations on model compounds indicate that a concerted mechanism features a low activation barrier.