Studies of the γ ← α transition in syndiotactic polystyrene

In this work we compare calorimetric and X-ray diffraction experiments realized on annealed sPS in helical γ forms resulting by different treatements: From clathrate δ form and from interaction of amorphous sample with acetone. The experimental results show that the γ form obtained by acetone converts into the more ordered final α” form modification; while the γ form, obtained by thermal treatments of δ form, transforms into the poorly ordered final α' form.     

Pd‐Catalyzed Carbonylative α‐Arylation of Aryl Bromides: Scope and Mechanistic Studies

Reaction conditions for the three‐component synthesis of aryl 1,3‐diketones are reported applying the palladium‐catalyzed carbonylative α‐arylation of ketones with aryl bromides. The optimal conditions were found by using a catalytic system derived from [Pd(dba)₂] (dba=dibenzylideneacetone) as the palladium source and 1,3‐bis(diphenylphosphino)propane (DPPP) as the bidentate ligand. These transformations were run in the two‐chamber reactor, COware, applying only 1.5 equivalents of carbon monoxide generated from the CO‐releasing compound, 9‐methylfluorene‐9‐carbonyl chloride (COgen). The methodology proved adaptable to a wide variety of aryl and heteroaryl bromides leading to a diverse range of aryl 1,3‐diketones. A mechanistic investigation of this transformation relying on ³¹P and ¹³C NMR spectroscopy was undertaken to determine the possible catalytic pathway. Our results revealed that the combination of [Pd(dba)₂] and DPPP was only reactive towards 4‐bromoanisole in the presence of the sodium enolate of propiophenone suggesting that a [Pd(dppp)(enolate)] anion was initially generated before the oxidative‐addition step. Subsequent CO insertion into an [Pd(Ar)(dppp)(enolate)] species provided the 1,3‐diketone. These results indicate that a catalytic cycle, different from the classical carbonylation mechanism proposed by Heck, is operating. To investigate the effect of the dba ligand, the Pd⁰ precursor, [Pd(η³‐1‐PhC₃H₄)(η⁵‐C₅H₅)], was examined. In the presence of DPPP, and in contrast to [Pd(dba)₂], its oxidative addition with 4‐bromoanisole occurred smoothly providing the [PdBr(Ar)(dppp)] complex. After treatment with CO, the acyl complex [Pd(CO)Br(Ar)(dppp)] was generated, however, its treatment with the sodium enolate led exclusively to the acylated enol in high yield. Nevertheless, the carbonylative α‐arylation of 4‐bromoanisole with either catalytic or stoichiometric [Pd(η³‐1‐PhC₃H₄)(η⁵‐C₅H₅)] over a short reaction time, led to the 1,3‐diketone product. Because none of the acylated enol was detected, this implied that a similar mechanistic pathway is operating as that observed for the same transformation with [Pd(dba)₂] as the Pd source.     

Studies on the Mass Spectra of N‐Aryl α,β‐Unsaturated γ‐Lactams

The mass spectra of a series of N‐aryl α,β‐unsaturated γ‐lactams were studied. Besides the molecular ion, the three characteristic fragments such as [M⁺‐29], [M⁺‐55], and [M⁺‐82] were commonly found in a series of N‐Aryl α,β‐unsaturated γ‐lactams in EI/MS. Further more the mechanism for the interpretation of these fragments is also de scribed.     

The Reaction Studies of α‐Chloroformylarylhydrazines with Thiols,Thioureas and α‐Cyclodiketones

The reactions of α‐chloroformylarylhydrazines 1 with various types of mercaptan, thiourea and α‐cyclodiketone have been studied intensively. 1‐Arylhydrazinecarbothioates 2 were obtained via thioesterization when α‐chloroformylarylhydrazines reacted with thiols. On the other hand, compounds 3 were obtained when α‐chloroformylarylhydrazines reacted with thio‐containing heterocyclic compounds, which suggested a totally different mechanism in these types of reactions. Further studies on the reaction of α‐chloroformylarylhydrazines 1 with thiourea compounds confirmed a novel cyclization and de‐cyclization mechanism, which led to give 2‐arylhydrazinecarboximidamides 5 and 1,3,4‐thiadiazolin‐5‐ones 6 . In addition, various 1,3,4‐oxadiazines 9 were obtained by reacting α‐chloroformylarylhydrazines with α‐cyclodiketones, showing ring cyclization was involved in this type of reaction.     

Mechanistic Studies on the Organocatalytic α‐Chlorination of Aldehydes: The Role and Nature of Off‐Cycle Intermediates

Herein we report the isolation and characterization of aminal intermediates in the organocatalytic α‐chlorination of aldehydes. These species are stable covalent ternary adducts of the substrate, the catalyst and the chlorinating reagent. NMR‐assisted kinetic studies and isotopic labeling experiments with the isolated intermediate did not support its involvement in downstream stereoselective processes as proposed by Blackmond. By tuning the reactivity of the chlorinating reagent, we were able to suppress the accumulation of rate‐limiting off‐cycle intermediates. As a result, an efficient and highly enantioselective catalytic system with a broad functional group tolerance was developed.     

Mechanistic Insights on the Iodine(III)‐Mediated α‐Oxidation of Ketones

The synthesis of α‐substituted carbonyl compounds is of great importance due to their ubiquity in both natural and man‐made biologically active compounds. The field of hypervalent iodine chemistry has been a great contributor to access these molecules. For example, the α‐oxidation of carbonyl compounds has been one of the most investigated iodine(III)‐mediated stereoselective transformations. Yet, it is also the transformation that has met the most challenge in terms of achieving high stereoselectivities. The different mechanistic pathways of the iodine(III)‐mediated α‐tosyloxylation of ketones have been investigated. The calculations suggest an unprecedented iodine(III)‐promoted enolization process. Indications that iodonium intermediates could serve as proficient Lewis acids are reported. This concept could have broad impact and foster new developments in the field of hypervalent iodine chemistry.     

Asymmetric Copper‐Catalyzed Vinylogous Mukaiyama Michael Addition of Cyclic Dienol Silanes to Unsaturated α‐Keto Phosphonates

A highly stereoselective vinylogous Mukaiyama Michael reaction (VMMR) leading to α‐keto phosphonate‐containing γ‐butenolides with two stereogenic centers is described. The presented transformation is catalyzed by a combination of a commercially available C₂‐symmetric bisoxazoline (BOX) ligand and a copper salt and tolerates a variety of nucleophiles and electrophiles. The stereoselectivities of the reactions are good to excellent and the products are obtained in moderate to high yields.     

Studies on the Reactivity of α-Cyano-α-isocyanoalkanoates – Versatile Synthons for the Assembly of Imidazoles

The reactivity and the synthetic potential of α-cyano-α-isocyanoalkanoates 2 were investigated. Interestingly, reaction of 2 with alkoxides gave (alkoxy)(alkyl)imidazoles 5 , whereas the analogous thiolates led to different products, namely substituted 4H-imidazoles 7 , together with compounds 6 , which formed by addition of thiolate to the isocyano group. Primary amines reacted, on one hand, in the same manner as thiolates to form of 4H-imidazoles 10 , and, on the other hand, cleavage of the molecule to the proposed unstable aminoimidazole 8 and the carbamate 9 was observed. Secondary amines add selectively to the isocyano group to form compounds 11 . Like simple isocyanides, α-cyano-α-isocyanoalkanoates 2 can be subjected to [4+1] cycloadditions and multicomponent reactions of the Passerini type. Mechanisms for the described reactions are discussed.     

Highly Diastereo‐ and Enantioselective Aziridination of α,β‐Unsaturated Amides with Diaziridine and Mechanistic Consideration on Its Stereochemistry

During studies of aziridination of α,β‐unsaturated amides with diaziridine, we found that we could prepare both the cis‐ and trans‐aziridinecarboxamides by choosing an appropriately substituted diaziridine. While 3‐monosubstituted diaziridine 2 was suitable for the trans‐selective aziridination, employment of 3,3‐dialkyldiaziridine 1 resulted in the formation of cis‐aziridine carboxamides, irrespective of the geometry of the substrate (Scheme 1 and Tables 1 and 2). To elucidate the unique nonstereospecificity and to expand these aziridinations to asymmetric ones, several optically active diaziridines were newly prepared. Aziridination with an optically active 3‐monosubstituted diaziridine, 3‐cyclohexyl‐1‐[(1R)‐1‐phenylethyl]diaziridine 16 , proceeded smoothly with high trans‐selectivity as well as excellent enantioselectivity (up to 98% ee; see Table 3). On the other hand, highly enantioselective cis‐aziridination was achieved (>99% ee) with optically active 3,3‐dimethyl‐1‐[(1R)‐1‐phenylethyl]diaziridine 15 , though the yield was low (4%). This aziridination was considered to proceed stepwise by way of the enolate intermediate (Scheme 2). Careful inspection of the stereochemistry and its solvent‐dependence suggested that the diastereoselection of the reaction was kinetically controlled: the 1,4‐addition of N‐lithiated diaziridine was a crucial step for determination of the stereochemical course of the aziridination (Figs. 2–4).     

Self‐Assembled Cyclic d,l‐α‐Peptides as Generic Conformational Inhibitors of the α‐Synuclein Aggregation and Toxicity: In Vitro and Mechanistic Studies

Many peptides and proteins with large sequences and structural differences self‐assemble into disease‐causing amyloids that share very similar biochemical and biophysical characteristics, which may contribute to their cross‐interaction. Here, we demonstrate how the self‐assembled, cyclic d,l ‐α‐peptide CP‐2 , which has similar structural and functional properties to those of amyloids, acts as a generic inhibitor of the Parkinson′s disease associated α‐synuclein (α‐syn) aggregation to toxic oligomers by an ?off‐pathway“ mechanism. We show that CP‐2 interacts with the N‐terminal and the non‐amyloid‐β component region of α‐syn, which are responsible for α‐syn′s membrane intercalation and self‐assembly, thus changing the overall conformation of α‐syn. CP‐2 also remodels α‐syn fibrils to nontoxic amorphous species and permeates cells through endosomes/lysosomes to reduce the accumulation and toxicity of intracellular α‐syn in neuronal cells overexpressing α‐syn. Our studies suggest that targeting the common structural conformation of amyloids may be a promising approach for developing new therapeutics for amyloidogenic diseases.     

Studies on the Reaction of α‐Chloroformylarylhydrazine Hydrochloride1 with N‐Heterocyclic Compounds

In addition to pyridines, α‐chloroformylarylhydrazine hydrochloride 1 can also react with some N‐heterocyclic compounds. The cycloaddition of 1 with isoquinoline was achieved to obtain 3 . The production of 4, 5, 6 given by cycloaddition of 1 with pyridazine was de pendent on the reaction condition. Some heterocyclic compounds bearing an X‐C=N (X:S, N) group on the ring can react with 1 to gain the derivatives of 2,4‐dihydro‐1,2,4‐triazol‐3‐one. 7, 8, 9 and 10 were given by reaction of 1 with 1,3,5‐triazine, 1,4,5,6‐tetrahydropyrimidine, 1,3‐thiazole and 2‐amino‐1,3‐thiazole, respectively. The reactions for 2‐amino‐1,3,4‐thiadiazole and 3‐amino‐1,2,4‐triazole had the same product 11 .     

A novel synthesis of α-hydroxy- and α,α′-dihydroxyketone from α-iodo and α,α′-diiodo ketone using photoirradiation

A novel reaction of α-iodo ketone (α-iodocycloalkanone, α-iodo-β-alkoxy ester, and α-iodoacyclicketone) with irradiation under a high-pressure mercury lamp gave the corresponding α-hydroxyketone in good yields. In the case of α,α′-diiodo ketone, α,α′-dihydroxyketone which little has been reported until now was obtained. This reaction affords a new, clean and convenient synthetic method for α-hydroxy- and α,α′-dihydroxyketone.