Total Regioselectivity Research Articles

Fast, Regioselective Aminolysis of Tetrasubstituted Cyclic Carbonates and Application to Recyclable Thermoplastics and Thermosets.

Herein, the long-standing challenge of the ring-opening aminolysis of CO2-derived tetrasubstituted cyclic carbonates at room temperature (r.T) is overcome under catalyst-free conditions. Molecular design of the cyclic carbonate by substitution of an alkyl group by a thioether unlocks quantitative conversion at r.T and ensures total regioselectivity toward highly substituted oxazolidone scaffolds. An in-depth rationalization of the high reactivity of these cyclic carbonate structures and of the aminolysis reaction mechanism is provided by a computational study supporting experimental observations. The high efficiency of the reaction is then translated to the deconstruction of high-performance thermoplastics containing tetrasubstituted cyclic carbonate linkages to deliver building blocks that are reused for designing recyclable thermosets bearing dynamic N,S-acetal linkages.

Metal free regio - and stereoselective semireduction of CF3-substituted N-allenamides.

We developed a chemoselective metal-free access for the 1,2- and 2,3-semireduction of CF3-N-allenamides. The enamide functionality of CF3-substituted N-allenamides could be efficiently reduced by Et3SiH/BF3·OEt2 in total regioselectivity and good stereoselectivity, whereas DBU promoted the isomerization of the resulting allyl amide leading exclusively to the E-configurated enamide.

Enantio‐ and Regioselective Palladium(II)‐Catalyzed Dioxygenation of (Aza‐)Alkenols

AbstractAn oxidative Pd‐catalyzed intra‐intermolecular dioxygenation of (aza‐)alkenols has been reported, with total regioselectivity. To study the stereoselectivity, different chiral ligands as well as different hypervalent‐iodine compounds have been compared. In particular, by using a C‐6 modified pyridinyl‐oxazoline (Pyox) ligand and hypervalent iodine bearing an aromatic ring, an excellent enantio‐ and diastereoselectivity has been achieved.

Enantio- and Regioselective Palladium(II)-Catalyzed Dioxygenation of (Aza-)Alkenols.

An oxidative Pd‐catalyzed intra‐intermolecular dioxygenation of (aza‐)alkenols has been reported, with total regioselectivity. To study the stereoselectivity, different chiral ligands as well as different hypervalent‐iodine compounds have been compared. In particular, by using a C‐6 modified pyridinyl‐oxazoline (Pyox) ligand and hypervalent iodine bearing an aromatic ring, an excellent enantio‐ and diastereoselectivity has been achieved.

Iron(II) and Copper(I) Control the Total Regioselectivity in the Hydrobromination of Alkenes.

A new method that allows the complete control of the regioselectivity of the hydrobromination reaction of alkenes is described. Herein, we report a radical procedure with TMSBr and oxygen as common reagents, where the formation of the anti-Markovnikov product occurs in the presence of parts per million amounts of the Cu(I) species and the formation of the Markovnikov product occurs in the presence of 30 mol % iron(II) bromide. Density functional theory calculations combined with Fukui’s radical susceptibilities support the obtained results.

The catalytic effects of a thiazolium salt in the oxa-Diels-Alder reaction between benzaldehyde and Danishefsky's diene: a molecular electron density theory study.

The oxa-Diels-Alder (ODA) reaction of benzaldehyde with Danishefsky's diene in the presence of a [thiazolium][Cl] salt, as a model of an ionic liquid, has been studied within Molecular Electron Density Theory (MEDT) at the M06-2X/6-311G(d,p) computational level. The formation of two hydrogen bonds (HBs) between the thiazolium cation and the carbonyl oxygen of benzaldehyde modifies neither the electrophilic character of benzaldehyde nor its electronic structure substantially but accelerates the reaction considerably. This ODA reaction presents an activation energy of 4.5 kcal mol-1; the formation of the only observed dihydropyranone is strongly exothermic by -28.8 kcal mol-1. The presence of the [thiazolium][Cl] salt decreases the Gibbs free energy of activation of the ODA reaction between benzaldehyde and Danishefsky's diene by 5.9 kcal mol-1. This ODA reaction presents total para regioselectivity and high endo stereoselectivity. This ODA reaction takes place through a highly asynchronous polar transition state structure (TS) associated with a non-concerted two-stage one-step mechanism. ELF analysis of para/endo TSs associated with the ODA reactions in the absence and presence of the [thiazolium][Cl] salt shows that the formation of the HBs at the TSs does not modify their electronic structure substantially. This MEDT study makes it possible to conclude that the acceleration found in the ODA reaction of benzaldehyde with Danishefsky's diene in ILs is a consequence of an increase of the global electron density transfer at TS3-pn, resulting from HB formation, and the greater strength of the HBs at the polar TS3-pn compared to that at the benzaldehyde : [thiazolium][Cl] complex, and that the strength in the HB formed is more relevant that than an increase of the electrophilic character of the interaction between reagent.

M-Type SrFe12O19 Ferrite: An Efficient Catalyst for the Synthesis of Amino Alcohols under Solvent-Free Conditions

Magnetically separable strontium hexaferrite SrFe12O19 was prepared using the chemical coprecipitation method, and the nanostructured material was characterized by X-ray diffraction, scanning electron microscopy (SEM), energy-dispersive spectrometry (EDS), and BET analysis. The SEM images showed the homogeneity of the chemical composition of SrFe12O19 and uniform distribution of size and morphology. The pore size of the nanomaterial and its specific area were determined by BET measurements. Strontium hexaferrite SrFe12O19 exhibited a strong magnetic field, which is highly suitable in the heterogeneous catalysis as it can be efficiently separated from the reaction. The magnetic nanocatalyst showed high activity and environmentally benign heterogeneous catalysts for the epoxide ring-opening with amines affording β-amino alcohols under solvent-free conditions. When unsymmetrical epoxides were treated in the presence of aromatics amines, the regioselectivity was influenced by the electronic and steric factors. Total regioselectivity was observed for the reactions performed with aliphatic amines. The magnetically SrFe12O19 nanocatalyst showed excellent recyclability with continuously good catalytic activities after four cycles.

Iron(III)‐Catalyzed Hydration of Unactivated Internal Alkynes in Weak Acidic Medium, under Lewis Acid‐Assisted Brønsted Acid Catalysis

AbstractAlkylarylalkynes are converted with full regioselectivity into the corresponding arylketones by formal hydration of the triple bond under weak acidic conditions, at times and temperatures (≤95 °C) comparable to those used for terminal alkynes. The process catalyzed by Fe2(SO4)3nH2O in glacial acetic acid exhibits good functional group compatibility, including that with bulky triple bond substituents, and can be extended to the one‐pot transformation of aryltrimethylsilylacetylenes into acetyl derivatives via a desilylation‐hydration sequence. The overall reactivity pattern along with proton affinity data indicate that the triple bond is activated by proton transfer rather than by π‐interaction with the metal ion. This mechanistic feature, at variance with that of noble metal catalysts, accounts for the total regioselectivity and the insensitivity to steric hindrance exhibited by the Fe2(SO4)3nH2O/AcOH catalytic system.magnified image

Synthesis of Highly Functionalized Allylic Alcohols from Vinyl Oxiranes and N-Tosylhydrazones via a Tsuji-Trost-Like "Palladium-Iodide" Catalyzed Coupling.

An unprecedented efficient palladium(0)-catalyzed reaction of vinyl oxiranes with N-tosylhydrazones, affording "skipped" allylic alcohols in total regioselectivity and stereoselectivity, with excellent functional-group compatibility, is reported. In this Tsuji-Trost-like allylation, we propose the use of N-tosylhydrazones as a synthetic equivalent of α-styryl anions. More than 20 new products are described, including naturally occurring derivatives. A catalytic system involving an iodide (I-) source is necessary to sustain the catalytic cycle.

Two-step enzymatic strategy for the synthesis of a smart phenolic polymer and further immobilization of a β-galactosidase able to catalyze transglycosydation reaction

A rapid and efficient enzymatic procedure for the preparation of an immobilized β-galactosidase has been described. In a first step, soybean peroxidase was used to catalyze the polymerization of a strategically activated phenol (N–Succinimidyl 3–(4–hydroxyphenyl)propionate, known as Bolton-Hunter reagent). The phenolic support was directly employed for immobilizing β–galactosidase from Bacillus circulans (ATCC 31382, β–Gal–3), giving rise to a new biocatalyst subsequently applied in the synthesis of a β–galatodisaccharide (Gal–β(1–3)–GlcNAc and Gal–β(1–3)–GalNAc). The reaction proceeded with high conversion rates and total regioselectivity. Reusability assays were performed with the same reaction conditions finding that the immobilized enzyme retains about 55% of its activity after eight batches. Finally and based on our results, the two-step enzymatic procedure presented here is a good and green alternative to the preparation of carbohydrates with biological activities.

Synthesis of New Annulated Pyrazinothienotriazolopyrimidinones and Triazolylthienopyrazines

New pyrazino[2′,3′:4,5]thieno[2,3-e][1,2,3]triazolo[1,5-a]-pyrimidin-5(4H)-ones were synthesized in an efficient, fast, and mild one-pot procedure from methyl 7-azidothieno[2,3-b]pyrazine-6-carboxylate. From the latter, some triazolothieno[2,3-b]pyrazine-6-carboxylates were also obtained with total regioselectivity by [2+3] cycloaddition with alkynes without any metal catalyst.

Metal-Free Regiodivergent Addition of Carbon Nucleophiles to α,β-Unsaturated Electrophiles.

A mild and metal-free regiodivergent addition of carbon nucleophiles to α,β-unsaturated electrophiles was developed. Total 1,2-regioselectivity was observed in the addition of nitrobenzyl chloride derivative 1 to α,β-unsaturated aldehydes 2 in the presence of TDAE. Moreover, the reaction between p-nitrobenzyl chloride 1a and α,β-unsaturated iminium salts 4 led to the formation of the 1,4-adduct with total regioselectivity.

A Molecular Electron Density Theory Study of [3+2] Cycloaddition Reaction between Azomethine Ylides and Electron‐Deficient Nitroalkenes

AbstractThe [3+2] cycloaddition (32CA) reaction of an azomethine ylide namely (S,E)‐3‐benzylidene‐2‐(tert‐butyl)‐1‐methyl‐5‐oxoimidazolidin‐3‐ium‐4‐ide, AZY6, toward a highly electron‐deficient ethylene derivative namely (E)‐(2‐nitrovinyl)benzene, NVB7, was theoretically studied at the B3LYP/6‐31G(d) computational level. This 32CA reaction takes place with a total regio‐ and stereoselectivity, and with a very low activation enthalpy, 4.2 kcal/mol, as a consequence of high pseudodiradical character of AZY6. Analysis of the conceptual density functional theory (DFT) reactivity indices allows explaining the high reactivity of AZY6 and NVB7, as well as the total regioselectivity experimentally observed. Both analyses of the molecular electrostatic potential (MEP) maps as well as non‐covalent interactions (NCIs) allow explaining the endo stereoselectivity. An electron localization function (ELF) topological analysis of selected points along the most favorable reactive channels allows establishing the non‐concerted two‐stage one‐step molecular mechanism.

Regioselective Synthesis of a Family of β-Lactams Bearing a Triazole Moiety as Potential Apoptosis Inhibitors.

Apoptosis is a biological process important to several human diseases; it is strongly regulated through protein–protein interactions and complex formation. We previously reported the synthesis of apoptosis inhibitors bearing an exocyclic triazole amide isoster by using an Ugi four‐component coupling reaction (Ugi‐4CC), followed by a base‐promoted intramolecular cyclization. Depending on the substitution patterns and the reaction conditions, this cyclization forms the six‐ or four‐membered ring. Two compounds bearing the β‐lactam scaffold turned out to be the most potent inhibitors. This encouraged us to optimize the modulation of the cyclization, and prepare a library of 15 β‐lactams with total regioselectivity. Moreover, we aimed to improve the bioavailability of these compounds through the introduction of diversity at different substitution positions. The activity of these compounds as apoptosis inhibitors in cellular extracts has been evaluated, showing an increase in their potency.

ChemInform Abstract: Recent Advances on Asymmetric Nitroso Aldol Reaction

AbstractReview: [91 refs.

New access to 4-aryl[2,2]paracyclophanes by high-pressure Diels–Alder reaction

The first synthesis of novel 4-aryl[2,2]paracyclophanes based on the Diels–Alder reaction of 4-carbomethoxyethynyl[2,2]paracyclophane as the dienophile with methyl-1,3-butadienes is described. Activation of the Diels–Alder reactions by high-pressure (8kbar) in combination with the Lewis acid EtAlCl2 allows to obtain in good yield and total regioselectivity the cyclohexadienyl-paracyclophane cycloadducts that are converted to the corresponding aryl-paracyclophanes by DDQ oxidation.

Recent Advances on Asymmetric Nitroso Aldol Reaction

The reaction of aromatic nitroso derivatives with enolizable carbonyl compounds (nitroso aldol reaction) to give either α-hydroxyamino or α-aminoxy carbonyl compounds is an important synthetic method. This review illustrates the recent advances in rendering the process regio- and enantioselective as well as catalytic. By employing metal and organic catalysts a range of α-amino (α-oxyamination) and α-hydroxy (α-aminoxylation) carbonyl derivatives can be generated with total regioselectivity and high levels of enantiomeric excess. 1 Introduction 2 Metal-Catalyzed Reactions 3 Organocatalyzed Reactions 4 Enamine Metal-Free Reactions 5 Concluding Remarks

A DFT study of the mechanism of Brønsted acid catalysed Povarov reactions

The molecular mechanism of the Brønsted acid (BA) catalysed Povarov reaction of N-phenyl-C-methoxycarbonyl imine with a methylenecyclopropane (MCP) has been investigated using DFT methods at the MPWB1K/6-31G(d) level. This BA catalysed Povarov reaction is a domino process initialised by the formation of a cationic intermediate which experiences a quick intramolecular Friedel–Crafts reaction yielding the final tetrahydroquinoline. Protonation of the imine nitrogen atom notably increases the electrophilicity of the corresponding species, accelerating the reaction through ionic processes. Analysis of the Parr functions in the initial nucleophilic attack of MCP to the protonated imine allows explaining the total regioselectivity experimentally observed. An electron localisation function quantum topological analysis of the bonding changes along the BA catalysed Povarov reaction permits a complete characterisation of the molecular mechanism.

Regioselective Synthesis of α-Perfluoroalkylated Ketals via Double Michael Addition of Alcohols to Activated Alkynes

An efficient method was developed for the synthesis of alkyl 3,3-dialkoxy-3-(perfluoroalkyl)propanoates from ethyl 3-(perfluoroalkyl)propynoates and alcohols using a base-catalyzed double Michael addition reaction (which was accompanied by transesterification in the case of MeOH, EtOH, PrOH, and BuOH). This method provides easy access to the product α-perfluoroalkyl ketals with reasonable to good yields with total regioselectivity. This procedure does not require the use of expensive supplementary additives for the preparation of α-perfluoroalkyl ketals which are very sensitive to acidic conditions.

ChemInform Abstract: Olefins as Unprecedented Feedstock for the Synthesis of Valuable Heterocycles: Regioselectivity Remains an Issue

AbstractReview: 8 refs.