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Original endocyclic enamides based on a bicyclic aza‐diketopiperazine (aza‐DKP) structure have been used as dienophile partners in the Povarov reaction. The reported method represents a successful strategy for the structural diversification of the aza‐DKP scaffold, giving access to a new family of fused tetracyclic N‐heterocycles, which contain at least four nitrogen atoms in the heterocyclic structure. Depending on the nature of the aldehyde partner, the cycloadditions have been performed either as a two‐component or a three‐component Povarov reaction (2CPR or 3CPR), in the presence of BF3 as a Lewis acid catalyst. With aliphatic aldehydes the reaction proceeds with high diastereoselectivities in favor of the cis compounds. Some mechanistic aspects of this cycloaddition have been examined computationally. [ABSTRACT FROM AUTHOR]

Despite their apparent similarities, vinyl (thio)ethers and enamines display divergent reactivities toward nitroalkenes. Whereas [4+2] cycloadduct derivatives are generally obtained in the first case, a variety of adducts are observed in the second, and depend on the substrates and reaction conditions. Herein, a rationalization of this versatility is proposed through a theoretical study, in which the interactions between these electron-rich alkenes and nitroethylene are compared in conjugate addition, [4+2] and [2+2] cycloadditions, and ene reaction processes. The conjugate zwitterionic adduct is shown to play a key role. With vinyl (thio)ethers, its formation is disfavored, whereas, for enamines, it appears as a stabilized intermediate, leading to the thermodynamically favored formal ene adduct. This adduct is, however, kinetically disfavored, which opens up the way to control the selectivity of the whole process. [ABSTRACT FROM AUTHOR]

The chemo-, regio-, and stereoselectivities of multicomponent [4 + 2]/[3 + 2] domino cycloaddition reactions involving nitroindole derivatives with vinylethers and acrylates are studied computationnally and compared to experimental results. In this process, the nitroarene first reacts as an electron-deficient heterodiene with the electron-rich alkene following an inverse electron-demand [4 + 2] process, leading to a nitronate intermediate in a fully selective way. This intermediate exclusively interacts, in a second step, with the electron-deficient alkene and undergoes a chemo- and regioselective [3 + 2] cycloaddition. The density functional theory calculations reported in this Article fully account for the selectivities observed experimentally. Electronic displacements along the reaction path are examined using a topological analysis of the electron-localization function (ELF). The first [4 + 2] reaction follows a classical concerted, although asynchronous process, which is reliably described by the frontier molecular-orbital (FMO) model. In contrast, the electronic displacements observed during the second [3 + 2] step are unexpected, involving an electron donation by the electron-deficient reaction partner. [ABSTRACT FROM AUTHOR]

Abstract: Asymmetric thia-Diels–Alder reactions involving new dithioesters bearing a chiral auxiliary are described, with diastereoselectivities up to 78%. Double-stereodifferentiating experiments employing chiral substrates in the presence of a chiral Lewis acid catalyst have been also carried out and, in this case, a diastereomeric excess of 90% was reached. The absolute stereochemistry of cycloadducts resulting from dithiooxalates and carbonyloxazolidinone dithioesters was assigned based on an X-ray structure and chemical correlation. In order to rationalize the sense of the chiral induction, stereochemical models for Cu(II)/bis(oxazoline)/dithioester complexes are proposed. [Copyright &y& Elsevier]

Abstract: The first example of a catalytic asymmetric thia hetero-Diels–Alder reaction, in which a chiral Lewis acid activates the thiocarbonyl dienophile, is described. The reactions catalyzed by copper(II)-bis(oxazolines) complexes of three dithioesters with simple dienes (such as cyclopentadiene or 2,3-dimethyl-1,3-butadiene) afford optically active dihydrothiopyrans with ees up to 82%. Some aspects of the reaction were investigated by computational means. [ABSTRACT FROM AUTHOR]

Abstract: We report results regarding the development of condensations of chiral β-alkoxycarbonylallylboronates on aldehydes and imines. These allylboronates add in a highly enantioselective and diastereospecific manner to afford biologically and synthetically useful chiral α-methylene-γ-butyrolactones and lactams. The nature of the electrophile (aldehyde vs imine) is shown to have a dramatic influence on the mechanism of the reaction, probably directing the stereoselectivity of the process through different transition states. [Copyright &y& Elsevier]

Abstract: Activation by Lewis acid catalysis and high pressure allows pyrrole derivatives to react with electron-rich dienes in normal electron demand [4+2] cycloadditions, provided that the aromatic ring is substituted by at least two electron-withdrawing groups. The dienophilic behavior of the heterocycle is expressed through the involvement of either the aromatic carbon–carbon double bond in an all-carbon process or the carbonyl moiety of the substituent in a heterocycloaddition reaction. In this regard, the nature of the heterocyclic substituents is shown to have a dramatic influence and to direct both the reactivity and the chemoselectivity of the cycloaddition. [Copyright &y& Elsevier]

Diels–Alder cycloaddition reactions have been studied on substituted (Z)-1-benzylidene-2-methylene cyclohexanes 3. The use of very reactive dienophiles allowed the formation of the expected polycyclic structures whereas hyperbaric conditions (16 kbar) were necessary to form the adducts with less reactive dienophiles. An exo stereoselectivity was observed during the reaction with acrylates. [Copyright &y& Elsevier]

The reaction between indole-3-carboxaldehyde 1a or indole-3-glyoxalate 1b and 2,3-dimethylbutadiene under thermal activation leads exclusively to the Diels-Alder cycloadducts resulting from the participation of the indole 2,3-carbon-carbon double bond. The concomitant use of zinc chloride and high pressure (16 kbar) induces the primary cycloadduct to react further, and biscycloadducts 11 and 12 are now isolated in high yields, the result of two consecutive [4 + 2] processes on, first, the indole 2,3 C=C bond and, second, the 3-carbonyl unit. The possibility of using two different dienes in a tandem, sequential process is demonstrated by the preparation of tetracycle 13. Interactions between the carbonyl dienophile and Danishefsky diene yield exclusively yet another type of product, namely the γ-dihydropyranones arising from the sequential [4 + 2] heterocycloaddition, hydrolysis of the silyl enol ether, and loss of methanol. Isolation of the Mukaiyama-type adduct 16 indicates that a stepwise mechanism may be involved, at least under zinc chloride catalysis. N,N-Disubstituted indole-3-glyoxamides undergo the expected, usual Diels-Alder process, with the 2,3 C=C bond acting as dienophile, and cycloadducts of the type 3 are obtained in high yields, regardless of the mode of activation. Remarkably, however, N-monosubstituted indole-3glyoxamides react almost exclusively as heterodienophiles, the 3-carbonyl unit being now the preferred site of reactivity, and γ-dihydropyranones of the type 6 are isolated in yields ranging from 72 to 92%. Conformational analysis of the Diels-Alder adducts based on both ¹H NMR spectrometry and X-ray diffraction data indicates that the newly created cyclohexene and cyclohexanone rings adopt a pseudoboat conformation. [ABSTRACT FROM AUTHOR]

Dearomative Diels‐Alder cycloadditions between nitroarenes and 2‐trimethylsilyloxycyclohexadiene are carried out under high pressure at room temperature in the absence of any chemical promoter. Reactions are performed with different arenes, including the highly aromatic naphthalenes and quinolines. They lead to 3D‐scaffolds with exquisite exo‐diastereoselectivity. The exo approach is characterized by lower distortion of the substrates in a late TS and by more favorable orbital interactions presumably between the nitro group and the dienic part, explaining the stereoselectivity. [ABSTRACT FROM AUTHOR]

Many natural products of plant or microbial origins are derived from enzymatic dearomative oxygenation of 2‐alkylphenolic precursors into 6‐alkyl‐6‐hydroxycyclohexa‐2,4‐dienones. These so‐called ortho‐quinols cyclodimerize via a remarkably selective bispericyclic Diels–Alder reaction. Whether or not the intervention of catalytic or dirigent proteins is involved during this final step of the biosynthesis of these natural products, this cyclodimerization of ortho‐quinols can be chemically reproduced in the laboratory with the same strict level of site‐specific regioselectivity and stereoselectivity. This unique yet unified process, which finds its rationale in the inherent chemical reactivity of those ortho‐quinols, is illustrated herein by an efficient and bioinspired first chemical synthesis of one of the most structurally complex and synthetically challenging examples of such natural cyclodimers, the bisditerpenoid (+)‐maytenone. [ABSTRACT FROM AUTHOR]

Many natural products of plant or microbial origins are derived from enzymatic dearomative oxygenation of 2‐alkylphenolic precursors into 6‐alkyl‐6‐hydroxycyclohexa‐2,4‐dienones. These so‐called ortho‐quinols cyclodimerize via a remarkably selective bispericyclic Diels–Alder reaction. Whether or not the intervention of catalytic or dirigent proteins is involved during this final step of the biosynthesis of these natural products, this cyclodimerization of ortho‐quinols can be chemically reproduced in the laboratory with the same strict level of site‐specific regioselectivity and stereoselectivity. This unique yet unified process, which finds its rationale in the inherent chemical reactivity of those ortho‐quinols, is illustrated herein by an efficient and bioinspired first chemical synthesis of one of the most structurally complex and synthetically challenging examples of such natural cyclodimers, the bisditerpenoid (+)‐maytenone. [ABSTRACT FROM AUTHOR]

The photocatalyzed dearomative reaction between various electron‐deficient aromatic compounds and a non‐stabilized azomethine ylide is successfully performed in a flow system. Whereas the use of supported eosin as organic photocatalyst exhibits limited efficiency, turning to the soluble Rose Bengal allows to transform a broad range of substrates from hetarenes (indole, benzofuran, quinoline, pyridine) to naphthalenes and benzenes. This photocatalyzed (3+2) dearomative cycloaddition under green light irradiation provides a simple and efficient access to tridimensional pyrrolidino scaffolds with a tetrasubstituted carbon center at ring junction and can be performed in the friendly ethyl acetate. Computational studies support the mechanism involving azomethine ylide as reactive species toward the electron‐poor arene. [ABSTRACT FROM AUTHOR]

The absorption and emission properties of a series of 44 aromatic molecules have been investigated in Time Dependent Density Functional Theory (TDDFT) using different exchange‐correlation functionals. Solvent effects have been included within linear response (LR) and state specific (SS) polarisable continuum model (PCM). The comparison with experimental UV‐Vis data showed reasonable agreement for all the aromatic molecules when ωB97XD with SS‐PCM is used. In particular, we found an accurate linear correlation between experimental and theoretical results which is revealed in an equation for absorption and another equation for emission derived from a linear fitting between theoretical and experimental data. Through these linear equations we propose a simple, pragmatic and effective approach able to describe and predict the absorption and the emission of aromatic molecules with a reasonable computational cost. [ABSTRACT FROM AUTHOR]

An efficient domino polycyclization combining different classes of pericyclic reactions leads to complex spiroxindoles under mild conditions. This domino process represents a rare example of an in situ formation of cyclopentadienol derivatives from an interrupted iso-Nazarov electrocyclization of 2,4-dienals and their use in [4 + 2] cycloaddition reactions. According to the reaction conditions, different polycyclic architectures are obtained in good yields and excellent diastereoselectivities. [ABSTRACT FROM AUTHOR]

Review: 207 refs. [ABSTRACT FROM AUTHOR]

An efficient domino reaction combining different classes of pericyclic reactions leads to chiral complex polycyclic indoline-based architectures from achiral starting materials under mild conditions. This practical method is based on the ability of iron(III) chloride to promote both 4π electrocyclizations of 2,4-dienals and the C2-C3 umpolung of N-acetylindoles during the dearomative (3 + 2) cycloadditions. [ABSTRACT FROM AUTHOR]

Simple nitroarenes such as nitronaphthalenes and nitroquinolines smoothly undergo dearomatizing [4+2] cycloadditions with silyloxydienes under 16 kbar. Highly functionalized 3-dimensional polycyclic adducts bearing a tetrasubstituted carbon centre at the ring junction are obtained in one step from simple raw materials. This unprecedented dearomative Diels–Alder process is performed at room temperature without any chemical promoter, illustrating the exceptional role of high pressure as a physical promoter. [ABSTRACT FROM AUTHOR]

Indoles, benzofurans and benzothiophenes substituted by a cyano group at positions 2 or 3 are shown to behave differently toward azomethine ylide 1,3‐dipole 1, in (3+2) cycloadditions. While the C2=C3 aromatic double bond of 3‐cyanoheteroarene reacts as dipolarophile to generate the corresponding dearomatized cycloadducts, the C≡N bond of 2‐cyanobenzofuran reveals more reactive and imidazoline are obtained in this case. 2‐Cyanoindole substituted by an electron‐withdrawing triflyl group on the nitrogen atom allows the formation of the bis‐cycloadduct where the C=C and C≡N moieties both reacted. The C≡N vs C=C reactivity is nicely supported by DFT computations. [ABSTRACT FROM AUTHOR]

The unique combination of hexafluoroisopropanol (HFIP) employed as solvent and hyperbaric conditions (10–15 kbar) allows unprecedented 1,4-addition of poor nucleophiles, such as aromatic amines, onto sluggish (cumbersome) Michael acceptors without any promoter or workup. [ABSTRACT FROM AUTHOR]

Indoles substituted by electron-depleted thio groups at positions 1 and 3 react as C2 = C3 dipolarophiles with an electron-rich azomethine ylide dipole under flow conditions. The dearomatizing (3 + 2) cycloadditions readily occur to afford the corresponding fluorinated 3D-pyrrolidinoindolines bearing a tetrasusbtituted carbon centre at the ring junction. [ABSTRACT FROM AUTHOR]

We have developed two efficient thiourea promoted dearomatizing processes involving the cycloadditions of 3-nitroindoles. The C2 C3 double bond of the heteroarene can be involved as electron-poor 2π dienophile in [4+2] cycloadditions. While the uncatalyzed process requires harsh conditions, the organocatalyzed reaction takes place at room temperature and atmospheric pressure. The C2 C3 N O motif of the heteroarene can also react as an electron-poor 4π heterodiene in [4+2] / [3+2] cycloadditions cascades, under high pressure. In contrast to Lewis acid activation, thiourea promotion thus proves efficient even under unconventional activation conditions and in the presence of acid sensitive reactants such as enol ethers. [ABSTRACT FROM AUTHOR]

Dearomatization of electron-poor benzofurans is possible through involvement of the aromatic 2,3-carbon-carbon double bond as dienophile in normal electron demand [4 + 21 cycloadditions. The tricyclic heterocycles thereby produced bear a quaternary center at the cis ring junction, a feature of many alkaloids such as morphine, galanthamine, or lunaridine. The products arising from the reaction have been shown to depend on different factors among. which the type of the electron-withdrawing substituent of the benzofuran, the nature of the reacting diene, and the method of activation. In the presence of all-carbon dienes, the reaction yields the expected Diels-Alder adducts. When thermal activation is insufficient, a biactivation associating zinc chloride catalysis and high pressure is required to generate the cycloadducts in good yields and high stereoselectivities, for instance, when cyclohexadiene is involved in the process. The use of more functionalized dienes, such as those bearing alkoxy or silyloxy substituents, also shows the limits of the thermal activation, and hyperbaric conditions are, in this case, well-suited. The involvement of Danishefsky's diene induces a competition in the site of reactivity. The aromatic 2,3-carbon-carbon double bond is unambiguously the most reactive dienophile, and the 3-carbonyl unit becomes a competitive site of reactivity with benzofurans bearing substituents prone to heterocyloaddition, in particular under Lewis acid activation. The sequential involvment of both the aromatic double bond and the carbonyl moiety as dienophiles is then possible by using an excess of diene under high-pressure activation. In line with the experimental results, DFT computations suggest that the Diels-Alder process involving the aromatic double bond is preferred over the hetero-Diels-Alder route through an asynchronous concerted transition state. However, Lewis acid catalysis appears to favor the heterocycloaddition pathway through a stepwise mechanism in some cases. [ABSTRACT FROM AUTHOR]

Electron-poor 6-oxo-1-sulfonyl-1,6-dihydropyridine-3-carboxylates 1b-d undergo cross-Diels-Alder reactions with electron-rich dienes 4a-f under hyperbaric conditions, reacting either as dienophiles to yield normal-electron-demand (NED) cycloadducts 10 and/or 11 or as dienes to give inverse-electron-demand (TED) cycloadducts 12 and/or 13. The latter are converted into 14 and/or 15 through an NED cycloaddition with a second equivalent of electron-rich diene. Acyclic dienes display a propensity to yield NED products, whereas cyclic dienes tend to favor lED cycloadducts. High-pressure activation compares favorably with thermal or microwave activation in terms of both yields and suppression of the transformation of 1 into unreactive pyridines 3. Whereas the Cope rearrangement from lED to NED occurs under thermal conditions, no evidence of its involvement under high pressure could be detected. These and other data point to similar activation energies for the NED and TED processes under these conditions. [ABSTRACT FROM AUTHOR]

The electrophilicity of 4 different 3-nitroindole derivatives has been evaluated by Mayr's linear free energy relationship (log k(20 °C) = sN(E + N)) and reveals unexpected values for aromatic compounds, in the nitrostyrene range. 3-Nitroindoles are sufficiently electrophilic to interact with a common diene namely the Danishefsky's diene at room temperature, in the absence of any activator, to furnish smoothly the dearomatized (4+2) cycloadducts in good yields. [ABSTRACT FROM AUTHOR]

Under high pressure, this transition state leads to the product, the natural (+)-maytenone, which was first isolated from the plant I Maytenus dispermus i , here appearing in the background image. Asymmetric synthesis, cycloaddition, hypervalent compounds, total synthesis, transition states Keywords: asymmetric synthesis; cycloaddition; hypervalent compounds; total synthesis; transition states EN asymmetric synthesis cycloaddition hypervalent compounds total synthesis transition states 15111 15111 1 06/23/21 20210625 NES 210625 B From the teaching class b with the bispericyclic Diels-Alder reaction of I ortho i -quinols drawn on the chalk board to the laboratory with the (+)-ferruginol substrate and a chiral bisiodyl reagent in the flask: The single I ortho i -quinol diastereomer thus produced combines in pairs to reach a I C i SB 2 sb -symmetric transition state in which [4+2] and [2+4] processes are equivalent, as described by Laurent Pouységu, Stéphane Quideau, and co-workers in their Research Article on page 14967. [Extracted from the article]

Keywords: asymmetric synthesis; cycloaddition; hypervalent compounds; total synthesis; transition states EN asymmetric synthesis cycloaddition hypervalent compounds total synthesis transition states 15239 15239 1 06/23/21 20210625 NES 210625 B Von der Kreidetafel b mit der bispericyclischen Diels-Alder-Reaktion von I ortho i -Chinolen zum Labor mit dem (+)-Ferruginol-Substrat und einem chiralen Bisiodyl-Reagenz im Kolben: Die so erzeugten I ortho- i Chinol-Diastereomere verbinden sich paarweise zu einem C SB 2 sb -symmetrischen Übergangszustand, in dem [4+2]- und [2+4]-Prozesse äquivalent sind, wie Laurent Pouységu, Stéphane Quideau et al. im Forschungsartikel auf S. 15094 berichten. Innenrücktitelbild: Bispericyclic Diels-Alder Dimerization of ortho-Quinols in Natural Product (Bio)Synthesis: Bioinspired Chemical 6-Step Synthesis of (+)-Maytenone (Angew. Asymmetric synthesis, cycloaddition, hypervalent compounds, total synthesis, transition states. [Extracted from the article]

The oxidative neutralisation of sulfur-containing CWAs (yperite and VX simulants) with Oxone has been developed in flow systems. In order to reach full selectivity towards harmless decomposition products, Oxone has to be used either in solid form (blister agent detoxification) or aqueous form (nerve agent detoxification). [ABSTRACT FROM AUTHOR]

We report an efficient 1,3‐dipolar cycloaddition involving non‐stabilized electron‐rich azomethine ylides and diversely substituted 2‐pyridones bearing two potential C=C dipolarophilic sites. The 1,3‐dipoles were prepared in situ under TFA catalysis and cycloadditions were studied according to the nature of the pyridones and position of the various substituents. These reactions occur under mild conditions, and lead to the expected cycloadducts in good yields and full control of the regioselectivity. Furthermore, mono‐ or biscycloadditions were performed, leading to the formation of polycyclic scaffolds bearing biologically relevant pyrrolidine rings, prevalent in natural products. The diastereoselectivity of the second cycloaddition was fully controlled by the first addition, leading to heterocycles with a trans relative stereochemistry of the two generated rings in the final tricyclo‐adduct. [ABSTRACT FROM AUTHOR]

The indol(in)e building block is one of the "privileged-structures" for the pharmaceutical industry since this fragment plays a central role in drug discovery. While the electron-rich character of the indole motif has been investigated for decades, exploiting the electrophilic reactivity of 3-nitroindole derivatives has recently been put at the heart of a wide range of new, albeit challenging, chemical reactions. In particular, dearomatization processes have considerably enriched the scope of C2＝C3 functionalizations of these scaffolds. This feature article showcases this remarkable electrophilic reactivity of 3-nitroindoles with electron-rich species and highlights their value in generating diversely substituted indol(in)es. This compilation underlines how these heteroaromatic templates have gradually become model substrates for electron-poor aromatic compounds in dearomatization strategies. [ABSTRACT FROM AUTHOR]

Herein, we introduce one of the first examples of asymmetric organocatalyzed synthesis of 1,2-dihydropyridines, affording enantioselective access to and partially solving regioselectivity challenges in the synthesis of dihydropyridines. We demonstrate that through modification of organocatalysts both 1,2- and 1,4-dihydropyridines (1,2- and 1,4-DHPs) can be obtained with high regioselectivity (ratio of 1,2-DHP/1,4-DHP from 95/5 to 0/100) and enantioselectivity (33% ee for 1,2-DHPs and up to 98% ee for 1,4-DHPs) in good yields (up to 87%). [ABSTRACT FROM AUTHOR]

High pressure effects on the Diels–Alder reaction in condensed phase are investigated by means of theoretical methods, employing advanced multiscale modeling approaches based on physically grounded models. The simulations reveal how the increase of pressure from 1 to 10 000 atm (10 katm) does not affect the stability of the reaction products, modifying the kinetics of the process by lowering considerably the transition state energy. The reaction profile at high pressure remarkably differs from that at 1 atm, showing a submerged TS and a pre-TS structure lower in energy. The different solvation between endo and exo pre-TS is revealed as the driving force pushing the reaction toward a much higher preference for the endo product at high pressure. [ABSTRACT FROM AUTHOR]

The generation and reactivity of two model vinyl carbenoids from gem-dibromoalkenes 1 were studied in microflow systems. From substrate 1a (R = Ph, CF3), the lithium-bromine exchange could be simply performed within 30 ms at 20 °C with very good E-selectivity whereas the reaction was unselective under batch conditions, even at −78 °C. Moreover, the unstable carbenoid generated from 1b (R = Ph, H) could be trapped as the major product while only the Fritsch-Buttemberg-Wiechell rearrangement product was obtained in a flask under cryogenic conditions. [ABSTRACT FROM AUTHOR]

3‐Nitroindoles are easily reacted with highly substituted γ‐allenoates in the presence of a commercially available phosphine catalyst. For instance, allenoates derived from biomolecules such as amino and deoxycholic acids are combined for the first time with 3‐nitroindole. The corresponding dearomatized (3+2) tricyclic cycloadducts are obtained as α‐regioisomers exclusively. DFT computations shed light on this multi‐step reaction mechanism and on the selectivities observed in the sequence. [ABSTRACT FROM AUTHOR]

We report an unprecedented domino polycyclization from readily available 2,4‐dienals and cyclic α,β‐unsaturated imines that is initiated by an iso‐Nazarov reaction. This Brønsted acid promoted reaction enables the concomitant formation of four bonds, three cycles, and four contiguous stereogenic centers to yield elaborated structures in a single operation. A range of fused hexacyclic molecules is obtained in a highly diastereoselective manner. [ABSTRACT FROM AUTHOR]

We report an unprecedented domino polycyclization from readily available 2,4‐dienals and cyclic α,β‐unsaturated imines that is initiated by an iso‐Nazarov reaction. This Brønsted acid promoted reaction enables the concomitant formation of four bonds, three cycles, and four contiguous stereogenic centers to yield elaborated structures in a single operation. A range of fused hexacyclic molecules is obtained in a highly diastereoselective manner. [ABSTRACT FROM AUTHOR]

The dearomatization of conventional nitroarenes by lithiated enolates derived from methyl vinyl ketones easily takes place, following a formal (4+2) cycloaddition process. While nitroindoles react readily with in situ generated conjugated enolates, the deaggregation of these latter species using HMPA extends the reaction scope to the more aromatic nitronaphthalenes and pyridines. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Efficient and novel access to functionalized 4-aryl-imidazolines and – imidazoles. • Development of a (3 + 2) heterocycloaddition involving cyanobenzenes and a non-stabilized azomethine ylide. • Proposed mechanistic pathway involving a concerted slightly asynchronous heterocycloaddition. Abstract An efficient access to 4-aryl imidazole scaffolds is described in two steps and one operation. Cyanoaryl-imidazolines are easily obtained by a (3 + 2) heterocyloaddition involving cyanobenzenes as dipolarophiles and a non-stabilized azomethine ylide as an electron-rich 1,3-dipole. Oxidation of the crude mixture affords an efficient two-steps access to the corresponding imidazoles. [ABSTRACT FROM AUTHOR]

An unexpected reaction sequence occurs when simple nitroarenes and the readily available enamine 4‐(cyclohex‐1‐en‐1‐yl)morpholine are placed under high pressure. This one‐pot transformation leads to the generation of highly substituted compounds and presents different advantages such as (1) a rapid increase of molecular complexity through converting simple, cheap, and seldom exploited starting materials into polycyclic structures never described before, (2) the absence of chemical catalysts, (3) a very low energy input. [ABSTRACT FROM AUTHOR]

The stereocontrolled synthesis of unprecedented sulfur-containing exo-bicyclic 1,3-dienes is reported through a palladium-catalyzed reductive cyclization of sulfur-linked 2-bromoneynes. The fused bicyclic structure provides a better stability to the thiacyclic diene compared to the simple 3,4-dimethylenetetrahydrothiophene. Their reactivity toward several dienophiles has been investigated, and various original thiacycle-fused polycyclic systems have been obtained with high or total diastereoselectivity. Moreover, they are the first exo-bicyclic dienes used in Diels-Alder reactions. The relative configurations of four cycloadducts have been unambiguously assigned by X-ray crystallographic analysis. Mechanistic details of the cycloadditions have been examined by computational means. [ABSTRACT FROM AUTHOR]

A method for the deprotonative silylation of aromatic C-H bonds has been developed using trifluoromethyltrimethylsilane (CF3SiMe3, Ruppert-Prakash reagent) and a catalytic amount of fluoride. In this reaction, CF3SiMe3 is considered to act as a base and a silicon electrophile. This process is highly tolerant to various functional groups on heteroarenes and benzenes. Furthermore, this method can be applied to the synthesis of trimethylsilyl group-containing analogs of TAC-101, which is a bioactive synthetic retinoid with selective affinity for retinoic acid receptor α (RAR-α) binding. We also report further transformations of the silylated products into useful derivatives. [ABSTRACT FROM AUTHOR]

The fast and effective neutralization of the mustard-gas simulant 2-chloroethyl ethyl sulfide (CEES) using a simple and portable continuous flow device is reported. Neutralization takes place through a fully selective sulfoxidation by a stable source of hydrogen peroxide (alcoholic solution of urea-H2O2 adduct/MeSO3H freshly prepared). The reaction progress can be monitored with an in-line benchtop NMR spectrometer, allowing a real-time adjustment of reaction conditions. Inherent features of millireactors, that is, perfect control of mixing, heat and reaction time, allowed the neutralization of 25 g of pure CEES within 46 minutes in a 21.5 mL millireactor ( t R=3.9 minutes). This device, which relies on affordable and nontoxic reagents, fits into a suitcase, and can be deployed by police/military forces directly on the attack site. [ABSTRACT FROM AUTHOR]

The fast and effective neutralization of the mustard-gas simulant 2-chloroethyl ethyl sulfide (CEES) using a simple and portable continuous flow device is reported. Neutralization takes place through a fully selective sulfoxidation by a stable source of hydrogen peroxide (alcoholic solution of urea-H2O2 adduct/MeSO3H freshly prepared). The reaction progress can be monitored with an in-line benchtop NMR spectrometer, allowing a real-time adjustment of reaction conditions. Inherent features of millireactors, that is, perfect control of mixing, heat and reaction time, allowed the neutralization of 25 g of pure CEES within 46 minutes in a 21.5 mL millireactor ( t R=3.9 minutes). This device, which relies on affordable and nontoxic reagents, fits into a suitcase, and can be deployed by police/military forces directly on the attack site. [ABSTRACT FROM AUTHOR]

A novel and efficient method for the generation of phosphinoyl radicals from the combination of diphenyliodonium salt (Ph2I+,-OTf) with triethylamine (Et3N) in the presence of secondary phosphine oxides is reported. By employing this practical and simple approach, a large variety of 6-phosphorylated phenanthridines have been synthesized through the addition of phosphinoyl radicals to isonitriles as radical acceptors. The reaction works smoothly in the absence of any transition metal or photocatalyst. On the basis of electron paramagnetic resonance (EPR) and density functional theory (DFT) calculations, the mechanism of this reaction is discussed. [ABSTRACT FROM AUTHOR]

The combination of hexafluoroisopropanol as solvent and high-pressure conditions enables the unprecedented 1,4-addition of poor nucleophiles like aromatic amines onto sluggish Michael acceptors without a promoter or work-up. [ABSTRACT FROM AUTHOR]

Enantiomerization of allylic trifluoromethyl sulfoxides occurs spontaneously at room temperature through the corresponding allylic trifluoromethanesulfenates via a [2,3]-sigmatropic . Dynamic high-performance (HPLC) analysis revealed the stereodynamics of these sulfoxides ranging from chromatographic resolution to peak coalescence at temperatures between 5 and 53 °C. The rate constant of enantiomerization and activation parameters were determined and compared with Density Functional Theory (DFT) calculations. Chirality 28:136-142, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The first enantioselective total syntheses of two marine sesquiterpenes (1R)-suberosenone and (1R)-suberosanone are achieved leading to revision of the AC of natural (1S)-suberosanone. Key elements of the synthesis include hyperbaric asymmetric Michael addition and highly efficient silver trifluoroacetate mediated α-alkylation for the formation of ring A. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

An unexpected C–C cross-coupling radical oxidation involving aldehydes and glycine enolate equivalents such as activated mesyl-sulfahydantoins leading to β,β′-disubstituted aspartate semialdehydes (ASA) instead of the expected threonine analogues was observed and various α-substituted non-proteinogenic amino acid analogues were synthesized. A radical mechanism was envisaged and supported by DFT calculations. [ABSTRACT FROM AUTHOR]