Reaction Of Nitrones Research Articles

Synthesis of 1,2,5‐Oxadiazinane Derivatives by Photochemical Cycloaddition of Nitrones with Diaminomethanes

Abstract1,2,5‐Oxadiazinanes have a unique heterocyclic skeleton and are expected to be applicable to the synthesis of drugs. However, there have been few reported methodologies to synthesize these structures. We report a facile synthesis of 1,2,5‐oxadiazinanes that is accomplished by the unprecedented photochemical cycloaddition reaction of nitrones with diaminomethanes. The photoreaction is a formal [3+3] cycloaddition, where a nitrone and a diaminomethane act as the 1,3‐dipole and the 1,3‐synthon, respectively. The reaction is significantly accelerated with benzophenone as a photosensitizer. A high degree of diastereoselective addition (d.r. >99 : 1) is observed in the reaction of (Z)‐N‐benzyl‐1‐phenylmethanimine oxide with di(pyrrolidin‐1‐yl)methane.

Metal free synthesis of 1‐azaspiro[4.4]nonane‐3‐one system via reactions of nitrones with 1,1‐disubstituted allenes

AbstractIn the cycloaddition reaction between fluorenone N‐aryl nitrones and 1,1‐disubstituted allenes, the initially formed cycloadduct underwent facile [1,3] shift to give 1′‐phenylspiro[fluorene‐9,2′‐pyrrolidin]‐4′‐ones. Although 1′‐phenylspiro[fluorene‐9,2′‐pyrrolidin]‐4′‐ones are stable in solid state, a few of them underwent facile aerial oxidation in solution to give the corresponding 1′‐phenylspiro[fluorene‐9,2′‐pyrrolidine]‐4′,5′‐diones in excellent overall yields.

Enantioselective 1,3-Dipolar Cycloaddition Reaction of Nitrones with α-(Acyloxy)acroleins Catalyzed by Dipeptide-Derived Chiral Tri- or Diammonium Salts

Organoammonium salts of dipeptide-derived chiral triamines or diamines with TfOH catalyzed the enantioselective 1,3-dipolar cycloaddition reactions of α-acyloxyacroleins with nitrones to give the corresponding adducts in good yields (up to 96%) and with high diastereo- and enantioselectivities (up to 89% ee). Although α-(p-methoxybenzoyloxy)acrolein is rather unstable under the reaction conditions, α-(3-pyrroline-1-carbonyloxy)acrolein is stable enough to be smoothly converted into the corresponding adducts with the aid of the chiral organoammonium salt catalysts.

Tandem Chiral Cu(II) Phosphate‐Catalyzed Deoxygenation of Nitrones/Enantioselective Povarov Reaction with Enecarbamates

A new catalytic enantioselective tandem deoxygenation/aza‐Diels‐Alder reaction of nitrones with enecarbamates was serendipitously discovered in the presence of chiral copper(II) diphosphate complexes. This process affords a wide range of 4‐aminotetrahydroquinolines in respectable yields under mild conditions with good to excellent ee values.

Catalytic Diastereo- and Enantioselective Synthesis of 2-Imidazolinones.

Chiral cyclic ureas (2-imidazolinones) were prepared by the reaction of nitrones and isocyanoacetate esters using a multicatalytic system that combines a bifunctional Brønsted base-squaramide organocatalyst and Ag+ as a Lewis acid. The reaction could be achieved with a range of nitrones derived from aryl- and cycloalkylaldehydes with moderate diastereo- and good enantioselectivity. A plausible mechanism involving an initial formal [3 + 3] cycloaddition of the nitrone and isocyanoacetate ester, followed by rearrangement to an aminoisocyanate and cyclization to the imidazolinone, is proposed.

Preparation and Charactrisation of 1,3-dipolar cycloaddition of nitrones with 4-amino antipyrene

Some nitrones (1-5), derived from N–phenyl hydroxylamine with substituted benzaldehyde such as (3-chlorobenzaldehyde, 4-chlorobenzaldehyde, 3-nitrobenzaldehyde, 4-florobenzaldehyde, 2-nitrobenzaldehyde). In subsequent 1,3-dipolar cycloaddition reactions of nitrones with 4-amino antipyrene give isoxazolidines (6-10), They have been identified by 1HNMR, 13CNMR, IR and Mass spectra

Reductive Bromodifluoromethylation of Nitrones Promoted by Visible Light

A method for the synthesis of bromodifluoromethyl‐substituted hydroxylamines via reaction of nitrones with dibromodifluoromethane is described. The reaction is mediated by an iridium photocatalyst activated by blue light and employs ascorbic acid as a reductant. In the products, the bromodifluoromethyl fragment can be reduced to the CHF2‐group or can be functionalized through the hydrofluoroalkylation process.

Photoredox Catalysis for the Coupling Reaction of Nitrones with Aromatic Tertiary Amines

Photoredox Catalysis for the Coupling Reaction of Nitrones with Aromatic Tertiary Amines

Concerted Albeit Not Pericyclic Cycloadditions: Understanding the Mechanism of the (4+3) Cycloaddition between Nitrones and 1,2‐Diaza‐1,3‐dienes

The mechanism of (4+3) cycloaddition reactions of nitrones with 1,2‐diaza‐1,3‐dienes has been studied by using density functional theory (DFT) methods. The cycloaddition reaction takes place through an asynchronous concerted transition state that reflects a two‐stage process in which the formation of the first bond occurs close to the transition state, while the second bond forms well after the transition state. The alternative stepwise mechanism is higher in energy than the concerted process. In this mechanism, the nitrone oxygen acts as a nucleophile by attacking the more electrophilic terminal carbon of the 1,2‐diaza‐1,3‐diene to form an intermediate. The second step of the reaction is the rate‐limiting one, which is higher in energy than that observed for the concerted process. Topological analysis of the gradient field of electron localization function (ELF) provides a complete characterization of the electron density changes during the course of the reaction.

Visible Light Promoted 2‐Bromotetrafluoroethylation of Nitrones

AbstractA reaction of nitrones with 1,2‐dibromotetrafluoroethane affording bromodifluoroethyl‐substituted hydroxylamines is described. The process is performed in the presence of a ruthenium photocatalyst and ascorbic acid as a stoichiometric reducing agent and is mediated by blue light irradiation. The fluroalkylation products can undergo chemoselective transformations involving either N−O or C−Br bonds furnishing various tetrafluorinated compounds.magnified image

Copper-Catalyzed Synthesis of Polysubstituted Pyrroles through [3+1+1] Cycloaddition Reaction of Nitrones and Isocyanides.

An efficient, copper-catalyzed [3+1+1] cycloaddition reaction was developed for the expedient synthesis of pharmacologically interesting polysubstituted pyrroles from easily available nitrones and α-acidic isocyanides. The given approach features a new mode of cycloaddition between nitrones and isocyanides with wide substrate scope, good functional group tolerance, and operational simplicity. The operando infrared spectroscopy was used for the characterization of reaction intermediates.

Efficient and mild Strecker-type reaction of nitrones catalyzed by MgI2 etherate

ABSTRACTAn efficient Strecker-type reaction of nitrones with trimethylsilyl cyanide (TMSCN) catalyzed by MgI2 etherate has been achieved in a short time under mild condition. The condensations of aromatic nitrones, heterocyclic nitrones, and aliphatic nitrones with TMSCN are performed in good to excellent yields. Further dehydration of α-cyanohydroxylamine smoothly produced the α-imine nitrile in good yields by hydrolysis with the treatment of 2.0 mol/L HCl in methanol.

Asymmetric [3+3] Cycloaddition for Heterocycle Synthesis

Asymmetric syntheses of six-membered ring heterocycles are important research targets not only in synthetic organic chemistry but also in pharmaceuticals. The [3+3]-cycloaddition methodology is a complementary strategy to [4+2] cycloaddition for the synthesis of heterocyclic compounds. Recent progress in [3+3]-cycloaddition processes provide powerful asymmetric methodologies for the construction of six-membered ring heterocycles with one to three heteroatoms in the ring. In this account, synthetic efforts during the past five years toward the synthesis of enantioenriched six-membered ring heterocycles through asymmetric [3+3] cycloaddition are reported. Asymmetric organocatalysis uses chiral amines, thioureas, phosphoric acids, or NHC catalysis to achieve high enantiocontrol. Transition-metal catalysts used as chiral Lewis acids to activate a dipolar species is an alternative approach. The most recent advance, chiral transition-metal-catalyzed reactions of enoldiazo compounds, has contributed toward the versatile and highly selective synthesis of six-membered heterocyclic compounds.1 Introduction2 Asymmetric Formal [3+3]-Cycloaddition Reactions by Organo­catalysis2.1 By Amino-Catalysis2.2 By N-Heterocyclic Carbenes2.3 By Bifunctional Tertiary Amine-thioureas2.4 By Chiral Phosphoric Acids3 Asymmetric Formal [3+3]-Cycloaddition Reactions by Transition-Metal Catalysis3.1 Copper Catalysis3.2 Other Transition-Metal Catalysis4 Asymmetric [3+3]-Cycloaddition Reactions of Enoldiazo Compounds4.1 Asymmetric [3+3]-Cycloaddition Reactions of Nitrones with Electrophilic Metallo-enolcarbene Intermediates4.2 Dearomatization in Asymmetric [3+3]-Cycloaddition Reactions of Enoldiazoacetates4.3 Asymmetric Stepwise [3+3]-Cycloaddition Reaction of Enoldiazoacetates with Hydrazones5 Summary and Outlook

Regioselectivity Change in the Organocatalytic Enantioselective (3+2) Cycloaddition with Nitrones through Cooperative Hydrogen-Bonding Catalysis/Iminium Activation.

The reaction of nitrones with enals through iminium activation can be modulated by using cooperative hydrogen-bonding catalysis to induce the participation of a nitrone ylide (C-N-C) instead of the classical C-N-O dipole. As a consequence, N-hydroxypyrrolidines are obtained, rather than the expected isoxazolidines. The reaction proceeds smoothly and high enantioselectivities are observed in all cases. By using the appropriate substrate, polysubstituted pyrrolidines incorporating quaternary stereocenters can be efficiently prepared.

A molecular electron density theory study of the [3 + 2] cycloaddition reaction of nitrones with ketenes.

The [3 + 2] cycloaddition (32CA) reaction between nitrones and ketenes has been studied within the Molecular Electron Density Theory (MEDT) at the Density Functional Theory (DFT) MPWB1K/6-311G(d,p) computational level. Analysis of the conceptual DFT reactivity indices allows the explanation of the reactivity, and the chemo- and regioselectivity experimentally observed. The particular mechanism of this 32CA reaction involving low electrophilic ketenes has been elucidated by using a bonding evolution theory (BET) study. It is determined that this reaction takes place in one kinetic step only but in a non-concerted manner since two stages are clearly identified. Indeed, the formation of the second C-O bond begins when the first O-C bond is already formed. This study has also been applied to predict the reactivity of nitrones with highly electrophilic ketenes. Interestingly, this study predicts a switch to a two-step mechanism due to the higher polar character of this zw-type 32CA reaction. In both cases, BET supports the non-concerted nature of the 32CA reactions between nitrones and ketenes.

Direct Asymmetric Aza-Vinylogous Mannich Reaction of Nitrones from Isatins and Ketimines

Direct Asymmetric Aza-Vinylogous Mannich Reaction of Nitrones from Isatins and Ketimines

A molecular electron density theory study of the [3 + 2] cycloaddition reaction of nitrones with strained allenes

The molecular electron density theory study of this [3 + 2] cycloaddition reveals that the strain present in the cyclic allene changes its reactivity to that characteristic of highly reactive radical species.

Lewis base-catalyzed diastereoselective [3 + 2] cycloaddition reaction of nitrones with electron-deficient alkenes: an access to isoxazolidine derivatives

A Lewis base-catalyzed [3 + 2] cycloaddition reaction of nitrones with electron-deficient alkenes has been achieved under mild reaction conditions, affording functionalized isoxazolidines as single diastereomers in moderate to excellent yields.

ChemInform Abstract: Cascade Reactions of Nitrones and Allenes for the Synthesis of Indole Derivatives

AbstractReview: 52 refs.

Cascade Reactions of Nitrones and Allenes for the Synthesis of Indole Derivatives.

Cascade reactions involving nitrones and allenes are known to facilitate the rapid synthesis of several indole derivatives. The chemoselectivity of these complicated transformations can be influenced by substrate functionalization, reaction conditions, and catalyst control. While seminal studies established primary reactivity patterns, recent work has illustrated the impact of these cascade reactions for creating diverse libraries, increased the breadth of these methods with facilitated access to challenging nitrones, and shown that these transformations can be controlled by asymmetric catalysis.