Cycloaddition Reactions Of Nitrones Research Articles

ChemInform Abstract: Tricyclic‐Isoxazolidine Analogues via Intramolecular 1,3‐Dipolar Cycloaddition Reactions of Nitrones.

AbstractThe process is applied to the preparation of a variety of isoxazolidines.

Regioselective transformation of 6/5-fused bicyclic isoxazolidines to second-generation cyclic aldonitrones

The cycloaddition reactions of 4-(2-hydroxy-2-propyl)-3,4,5,6-tetrahydropyridine 1-oxide with mono- and di-substituted alkenes have been found to be highly stereo- as well as face-selective. In solution, the 6/5 fused bicyclic cycloadducts remain solely as the cis-fused invertomers in order to accommodate the bulky tertiary substituent 2-hydroxy-2-propyl in the equatorial orientation. The cycloadducts, upon peracid oxidation, leads to the exclusive formation of synthetically important second-generation cyclic aldonitrones. The stereo- and face-selectivity of the cycloaddition reactions of these second-generation nitrones bearing substituents at C(4) and C(6) have been briefly examined. One interesting finding was that treatment of the first generation nitrone i.e., 4-(2-hydroxy-2-propyl)-3,4,5,6-tetrahydropyridine 1-oxide, with mercury(II) oxide afforded a novel bicyclic nitrone, 1-oxa-5,6-dehydro-6-azabicyclo[3,2,1]heptane 6-oxide.

ChemInform Abstract: Cycloaddition of Nitrones to Metal‐Activated Nitriles and Isocyanides

AbstractReview: 69 refs.

Synthesis of novel β-lactam fused spiroisoxazolidine chromanones and tetralones as potent antimicrobial agent for human and plant pathogens

Synthesis of novel β-lactam fused spiroisoxazolidine chromanones and tetralones ring systems has been achieved by intermolecular 1,3-dipolar cycloaddition reaction of bicyclic nitrone with unusual dipolarophiles, arylidene chromanones/tetralones under different reaction conditions. The synthesized compounds were evaluated for antimicrobial activities. It was observed that two of the synthesized compounds exhibited relatively good antibacterial and antifungal activities.

Locked Nucleosides Based on Oxabicyclo[3.2.1]octane and Oxabicyclo[2.2.1]heptane Skeletons

Intramolecular nitrone cycloaddition (INC) reaction on a d-glucose derived substrate carrying an allyl group at C-1 and an enose-nitrone at C-5 or an aldehyde-nitrone at C-1 and vinyl group at C-4 furnished a tricyclo[6.2.1.0(2,6)]undecane or a tricyclo[5.2.1.0(2,6)]decane ring structure. These tricycles were converted to bicylic nucleosides with oxabicyclo[3.2.1]octane and oxabicyclo[2.2.1]heptane rings in three steps. An oxabicyclo[3.2.1]octane ring compound could alternatively be formed by RCM reaction between C-1-allyl and C-4-vinyl moieties and transformed to nucleoside analogues through a nucleophilic substitution reaction. Participation of a neighboring benzyl ether substituent in one case paved the way for an enantiodivergent synthesis.

α-N-Methyl/Phenyl Furan Derivatives as Dipolarophiles for Synthesis of Spiro Isoxazolidine Derivatives with α-Chloro and Simple Nitrones

1,3-Dipolar cycloaddition reactions of α-chloro and simple nitrones have been studied with novel α-N-methyl/phenyl furan derivatives as new dipolarophiles. The reactions are found to be highly regioselective to afford single 5-spiro isoxazolidines with high yield in a short reaction time.

ChemInform Abstract: Water as the Medium of Choice for the 1,3‐Dipolar Cycloaddition Reactions of Hydrophobic Nitrones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Carbonyl Imines from Oxaziridines: Generation and Cycloaddition of NOC Dipoles

Cycloaddition reactions of nitrones,i azides,ii and related 1,3-dipolar species iii have become recognized as powerful tools for the construction of compounds with great utility in organic synthesis, chemical biology, and materials science. The conceptual model that underpins our understanding of this broad class of reactions was first formalized by Huisgen in 1963. iv This seminal contribution to organic chemistry provided chemists with a unified framework for understanding the structure and reactivity of 1,3-dipolar compounds, and also predicted the structures of several elementary 1,3-dipoles that were unknown at the time. Subsequent research has identified cycloaddition reactions of many of these predicted 1,3-dipolar species.v However, carbonyl imines (e.g., 3, Scheme 1) have remained elusive in the half-century since Huisgen’s initial prediction. Although these unusual dipoles have been postulated to be intermediates in the photochemical decomposition of nitroarenes,vi no compounds resulting from dipolar cycloadditions of carbonyl imines have previously been reported. In this communication, we demonstrate that carbonyl imines can be efficiently generated by Lewis acid-catalyzed rearrangement of N-sulfonyl oxaziridines and trapped by cycloaddition with a variety of dipolarophiles.

Synthesis of (+)-Batzelladine K

Total synthesis of batzelladine K (1), a marine guanidine alkaloid, was achieved based upon successive 1,3-dipolar cycloaddition reaction of cyclic nitrone. The relative and absolute stereochemistry of 1 was established by spectral comparison of the natural and synthetic products and the trans-isomer, which was also synthesized.

Study on Synthesis, Characteristics and Catalysis Properties of Novel Chiral Metal Complexes Catalysts for 1,3‐Dipolar Cycloaddition Reactions of Nitrone with Electron‐Rich Alkene

AbstractAs a new class of potential catalysts for 1,3‐dipolar cycloaddition reactions, fourteen L‐amino acid Schiff base Cu(II) and Ti(IV) complexes were synthesized, characterized, and evaluated for their catalytic activities in the reaction between C,N‐diphenylnitrone and electron‐rich ethyl vinyl ether under both homogeneous and in situ conditions. The methods for preparation and utilization of the catalysts were elucidated in detail, and the results of the catalytic reactions were described and discussed as well. Excellent reaction results were found in the presence of some catalysts (20 mol%) with > 90% endo‐isoazolidines produced, compared with predominantly exo‐isoazolidine produced without a catalyst. In addition, the reaction rate is found to be enhanced remarkably by a Cu(II) complex Schiff base catalyst at room temperature.

Peracid-induced ring opening of some hexahydro-2H-isoxazolo[2,3-a]pyridines to second-generation cyclic aldonitrones

A study of the stereo- and face selectivity of the cycloaddition reactions of several mono- and disubstituted alkenes with 4-hydroxymethyl-3,4,5,6-tetrahydropyridine 1-oxide has been carried out. The addition reactions have displayed a very high degree of face selectivity in the range 13-48:1. Use of dimethyl methylenemalonate as a protective group in nitrone cycloaddition reactions has been demonstrated. The invertomeric analysis revealed that the bicyclic cycloadducts remain predominantly as the cis-fused isomer, which leads to the formation of synthetically important second-generation cyclic aldonitrones via peracid oxidation. One interesting finding was that treatment of the cycloadducts with two equivalents of peracid afforded the cyclic N-hydroxy lactams, presumably via further oxidation of the aldonitrones. The piperidine ring has been elaborated by cycloaddition reaction of the second-generation nitrones with several alkenes, which in most cases gave the cycloadducts in a stereoselective manner.

Synthesis of Pentahydroxylated Pyrrolizidines and Indolizidines

1,3-Dipolar cycloaddition reaction of nitrone 7 and chemo-enzymatically obtained alkenediols 12 and 13 has been used in the synthesis of pentahydroxylated pyrrolizidines (8 and 10) and indolizidines (9 and 11). The pyrrolizidinic and indolizidinic skeletons were built after internal n-alkylation of the suitably functionalized pyrroloisoxazolidine intermediates obtained by the necessary protecting group manipulations. This method expands the scope of cycloaddition reactions in the synthesis of new and highly polyhydroxylated sugar-like alkaloids.

Asymmetric 1,3-dipolar cycloaddition reaction of α,β-unsaturated nitriles with nitrones catalyzed by chiral-at-metal rhodium or iridium complexes

The aqua complexes ( S M, R C)-[(η 5-C 5Me 5)M{( R)-Prophos}(H 2O)](SbF 6) 2 (M = Rh, Ir; ( R)-Prophos = 1,2-bisdiphenylphosphino propane) catalyze the 1,3-dipolar cycloaddition reaction (DCR) of nitrones with α,β-unsaturated nitriles with low-to-moderate enantioselectivity. The involved catalysts [(η 5-C 5Me 5)M{( R)-Prophos}(α,β-unsaturated nitrile)](SbF 6) 2, isolated as mixtures of the ( S M, R C)- and ( R M, R C)-diastereomers, have been fully characterized, and the molecular structure of the complexes ( S Rh, R C)-[(η 5-C 5Me 5)Rh{( R)-Prophos}( cis-2-pentenenitrile)](SbF 6) 2 and ( S Ir, R C)-[(η 5-C 5Me 5)Ir{( R)-Prophos}(acrylonitrile)](SbF 6) 2 has been determined by X-ray diffraction. The ( R)-at-metal epimers isomerize to the ( S)-at-metal counterparts. Diastereopure ( S M, R C)-[(η 5-C 5Me 5)M{( R)-Prophos}(α,β-unsaturated nitrile)](SbF 6) 2 complexes catalyze the above-mentioned DCR in a stoichiometric manner with up to 97% ee. The results make clear the influence of the metal configuration on the catalytic stereochemical outcome. The catalysts can be recycled without significant loss of either activity or selectivity.

A study of conformational behaviour in some hexahydro-2H-isoxazolo[2,3-a]pyridines

A study of the effects of substituents on the conformational behaviour of a series of hexahydro- 2H-isoxazolo(2,3-a)pyridines (a 6/5 fused ring system), prepared via nitrone cycloaddition reaction of 4-butyloxycarbonyl-3,4,5,6-tetrahydropyridine-1-oxide with mono- and disubstituted alkenes, has been carried out. Some of these bicyclic cycloaddition products show the presence of two isomers (cis-and trans-fused system), equilibrating via relatively slow nitrogen inversion process, while the rest exist solely as the trans-invertomer. Stereochemistry of the ring fusion was determined by NMR spectral analyses. The effect of substituents and solvents - CDCl3 toluene-d6, and CD3OD - on the population ratio of the invertomers and inversion barriers has been investigated. The nitrogen inversion barriers, determined using complete line-shape analysis, are in the range 62.1-72.3 kJ mol -1 .

Cascade condensation, cyclization, intermolecular dipolar cycloaddition by multi-component coupling and application to a synthesis of (±)-crispine A

A general approach for the synthesis of various nitrogen-containing heterocyclic compounds is described using an intermolecular dipolar cycloaddition reaction of azomethine ylides and nitrones. Stabilized and non-stabilized azomethine ylide dipoles or the related nitrones were generated by condensation of 4-, 5- or 6-halo-aldehydes with a readily available amino-acid, amino-ester or hydroxylamine to give an imine followed by cyclization and either decarboxylation or loss of a proton. After intermolecular cycloaddition with an activated dipolarophile, bicyclic or polycyclic (if the ylide dipole and/or dipolarophile contain a ring) amines were produced. A short synthesis of the alkaloid (+/-)-crispine A was achieved based on this tandem/domino 3-component coupling chemistry.

Water as the medium of choice for the 1,3-dipolar cycloaddition reactions of hydrophobic nitrones

1,3-Dipolar cycloadditions of different hydrophobic nitrones 1, 2, 3, 4 with acrylates 5 and 6 were studied in both homogenous organic solutions and aqueous suspensions. Reactions in water suspensions showed great rate accelerations over homogenous solutions. Small changes were also observed to the stereoselectivities of the reactions. Hydrophobic interactions are invoked for the observed behaviour.

ChemInform Abstract: Regio‐ and Stereoselective Synthesis of Isoxazolidine Derivatives by Asymmetric 1,3‐Dipolar Cycloaddition Reaction of Chiral Nitrones with 1‐Propene‐1,3‐sultone.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A DFT study of 1,3-dipolar cycloaddition reactions of 5-membered cyclic nitrones with α,β-unsaturated lactones and with cyclic vinyl ethers: Part 1

The 1,3-dipolar cycloaddition of cyclic nitrones with electron-poor and electron-rich cyclic dipolarophiles (α,β-unsaturated lactones and vinyl ethers) is studied. The energies of the cycloaddition reactions have been investigated through molecular orbital calculations at the B3LYP/6-31+G(d) level theory. Different reaction channels and reactants approaches, effective in regio- and stereochemical preferences are discussed. The results were compared with experimental data to find a good agreement.

Regio‐ and stereoselective synthesis of isoxazolidine derivatives by asymmetric 1,3‐dipolar cycloaddition reaction of chiral nitrones with 1‐propene‐1,3‐sultone

Abstractmagnified imageAsymmetric 1,3‐dipolar cycloadditions of chiral nitrones to 1‐propene‐1,3‐sultone (1) were investigated. Chiral nitrones 6a‐e reacted with sultone 1 in toluene at 90 °C for 24‐36 h to give the corresponding isoxazolidines in moderate yields with high regioselectivities and stereoselectivities. The diastereoselectivity of this reaction varied with the choice of dipolarophile and the steric demands of nitrones. When sultone 1 was allowed to react chiral nitrone 6e, a much better diastereoselectivity of up to 5.1:1 was observed.

ChemInform Abstract: Catalytic Asymmetric 1,3‐Dipolar Cycloaddition Reaction of Nitrones with α′‐Phosphoric Enones by a Chiral Ligand‐Copper(II) Triflate Complex.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.