Intramolecular Oxime Olefin Cycloaddition Research Articles

An investigation of structure-reactivity relationships of δ-alkenyl oximes; competitive thermal reactions leading to cyclic nitrones and/or N-unsubstituted bicyclic isoxazolidines

Thermal reactions of C-aryl δ-alkenyl oximes give N-unsubstituted bicylic lactone, lactam and pyrrolidine fused isoxazolidines by an intramolecular oxime olefin cycloaddition pathway (IOOC) and/or cyclic nitrones by an azaprotio cyclotransfer (APT) route; a number of factors, including the nature of the aryl group, the oxime geometry and the structure of the linker between the oxime and the terminal alkene, contribute to the competition.

Synthesis of Chiral Oxepanes and Pyrans by 3‐O‐Allylcarbohydrate Nitrone Cycloaddition (3‐OACNC).

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Synthesis of chiral oxepanes and pyrans by 3- O-allylcarbohydrate nitrone cycloaddition (3-OACNC)

3- O-Allylcarbohydrate nitrone cycloaddition (3-OACNC) furnished pyran and oxepane derivatives from 3- O-allyl hexose N-benzyl nitrones and 3- O-allyl furanoside-5-aldehyde N-benzyl/methyl nitrones. The regioselectivity of 3-OACNC was found to depend on the following factors (a) the structural nature of the nitrone (b) substitution and stereochemistry at 3-C of the carbohydrate backbone (c) substitution at the terminus of the O-allyl moiety. Oxepanes or pyrans obtained from a particular set of a hexose nitrone and the corresponding furanoside nitrone were converted to enantiomeric cyclic ethers through degradation. A mixture of an oxepane and a pyran was formed in the intramolecular oxime olefin cycloaddition (IOOC) of a 3- O-allylcarbohydrate derived oxime.

Mechanistic Considerations on the Oxime–Nitrone Isomerization and Intramolecular Cycloaddition Reaction of 3-(Alk-2-enylamino)propionaldehyde Oximes

Abstract 3-(Alk-2-enylamino)- and 3-(acryloylamino)-2,2-dimethylpropionaldehyde oximes underwent thermally induced 1,3-dipolar cycloaddition under mild conditions, leading to perhydroisoxazolo[4,3-c]pyridine derivatives. The features of the intramolecular oxime–olefin cycloaddition in this system and the roles of the geminal methyl groups at the 2-position and the alkenylamino nitrogen in the oxime–nitrone isomerization process are discussed based on kinetic studies.

Stannous Chloride Reduction of Nitroalkenes in Amines. Synthesis and Cycloaddition of α-Dialkylaminoaldoxime

α-Dialkylamino aldoximes 12 were prepared by stannous chloride reduction of nitroalkenes in amines. An intramolecular Michael addition-deoxygenation mechanism is suggested. α-Allylamino aldoxime underwent an efficient Intramolecular Oxime Olefin Cycloaddition (IOOC) giving 13

Synthesis of a new isoxazolidine from diacetone glucose

The synthesis of a new furo-pyran-based isoxazolidine, making use of an intramolecular oxime–olefin cycloaddition (IOOC) reaction, is reported here, starting from diacetone glucose.

Stereoselective Intramolecular Oxime Olefin Cycloadditions Involving Carbohydrate Derived Precursors

Intramolecular oxime olefin cycloaddition reactions of carbohydrate derived precursors can be used to prepare highly functionalised 3-oxa-2-azabicyclo[3.3.0]hexanes with good to excellent levels of stereocontrol.

Stereoselective Formation of Functionalized 2-Aryl-tetrahydrofurans from Aromatic Aldehydes via Intramolecular 1,3-Dipolar Cycloadditions (INOC and IOOC)

Abstract α-Allyloxyaldoximes 8, formed by the reduction of β-nitrostyrenes 5 with SnCl2-2H2O in the presence of an unsaturated alcohol, undergo either thermally induced intramolecular oxime olefin cycloaddition (IOOC) to bicyclic isoxazolidines 7, with stereospecific introduction of three stereocenters, or nitrile oxide olefin cycloadditions (INOC) to bicyclic isoxazolines 6. This provides an entry into functionalized tetrahydrofurans and tetrahydropyrans.

Stereoselective synthesis of fused γ-lactams by intramolecular nitrone cycloaddition

A series of nitrones 5 joined by amides to olefines were prepared in situ from the related aldehydes with N-methylhydroxylamine. The nitrones added intramolecularly to the olefin, and the cycloadditions gave fused γ-lactams 6 stereoselectively. A stereocentre located in position α to the nitronic functionality 13 completely controls the stereochemical course of the intramolecular cycloadditions, which exclusively affords compound 14 with simultaneous introduction of four stereocentres. The formation of this latter compound was also supported by PM3 calculations. Furthermore, simple heating of unsaturated oxime 17 led to compound 19 via intramolecular oxime olefin cycloaddition.

Utilization of L-serine in an oxime olefin cycloaddition route to a functionalized asymmetric pyrrolidine, a selective α-glucosidase inhibitor

A new route for asymmetric aza-sugar analogs starting with L-serine and utilizing an intramolecular oxime olefin cycloaddition has been successfully developed. A member of this family of branched chain sugar amino di(hydroxymethyl) pyrrolidines ( 1 and 2) exhibits selective inhibition of α-glucosidase, while no inhibition of β-glucosidase was detected.

ChemInform Abstract: Stereochemistry. Part 82. On the Conformations of Fused Five‐Membered Heterocyclic Rings Derived from the Intramolecular Oxime Olefin Cycloaddition Reaction.

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Stereochemistry. 82. Conformation of fused five-membered heterocyclic rings derived from the intramolecular oxime olefin cycloaddition reaction

Thermal intramolecular oxime olefin cycloaddition of α-allylamino aldoximes and ketoximes 4 led stereospecifically to formation of oxadiazabicyclo[3.3.0]octanes 6. The presence of heteroatoms in these bicyclic fused 5-membered rings permits for the first time an evaluation of the conformation of this system by means of NMR. We found that some substituents in 6 restrict the conformational mobility of these five-membered rings to the extent that only one conformer was detected at 20 o C. In other cases an equilibrium between two major conformers was revealed by NMR. Equilibrium measurements indicated a free energy of conversion of 13.2-13.4 kcal/mol, apparently a manifestation of the N-inversion in the isoxazolidine ring. NMR studies also showed that the NH-proton in isoxazolidines 6 prefers an axial orientation. Empirical force field data were adjusted for MM calculations in these bicyclic heterocycles. The MM2 force field with AMBER charge gave the best fit between calculated and experimental coupling constants

A synthesis of (−) supinidine and its regioisomer by intramolecular oxime olefin cycloaddition.

A synthesis of (−) supinidine 1 and its regioisomer 2 from L-proline is described. The key step is a thermal intramolecular oxime-olefin cycloaddition; dimerization products resulting from intramolecular nitrone formation were also isolated.

Cycloadditions. 46. Thermally induced intramolecular oxime olefin cycloadditions leading to N-bridgehead systems. Stereochemistry and molecular mechanics calculations

The intramolecular oxime olefin cycloaddition (IOOC) of proline and pipecolinic acid derivatives proceeds thermally with a high degree of stereoselectivity to provide a new route to functionalized pyrrolizidines, indolizidines, or quinolizidines. The ring closure proceeds with simultaneous stereoselective introduction of three or four stereocenters. Molecular mechanics calculations have been refined to accurately predict not only which stereoisomer is preferred but also the syn and anti coupling constants in these tricyclic molecules