ZH Systems Research Articles

XYZH systems as potential 1,3-dipoles. Part 36. 1,5-Electrocyclisation processes via oxidation of tertiary amines. Pyrrolo-dihydroisoquinolines and -dihydro-β-carbolines.

A range of tertiary N-allylamines derived from 1,2,3,4-tetrahydroisoquinoline undergo oxidative cyclisation, induced by Ag 2CO 3, to pyrrolo-dihydroisoquinolines in moderate to good yield. Analogous oxidative cyclisations are reported for N-allyl-tetrahydro-β-carbolines and a pyrrolidine. The reactions proceed via formation of a 1,5-dipole followed by an electrocyclisation and subsequent aromatisation.

XYZH systems as potential 1,3 - dipoles. Part 25. Intramolecular cycloadditon reactions of pyridoxal imines of ε-alkenyl α-amino esthers. A possible new approach to pyridoxal enzyme inhibition

Pyridoxal mines of ε-alkenyl α-amino esters undergo an intramolecular cycloaddition, via an intermediate azomethine ylide, on keeping at room temperature for a prolonged period of time. The implications of this observation for the design of inhibitors of pyridoxal phosphate-dependent enzymes is discussed.

XY–ZH systems as potential 1,3-dipoles. Part 10. The decarboxylative route to azomethine ylides. Background and relevance to pyridoxal decarboxylases

The reaction of primary and α,α-disubstituted α-amino acids with pyridoxal in the presence of N-phenylmaleimide in various solvents at temperatures up to 120 °C gives rise to two series of cycloadducts. One series arises from azomethine ylides formed by decarboxylation of the intermediate pyridoxal imines whilst the other series arises via azomethine ylides derived by 1,2-prototropy in the same pyridoxal imines. The relevance of the decarboxylative route to azomethine ylides to the Strecker degradation and to pyridoxal-mediated decarboxylase enzymes is discussed.

XY–ZH systems as potential 1,3-dipoles. Part 9. Aza-allyl anion precursors from the reaction of (1,3-dioxoindan-2-ylidene)malononitrile with α-amino acids and their methyl esters

Glycine, valine, and α-amino acid esters react with (1,3-dioxoindan-2-ylidene)malononitrile (1) by a Michael addition–elimination mechanism with replacement of one cyano group by the α-amino acid or α-amino acid ester entity. These adducts undergo a triethylamine-catalysed stereospecific cycloaddition to N-methylmaleimide at room temperature with loss of the remaining cyano group in > 70% yield. The cycloaddition is believed to be a [3 + 2] anionic cycloaddition involving a hydrogen-bonded aza-allyl anion.

XY–ZH systems as potential 1,3-dipoles. Part 11. Stereochemistry of 1,3-dipoles generated by the decarboxylative route to azomethine ylides

The decarboxylative reaction of aryl aldehydes with cyclic secondary α-amino acids or primary α-amino acids in the presence of N-methyl- or N-phenyl-maleimide leads, via an intermediate azomethine ylide, to mixtures of bicyclic pyrrolidine cycloadducts in good yield. Cyclic secondary α-amino acids, where the carboxylic group is non-benzylic, give cycloadducts arising from a stereospecifically generated anti-dipole. Acyclic α-amino acids, and cyclic secondary α-amino acids with the carboxylic group located at a benzylic site, give rise to cycloadducts derived from both anti- and syn-configurations of the intermediate azomethine glides. The reactions show little discrimination between endo- and exo-transition states for the cycloadditions.

XY–ZH systems as potential 1,3-dipoles. Part 12. Mechanism of formation of azomethine ylides via the decarboxylative route from α-amino acids

The effect of temperature, solvent, and type of aldehyde on the stereospecific or stereoselective formation of azomethine ylides by the decarboxylative condensation of aldehydes with three types of α-amino acids, (i) cyclic secondary α-amino acids, (ii) cyclic secondary α-amino acids with a benzylic carboxy group, and (iii) acyclic primary α-amino acids, has been studied. Stereospecific anti-dipole formation in (i) and temperature dependent stereoselective anti-dipole formation in (ii) and (iii) is inferred from the stereochemistry of cycloadducts of the azomethine ylides with N-methylmaleimide. These results are used to support a mechanistic scheme involving loss of carbon dioxide from intermediate oxazolidin-5-ones in a stereospecific cycloreversion reaction.

XY–ZH systems as potential 1,3-dipoles. Part 7. Stereochemistry of the cycloaddition of imines of α-amino acid esters to fumarate and maleate esters

Aryl imines of α-amino acid esters undergo 1,3-dipolar cycloadditions with maleate and fumarate esters in quantitative yield when heated in boiling toluene to give mixtures of mainly two pyrrolidines. The major isomer in each case arises from cycloaddition via an endo-transition state to the same kinetically formed dipole. In aryl imines of methyl phenylglycinate the kinetic dipole undergoes partial stereomutation giving ca. 3:1 mixtures of cycloadducts derived from the kinetic dipole and the stereomutated dipole. Structural assignments are based on 1H n.m.r. data including n.O.e. difference spectroscopy.

XY–ZH Systems as potential 1,3-dipoles. Part 8. Pyrrolidines and Δ5-pyrrolines (3,7-diazabicyclo[3.3.0]octenes) from the reaction of imines of α-amino acids and their esters with cyclic dipolarophiles. Mechanism of racemisation of α-amino acids and their esters in the presence of aldehydes

Imines of α-amino acid esters with aromatic, heterocyclic, and aliphatic aldehydes generate azomethine ylides stereospecifically by a prototropic shift on heating in toluene. The azomethine ylides undergo cycloaddition to N-phenylmaleimide, maleic anhydride, and p-naphthoquinone via an endo-transition state to give racemic, single diastereoisomeric, cycloadducts. α-Amino acids undergo analogous cycloadditions, without decarboxylation, in hot acetic acid. Mechanisms of racemisation of α-amino acids and their esters in the presence of aldehydes are discussed. The pyrrolidine cycloadducts (22) are smoothly oxidised to the corresponding Δ5-pyrrolines (33) by dichlorodicyano-p-benzoquinone.

XY–ZH systems as potential 1,3-dipoles. Part 6. Metallo-1,3-dipoles. Cycloadditions of divalent metal complexes of glycine and alanine imines to electronegative olefins

Copper(II), zinc(II), and cadmium(II) complexes of imines derived from α-oxo acids and glycine or alanine undergo stereospecific cycloaddition at room temperature to 1,2-disubstituted electronegative olefins in the presence of weak base. Corresponding reactions of lead(II) complexes give insoluble cycloadducts. In contrast, the reactions of the same metallo imines with methyl acrylate, phenyl vinyl sulphone, and acrylonitrile frequently give mixtures of regio- and stereo-isomers. These mixtures are shown to arise by stereoisomerisation of initial cycloadducts formed by a 4π+ 2π concerted cycloaddition of intermediate metallo-1,3-dipoles.

In situ generation of 4π-sulphinylaminomethanide species from WXY–ZH systems and their cycloaddition reactions

Sulphonyl group transfer from N-sulphonylaniline to α-amino acids and α-amino acids esters in solution at 25–110 °C gives rise to 4π-electron species believed to be sulphinylaminomethanide anions which can be trapped in good yield by N-substituted maleimides in 4π+ 2π cycloadditions.

XY–ZH systems as potential 1,3-dipoles. Part 2. Oxime cycloadditions: formation of 2 : 1 adducts

Cycloaddition of aldehyde and ketone oximes are shown to give mixtures of all possible isoxazolidine regioisomers and stereoisomers. The products are 2 : 1 adducts with the second molecule of the di-polarophile attached to the isoxazolidine N-atom. The stereochemistry of the major isomer from benzaldehyde oxime and acrylonitrile was established by an X-ray crystal structure analysis. The cycloaddition is shown to be weakly catalysed by 2,4-dinitrophenol and to proceed best in acetonitrile. More polar solvents slightly favour the 5-isoxazolidine regioisomer. The mechanism of the reaction is discussed.

New Prototropic Processes in the Synthesis of Heterocyclic Compounds

AbstractXYZH systems are considered in general terms and divided into four classes according to the number of constituent atoms that possess lone pair electrons. Those systems in which the central Y atom possesses a lone pair are shown to be capable of participating in formal 1,2‐H shifts generating 1,3‐dipolar species. The scope, regiochemistry and stereochemistry of the cycloadditions of these 1,3‐dipoles is discussed including the relevance of these processes to the biochemistry of pyridoxal enzymes.

XY–ZH systems as potential 1,3-dipoles. Part 1. Background and scope

XY–ZH Systems are considered in general terms and divided into four classes according to the number of constituent atoms that possess lone-pair electrons. Those systems in which the central Y atom possesses a lone pair are shown to be capable of participating in formal 1,2-H shifts generating 1,3-dipolar species. The scope of the reaction, including its possible relevance to the biochemistry of pyridoxal enzymes is discussed and the influence of structure on reactivity is demonstrated with rate data for the cycloaddition of a series of aryl imines of phenylglycine and alanine methyl esters to N-phenylmaleimide.

XY–ZH systems as potential 1,3-dipoles. Part 3. Isoxazolidines from the 1:1 cycloaddition of oximes with dipolarophiles

The 2-oximes of 1,2,3-tricarbonyl systems undergo cycloaddition to N-phenylmaleimide to give isoxazolidines. Proton transfer from oxygen to nitrogen, possible via an intramolecular 1,5-H shift, is believed to generate a 1,3-dipole as the reactive intermediate. The products are 1 :1 adducts in contrast to the cycloadducts of simple aldehyde oximes and ketone oximes which incorporate a second molecule of dipolarophile on the isoxazolidine N-atom. Attempts to extend the cycloaddition to several other electronegative olefins were unsuccessful, whilst dihydropyran gave Michael adducts.

ChemInform Abstract: X:Y‐ZH SYSTEMS AS POTENTIAL 1,3‐DIPOLES. 1,5‐ELECTROCYCLIZATION OF IMINES

AbstractZH Systems as Potential 1,3‐Dipoles.