James Kemp

X-Y-ZH Systems as potential 1,3-dipoles : Part 15. Amine generated azaallyl anios versus metallo-1,3-dipoles in cycloadditions of α-amino acid esters. Facile regio- and stereo-specific formation of pyrrolidines

Abstract Kinetic studies of the deprotonation of arylidene imines of alanine and phenylglycine esters by tertiary amines and pyridine and cycloaddition of the resultant 4π-azaallyl anions to N-phenylmaleimide show the expected dependance on the p-substituent in the aryl ring. e.g. p-NO2 > H > OMe >fs NMe2. A combination of metal salt (silver, lithium. or zinc) and triethylamine in THF, dipolar aprotic solvents (MeCN, DMSO, DMF) or N-methylacetamide effects regio- and stereo-specific or highly stereo-selective inter- and intra-molecular cycloaddition of imines of phenylglycine. alanine and glycine esters to a range of dipolarophiles probably via metallo-1,3-dipole formation at room temperature. Silver acetate is a more efficient and selective catalyst than lithium bromide and reactions in acetonitrile, DMSO or N-methylacetamide, are especially rapid (O.1–3.5h).

X=Y-ZH systems as potential 1,3-dipoles. The stereochemistry and regiochemistry of cycloaddition reactions of imines of α-amino-acid esters.

Abstract The stereochemistry and regiochemistry of cycloadditions of α-amino acid ester imines is dependent both on imine structure and on the reactivity of the dipolarophile. Phenylglycine imines undergo competing dipole stereomutation and cycloaddition with some dipolarophiles.

XY–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.

1,3-Dipolar cycloaddition reactions of imines of α-amino-acid esters: X-ray crystal and molecular structure of methyl 4-(2-furyl)-2,7-diphenyl-6,8-dioxo-3,7-diazabicyclo[3.3.0]octane-2-carboxylate

Imines of α-amino acid esters undergo a wide range of cycloadditions probably via their 1,3-dipolar tautomers and the stereochemistry of one adduct has been determined by X-ray crystallography.

XY–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 Compounds as potential 1,3-dipoles. Part 30. Cycloaddition of arylidene imines of α-amino esters to acetylenic dipolarophiles and pyrrole forming rearrangements

Abstract Arylidene imines of α-amino esters undergo cycloaddition to ethyl phenylpropiolate, methyl propiolate and dimethyl acetylenedicarboxylate (ADE) on heating in toluene (110°C)or o-xylene (135- 145°C). The reactions proceed via stereospecific azomethine ylide formation and give single 3-pyrroline cycloadducts in moderate to good yield. Reaction of certain of the imines with 2 mol. of ADE leads to a pyrroles formed by rearrangement. The mechanism of the rearrangement is discussed.

X=Y-ZH systems as potential 1,3-dipoles: Part 17. Sequential michael addition-5-endo-trig cyclisation of arylidene imines of α-amino acid esters111. Preliminary communication, R. Grigg, J. Kemp, J.F. Malone and A. Tangthongkum, J.Chem.Soc.,Chem.Commun., 1980, 648.222. Part 16. P. Armstrong and R. Grigg, Tetrahedron, 1988, 1523.

Abstract Imines of α-amino acid esters undergo regiospecific Michael addition to methyl acrylate or acrylonitrile in good yield in benzene at 25°C catalysed by benzyItrimethyl ammonium methoxide (BTAM). The Michael adducts cyclise to a mixture of two stereoisomeric polysubstituted proline ester derivatives in the presence of 1 mol. of BTAM. Mechanistic studies, involving chiral intermediates, show this cyclisation to be an example of a disfavoured 5-(enolexo)-endo-trig process.

X=y-zh systems as potential 1,3-dipoles : Part 22.1 cycloaddition reactions of pyridoxal imines. relevance to a-amino acid racemases and transaminases.

Abstract Pyridoxal imines of ∞-amino acid esters and related amines undergo cycloaddition to N-phenylmaleimide on heating in acetonitrile, toluene or xylene. The cyclo-additions proceed in good yield, are stereospecific, and involve an endo-transition state. The reactive intermediates are postulated to be NH azomethine ylides produced stereospecifically from the imines by prototropy.

XY–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.

Reaction of Δ3-pyrrolines with dimethyl acetylenedicarboxylate. A novel pyrrole forming rearrangement

Abstract Reaction of arylidene imines of methyl phenylglycinate with 2 moles of dimethyl acetylenedicarboxylate (ADE) leads, via an intermediate Δ 3 -pyrroline, to loss of the original methyl phenylglycinate moiety and formation of 2-aryl-3,4,5-tricarbo methoxypyrroles.