Christopher J. Easton

Selective modification of glycine residues in dipeptides

Abstract Reaction of dipeptides with N-bromosuccinimide results in selective α-bromination of glycine residues. Subsequent reactions of brominated peptides with diethyl malonate and allyltributyltin afford the diethyl malonyl- and allyl-substituted glycine derivatives, respectively.

Cycloaddition Reactions of Nitrile Oxides with Alkenes

Publisher Summary This chapter reviews the cycloaddition reactions of nitrile oxides with alkenes. It covers the literature published between 1985 and 1992. The chapter emphasizes on the dramatic improvements in the degree of stereocontrol that has been attained in intermolecular reactions and to the developments in the use of intramolecular nitrile oxide cycloaddition (INOC) reactions, where the predisposition of the reacting groups within a molecule greatly enhances the regio and stereo-selectivity. The synthesis of benzonitrile oxide by chlorination of benzaldoxime, in order to give benzhydroximinoyl chloride followed by dehydrohalogenation with sodium carbonate forms the basis of the most common approach for the synthesis of nitrile oxides. The reactions of nitrile oxides with alkenes are essentially 1,3-dipolar cycloadditions and their mechanism have been subject of numerous investigations. The chapter also describes reactivity, regioselectivity, stereoselectivity, and the uses of isoxazolines. In specific, cycloaddition rates range over several orders of magnitude and to predict the likely success of a reaction, when alternative reaction pathways, such as nitrile oxide dimerization are possible, it becomes necessary to understand the reactivity of the system.

Reversal of regiochemistry in the synthesis of isoxazoles by nitrile oxide cycloadditions

Abstract The isoxazolines 2a , 2b and 8 obtained from nitrile oxide cycloadditions to cyclohex-2-enone 1a and its analogues 1b and 7 reacted with nickel peroxide to give the isoxazoles 3a , 3b and 9 . In contrast, the corresponding 2-bromocyclohex-2-enones 4a , 4b and 10 , prepared by bromination of the corresponding alkenes 1a , 1b and 7 , underwent nitrile oxide cycloadditions to afford the regioisomeric isoxazoles 6a , 6b and 12 , respectively.

Stereocontrolled synthesis of β-hydroxyphenylalanine and β-hydroxytyrosine derivatives

Abstract Side-chain bromination of N -phthaloyl-( S )-phenylalanine and tyrosine derivatives, followed by treatment of the product bromides with silver nitrate in aqueous acetone, affords the corresponding (2 S ,3 R )-β-hydroxy-α-amino acids, enantiospecifically and diastereoselectively. The diastereoselectivity depends on the carboxyl protecting group. tert -Butyl esters display greater stereoselectivity than the corresponding methyl esters, presumably as a result of a steric effect, while N-tert -butylamides react diastereospecifically due to a combination of steric and electronic effects.

Synthesis of homochiral hydroxy-α-amino acid derivatives

Abstract Treatment of N-phthaloyl-α-amino acid methyl esters with N-bromosuccinimide, followed by reaction with silver nitrate in aqueous acetone, affords homochiral hydroxy-(α-amino acid derivatives, the stereochemistry of which is predetermined by that of the starting amino acids.

A new α-haloglycine template for the asymmetric synthesis of amino acid derivatives

Abstract Reaction of (S)-N,N-diacylvalylglycine anhydride with N-bromosuccinimide afforded the corresponding α-bromoglycine derivative, which reacted diastereoselectively with allyltributyltin and deuterium) over palladium chloride to give the corresponding α-allyl- and α-deuterio-glycine derivatives, respectively.

Aryl nitrile oxide cycloaddition reactions in the presence of baker's yeast and β-cyclodextrin

Abstract Contrary to recent reports, bakers yeast is not required for reactions of nitrile oxides with either ethyl cinnamate or 4-vinylpyridine to give isoxazolines. β-Cyclodextrin may alter the ratio of isomers isolated from the reactions of the cinnamate but only at concentrations of reactants much lower than those reported, and this effect is most likely due to selective product complexation rather than selective product formation.

Selective γ-hydrogen atom abstraction in reactions of N-acetylamino acids and N-alkylacetamides with titanous ion and hydrogen peroxide

Abstract Whereas reactions of N-acetylglycine, N-acetylalanine, and pyroglutamic acid, with TiCl3/H2O2 in a flow system give e.p.r. spectra arising from the corresponding α-centred radicals ( 1 – 3 ), reactions of N-acetylvaline, 2-acetamido-butyric acid, N-propylacetamide, and N-(2-methylpropyl)-acetamide, give spectra arising from the respective γ-centred radicals ( 4 – 7 ). Production of the γ-centred radicals ( 4 – 7 ) is attributed to complexation of titanium to the amide group of the substrates.

Exocyclic bromination of N-substituted β- and γ-lactams

Abstract Regioselective halogenation of the N-susbtituted lactams (3a)-(3d) affords the corresponding exocyclic bromides (4a)-(4d). The procedure provides a novel alternative route to N-(α-haloalkyl)-substituted lactams, which are of particular interest in the synthesis of β-lactam antibiotics.

Reactions of α-substituted glycine derivatives with stannanes

Abstract α-Benzoyloxy- and α-methoxy-substituted glycine derivatives are more stable than the corresponding bromides, yet they undergo analogous reactions with stannanes. Their reactions with mixtures of hexabutylditin and dialkyl disulphides give α-alkylthio-substituted glycine derivatives, a procedure that is applicable to the synthesis of cross-linked amino acid derivatives.