Brian D. Judkins

Synthesis of imidazo-fused bridgehead-nitrogen 2′-deoxyribo-C-nucleosides: coupling-elimination reactions of 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonic acid

A short synthesis of imidazo-fused bridgehead-nitrogen 2′-deoxyribo-C-nucleosides has been developed. This is based on a coupling–elimination reaction of 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonic acid with a series of aminoalkyl-substituted heterocycles and alcohols. The intermediate α,β-unsaturated carboxamides and esters thus formed are converted into novel imidazo[1,5-a]pyridine, imidazo[1,5-b]pyridazine, and imidazo[5,1-f][1,2,4]triazine 2′-deoxyribo-C-nucleosides, including analogues of 2′-deoxyguanosine and 2′-deoxyadenosine. Assignment of the anomeric configuration of the nucleosides is made on the basis of proton n.O.e. experiments.

Synthesis of imidazo-fused bridgehead-nitrogen C-nucleosides via dehydrative coupling reactions of 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonic acid

A short, efficient synthesis of novel imidazo-fused bridgehead-nitrogen C-nucleosides has been developed. Dehydrative coupling of 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonic acid (14) with a series of aminoalkyl-substituted heterocycles (6)–(8) gives the amides (15)–(17). The latter are subsequently converted into novel imidazo[1,5-a]pyridine, imidazo[1,5-a]pyrazine, imidazo[1,5-b]pyridazine, and imidazo[5,1-f]-1,2,4-triazine C-nucleosides (20) and (21). The synthesis of a novel adenosine isostere, 8-amino-3-β-D-ribofuranosylimidazo[1,5-a]pyrazine (32), is described.

Intermolecular trapping of sulphenylnitrenes by alkenes

Oxidation of 2,4-dinitrobenzenesulphenamide with lead tetra-acetate in the presence of electron-rich alkenes (styrene, (E)- and (Z)-1-phenylpropene, 2-phenylpropene, (Z)-but-2-ene, and butadiene) gives the corresponding substituted N-(2,4-dinitrophenylsulphenyl)aziridines. Intermolecular trapping of a presumed sulphenylnitrene intermediate is also successful in the oxidation of 2-nitrobenzenesulphenamide but fails for RSNH2 when R = PhCO, 4-ClC6H4, or 4-NO2C6H4.

Rotational isomerism in N-(N-heteroaryl)arenesulphenamides

N-(1,2-Dihydro-2-oxoquinolin-1-yl)-N-(1-methylallyl)-4-chlorobenzenesulphenamide (5) has previously been isolated in two stereoisomeric forms. From examination of a number of analogues of (5), it is concluded that the phenomenon which allows isolation of these stereoisomers is restricted rotation around the N–N bond.

2,4-Dinitrobenzenesulphenylnitrene: addition to (Z)- and (E)-1-phenylpropene

Oxidation of 2,4-dinitrobenzenesulphenamide (1) with lead tetra-acetate in the presence of (Z)-1-phenylpropene gives a ca. 3:1 mixture of cis- and trans-aziridines (3) and (4), respectively. This ratio is unchanged over a tenfold decrease in concentration of (Z)-1-phenylpropene. The ratio of compounds (3) : (4) is unaffected by carrying out the oxidation in the presence of 1,1-diphenylethene, 2-phenylpropene or oxygen (triplet traps), although both the last-named alkenes react preferentially with the intermediate(s) generated in the reaction. The ratio (3) : (4)is affected by carrying out the oxidation in the presence of an allyl aryl sulphide, a particularly effective singlet nitrene trap. It is concluded that at least two intermediates are involved in the addition to (Z)-1-phenylpropene, one of which is a singlet nitrene; however the other is not the triplet nitrene.Partial isomerisation of the (Z)-1-phenylpropene to (E)-1-phenylpropene in these reactions is attributed to the reversible addition of the 2,4-dinitrobenzenesulphenamidyl radical, 2,4-(NO2)2PhSṄH to the (Z)-alkene

Optical activity as a consequence of an N–N-chiral axis: resolution of N-benzyl-N-(1,2-dihydro-2-oxo-1-quinolyl)glycine

The title compound (6) has been synthesised and the pure, laevorotatory enantiomer separated via the quinine salt. Rates of racemisation give a barrier for rotation around the N–N bond of 26 ± 0.5 kcal mol–1.

Oxidation of 2,4-dinitrobenzenesulphenamide in the presence of 2,3,4,5-tetraphenylpyrrole.

Oxidation of the title sulphenamide (1) with lead tetra-acetate in the presence of 2,3,4,5-tetraphenylpyrrole gave 2,4,5,6-tetraphenylpyrimidine (3) and 2-(2,4-dinitrophenylthioamino)-2,3,4,5-tetraphenyl-2H-pyrrole (7) as major products. The structure of (7) has been confirmed by X-ray crystallography.

Resolution of N-benzyl-N-(1,2-dihydro-2-oxoquinolin-1-yl)glycine

Abstract The N  N chiral axis in the title glycine derivative has allowed its resolution into enantiomers: the barrier Δ G≠ for racemisation (rotation around the N  N bond) is 26.2 Kcal mol−1.

Oxidation of 2,4-dinitrobenzenesulphenamide in the presence of alkenes: formation of aziridines

Oxidation of 2,4-dinitrobenzenesulphenamide in the presence of electron-rich alkenes yields N-2,4-dinitrophenylthioaziridines which have been converted into the corresponding N–H aziridines by reduction.

2,4-Dinitrobenzenesulphenylnitrene as a reactive intermediate

A study of the stereospecificity of addition of the title nitrene, generated by oxidation of the corresponding sulphenamide, to cis- and trans-propenylbenzene suggests that singlet and triplet nitrene spin states are in equilibrium, with addition of the triplet state to cis-propenylbenzene being reversible.