Gordon W. Kirby

Asymmetric induction in the diels-alder reactions of α-hydroxyacylnitroso compounds

Abstract Transient, chiral α-hydroxyacylnitroso compounds (2), able to form intramolecular hydrogen bonds, react stereoselectively with cyclopentadiene and cyclohexa-1,3-diene; the cycloadduct (6) of the latter diene and the nitroso derivative of ( S )-mandelic acid has been converted into the known (-)-oxazine derivative (9).

O(Diphenylphosphinyl)hydroxylamine: A new reagent for electrophilic C-amination

Abstract O -(Diphenylphosphinyl)hydroxylamine efficiently aminates a variety of stabilised carbanions and certain Grignard reagents.

Intramolecular enë reactions of transient, allylic, and homoallylic C-nitrosoformate esters

Various allylic and homoallylic alcohols have been treated successively with phosgene and hydroxylamine to form the corresponding N-hydroxycarbamic esters (3). Oxidation of these hydroxamic acid derivatives with sodium or tetraethylammonium periodate in the presence of cyclopentadiene gave the cycloadducts (5) derived from transient allylic and homoallylic C-nitrosoformate esters (4) and cyclopentadiene. When the cycloadducts were heated in benzene at 80 °C, or toluene at 111 °C, they dissociated and the C-nitrosoformate esters underwent intramolecular ‘ene’ reactions to give hydroxamic acid derivatives having newly formed, five- six- or seven-membered heterocyclic rings.

Selenoaldehydes formed by 1,2-elimination and trapped as Diels–Alder adducts

Various selenenyl derivatives, RO2C·CH2SeX, underwent elimination with triethylamine to form selenoaldehydes, RO2C·CHSe, which were trapped in situ as cycloadducts with conjugated dienes; the adduct of ethyl selenoxoacetate and anthracene dissociated upon heating thereby allowing transfer of the selenoaldehyde to 2,3-dimethylbuta-1,3-diene.

Biosynthesis of bisdethiobis(methylthio)gliotoxin, a new metabolite of Gliocladium deliquescens

Bisdethiobis(methylthio)gliotoxin (2) has been identified as an amorphous, minor metabolite of Gliocladium deliquescens and characterised via the crystalline bis-4-bromobenzoate of the corresponding didehydro-derivative. The new metabolite has been synthesised from gliotoxin (1) by reduction and methylation. Feeding experiments with [14C]-(1) and -(2), prepared biosynthetically from L-[U-14C]phenylalanine, have shown that bisdethiobis(methylthio)gliotoxin is formed (8.6% incorporation), apparently irreversibly, from gliotoxin in G. deliquescens.

The transient dienophile diethyl thioxomalonate and its S-oxide (sulphine) formed by retro-Diels–Alder cleavage reactions

Diels–Alder adducts 3 and 4 of diethyl thioxomalonate 1, formed from diethyl oxomalonate (mesoxalate) and phosphorus pentasulphide, with cyclopentadiene and anthracene, dissociate at 111 °C to release the reactive thioketone 1. This was trapped in situ with 2,3-dimethylbuta-1,3-diene to give the corresponding cycloadduct 2. Similarly, the thioketone 1 reacted with 2-trimethylsiloxybuta-1,3-diene 8 to form only the 5-trimethylsiloxythiine 13, and with β-pinene 16 to form only one ‘ene’ product 17b, with C–S bond formation. The S-oxide 19 of the anthracene adduct 4 and the exo-S-oxide 27 of the cyclopentadiene adduct 3 likewise dissociated thermally to release the corresponding sulphine, diethyl thioxomalonate S-oxide 21, which was trapped in situ as the dimethylbutadiene adduct 23. The exo-sulphoxide 27, when heated alone, gave the sultene 29, presumably via[2,3]-sigmatropic rearrangement of the transient endo-sulphoxide 28. The sulphine 21, generated by flash vacuum pyrolysis of the anthracene adduct 19, reacted at low temperature with cyclopentadiene to give the exo-sulphoxide 27, and with water to give diethyl malonate.

New co-metabolites of gliotoxin in Gliocladium virens

Chromatographic separation of extracts of Gliocladium virens, grown on a medium containing [35S]sulphate, has led to the identification of 5 co-metabolites of gliotoxin (1a), new to this fungus, viz. the epitrisulphide, glioto din E (1b), the 3-hydroxymethylbut-2-enyl ether (3c), didehydrogliotoxin (5), bas-N-norgliovictin (6), and the 3-methylbut-2-enyl ether of cyclo-(glycyl-L-tyrosyl)(7); the metabolites (3c), (6), and (7) are new natural products. The synthesis of the epitri- and epitetrasulphides, gliotoxin E (1b) and gliotoxin G (1c), from gliotoxin (1a) is described, as is that of the 3-methylbut-2-enyl ether (7) from cyclo-(glycyl-L-tyrosyl). The biosynthetic significance of the dioxopiperazines (6) and (7) is briefly discussed.

Thioaldehydes in Synthesis

Abstract Thioaldehydes, ZCHS, where Z is an electron-withdrawing group, have been prepared by base-mediated, 1,2-elimination reactions of sulfenyl derivatives, ZCH2SX, where X is a heteroatomic leaving group, e.g. Cl, N-phthaloyl, SO2Tol and SO3Na. The transient thioaldehydes were trapped in situ with conjugated dienes to give Diels-Alder cycloadducts. The cycloadducts of anthracene, 9,10-dimethylanthracene and cyclopentadiene dissociate in toluene at 111°C and thereby serve as synthetically useful, auxiliary precursors of the labile thials. α-Alkylation of anthracene adducts provides precursors of thioketones and S-oxidation precursors of sulfines. Anthracene and cyclopentadiene adducts of unsaturated esters of thioxoacetic acid, RO2C. CHS, have been used to study intramolecular ene cyclisations of thioaldehydes. The Diels-Alder adducts of thioaldehydes have been used in the synthesis of new opiate analgesics, derived from thebaine, and of 6-thiashikimic acid, a sulfur analogue of the key intermediate in...

Thialactones formed by intramolecular ‘ene’ reactions of thioaldehydes

ω-Vinylalkyl esters (3) of thioxoacetic acid, generated by retro-Diels–Alder cleavage of their cyclopentadiene cycloadducts (2), underwent Type III intramolecular ‘ene’ reactions during flash vacuum pyrolysis at 500 °C to give 3-thialactones having 6- to 11-membered rings.

Detection by microwave spectroscopy of HNO produced by a retro-Diels–Alder reaction

Nitroxyl (nitrosyl hydride), HNO, has been generated by the dissociation of 9,10-dihydro-9,10-epoxyimino-9,10-dimethylanthracene at 70 °C and studied by microwave spectroscopy in the range 18–32 GHz.