Ei reaction of sulphilimines and related compounds

Ei reaction of tertiary amine oxides, i.e. the Cope elimination and that of sulphoxides, are briefly reviewed. N-p-Tosylsulphilimines also undergo facile Ei reaction upon heating and the stereospecificity of the reaction is better than that of the corresponding sulphoxides and even somewhat better than that of the tertiary amine oxides.A general outlook on research on the Ei reactions of sulphilimines and the mechanism of the reaction are discussed in comparison with those of similar Ei reactions which proceed via 5-membered cyclic transition states.     

Synthesis, stereochemistry, and circular dichroism of optically active o-substituted diphenyl sulphilimines and related compounds

Optically active o-substituted diphenyl N-substituted sulphilimines are readily synthesised by the reaction of the corresponding sulphides and t-butyl hypochlorite in the presence of l-menthol and amide anions. (−)-N-p-Tolylsulphonylsulphilimines (1, 2) obtained were converted to the corresponding (−)-N-unsubstituted sulphilimines (8, 9) by treating them with concentrated sulphuric acid. When (−)-S-o-anisyl S-phenyl N-(unsubstituted) sulphilimine (8) was treated with acylating agents or acrylonitrile, the corresponding optically active (−)-N-substituted sulphilimines were prepared with complete retention at sulphur. The absolute configuration of (−)-S-o-anisyl S-phenyl N-p-tolylsulphonylsulphilimine (1) was determined by converting it to (+)-S-o-anisyl sulphoxide (17). CD curves of (−)-o-substituted diarylsulphilimines exhibited a negative Cotton effect at around 270–285 nm, which was assigned to (S)-configuration at sulphur by comparing with the analogous sulphoxides. The substituent on the imino group of the sulphilimine gave no appreciable effect on the CD behavior and the lack of substituent effect was considered to be due to the semi-polar character of the S(IV)-N bond. Unusual effect of o-methoxy group on the CD curves was discussed in connection with solvent effect. Mechanism of this asymmetric synthesis has been investigated, and it has become apparent that the diastereomeric menthoxysulphonium chloride was an excess of (RR)-configuration was formed initially and the amide anion attacks the S atom of the salt with net inversion.     

The stereochemistry of the SRN1 reaction in some cyclohexane derivatives

The substitution reactions of nitrocyclohexanes 8, 9, 12 and 23 with various nucleophiles were studied and were found to proceed by the electron-transfer initiated S_RN1 mechanism. Epimeric products were formed and the proportion of epimers under both thermodynamic and kinetic control normally reflected the bulk of the incoming nucleophile relative to the substituent which was present at the reaction site. In the reaction of 23 with relatively high concentrations of PhS^? in HMPA the reaction proceeded with high stereoretention. The results of these reactions are discussed in terms of the stability of radical configuration and the rate and mode of radical anion dissociations and associations.     

On the stereochemistry of the Pictet-Spengler reaction

A pathway for the Pictet-Spengler reaction is proposed herein, which is consistent with all of the known mechanistic and sterochemical observations concerning the formation of tetrahydro-β-carbolines by this method.     

Effects of Si substitution on the Ei reaction of alkyl sulfoxides

A computational study has been carried out on the effects of SiH3 substitution on the Ei reaction of alkyl sulfoxides. SiH3 substitution in the beta-position (relative to the sulfur atom) is found to lower the barrier to elimination about 5 kcal mol(-1), in line with qualitative experimental observations. However, SiH3 substitution at the alpha-position has a similar, if smaller, effect. It is argued that the barrier-lowering in the latter case is mainly correlated with changes in the overall deltaH of the elimination reaction. In contrast, electronic effects in the transition state overcome an unfavorable delta(deltaH) when SiH3 is in the beta-position. On the basis of estimated magnitudes of the various energy changes and the fractional change in bond orders in the transition state, it is argued that both hyperconjugative stabilization and inductive effects of Si substitution contribute. Finally, it is shown that the elimination reaction by SiH3 transfer from Cbeta to O has a surprisingly high enthalpic barrier, given its modest endothermicity, and it is suggested that this is due to a forced unfavorable geometry at the Si center in the transition state.     

The stereochemistry of the reaction of 2-norbornylmagnesium bromide with formaldehyde

Diastereomeric $\text{endo}$-2-norbornylmagnesium bromide and mixtures of $\text{endo}$- and $\text{exo}$-2-norbornylmagnesium bromide react stereospecifically with retention of configuration at the carbon-magnesium bond with formaldehyde to form the expected primary alcohol. This stereochemical result, which is comparable to that observed previously in electrophilic substitutions of stereoisomeric organomagnesium reagents, is observed even when 5 mole % ferric chloride is added. The stereospecificity observed both with and without added metal salts suggests that single electron transfer is not important in 1,2 addition of $\text{sec}$-alkylmagnesium reagents to simple aliphatic aldehydes.     

Acid-catalysed hydrolysis of N-sulphonyl sulphilimines—II

The basicity and the acid-catalysed hydrolysis of ph(R)SNTs and o-HC₆H₄(Me)SNTs sulphilimines have been studied by UV spectrophotometric and kinetic methods, respectively, in aqueous HClO₄ (1–10 M) and 1:1 (v/v) EtOH/H₂O-HClO₄ (0.5–6 M). Depending on the constitution of the substrates, sulphilimine hydrolysis can follow three different courses, according to rate-acidity profiles, Bunnett-Olsen's treatment, activation parameters and product analysis. Most typical for sulphilimines is S_N2 hydrolysis with S^IV-N bond cleavage. In this case the reaction starts with the nucleophilic addition of water and is promoted by acid-base catalysis. If a relatively stable carbenium ion can be formed from R group, an S_N1 reaction with S^IVC bond cleavage takes place. Sulphilimine with X = o-CO₂H due to neighbouring-group participation hydrolyses very rapidly via acyloxy-sulphurane and acyloxy-sulphonium ion intermediates with five-memembered ring (S_Ni reaction involving S^IVN bond cleavage).     

The stereochemistry of reaction of P-chiral dialkyl hydrogen phosphorothioates with [18O]-dimethyl sulphoxide

Cis- and trans-2-hydroxy-2-thiono-4-methyl-1,3,2-dioxaphosphorinanes are cleanly transformed by means of [¹⁸O]- DMSO into corresponding 2-([¹⁸O]-oxo)-derivatives with ca 90% inversion of configuration at phosphorus atom.     

Integrity of alkene stereochemistry in the Diels—Alder reaction

The Diels—Alder reaction of hexachlorocyclopentadiene and α-methylstyrene produces both exo-phenyl and endo-phenyl adducts, with the latter in preponderance. A deuterium label at the β position of the alkene provides a probe for determining whether the vicinal stereochemical relationship between groups on the alkene is retained in the adducts. From the alkene labeled 77.6±2.3% E and 22.4±2.3% Z was produced the major (endo-phenyl) isomer with 79.4±1.1% exo-d and 20.6±1.1% endo-d and the minor (exo-phenyl) isomer with 78.9±0.5% endo-d and 21.1±0.5% exo-d. Thus both adducts are produced with complete retention of alkene stereochemistry.     

The stereochemistry of heterocycles

Fifteen previously unreported 2-alkyl- and 5-alkyl-2, 2-dimethyl-1, 3-dithianes have been synthesized by the condensation of 2-alkylpropane-1, 3-dithiols with acetaldehyde, isobutylraldehyde, and acetone, and their structures have been confirmed by their IR spectra. The existence of stereoisomers in a number of the thioacetals has been shown by GLC and TLC. Some of the stereoisomeric 2, 5-diakyl-1, 3-dithianes have been separated by fractionation in an efficient column into the individual isomers, the purity of which was confirmed by TLC, GLC, and IR spectroscopy.For part III, see [11].     

The stereochemistry of ketoreduction

In this issue of Chemistry & Biology, Leadlay and coworkers report overproduction of a number of ketoreductase domains from modular polyketide synthases. These discrete enzymes allow the stereochemistry of polyketide ketoreduction to be studied in isolation.     

The stereochemistry of nevskin

Summary The relative configurations of the substituents in nevskin have been determined from the H¹ NMR spectra in CDCl₃ with additions of Eu(FOD)₃ as paramagnetic shift reagent.Institute of Botany, Academy of Sciences of the Azerbaidzhan SSR, Baku. All-Union Scientific-Research Institute of Medicinal Plants, Moscow. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 450–452, July–August, 1976.     

The stereochemistry of quassin

The relative configuration of quassin and several of its derivatives has been derived.