Nucleophilic substitutions using O‐alkyl‐N,N′‐dialkylisoureas. Applications to ephedrines

Abstract

Abstract. Dialkylcarbodiimides in the presence of a Cu' catalyst react cleanly with the hydroxyl group of N-methylated (lR,2S)-ephedrine and (lS,2S)-pseudoephedrine. These adducts react with nucleophiles like alkyl and aryl thiols as well as thioic acids and phthalimide to form the substitution products with overall retention of configuration. It is postulated that intramolecular participation of the amino group via an SN2 reaction leads to aziridium salts, which are subsequently opened by the nucleophiles via a second sN2 reaction. This synthetic approach is also useful for the inversion of simple secondary alcohols; on treatment with dicyclohexylcarbodiimide followed by benzothioic acid and treatment with LiAlH,, menthol was converted in good yield to neomenthane thiol.

The First Successful Use of Simple 1,2-Aminothioethers as Hybrid Ligands in the Palladium-Catalysed Asymmetric Allylic Substitution Reaction

“…17 According to the literature, 18 in analogous reactions, formation of the mesylate is followed by intramolecular nucleophilic attack by the ring nitrogen atom, so furnishing the aziridinium ion as a reactive intermediate with inversion of configuration. 17 According to the literature, 18 in analogous reactions, formation of the mesylate is followed by intramolecular nucleophilic attack by the ring nitrogen atom, so furnishing the aziridinium ion as a reactive intermediate with inversion of configuration.…”

Isoureas: Versatile Alkylation Reagents in Organic Chemistry

“…10 (H) Phenol ether and thiophenolether can be prepared via the reaction of O-alkyl isoureas with phenol and thiophenol, respectively. 11,12 (I) O-alkyl isoureas were reported as allyl reagents in C-C bond formation reactions in the presence of a palladium catalyst. 13 (J) The dehydration of secondary, tertiary and benzylic alcohols could be carried out in good yield in the presence of carbodiimide and catalytic amount of CuCl.…”

“…11,12 (I) O-alkyl isoureas were reported as allyl reagents in C-C bond formation reactions in the presence of a palladium catalyst.…”

Mechanochemical Nucleophilic Substitution of Alcohols via Isouronium Intermediates**

“…Indeed, O ‐alkyl isouronium salts can be obtained by the reactions of alcohols with halouronium salts [e. g., TCFH or its analogue fluoro‐ N , N , N ′, N ′‐tetramethylformamidinium hexafluorophosphate (TFFH)], a process commonly utilized for the preparation of amide coupling reagents. [ 42 , 43 ] Similarly to O ‐alkyl isoureas generated from alcohols and carbodiimides,[ 44 , 45 , 46 , 47 , 48 ] isouronium salts can act as reactive intermediates in nucleophilic displacement reactions. [ 49 , 50 ] However, none of these alcohol‐activation techniques have been previously attempted under solvent‐free conditions or utilized for the synthesis of amines.…”