Thioimidates reduction

The reduction of thioimidates to the aldehyde oxidation level can be accomplished with aluminum amalgam. The reaction has not been investigated as a general method, but was developed to solve a spe-... 

In an attempt to increase the Wittig-type reactivity of amide derivatives the reaction of phosphonium ylides, e.g. (91), with thioimides, e.g. (92) and (93), has been investigated.49 Although the thio-Wittig reaction takes place, S-alkylation and oxidation-reduction occur in competition and reduce the usefulness of this reaction in synthesis. Further studies of the reactions of a-perfluoroacylalkylphosphonium salt (94),50.51 generated by... 

The mechanism was postulated to involve a Cu(l)-carboxylate as the active species, which promotes oxidative addition of the thioimide. Subsequent transme-talation and C-S reductive elimination generates the thioether product. An excess of boronic acid is often required, as copper catalysts may competitively oxidize aryl substituted boronic acids to the corresponding phenol in the presence of adventitious water [21]. The rate of acceleration observed with amino acids and carboxylate-based ligands, such as 3-methylsalicylate, is attributed to stabilization of a 7i-Cu intermediate generated through a nucleophilic aromatic substitution type mechanism (Scheme 1) [72]. The amino acid or carboxylate ligand may also simply stabilize putative Cu(lll) intermediates. 

A Pinner reaction between the primary amine (403) and the thioimidate (404) (from the thioamide and iodomethane) gave xylamidine (405) (Scheme 5.94.). Base catalysed reaction between 2-chloropropionitrile and 3-methoxyphenol followed by lithium aluminium hydride reduction provided the amine (403). Xylamidine is a powerful 5HT2 receptor antagonist, and has some value in pharmacological research [551],... 

Alternatively, boronic acids react under the influence of Cu-catalysis with electrophilic iV-thioimides under mild conditions and in the absence of base (Eqn. 1-7). Various copper carboxylates can be used (e.g., CuMeSal, CuTC, and CuOAc) but not salts such as CuCl, CuCN, or CU2O. A presumed Cu(I)/Cu(III) cycle is put forth, where the thioimide is oxidatively added to the Cu(I) catalyst, and the RB(0H)2 supplies the R group on the metal (with loss of imide-B(OH)2) prior to reductive elimination. Several biaryl thioethers were made in this way (e.g., 85,86) in THF (or dioxane), along with aryl alkenyl derivative 87. All bases examined (K2CO3, NaOH, TBAF, pyridine, EtsN) inhibited the reaction. 

Another convenient method for the transformation of tertiary amides to the corresponding amines, via the reduction of the thioimidates (21) with sodium borohydride or cyanoborohydride, has appeared (cf. Vol. 5, p. 190), This method avoids the use of triethyloxonium tetrafluoroborate (Scheme 23). 

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