[Sigma]-intermediates in the chemistry of nitrogen heterocycles

Abstract

Using nmr spectroscopy, stable σ-intermediates were detected in the reactions of organolithium compounds with pyridine and several substituted pyridines. In the reactions of phenyllithium with 3-picoline (or with 3-ethylpyridine) the ratio of isomeric intermediates corresponded closely to that of the products. This finding confirmed a proposed mechanism that the intermediate-formation step (rather than the hydride elimination stage) determined the product distribution. The nmr spectra of reaction mixtures containing equimolar amounts of pyridine and 3-picoline (or 3-ethylpyridine) and limited amounts of phenyllithium revealed the competitive formation of various σ-intermediates; the ratio of intermediates formed in these reaction mixtures corresponded well with the ratio of the products. The methyl group in 3-piaoline was found to activate the heterocyclic substrate towards a nucleophilic addition by phenyllithium, whereas the ethyl group in 3-ethyl pyridine had a deactivating influence. This observation is in agreement with other previous reports. A mechanism for the reaction of organolithium reagents with pyridine has been proposed. 1-Lithio-2-phenyl-1,2-dihydropyridine, the σ-intermediate isolated from the reaction of phenyllithium and pyridine, was found to be a unique reducing agent. Unlike the mixture from which it was isolated, it reduced benzophenone rapidly and in near quantitative yields. Based on its reactions with various 4-substituted benzophenones, the mechanism of the reduction appeared to be similar to that proposed for lithium tetrakis-N-dihydropyridyl aluminate (LDPA). The deuterated analogue of the σ-intermediate promises to be an excellent reagent for deuterium labelling. ...