Lukes reduction formic acid

The remaining major method for the reduction of the C=N+ functionality is the reaction with formic acid. The first report was that of Luke , who found (95) that thermal cleavage of l,l-dimethyl-2-methylenepyrrolidinium formate was accompanied by reduction. Lukes then explored the generality... 

That the reduction with formic acid proceeds by a hydride transfer reaction was proposed by Lukes and Ji2ba 100) and finally proven by Leonard and Sauers 63). The use of variously deuterated formic acid allowed Leonard and Sauers to determine that (1) protonation or... 

Reduction of both the free bases and their quaternary salts proceeds by similar mechanisms. In pyridine and its quaternary salts, a hydride ion, or its equivalent, attacks a position of a low electron density, i.e. the 2- or 4-position. The mechanism of the reduction of quaternary salts of pyridine and its homologs (LukeS and Ferles414) has been elucidated using deuterated formic acid.415 The hydride ion attack in position 2 is followed by addition of a proton to the enamine grouping with the formation of A 3-piperideines (124). If the reduction commences with attack in the 4-position, a saturated base (125) is the final product. In agreement, a-picoline methobromide yields 1,2-dimethyl-... 

Piperideines unsubstituted at the nitrogen atom may be prepared from the corresponding pyridine compounds by partial reduction with sodium and boiling alcohols (the Ladenburg reduction), by electrolytic reduction, or, preferably, by reduction with aluminum hydride. l-Alkyl-3-piperideines are prepared by reduction of quaternary pyridinium salts with formic acid (the Lukes reduction) or with complex hydrides. 

Reduction of quaternary pyridinium halides (or, more precisely, formates) with formic acid in the presence of potassium formate at about 150°C is usually referred to as the Lukes reduction.80-95 Instead of potassium formate, triethylamine may be used, especially with quaternary pyridinium iodides.85,86 Mixtures of l-alkyl-3-piperideines (77) and 1-alkylpiperidines (78) are usually obtained. Formation of piperideines (77) might be explained by analogy with the Ladenburg reduction of pyridine bases the double bond at position 3 is resistant toward further reduction by formic acid or by... 

Cervinka and Kriz95 investigated the mechanism of the Luke reduction with the use of deuteriated formic acid. 1-Methylpyridinium iodide afforded a mixture of l-methyl-5-deuterio-3-piperideine (92, R = H) and l-methyl-3,5-dideuteriopiperidine (93, R = H). A mixture containing l,3-dimethyl-3,5-dideuteriopiperidine (93, R = Me) was obtained from 1,3-dimethylpyridinium iodide. 

The reduction of pyridinium species with formic acid in the presence of its salts at elevated temperatures is often referred to as Lukes reduction and has been reviewed. Mixtures of tetrahydropyridines (98) and piperidines (99 Scheme 20) commonly result. The isolated double bond is resistant to further reduction under these conditions. Reductive cleavage and subsequent cyclization have also been observed, producing ketones as by-products. ... 

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