Nitrogen reaction with organolithium

The mechanism of organolithium addition to naphthyl oxazolines is believed to occur via initial complexation of the alkyllithium reagent to the oxazoline nitrogen atom and the methyl ether to form chelated intermediate 17. Addition of the alkyl group to the arena 7t-system affords azaenolate 18, which undergoes reaction with an electrophile on the opposite face of the alkyl group to provide the observed product 4. The chelating methyl... 

A great nnmber of chiral bidentate nitrogen and oxygen ligands, which served well with other cations than lithinm, are known . Only very limited success was achieved with organolithium compounds in the classical examples of addition reactions onto aldehydes 335-337... 

There is no doubt that in these. reactions the nitrogen atom of the pyridine ring is complexed with either the lithium alkyl or aryl or with the lithium bromide which is usually present in many preparations of organolithium compounds. It has been established that, either in the presence of an excess of lithium bromide or in the total absence of this salt, phenyllithium still gives the same ortho .para ratio on reaction with 3-picoline.229 To account for the predominant formation of the 2,3-isomer in the reaction of CH3Li with 3-alkylpyridines, it was suggested261 that the transition states for these reactions were similar... 

Organomagnesium compounds usually resemble organolithium compounds in their reactions with nitrogen heterocyclic aromatic compounds [E, G], but they generally give inferior results for preparative purposes. Thus, as in the case of organolithium compounds, addition normally occurs at the 2-position of pyridine, and subsequent elimination or oxidation gives the 2-substituted pyridine [1] ... 

Reaction with (172) and other aldoximes may require oxime activation, which can be achieved with the addition of 1 equiv. of BF3-OEt2." " Yields in the addition of organometallic reagents to substituted aldoximes are modest and are a function of the isomeric composition of the oxime ethers, as the (Z)-oxime isomers are reported to preferentially react with organolithium reagents (entries 1 and 2, Table 13). ° The reaction has been employed for the preparation of 6-aminoalkyl-substituted pencillins (entry 3, Table 13)."° Cyclic oxime ether additions have also been evaluated (entries 4 and 5, Table 13). ° With the lability of the nitrogen-oxygen bond, addition to S-substituted isoxazolines provides a potential avenue for stereospecific synthesis of substituted 3-aminoalcohols (entry 5, Table 13). 

Other bases may be employed, e.g. lithium hydride, sodium hydride, sodium amide or sodium in ethylene glycol with sodium in ethylene glycol, the reaction is called the Bamford-Stevens reaction. Aldehyde tosylhydrazones (200) do not form dianions with organolithiums, but the reagent adds to the carbon-nitrogen double bond to give the dilithium derivative (201) which decomposes to the organolithium compound (202). 

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