Amines ortholithiation

Addition of a lithiated secondary amine to an aldehyde both protects the aldehyde from attack by RLi and turns it into an ortholithiation directing group. The best lithioamines for this purpose are A-lithio-A-methylpiperazine 53, iV-lithio-iV,iV,iV -trimethylethylene-diamine 56 and Al-lithio-Al,0-dimethylhydroxylamine 58 , which optimize the opportunity for coordination of BuLi to the intermediate alkoxide (54) (Scheme 27) . ... 

The dimethylaminomethyl group must operate solely by coordination to Li, and it is assumed, as for ortholithiation, that the deprotonation takes place after the initial equilibrium formation of a BuLi-amine complex. 

The example below shows ortholithiation, activated by the nitrogen atom of a tertiary amine, being used to make a new C—C bond. Here it is the nitrogen atom that directs attack of the butyllithium, again by complexation with the Li atom. 

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