Imines ortholithiation

It is just about possible to ortholithiate imines, but in nearly all cases, the side reaction of nucleophilic attack at C=N is at least as important. Ortholithiation can overcome this side-reaction if it is assisted by an additional directing group (Scheme 58) . ... 

These reactions have been used in the synthesis of aikaioids such as corydalic acid methyi ester 502 (Scheme i95). Isoiated from Corydalis incisa, 502 is derived from a proposed biosynthetic intermediate in the route to the tetrahydroprotoberberine aikaioids. The 1,2,3,4-tetrasubstituted ring of 502 demands control by an ortholithiation strategy, and the synthetic route proposed by Clark and Jahangir employs a lateral lithiation of 503 and addition to an imine as the key disconnection at the centre of the molecule. 

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