Lithiated cyclic enamines

Lithiated cyclic enamines 691 " 5 996 and amidines 692989,997 have been prepared by deprotonation of the corresponding heterocycles with f-BuLi in THF at — 78 °C, being allowed to react with several electrophiles. This methodology has been applied to the synthesis of pyrrolidine and piperidine derived compounds, intermediates 691 and 692 acting in these cases not as acyllithium equivalents. 

The fact that lithiation usually occurs in hydrocarbon solvents suggests that the enamine deprotonation will only occur if it undergoes a Lewis acid-base interaction forming a complex with the base used. This is consistent with the assertions of a number of authors that formation of a cyclic transition state is necessary to explain the regiochemistry of these reactions53. 

Asymmetric Alkylations. The use of nitrogen derivatives of carbonyl compounds (imines, imides, amides, sultams, oxazo-lines) is often the most efficient procedure for achieving a-alkylations. Chiral auxiliaries bearing heteroatoms in a 1,2-relationship appear to work best, as they have chelation sites for the metal cation. High levels of asymmetric induction can thus be achieved due to the system rigidity. Cyclic ketones have been alkylated via the lithiated enamine formed from L-f-leucine f-butyl ester (eq 1). High enantiomeric excesses and predictability of absolute configuration make this method attractive. 

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