Explanation of Different Regioselectivities in theortho-Lithiation of Ferrocenyl(phenyl)methanamines

Diastereoselective ortho-lithiation of ferrocenes is a principal strategy for the synthesis of chiral ferrocene ligands. Dilithiation of (R)-1-(2-bromophenyl)-1-ferrocenyl-N,N-dimethylmethanamine leads to a dilithium intermediate, which can be transformed to a Taniaphos ligand with (R,Rp)-configuration. On the other hand, lithiation of (R)-1-phenyl-1-ferrocenyl-N,N-dimethylmethanamine affords a lithiated product with opposite configuration of the stereogenic plane. Presumably, the second lithium atom attached at the ortho-position of the phenyl ring is responsible for this difference through the intramolecular multicenter arrangement involving both lithium atoms and their adjacent carbon atoms, the iron atom of the ferrocenyl moiety, and the nitrogen atom of the amino group. This hypothesis has been supported also by quantum chemical calculations.