Molecular Mechanics Analysis of Structure and Diastereoselectivity toward Lithiation in Amido- and α-Aminoferrocene Complexes

A molecular mechanics force field has been developed for the conformational analysis of amido- and α-aminoferrocenes. Parameterization for ring-substituent rotational barriers in amidoferrocenes and other cross-conjugated derivatives have been calculated using DFT on both the free and complexed cyclopentadienyl ligand. Modeled structures of (diisopropylamido)- and (dimethylamido)ferrocene and N,N-dimethyl-α-ferrocenylethylamine are in agreement with those determined through single-crystal X-ray diffraction. The diastereoselective lithiation of N,N-dimethylferrocenylethylamine and sparteine-mediated enantioselective lithiation of (diisopropylamido)ferrocene using MeLi have been modeled through an assumed reversible adduct formation at the amine nitrogen or amide oxygen, followed by an irreversible ring lithiation. Results indicate that selectivity results from ring lithiation via the adduct conformer with the shortest C−Hring- - -H3C−Li interaction.