From 2- to 3‑Substituted Ferrocene Carboxamides or How to Apply Halogen “Dance” to the Ferrocene Series

Two methods were compared to convert
ferrocene into N,N-diisopropyl­ferrocenecarboxamide, N,N-diethyl­ferrocene­carboxamide, N,N-dimethyl­ferrocene­carboxamide,
and (4-morpholinocarbonyl)­ferrocene, namely, deprotometalation followed
by trapping using dialkylcarbamoyl chlorides and amide formation from
the intermediate carboxylic acid. The four ferrocenecarboxamides were
functionalized at C2; in the case of the less hindered
and more sensitive amides, recourse to a mixed lithium–zinc
2,2,6,6-tetramethylpiperidino-based base allowed us to achieve the
reactions. Halogen migration using lithium amides was next optimized.
Whereas it appeared impossible to isolate the less hindered 3-iodo­ferrocene­carboxamides,
3-iodo-N,N-diisopropyl­ferrocene­carboxamide
proved stable and was converted to new 1,3-disubstituted ferrocenes
by Suzuki coupling or amide reduction. DFT calculations were used
to rationalize the results obtained.