From 2- to 3-Substituted Ferrocene Carboxamides or How to Apply Halogen "dance" to the Ferrocene Series

Abstract

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.