The ferrocene halogen “dance” has been deemed hardly controllable. Here, we describe the first efficient examples of this reaction. Conversion of 1-fluoro-2-iodo (or 1-chloro-2-iodo) to 1-fluoro-3-iodo (or 1-chloro-3-iodo) ferrocenes was ensured by suitably protecting the free 5-position.

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 C 2 ; in the case of the less hindered and more sensitive amides, recourse to a mixed lithium-zinc 2,2,6,6-tetramethylpiperidinobased base allowed 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.

A series of N-aryl and N-heteroaryl pyrazoles have been deproto-metallated using a 2,2,6,6-tetramethylpiperidino-based mixed lithium-zinc combination. Mono-, di-, and tri-iodides have been obtained after subsequent trapping with iodine, depending on the substrate and on the quantity of base used. The results have been discussed in the light of the CH acidities of the substrates, determined both in the gas phase and in THF solution using the DFT B3LYP method.

A series of chloro- and bromopyridines have been deprotometalated by using a range of 2,2,6,6-tetramethylpiperidino-based mixed lithium-metal combinations. Whereas lithium-zinc and lithium-cadmium bases afforded different mono- and diiodides after subsequent interception with iodine, complete regioselectivities were observed with the corresponding lithium-copper combination, as demonstrated by subsequent trapping with benzoyl chlorides. The obtained selectivities have been discussed in light of the CH acidities of the substrates, determined both in the gas phase and as a solution in THF by using the DFT B3LYP method.

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