Homoleptic zincate-promoted room-temperature halogen-metal exchange of bromopyridines

Article abstract of DOI:10.1002/chem.201001664

Homoleptic lithium tri- and tetraalkyl zincates were reacted with a set of bromopyridines. Efficient and chemoselective bromine-metal exchanges were realized at room temperature with a substoichiometric amount of nBu ₄ZnLi₂·TMEDA reagent (1/3 equiv; TMEDA=N,N,N′,N′-tetramethylethylenediamine). This reactivity contrasted with that of tBu₄ZnLi₂·TMEDA, which was inefficient below one equivalent. DFT calculations allowed us to rationalize the formation of N...Li stabilized polypyridyl zincates in the reaction. The one-pot difunctionalization of dibromopyridines was also realized using the reagent stoichiometrically. The direct creation of C-Zn bonds in bromopyridines enabled us to perform efficient Negishi-type cross-couplings. Mild zincation! nBu₄ZnLi₂·TMEDA (in substoichiometric amounts) promoted efficient and chemoselective room-temperature bromine-metal exchange of a range of bromopyridines (see scheme). DFT calculations strongly supported the formation of a stabilized tripyridylzincate, which could be reacted with electrophiles or be directly involved in palladium-catalyzed cross-coupling reactions.