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

Nguyet Trang Thanh Chau (1) , Maxime Meyer (1) , Shinsuke Komagawa (2) , Floris Chevallier (3) , Yves Fort (1) , Masanobu Uchiyama (2) , Florence Mongin (3) , Philippe C. Gros (1)

1 SRSMC - Structure et Réactivité des Systèmes Moléculaires Complexes
2 Graduate School of Pharmaceutical Sciences
3 CPM - Chimie et Photonique Moléculaires

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 nBu4ZnLi2*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.

Mots clés: bromopyridines; crosscoupling; halogen-metal exchange; lithium; zinc

Domaines: Chimie organique

Nguyet Trang Thanh Chau, Maxime Meyer, Shinsuke Komagawa, Floris Chevallier, Yves Fort, et al.. Homoleptic zincate-promoted room-temperature halogen-metal exchange of bromopyridines. Chemistry - A European Journal, 2010, 16, pp.12425-12433. ⟨10.1002/chem.201001664⟩. ⟨hal-01010436⟩