Pyridine 3- bromo-2-chloro-, metalation

The scope of various pyridine derivatives with 1-hexene was examined with L45c-Sc/[Ph3C][B(C6F5)4] as the catalyst (Table 5.8). The asymmetric alkylation of 2-Me, 2-Et, 2- Pr, 2- Bu, and 2-phenyl-substituted pyridines 188 could also be achieved similarly in high yields (83-94%) and enantioselectivity (up to 94 6 er) (entries 1-5). Notably, the C—H bond activation reaction occurred selectively at the pyridine unit rather than at the phenyl group in the case of 2-phenylpyridine, which is in contrast with the reactions catalyzed by late transition metal complexes. The iodo, bromo, and chloro substituents in the picoline substrates are well compatible (entries 6-8). No alkylation reaction was observed with unsubstituted pyridine or quinoline, probably due to the poisoning effect of the N atom of pyridine to the metal center. 

Cottet, F. Manill, M. Mongin, F. Espinosa, D. Schlosser, M. Further metalations and functionalizations of chloro-, bromo- and iodo(trifluoromethyl)pyridines. Synthesis 2004, (10), 1619-1624. 

The regioselective functionalization of pyridines using metallation or halogen/metal exchange reactions has been reviewed. There has been a detailed mechanistic study of the ort/io-lithiation of 2-fluoro- and 2,6-difluoro-pyridines by lithium diisopropy-lamide (LDA) in tetrahydrofuran at -78°C where aggregation and aggregate-exchange phenomena are critical.The mono-lithiation of the boron trifluoride adduct of 3-chloro- and 3-bromo-pyridines results in reaction at the 2-position. However, with two equivalents of LDA, the 2,6-dilithiated derivatives may be formed. Subsequent reaction with electrophiles may result in the formation of 2-, 6-, or 2,6-substituted products. " ... 

---