Lithium-halogen exchange bromo pyridine

Schlosser and co-workers have reported the shift of lithium in lithiated l-bromo-3-(tri-fluoromethyl)benzene 2,fa Quenching at — 100 C gives exclusively the product derived from 2, whereas after 2 hours at — 75 C, arene 2 is completely converted into less basic 3. A lithium-iodine exchange takes place in lithiated 2-chloro-3-iodo-6-(trifluoromethyl)pyridine 4, which at —85 C is totally converted into the less basic isomer 5.7 These rearrangements have been discussed in terms of a base-catalyzed halogen dance or halogen-shuffling mechanism. 

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. " ... 

---