Abstract
The reaction of lithiating agents with various 3-bromopyridines has been investigated.
An unprecedented selectivity was observed with t -BuLi, which effected a clean lithiation at C-4. With 3-bromo and 2-chloro-3-bromo
pyridines, the ortholithiation-exchange ratio was strongly electrophile and addition
order dependent while 2-chloro-5-bromopyridine always gave exclusive C-4 substitution.
Key words
bromine-lithium exchange - ortholithiation - bromopyridines - regioselectivity
References
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General Procedure for Ortholithitaion of 4 with
t
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t -BuLi (1.17 mL, 2 mmol) was added dropwise under nitrogen. After 5 min at -78 °C,
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mmol) in THF (4 mL). The reaction medium was then allowed to warm to r.t. (1 h) and
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Under these reaction conditions (1 equiv, -78 °C in THF), t -BuLi did not metallate pyridine even after 1 h, and gave only 2-tert -butylpyridine in 10-15%.
