Mechanism of lithium diisopropylamide-mediated substitution of 2,6-difluoropyridine.
Treatment of 2,6-difluoropyridine with lithium diisopropylamide in THF solution at -78 degrees C effects ortholithiation quantitatively. Warming the solution to 0 degrees C converts the aryllithium to 2-fluoro-6-(diisopropylamino)pyridine. Rate studies reveal evidence of a reversal of the ortholithiation and a subsequent 1,2-addition via two monomer-based pathways of stoichiometries [ArH*i-Pr(2)NLi(THF)](double dagger) and [ArH*i-Pr(2)NLi(THF)(3)](double dagger). Computational studies fill in the structural details and provide evidence of a direct substitution without the intermediacy of a Meisenheimer complex.
Viciu
Mihai S
MS
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301, USA.
Gupta
Lekha
L
Collum
David B
DB
D007700:Kinetics; D011437:Propylamines / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D012996:Solutions; D013055:Spectrophotometry, Infrared; D013696:Temperature
C518916:2,6-difluoropyridine; D011437:Propylamines; D011725:Pyridines; D012996:Solutions; C007442:diisopropylamine
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