Synthesis of a 7-azaindole by chichibabin cyclization: reversible base-mediated dimerization of 3-picolines.
The lithium diisopropylamide (LDA)-mediated condensation of 2-fluoro-3-picoline and benzonitrile to form 2-phenyl-7-azaindole via a Chichibabin cyclization is described. Facile dimerization of the picoline via a 1,4-addition of the incipient benzyllithium to the picoline starting material and fast 1,2-addition of LDA to benzonitrile cause the reaction to be complex. Both adducts are shown to reenter the reaction coordinate to produce the desired 7-azaindole. The solution structures of the key intermediates and the underlying reaction mechanisms are studied by a combination of IR and NMR spectroscopies.
Ma
Yun
Y
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301, USA.
Breslin
Sean
S
Keresztes
Ivan
I
Lobkovsky
Emil
E
Collum
David B
DB
D003500:Cyclization; D004095:Dihydropyridines / Q000138:chemical synthesis; D019281:Dimerization; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis*; D007700:Kinetics; D018020:Lithium Compounds / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010847:Picolines / Q000737:chemistry*; D012997:Solvents; D013055:Spectrophotometry, Infrared
C023422:7-azaindole dimer; D004095:Dihydropyridines; D007202:Indicators and Reagents; D007211:Indoles; D018020:Lithium Compounds; D010847:Picolines; D012997:Solvents