Regioselectivities in deprotonation of 2-(4-chloro-2-pyridyl)benzoic acid and corresponding ester and amide

Upon treatment of ethyl 2-(4-chloro-2-pyridyl)benzoic acid, 2-(4-chloro-2-pyridyl)benzoate, and NN-diisopropyl-2-(4-chloro-2pyridyl)benzamide with LTMP at -75 degreesC in THF, the lithio derivatives at C5' are generated regiospecifically, as demonstrated by subsequent quenching with electrophiles. The lithio derivative at C3' is only evidenced from the benzamide at higher temperature (-50 degreesC, when treated with LTMP in THF; it instantly cyclizes to 1-chloro-4-azafluorenone. The latter is converted to onychine, an alkaloid endowed with anticandidal activity. (C) 2004 Elsevier Ltd. All rights reserved.