The metalation of 1-and 2-(trifluoromethyl)naphthalenes: noteworthy site selectivities

This article provides insight into the various factors by which electronegative substituents affect the kinetic acidity of arenes and, more specifically, naphthalenes. Both 1- and 2-(trifluoromethyl)naphthalenes were consecutively treated with an organometallic or lithium dialkylamide-type base and carbon dioxide. Due to single electron-transfer triggered side reactions, the yields of (trifluoromethyl)naphthoic acids were moderate to poor. 1-(Trifluoromethyl)naphthalene was exclusively attacked at the 2-position as expected. The 2-isomer reacted with tert-butyllithium in the presence of potassium tert-butoxide solely at the 1-position, but with sec-butyllithium in the presence of N,N,N',N'-tetramethylethylene-diamine concomitantly at the 3- and 4-positions. Authentic samples of the key acids 1, 4, 5 and 6 were prepared based on independent, unambiguous methods.