1,2,4-Tris(trifluoromethyl)benzene: selective lithiation and subsequent electrophilic substitution

1,2,4-Tris(trifluoromethyl)benzene quant. undergoes a hydrogen/metal exchange when treated with an ethereal soln. of lithium 2,2,6,6-tetramethylpiperidide. Proton abstraction occurs concomitantly from positions 5 and 6, the ratios varying from 80:20 to 90:10, depending on the reaction conditions. Pure 5-iodo-1,2,4-tris(trifluoromethyl)benzene was readily obtained by fractional crystn. of the regioisomeric mixt. and was used to prep. 5-substituted derivs. of 1,2,4-tris(trifluoromethyl)benzene by consecutive reaction with tert-butyllithium and an electrophile. [on SciFinder (R)]