Variation in the site of lithiation of 2-(2-methylphenyl)ethanamine derivatives

Unexpectedly, lithiation of N′-(2-(2-methylphenyl)ethyl)-N,N- dimethylurea with 3 equiv of n-butyllithium in anhydrous THF at 0 C takes place on the nitrogen and on the CH₂ next to the 2-methylphenyl ring (α-lithiation). The lithium reagent thus obtained reacts with various electrophiles to give the corresponding substituted derivatives in excellent yields. Similarly, lithiation of N-(2-(2-methylphenyl)ethyl)pivalamide under similar reaction conditions followed by reaction with benzophenone as a representative electrophile gave the corresponding α-substituted product in high yield. Surprisingly, no products resulting from lateral lithiation were observed under the conditions tried, which sharply contrasts with the reported results for lateral lithiation of tert-butyl (2-(2-methylphenyl)ethyl)carbamate.