Lithiation and Substitution of N′-(ω-Phenylalkyl)-N,N-dimethylureas

Lithiation of N'-phenethyl-N,N-dimethylurea with three equivalents of tert-butyllithium in anhydrous tetrahydrofuran at -78 degrees C takes place on the nitrogen and on the side-chain of the CH2 next to the phenyl ring (alpha-lithiation). The 2-lithio isomer can be obtained via bromine-lithium exchange of N'-2-(2-bromophenyl)ethyl-N,N-dimethylurea using methyllithium followed by tertbutyllithium in tetrahydrofuran at -78 degrees C. The lithium reagents thus obtained react with various electrophiles to give the corresponding substituted derivatives in excellent yields. Lithiation of N'-(3-phenylpropyl)-N, N-dimethylurea takes place on the alpha-CH2 with tert-butyllithium at 0 degrees C. On the other hand, lithiation of N'-(4phenylbutyl)-N,N-dimethylurea with tert-butyllithium at 0 degrees C takes place on one of the methyl groups of the urea unit.