Side-Chain Lithiation of N^′ -(4-Chlorophenethyl)- and N^′ -(4-Methylphenethyl)-N, N-dimethylureas: Experimental and Theoretical Approaches

α -Lithiation of N^′-(4-chlorophenethyl)- and N^′-(4-methylphenethyl)-N, N-dimethylureas occurs using t-butyllithium (3.3 molar equivalents) in dry tetrahydrofuran at - 60 to 0 ^∘C on NH and on the CH ₂ next to the aryl ring. The lithium reagents generated in situ are trapped with several electrophiles (benzophenone, cyclohexanone, 2-butanone, 4-anisaldehyde, and benzaldehyde) to afford the corresponding substituted ureas in 79–96% yields. The experimental results were sustained by density functional theory calculations, which show that the side chain on the CH ₂ adjacent to the aryl ring is the most favorable site for the α -lithiation of N^′-(4-chlorophenethyl)-N, N-dimethylurea and N^′-(4-methylphenethyl)-N, N-dimethylurea.