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

Abstract

Lithiation of N ′-phenethyl- N , N -dimethylurea with three equivalents of tert -butyllithium in anhydrous tetrahydrofuran at –78 °C takes place on the nitrogen and on the side-chain of the CH 2 next to the phenyl ring (α-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 tert -butyllithium in tetrahydrofuran at –78 °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 α-CH 2 with tert -butyllithium at 0 °C. On the other hand, lithiation of N ′-(4-phenylbutyl)- N , N -dimethylurea with tert -butyllithium at 0 °C takes place on one of the methyl groups of the urea unit.