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 CH₂ 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-CH₂ 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.

Key words

N′-phenethyl-N,N-dimethylurea - side-chain lithiation - bromine–lithium exchange - electrophile - synthesis

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