Synthesis 2012; 44(13): 2013-2022
DOI: 10.1055/s-0031-1291008
paper
© Georg Thieme Verlag Stuttgart · New York

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

Keith Smith*
,
Gamal A. El-Hiti*
,
Mohammed B. Alshammari
Further Information

Publication History

Received: 12 February 2012

Accepted after revision: 11 April 2012

Publication Date:
05 June 2012 (online)


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.

 
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