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Updated: May 16, 2026

A Protocol for Safe Lithiation Reactions Using Organolithium Reagents
Published on: November 12, 2016
Variation in the site of lithiation of 2-(2-methylphenyl)ethanamine derivatives
Keith Smith1, Gamal A El-Hiti, Mohammed B Alshammari
1School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, UK. smithk13@cardiff.ac.uk
Abstract:
Unexpectedly, lithiation of N'-(2-(2-methylphenyl)ethyl)-N,N-dimethylurea with 3 equiv of n-butyllithium in anhydrous THF at 0 °C takes place on the nitrogen and on the CH(2) next to the 2-methylphenyl ring (α-lithiation). The lithium reagent thus obtained reacts with various electrophiles to give the corresponding substituted derivatives in excellent yields. Similarly, lithiation of N-(2-(2-methylphenyl)ethyl)pivalamide under similar reaction conditions followed by reaction with benzophenone as a representative electrophile gave the corresponding α-substituted product in high yield. Surprisingly, no products resulting from lateral lithiation were observed under the conditions tried, which sharply contrasts with the reported results for lateral lithiation of tert-butyl (2-(2-methylphenyl)ethyl)carbamate.
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