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Updated: Mar 13, 2026

A Protocol for Safe Lithiation Reactions Using Organolithium Reagents
Published on: November 12, 2016
Lithium Enolates Derived from Weinreb Amides: Insights into Five-Membered Chelate Rings
Michael J Houghton1, David B Collum1
1Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University , Ithaca, New York 14853-1301, United States.
Abstract:
Enolization of O-methyl hydroxamic acids (Weinreb amides) in tetrahydrofuran solution with lithium diisopropylamide affords predominantly tetrameric enolates. Aryl substituents on the enolates promote deaggregation. The aggregation states are assigned by using the method of continuous variation in conjunction with 6Li NMR spectroscopy. Decoalescence of the tetramer resonance below -100 °C shows considerable spectral complexity attributed to isomerism of the methoxy-based chelates. Density functional theory calculations were used to examine the consequences of the bite angle of five-membered chelates in cubic tetramers and resulting solvation numbers that were higher than anticipated.
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