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Updated: Oct 1, 2026

A Protocol for Safe Lithiation Reactions Using Organolithium Reagents
Published on: November 12, 2016
A theoretical investigation into the inversion barrier of dipole-stabilized alpha-aminoorganolithiums
Fredrik Haeffner1, Peter Brandt, Robert E Gawley
1Department of Physics, Stockholm University, SCFAB, S 106 91 Stockholm, Sweden. haeffner@physto.se
Abstract:
[reaction: see text] Results from density functional theory calculations (B3LYP/6-31+G) suggest that inversion of the monomer of 2-lithio-N-formylpyrrolidine (2) in coordinating ethereal solvent occurs with an activation barrier of 15.7 kcal/mol, while the inversion of the monomer in a noncoordinating hydrocarbon solvent is considerably slower. However, aggregation into a trimer in hydrocarbon solvent restores the low inversion barrier. This study suggests that solvation and aggregation may influence the mechanism and rate of racemization of dipole-stabilized alpha-aminoorganolithiums.
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