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Updated: Aug 24, 2025

A Protocol for Safe Lithiation Reactions Using Organolithium Reagents
Published on: November 12, 2016
In Situ Quench Reactions of Enantioenriched Secondary Alkyllithium Reagents in Batch and Continuous Flow Using an
Alexander Kremsmair1, Henrik R Wilke1, Johannes H Harenberg1
1Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, Haus F, 81377, München, Germany.
Abstract:
We report a practical in situ quench (ISQ) procedure involving the generation of chiral secondary alkyllithiums from secondary alkyl iodides (including functionalized iodides bearing an ester or a nitrile) in the presence of various electrophiles such as aldehydes, ketones, Weinreb amides, isocyanates, sulfides, or boronates. This ISQ-reaction allowed the preparation of a broad range of optically enriched ketones, alcohols, amides, sulfides and boronic acid esters in typically 90-98 % ee. Remarkably, these reactions were performed at -78 °C or -40 °C in batch. A continuous flow set-up permitted reaction temperatures between -20 °C and 0 °C and allowed a scale-up up to a 40-fold without further optimization.
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