In Situ Quench Reactions of Enantioenriched Secondary Alkyllithium Reagents in Batch and Continuous Flow Using an I/Li-Exchange

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.