Mischmetall, an alloy of the light lanthanides, has been used in a variety of organicreactions, either as a coreductant in samarium(II)-mediated reactions (Barbier and Grignard-type reactions, pinacoliccouplingreactions) or as the promoter of Reformatsky-type reactions. It has been also employed as the starting material for easy syntheses of lanthanide trihalides, the reactivity of which has been
Development of a Scalable Lanthanide Halide/Quaternary Ammonium Salt System for the Nucleophilic Addition of Grignard Reagents to Carbonyl Groups and Application to the Synthesis of a Remdesivir Intermediate
作者:Andrew C. Stevens、Katrien Brak、W. Stacy Bremner、Angela M. Brown、Andrei Chtchemelinine、Lars Heumann、James A. Kerschen、Witold Subotkowski、Tiago Vieira、Lydia C. Wolfe、Boran Xu、Chia-Yun Yu
DOI:10.1021/acs.oprd.1c00191
日期:2022.3.18
implementation of a scalable additive system, consisting of a lanthanide salt and a solubilizing quaternary ammonium salt, to improve the yield and robustness of the addition of an organomagnesium reagent to a ribonolactone en route to remdesivir. This system was found to be generally applicable in enhancing other challenging organomagnesium additions to enolizable and hindered carbonyl-containing compounds
The addition of Grignardreagents to ketones using sub-stoichiometric amounts of LaCl 3 ·2LiCl was studied. Catalytic amounts of LaCl 3 ·2LiCl (30 mol%) provide, in most cases, yields similar to those obtained using a stoichiometric amount.