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
Andrew C. Stevens, Katrien Brak, W. Stacy Bremner, Angela Brown, Andrei Chtchemelinine, Lars V. Heumann, James A. Kerschen, Witold Subotkowski, Tiago O. Vieira, Lydia Wolfe, Boran Xu, Chia-Yun Yu
Abstract
This manuscript describes the development and 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.
Topics & Concepts
ReagentHalideChemistrySalt (chemistry)Nucleophilic additionAmmoniumLanthanideGrignard reagentCombinatorial chemistryPhosphonium saltNucleophileMedicinal chemistryOrganic chemistryCatalysisIonCoordination Chemistry and OrganometallicsChemical Reaction MechanismsSynthesis and Catalytic Reactions