Rh(<scp>iii</scp>)-Catalyzed diastereoselective transfer hydrogenation: an efficient entry to key intermediates of HIV protease inhibitors
Fangyuan Wang, Long‐Sheng Zheng, Qiwei Lang, Congcong Yin, Ting Wu, Phannarath Phansavath, Gen‐Qiang Chen, Virginie Ratovelomanana‐Vidal, Xumu Zhang
Abstract
A highly efficient diastereoselective transfer hydrogenation of α-aminoalkyl α'-chloromethyl ketones catalyzed by a tethered rhodium complex was developed and successfully utilized in the synthesis of the key intermediates of HIV protease inhibitors. With the current Rh(iii) catalyst system, a series of chiral 3-amino-1-chloro-2-hydroxy-4-phenylbutanes were produced in excellent yields and diastereoselectivities (up to 99% yield, up to 99 : 1 dr). Both diastereomers of the desired products could be efficiently accessed by using the two enantiomers of the Rh(iii) catalyst.
Topics & Concepts
Transfer hydrogenationChemistryRhodiumCatalysisProteaseCombinatorial chemistryHuman immunodeficiency virus (HIV)StereochemistryEnzymeOrganic chemistryVirologyBiologyRutheniumAsymmetric Hydrogenation and CatalysisHIV/AIDS drug development and treatmentCyclopropane Reaction Mechanisms