Dexibuprofen

We report a tandem asym. Cu-catalyzed propargylic amination (ACPA)/Ag-catalyzed carboxylative cyclization (SCC) with CO₂ to 5-methylidene-2-oxazolidinones, even with tetrasubstituted stereocenters.By varying pyridine bisoxazoline (PYBOX) ligands, a general and highly enantioselective ACPA of unprecedentedly broad scope of secondary propargylic acetates and primary amines is achieved.Both α-aryl and α-aliphatic propargylic acetates could react with either aromatic or aliphatic primary amines to give the corresponding N-aryl or N-aliphatic ethynylamines with α-aliphatic or α-aryl groups in over 90% ee for use in the next step.The key to developing this one-pot sequence is to use a chelator triethylenetetramine (TETA) to mask the copper ion, to avoid its neg. effect on Ag-catalyzed cyclization, while releasing PYBOX to activate the silver catalyst.With the methylidene moiety, these oxazolidinones can be readily elaborated.The value of the sequence is further shown by the catalytic enantioselective total synthesis of (-)-cytoxazone and the potent ezetimibe analog.

Herein, aromaticity-driven thio(seleno)ester group transfer from novel 1,4-dihydropyridine thio(seleno)esters to alkene feedstocks is disclosed by merging palladium and photoredox catalysis. In this process, photoactivation of dihydropyridine thio(seleno)esters is integrated with regioselective hydrometalation of alkenes, avoiding photoinduced Pd-C bond homolysis of organopalladium intermediates. Additionally, a regioselective hydroselenocarbonylation of an alkene is accomplished for the first time using a bench-stable selenoester reagent. The activation mode of novel dihydropyridine thioesters has been illustrated by detailed mechanistic studies, spectroscopic analysis, intermediate trapping, and isotope labeling experiments.