Asymmetric Catellani Reaction And Enantioselective Ring-Opening Reaction Of Cyclic Diaryliodonium

Axially chiral biaryls represent an important class of stereoisomers.They can be found among natural products,ligands and pharmaceutical molecules.The synthesis of optically active biaryl atropisomers constitutes a significant challenge,such as divergent synthesis and atom-economy with low or even no waste.This thesis contains two chapters:(a)the application of asymmetric Catellani reaction in synthesis of Rhazinilam family natural products;(b)copper-catalyzed enantioselective ring-opening reaction of cyclic diaryliodoniums.The first chapter:the study of synthesis of(+)-rhazinal,(+)-rhazinilam,and(+)-kopsiyunnanine C1-3 via asymmetric Catellani reaction.We developed the first catalytic asymmetric palladium/norbornene-catalyzed reaction,where α-aryl tetrahydroquinoline derived phosphoramidite ligand is found to be the optimum ligand.Taking advantage of this transformation,the core skeleton of rhazinal was achieved in 65%yield with 88%ee.Then concise and unified enantioselective syntheses of(+)-rhazinal,(+)-rhazinilam,and(+)-kopsiyunnanine C3 are realized.We also discovered acid-catalyzed etherification of(pyrrol-2-yl)methanol,which provided a convenient approach for the synthesis of kopsiyunnanine C1-2.The second chapter:copper-catalyszed enantioselective ring-opening reaction of cyclic diaryliodoniums.We described a highly enantioselective copper-catalyzed ring-opening reaction of cyclic diaryliodoniums(99%yield,up to>99%ee),where the relatively poor reactivity of the cyclic diaryliodonium was improved by increasing the torsional strain of the diaryliodonium salts.This method enabled us to access enantioenriched amino aryliodide with high atom-economy,which are precursors for divergent synthesis of axially chiral compounds via cross-coupling of the Ar-I functionality.We also proposed a rational mechanism based on some control experiments and then we confirmed our hypothesis via kinetic experiment and DFT calculations.