Studies On Copper-catalyzed Asymmetric Ullmann Coupling Reaction For The C-n Bond Formation

Copper-catalyzed coupling reactions of aryl halides with amines may be the most powerful methods for theformation of N-arylation products.Achieving enantioselectivity in Ullmann-type reactions still remains as a significant challenge, since the copper-catalyzed aryl carbon-heteroatom coupling didn’t involve with the direct formation of a chiral centers. The main content of this paper focuses on:Copper-catalyzed Ullmann coupling reaction for building the chiral N-Heterocycles through asymmetric desymmetrizations and kinetic resolutionsPart I Desymmetric Intramolecular Ullmann C-N CouplingEnantioselective desymmetrization is an efficient method in asymmetric synthesis. In this paper,we are developing copper-catalyzed asymmetric Ullmann coupling reaction to build C-N bound. Starting from3-amino-2,2-bis(2-iodobenzyl) propanenitrile, under the Cul and (R)-BINOL-derived ligands, we synthesied the1,2,3,4-tetrahydroquinolines in highly enantioselectively through intramolecular Ullmann coupling.The product enantiomeric excesse could up to94%,yiled90%.Part II Intramolecular Ullmann C-N coupling via kinetic resolutionThe kinetic resolution is an efficient method to obtain highly enantioselective products in the studies of asymmetric catalysis. Based on the asymmetric desymmetrization strategy, the products bear two aryl rings with similar substitutes, To overcome these problems and increases variations in copper-catalyzed intramolecualr N-arylation.This work started from3-amino-2-benzyl-2-(2-iodobenzyl)propanenitrile, under the CuI and (R)-BINOL-derived ligands,1,2,3,4-tetrahydroquinolines were sythesied though intramolecular Ullmann coupling. The residue substrate could up to85%and pruduct to75%.In summary,this work studied copper-catalyzed Ullmann-type reactions through asymmetric desymmetrizations and kinetic resolutions in detail.We successful developed C-N coupling reaction bearing a chiral quaternary carbon center...