Asymmetric Catalytic Synthesis Of 1,4-benzodioxanes And ?-trifluoromethyl Tertiary Alcohols

The efficient construction of chiral compounds has always been a hot research direction in the fields of organic chemistry and drug discovery.Among them,chiral seven-membered oxa-heterocycles and ?-trifluoromethyl tertiary alcohols are very important building blocks in organic synthesis,and also important motifs in many natural products and biologically active molecules.Therefore,it is of great significance to develop efficient synthetic methods to prepare such compounds.In this paper,with chiral phosphoric acid catalysis and nickel metal catalysis,we have developed two highly efficient asymmetric catalytic reactions for the synthesis of chiral 1,4-benzodioxanes and ?-trifluoromethyl tertiary alcohols,respectively.Chiral phosphoric acids are a typical type of bifunctional organocatalysts,which have been successfully used in many asymmetric catalytic reactions.In the first part of our work,we have developed a chiral phosphoric acid-catalyzed intramolecular oxetane desymmetrization for the highly efficient enantioselective synthesis of chiral1,4-benzodioxanes.We studied the effects of catalyst temperature,concentration,and solvent on the reaction.With the optimal reaction conditions established,we explored the substrate scope and obtained the target products with high yields and enantioselectivities(up to 99% and 95% ee).Moreover,we carried out a gram-scale catalytic reaction and the product transformations.They were performed well and the high enantiopurity essentially remained intact.In the second part of our work,with chiral bisoxazoline ligands/ nickel salts as catalysts,we developed a nickel-catalyzed asymmetric decarboxylation aldol reaction of hemithioester malonates with benzothiazole trifluoromethyl ketone hydrates for the synthesis of chiral ?-trifluoromethyl tertiary alcohols.We investigated the effects of metal catalysts,chiral ligands,temperature,additives,and catalyst loading on the reaction.With the optimal reaction conditions established,we explored the substrate scope.A series of chiral ?-trifluoromethyl tertiary alcohols were obtained with high yield and enantioselectivity.In addition,we conducted a gram-scale catalytic reaction and the product derivatizations.They were both performed well and the high enantiopurity remained unchanged.