Enantioselective Phosphorylation And Trifluoromethylthiolation Of Cyclic Lodonium Salts

Biaryl axial chirality widely presents in natural products and chiral ligands for catalytic asymmetric reactions.Due to the steric hindrance and differences of the axial ortho-position substituents,the single bond of biaryl scalfold cannot rotate freely,which makes the molecule different from its mirror one.Upon the wide exist of axially chiral skeleton in natural products and numerous applications in asymmetric synthesis,the stereoselective construction of axially chiral molecules has become an significant research topic.The research work of thesis focuses on the copper-catalyzed asymmetric ring-opening reaction of cyclic diaryliodonium salts for the preparation of phosphorus-containing compounds and the trifluoromethylthiolethers.The work includes the following two parts:The first part is the copper-catalyzed asymmetric ring-opening phosphorylation reaction of cyclic diaryliodonium salts.In the presence of TEMPO,the copper-catalyzed ring-opening reaction of cyclic diaryliodonium salts and diarylphosphine oxides underwent a C-O bond coupling reaction to produce phosphate products with high yields and high selectivity.Oxygen isotope(18O)labeling experiments showed that the oxidation process of the phosphorylation reaction occurs before the C-O bond formation.Lithium or magnesium exchange between tert-butyl lithium or tert-butyl magnesium chloride and the axially chiral aryl iodide generated aryllithium or arylmagnesium in situ,which underwent an intramolecular nucleophilic addition to phosphate to realize the phosphine oxide migration reaction.In this reaction,the optical activity of the substrates almost completely maintained to obtain an axially chiral triarylphosphine oxide compound;further reduction gave chiral phosphine ligands.The DFT calculation showed that the transfer of phosphine oxide proceeded through the concerted process of C-P bond formation and P-O bond dissociation.The second part studied the copper-catalyzed asymmetric trifluoromethylthiolation of cyclic diaryliodonium salts.Direct trifluoromethylthiolation reaction with CsSCF3 as the reactant can be achieved when symmetric diaryliodoniums were used.The reaction was conducted under mild conditions,and the enantioselectivity can reach to 90%-99%.For unsymmetric iodonium salts,an indirect trifluoromethylthiolation strategy is necessary.Enantioselective ring-opening/thiosulfonation with PhSO2SNa regioselectively gave thiosulfonates,which would gave trifluoromethylthiolation products through S-trifluoromethylation upon the treatment of TMSCF3.