Catalytic Asymmetric Synthesis Of Chiral Sulfonamides And P-stereogenic Phosphorus Heterocycles

Chiral sulfonamides and P-stereogenic phosphorus heterocycles as "privileged structural motifs" molecules are important and irreplaceable in asymmetric catalytic synthesis and drug screening.It is of great academic significance and practical value to develop asymmetric synthesis methods for the concise synthesis of these two types of chiral molecular.In this thesis,an inexpensive copper-catalyzed asymmetric carbon-hetero cross-coupling reaction was conducted for the enantioselective synthesis of N-arylsulfonamides and P-stereogenic phosphorus heterocycles.Sulfamides,as the skeleton of sulfa drugs,are widely used for antibacterial drugs and other biological activities.The first part of the work reports the copper/chiral ethylenediamine catalyzed intermolecular asymmetric C-N coupling reaction of cyclic diaryliodonium salts and sulfonamide compounds for the synthesis of chiral N-arylsulfonamides by asymmetric desymmetrization.The absolute configuration of the product was determined by X-ray single crystal diffraction,and the possible asymmetric catalytic model and reaction mechanism were proposed.Chiral phosphine compounds are widely used as ligands,organic catalysts,bioactive molecules and so on in pharmaceutical industry.P-Stereogenic phosphine compounds show prominent chiral induction stemming from chirality proximate to the catalytic center.The asymmetric catalytic synthesis of central chiral phosphine compounds still remains great difficulties and its applications are limited.The second part of the work reports the copper/ethylenediamine-catalyzed dynamic kinetic asymmetric aryl C-P coupling/cyclization reaction for the concise synthesis of six-,seven-and eight-membered P-stereogenic phosphorus heterocycles,the products were obtained in excellent yields and excellent enantioselectivities.To illustrate the greenness and practicability of the reaction,a one?pot gram?scale synthesis of the stable P?stereogenic P?heterocycle was carried out,without the need to isolate intermediate phosphinate.The target product cyclic phosphonolactone can be obtained with excellent yield and excellent enantioselectivity in one-pot reaction,which can be further reacted with an organolithium reagent to afforded tertiary P?stereogenic phosphine oxide.Finally,experiments were conducted to investigate the racemization of the H?phosphinate.We found that copper can catalyze the racemization of H-phosphinate in the presence of bases or ligands,and further proposed a possible substrate racemization process and asymmetry catalytic model.