C-N(P) Bond Formation:Research On Asymmetric P-S Reaction,Asymmetric Ugi Reaction And Pudovik Reaction

Chiral nitrogen-containing compounds exist widely in organisms.As important bioactive substances,they play an important role in the life activities of organisms.For a long time,the structure with nitrogen is also an important direction of the development of bioactive molecules such as medicine,which has attracted the attention of scientists in the fields of medicine,biology,chemistry,and materials.The construction of chiral C-N bond is an important method for the synthesis of active nitrogen-containing compounds.In particular,the efficient preparation of these compounds by asymmetric catalysis has been the research focus of synthetic chemists.In this paper,based on the literature review and previous work,imidodiphosphoric acids catalysts were applied to asymmetric reactions for the construction of chiral C-N bonds.The asymmetric Pictet-Spengler reaction,multicomponent asymmetric Ugi reaction and Ugi-Smile reaction were deeply studied and obtained good results.Firstly,seven 3,3’ different substituents imidodiphosphoric acids were synthesized.The catalysts were expanded,which laid a foundation for the catalytic asymmetric reaction.Chiral benzodiazepines have important biological activities.Imidodiphosphoric acids were applied to the asymmetric Pictet-Spengler reaction of pyruvates and furaldehyde with 1-phenylindolin-7-amines and 2-(indolin-1-yl)anilines to the formation of seven-membered rings to synthesize indolin-benzodiazepine.After the investigation of yields and enantioselectivities,1-naphthyl substituented imidodiphosphoric acid was selected as the catalyst and 18 substrates were expanded.Several indoline-benzodiazepines were synthesized with 87-97 % yields and 78-99%ee.The study of asymmetric Ugi reaction is a hot topic for synthetic chemists.Ugi reaction of aldehyde,aniline,isocyanide,and benzoate.After the investigation of reaction yields and enantioselectivities,phenyl substituented imidodiphosphoric acid was selected as the catalyst and anisole as the solvent.After the dosage of catalysts,additives and reaction temperature were further investigated,18 substrates were expanded with 56-78 % yields and 75-97% ee.The amide bond in the products of Ugi-smiles reaction is the basic chemical bond to form polypeptide chain,which is suitable for the synthesis of various bioactive structural chemicals.Imidodiphosphoric acid catalysts derived from BINOL were applied to the asymmetric Ugi-smiles four component reactions of aldehydes,amines,isocyanides,and electron-withdrawing substituted phenols.After investigating the enantioselectivity of the reaction,we determined that BINOL imidodiphosphoric acid with 2-naphthyl at 3,3’ position was the best catalyst and anisole was the best solvent.The substrates were expanded and the yield of 35%-83%and ee value of 88%-99% were obtained.Chiral chloroquine derivatives with high enantioselectivity(91% ee)were synthesized.Finally,catalyst free synthesis for α-functionalized phosphates was introduced.Under the catalyst free conditions,3-hydroxy-3-indolyloxindoles reacted with phosphite to synthesize α-functionalized phosphates.We expanded 17 examples and got a variety of α-functionalized phosphates with high yields(90-99%).