Asymmetric 1,3-Dipolar Cycloaddition Reaction Of Diazomethylphosphonate To Access Pyrazoline Derivatives

Organophosphorus compounds are widely found in organisms and natural products.Phosphorus plays an important regulatory role in living organisms.It is the essential component of deoxyribonucleic acid(DNA),ribonucleic acid(RNA),adenosine triphosphate(ATP),biofilm phospholipids and enzymes.Aza-heterocyclic compounds are widely found in nature and have high biological activity.The pyrazolines is a class of nitrogen-containing five-membered heterocyclic compounds and have been widely used in medicine because of their excellent biological activity such as fungicidal,immunosuppressive,antibacterial,and antiviral effects,has been widely used in medicine,pesticides,fine chemicals,materials science and dyes,etc.The synthesis of such compounds has attracted the attention of many organic chemists.Diazo compound is a common synthetic intermediate.It is widely used in organic synthesis,polymer synthesis,pharmaceutical chemistry,chemical biology,material science and many other fields.Due to the special chemical nature of diazo compounds,they can participate in a wide variety of reactions and can effectively construct carbon-carbon bonds and carbon-hetero bonds.As a kind of diazo compound,diazomethylphosphonate can effectively introduce phosphate groups into compound molecules,thereby realizing the synthesis of phosphorus-containing compounds.It has a wide range of applications in the field of pesticide chemical,pharmaceutical and plastics industry.The chiral pyrazoline phosphate compound can be efficiently constructed by an asymmetric 1,3-dipolar cycloaddition reaction of an activated olefin with a diazophosphate,however,due to the lower activity of the diazophosphate,to achieve a high yield,regio-and stereo-selective synthesis of pyrazoline phosphates remains a challenge.This thesis describes the research work on the synthesis of the chiral pyrazoline phosphate compounds in the following two parts:Part ?:A series of chiral tertiary amine multifunctional thiourea catalysts were designed and used to catalyze the asymmetrical 1,3-dipolar cycloadditionof a-diazophosphonate and 3-methyleneindolinones.In this reaction,chiral 3,3'-spiro-phosphonylpyrazoline oxindoles derivatives were obtained.The effects of catalysts,solvents,temperature,additives and other factors on the reaction were systematically studied.It was finally established that under the catalysis of 10 mol%of catalyst 132 and DBN,toluene was used as solvent at-50? to obtain the best results.95%,ee up to 93%and dr>20:1,This method exhibits high functional group compatibility,where a wide range of methyleneindolinones with various substituents and heterocyclic rings are accommodated by this reaction.The resulting chiral 3,3'-spiro-phosphonylpyrazoline oxindoles can be further transformed into spirophosphonylcyclopropane oxindoles by ring contraction.Part ?:The 1,3-dipolar cycloaddition reaction of a-substituted diazophosphonates and ?,?-unsaturated oxazolidin-2-one was achieved under the catalysis of magnesium-chiral bisoxazole coomplex.A series of chiral pyrazoline phosphates were synthesized.The synthesized pyrazoline compounds can be transferred to,via reduction and simple transformations,chiral tetrahydropyrazole phosphates which hold potential biological activities.