Application Of Conjugate Addition Reaction In Synthesis Of Organic Nitrogen Compounds

Conjugated addition reaction is a high-efficient method of constructing C-C,C-N and C-S framework,which is widely applied in organic synthesis because of its atom economy.Nitrogen is one of the most important elements in natural products and nitrogenous organic compounds also play an irreplaceable role in our daily life.Therefore,green synthesis of nitrogenous organic compounds is a crucial topic in chemical engineering.In this thesis,a series of new kind of nitrogenous organic compounds was furnished through conjugated addition way.There contains three works which mainly focus on conjugated addition reaction approaching nitrogenous organic compounds in the thesis.（1）Pyrroloquinoline derivatives are biologically active medicinal compounds and natural products.The previous studies focused on the approach to pyrroloquinoline derivatives involving multi-step synthetic methods which have a few drawbacks,such as more steps,time consuming,complex work,energy dissipation,costing reagents and solvents and inconsiderable yields.While in this thesis,tetrahydro-1H-pyrrolo[3,4-c]quinoline containing four chiral centers was synthesized through Michael/Mannich cascade reaction.This approach contains only one purification operation,and the diastereoselectivity is satisfactory（d.r.> 20:1）.The optimized reaction condition was determined by screening of PTC（TBAB,10 mol%）,base（Cs2CO3,3 equiv.）and reaction solvents（Et2O/Ph Me=2:1）,with a overall yield of 21%-88%.A broad varies of substitutes with ortho-,meta-,para-electron-withdrawing or electron-donating phenyl or aryl can smoothly furnish the target product with moderate yields.The synthesized pyrrolo[3,4-c]quinoline can be easily derived to other kinds of compounds through reduction or oxidation.（2）Unsymmetrical geminal amino diarylmethane motifs exist in plenty of biologically active medicinal compounds and natural products.The previous studies about synthesis of unsymmetrical amino diarylmethane and its derivatives mostly involved conducting with hydrogen,heavy metal catalysts or strong reductants,which were risky or energy consuming.Research about 1,2-addition and 1,4-addition between nucleophile and conjugated olefin with electron-withdrawing group was widely reported,while studies of 1,6-conjugated addition were less concerned.Aza-1,6-conjugated addition was still neglected by most researchers,and most ofthese works focus on chroman-4-one-acrylate as electrophile.We firstly reported the efficient synthesis of unsymmetrical geminal amino diarylmethane derivatives through aza-1,6-conjugated addition under a very mild reaction condition without heavy metal catalysts or heat.The approach furnished the target molecular with considerable yield and good tolerance of functional groups.The optimized reaction condition was determined by screening-with catalysis of 20 mol% of DBU,in MeCN,and 12 hours at room temperature-with the highest yield of 95%.A broad varies of substitutes with ortho-,meta-,para-electron-withdrawing or electron-donating phenyl or aryl can smoothly furnish the target product with considerable yields.Moreover,optically active and symmetric amino diarylmethanes were also synthesized through the aza-1,6-conjugated addition route which could be derived to a kind of chiral ligands.（3）α-diazocarbonyl compounds are widely applied in organic synthesis because of their easy preparations and versatile chemical transformations under mild condition.These chemical transformations include α,α-substitution,C-H insertion,cyclopropanation,Aldol reaction,etc.Ethyl diazoacetate is a typical α-diazocarbonyl compound,already reported in Aldol reaction as a nucleophile.However,the conjugated addition of ethyl diazoacetate as a nucleophile was not reported yet.Hence,conjugated addition between para-quinone methides and ethyl diazoacetate was studied in this thesis to obtain a new type of diazo-compound which can be easily derived with moderate yield.The optimized reaction condition was determined by screening-with catalysis of TBAB,Cs₂CO₃ as the base needed,and 12 hours at room temperature-with the highest yield of75%.A broad varies of substitutes with ortho-,meta-,para-electron-withdrawing or electron-donating phenyl or aryl can smoothly furnish the target product with moderate yields.