Studies On The Reaction Of Sec-N-Arylamides With Isocyanate And Explorations Of Asymmetric Synthesis Of (-)-Quinocarcin

This thesis contains two parts:Part Ⅰ,studies on the preparation of quinazolinones based on the activation of amide with trifluoromethane anhydride;Part Ⅱ,explorations toward asymmetric synthesis of tetrahydroisoquinoline alkaloid(-)-quinocarcin.1.Studies on the reaction of sec-N-arylamides with isocyanate for the synthesis of 2,3-disubstituted-3H-quinazolinc-4-one.(Chapter 2)Based on the activation of Tf2O/2-Br-Pyr.system,a general method for direct construction of 2.3-disubstituted-3H-quinazoline-4-one structures by the reaction of sec-N-arylamides with isocyanate has been developed.It is important that this is the first report on the synthesis of quinazolinone using secondary amide as substrate.In this method,amide activation,isocyanate addition,annulation of imine onium and aromatic ring are completed in "one-pot",and the yield is between 92%and 42%.This protocol is characterized by its mild conditions,efficiency and tolerability of functional groups.Since it is started from ordinary aniline compounds,compared with the traditional substituted aniline compounds,it is particularly useful for preparing substituted Quinazolinones.2.The exploration of asymmetric total synthesis of(-)-quinocarcin.(Chapter 3)The research objective of this subject is to explore an efficient synthesis route for(-)-quinocarcin.Based on this objective,the results of this exploration are as follows:The key reaction of pyrrolidine intermediate with three chiral centers is directly constructed in a one-pot reaction using cinnamaldehyde imine as substrate via Cu-catalyzed asymmetric 1,3-dipole cycloaddition in cascade with Borch reaction,with the yield being 45%.Combined with imine synthesis,the two-step yield is 42%.After that,olefin ozonation,which is protected by hydrochloric acid,and Wittig reaction is linked together to form terminal olefin,with the yield being 63%.The ring-closing substrate was synthesized by selective hydrolysis of methyl ester cascade with amideation,with the yield being 78%.In the final ring-closing reaction between secondary amides and terminal olefin,we tried Pd(OAc)2,Cu(EH)2.Pd(OAc)2/Cu(OAc)2 and other catalytic systems.But unfortunately,the reaction didn’t produce the desired product.Finally,asymmetric total synthesis of(-)-quinocarcin was not completed.Besides,in the exploration process of(-)-quinocarcin synthesis,asymmetric 1,3-dipole cycloaddition of alkynyl imine was completed for the first time.