Efficient Tandem Cyclizations Directed By Weakly Directed Groups

Tandem reaction undergoes two or more reactions in one pot without new operations.It has the advantages of fewer experimental steps,high synthesis efficiency,and environmental friendness.If combining the tandem reaction with C-H bond functionalization,organic compounds with important application can be directly synthesized from the commercially availble C-H compounds.In recent years,tandem reactions based on C-H bonds functionalization have attracted great attention,and have been widely used in the synthesis of complex compounds,especially cyclic compounds.Aldehyde is cheap and easily available,and is one of the widely available and easily available raw materials.Therefore,the development of C-H bond direct functionalization reaction with aldehyde as substrate has important significance.In this thesis,the following two works were carried out employing aromatic aldehydes as starting materials via weak directing groups assisted tandem cyclization reaction based on C-H bonds activation:The mechanism of the one-step synthesis of 1-trifluoroethoxy substituted indanpyrrolidine-2,5-dione compounds with aromatic aldehydes and maleimide as raw materials was studyed.The intermediate of this reaction was confirmed.Moreover,a series of 1-hydroxy-substituted indanpyrrolidine-2,5-dione compounds were prepared with good to excellent yields.The results display that the raction of aromatic aldehyde and maleimide undergoes a sequence of 1,4-conjugated addition,intramolecular nucleophilic addition,protonation to afford 1-hydroxyl substituted product.With the help ofAgNTf2,carbocation intermediates is formed,which reacts with trifluoroethanol to deliver 1-trifluoroethoxy substituted products.The method synthesising 1-hydroxysubstituted indanpyrrolidine-2,5-dione compoundsis characterized by exclusive stereoselectivity,air atmosphere,short reaction time(less than 3 h),and being free of nitrogen-based transient directing groups.It is worth to note that an important intermediate of the antihypertensive drug hexahydroindeno(1,2-c)pyrrole was efficiently synthesized via this method.Using aromatic aldehydes and acrylates as raw materials,Co(acac)2,[Cp*RhCl2]2 as catalysts,and oxygen as oxidant,a series phthalides were synthesized in neat water.In the reaction,Co(acac)2 catalyzes oxygen to oxidize aldehyde to acid,[Cp*RhCl2]2 catalyzes the cross dehydrogenation coupling reaction between the ortho C-H bonds of the carboxyl and methyl acrylate.Succeeded by intramolecular Michael addition,the phthalide compounds were obtained.The reaction has the advantages of easy availability of raw materials,simple operation,mild reaction conditions,and environmental friendness.