Study On Cyclization Reactions Of Constructing N-heterocyclic Skeleton Based On P-Quinone Methides

para-Quinone Methides(p-QMs)are efficient and versatile organic synthetic intermediates with excellent chemical reactivity,and they have been widely used in pharmaceutical chemistry,biochemistry,material chemistry and other fields.In recent years,various synthetic reactions using p-QMs as substrate have been reported,especially the cyclization reactions,which have attracted great attention of researchers.As a kind of unique Michael receptors,p-QMs can be used to construct a variety of ring compounds,but due to the limitations of their structural types,they are rarely used to construct nitrogen-containing heterocycles.By introducing an amino group into the phenyl ortho position of p-QMs,we designed and synthesized o-aminophenyl p-QMs.The cyclization reactions of these o-aminophenyl p-QMs provide an efficient method for the construction of nitrogen-containing heterocycles.Firstly,we used the precursors of o-aminophenyl p-QMs as substrates.A novel[4+2]cyclization reaction between in situ.generated o-aminophenyl p-QMs and isatin-derived enoates in the presence of oxidant and alkali catalyst has been developed.Through optimizing the reaction conditions and expanding the substrates,we designed and synthesized 24 new 3,3’-tetrahydroquinoline spirooxindole derivatives.The practicability and asymmetric form of the reaction were also investigated.The novel[4+2]cyclization in the form of one pot process not only has mild reaction conditions and high yields,but also has a wide substrate scope,which provides an efficient and convenient method for the construction of 3,3’-tetrahydroquinoline spirooxindole scaffold with diverse structures.In addition,an unprecedented regioselective cyclization reaction of o-aminophenyl p-QMs and vinylethylene carbonates(VECs)for the synthesis of medium-sized heterocyclics was developed.Through optimizing the reaction conditions and expanding the substrates,we designed and synthesized 24 nine-membered and 11 seven-membered heterocycle compounds with new structures.The conversion reaction of these products and the practicability of the reaction were investigated.The characteristic of this cyclization reaction is that the regioselectivity of the reaction can be achieved by controlling the steric hindrance of substituents on VECs,so as to construct nine and seven-membered nitrogen heterocycles.When the substituent on VECs is a large steric hindrance group,[4+5]cyclization proceeds smoothly to deliver nine-membered heterocycles.Changing the substituent to small steric hindrance hydrogen completely reverses the regioselectivity.The reaction takes the form of[4+3]cyclization to generate seven-membered heterocyclics.Furthermore,our approach could also extend to six-membered vinyl carbonates to divergent synthesize ten-membered and eight-membered heterocycles.In summary,o-aminophenyl p-QMs,as a new type of four-atom unit,can be used in various cyclization reactions.Our research not only enriches the structural types of p-QMs,but also provides an efficient method for the construction of nitrogen heterocycles of different sizes,especially medium-sized rings.