Lewis Acid Catalyzed[4+2] Cycloaddition Of N-Tosylhydrazones With Ortho-Quinone Methides

Sulfonyl hydrazone compounds have been developed and widely used in organic chemistry in the past seven decades.Recent applications developed by researchers are mainly focused on transition-metal catalysis to achieve various transformations.A large number of studies are based on the fact that sulfonyl hydrazone compounds can generate diazo compounds in situ under basic conditions,which avoided the use of toxic and potentially explosive diazo compounds.Sulfonyl hydrazones,as the precursors of carbene,can participate in many types of reactions,like migration insertions and[1+n]cycloadditions.They are also an ambiphilic reagent capable of reacting with itself or with substrates of the same type,and participating in a series of[3+n]cyclic addition reactions as 1,3-dipole reactants.On the other hand,ortho-quinone methides(o-QMs)are highly active intermediates which are widely utilized as Michael acceptors and 1,4-dipole reactants in cycloaddition reactions.Recently,a[4+1]-cycloannulation of o-QMs with?-diazoketones and[4+3]-annulation reaction of aza-o-QMs with arylcarbohydrazonoyl chlorides were reported,which broaden the substrate types capable of cyclization with o-QMs.After literature research,it was found that sulfonyl hydrazone compounds were rarely used as 1,2-dipoles to participate in the reactions under basic conditions.Therefore,the reaction of sulfonyl hydrazone under acidic conditions is worth trying to explore new reactivity.On the basis of the fact that the formation of o-QMs is well compatible with acidic reaction conditions,the reaction is designed between o-QMs and sulfonylhydrazone.In this thesis,the reaction between sulfonyl hydrazone and o-QMs was investigated in detail,involving the following three aspects:(1)For the cycloaddition reaction between o-QMs and sulfonyl hydrazone with stereoscopic specificity under acidic condition,we investigated the effects of different types of lewis acid catalysts,various solvents,dosage of additive and temperature on the yield of products.After extensive screening of reaction conditions,the best condition was obtained:Sc(OTf)₃(5 mol%),4?molecular sieve(100 mg/0.2 mmol),diol substrates(1.0 equivalent),sulfonyl hydrazones (1.3 equivalent),DCM(0.1 M),under the protection of nitrogen,reaction temperature(25?),reaction time(half an hour).(2)With the optimal reaction conditions in hand,we next sought to investigate the substrate scope,including o-QMs precursors with different substitutions and hydrazones.It was found that sulfonylhydrazones stemmed from various substituted aromatic aldehydes and ketones both went on the reactions smoothly. Notably,natural products derived sulfonylhydrazones were also successful reactants in the system.In addition,we also found that the oxime compound was compatible in our system.The broad universality of substrate is indicated by the expansion of a large number of substrates.(3)A set of control experiments were designed and performed to probe the reaction mechanism.Based on these results,two plausible mechanisms are proposed.First, in the presence of Lewis acid Sc(OTf)₃,diols are converted into o-QMs by dehydration.Then,o-QMs are activated by Sc(OTf)₃ to form highly active intermediates which consist of two resonance structures,As a result,two reaction pathways are generated.Sulfonyl hydrazones,as 1,2-dipoles,participate in synergistic[4+2]cycloaddition in pathway 1,and nucleophilic attack occurred in pathway 2,all furnishing the final products.In summary,a Sc(OTf)₃ catalyzed[4+2]cycloaddition reaction between sulfonyl hydrazone and o-QMs has been developed in this thesis.affording a series of benzoxazine derivatives.It is a new reaction mode of sulfonyl hydrazone as a 1,2-dipole under the acidic condition.In this transformation,the substrate scope is broad,and the products are formed with high diastereoselectivities in most cases,which have untapped application prospects.