Studies on the Preparation and Reactions of 4-diazoisochroman-3-imines

Author:Ren An Ni

Supervisor:wang yan guang lv ping


Degree Year:2018





Diazo Compounds are versatile and important synthetic intermediates,which demonstrate wide applications in so many different fields like chemistry,biochemistry,drug discovery,material science and even flow chemistry.In this thesis,classic preparation methods of diazo compounds and types of their practical applications have been comprehensively reviewed.With all these information in mind,we have developed a new kind of diazo compound bearing isochroman structure and proved its potential as a key intermediate in the conversion to these related heterocyclic compounds.The details are summarized as following:(1)On the basis of our group’s previous work of 3-diazoindole-2-imines,we explored the synthesis methods for a new class of diazo compounds with Benzo six membered ring structures.We successfully synthesized 4-diazoisochroman-3-imines by reacting(2-ethynylphenyl)methanols with sulfonyl azides.Owning to the poor stability and low concentration,the resulting enamine intermediate couldn’t be captured by usual methods.To prove the enamine’s existence during the reacting process,we designed an intramolecular Claisen rearrangement under standard conditions and isolated the rearrangement product.With all these evidence,we proposed the CuAAC cascade diazo transfer reaction as the mechanism.(2)We further studied the synthetic applications and found 4-diazoisochroman-3-imines could readily react with a variety of primary amines under catalyst-free conditions to furnish 3,5-dihydroisochromeno[3,4-d][1,2,3]triazoles.The substrates were readily available and the procedure is facile,efficient and general.(3)4-Diazoisochroman-3-imines were investigated for their synthetic appications as new class of metal carbene precursors.Under the catalysis of Rh(II)complex,this class of a-diazo imidates reacted with alkenes and conjugated dienes through a formal[2 + 1](i.e.,cyclopropanation)or[4 + 3]cycloaddition to furnish spiro[cyclopropane-1,4’-isochroman]-3’-imines and tetrahydroisochromeno[3,4-b]azepines,respectively.When Rh(Ⅱ)/AgOTf were used as co-catalyst,the formal[4+3]cycloaddition.When we use Rh(Ⅱ)/AgOTf as cocatalyst,the formal[3+2]cycloaddition of 4-diazoisochroman-3-imines with terminal alkynes took place,leading to the synthesis of 2-aryl-3,5-dihydroisochromeno[3,4-b]pyrroles.