Construction Of A New One-Pot Reaction Based On Quaternary Carbon Captured By Active Intermediates

Chiral quaternary carbons,especially continuous acyclic chiral quaternary carbons,are a type of substances with important biological activities.There are great challenges in construction of quaternary carbons.The control of high-energy barrier transition states and stereoselectivity are the two key scientific problems.Being solved these problems have an important academic significance and practical application value.The two-component active intermediates are formed from metal carbene.Intermediates have a higher relative energy,it is more suitable in the matching degree of energy barrier,which is expected to overcome total high energy barrier in the reaction process and promoted the occurrence of new transformation.It is possible to construct chiral quaternary carbon by one-pot method that electrophilic reagents capture active ylide or ion-pair intermediates.Developing and designing a series of new electrophilic reagents can successfully capture of two-component active intermediates by electrophilic reagents and overcome the problems of high-energy barrier and high resistance effect in the construction of quaternary carbon,the polycyclic continuous quaternary carbon and acyclic continuous quaternary carbon centers.This graduation thesis provides a new idea and new way for the construction of continuous acyclic chiral quaternary carbon.The continuous acyclic chiral quaternary carbon complex compounds can be constructed from simple compounds in one-step.In this process,the mechanism of reaction was systematically studied,focusing on diazo carbene chemistry,ylide chemistry and active ion-pair intermediate chemistry based on transition metal catalysis,to enrich the research of transition metal carbene chemistry and diazo chemistry.In Chapter 2,we realized that the active ylides formed by aryl diazoacetate methyl esters and nucleophiles(amine,alcohol)were captured by quinolyl olefins,and efficiently completed the study on the construction of quaternary carbon of quinoline derivatives.A novel active compound-quinoline structural unit containing quaternary carbon centers was synthesized.The reaction has a wide range of substrates,high yields,even a quantitative conversion,and certain universalities.The results show that Br(?)nsted acid(binaphthol phosphate)forms anhydride analogues through the interaction with the antibody anion OTf^-of Lewis acid(Sc(OTf)₃)detected by mass spectrometry and on-line infrared,so as to enhance the acidity of Lewis acid.At the same time,A new type of?-cation interaction of the benzene ring in quinolyl olefin and metal scandium which has not been reported in the literature through theoretical calculation was found,assisted to activate the intermediate of N-atom of quinolyl olefin and scandium,resulting in the high-efficiency capture of active ylide intermediate as a new Michael receptor.It provides a new method for the construction of quaternary carbon center.Quinoline compounds contain quaternary carbon were synthesized by one-pot method which have important to guide significance in the synthesis of building blocks and the construction of complex quaternary carbon compounds.In Chapter 3,we developed a convenient,mild,and efficient method to construction of continuous quaternary carbons,which can quickly construct poly-substituted tetrahydrocarbazole derivatives in one-pot.By using intramolecular ketones to capture ions to capture active intermediates,poly-substituted multifunctional tetrahydrocarbazole/spiro tetrahydrocarbazole derivatives containing continuous quaternary carbon can be synthesized by one-pot.The changes of species in the reaction process were intuitively displayed by on-line infrared spectroscopy.This method can rapidly synthetize polycyclic complex compounds from simple compounds,and shows a good synthetic application prospect.This method not only enriches the construction of continuous quaternary carbon in the ring,but also expands the development of carbene chemistry in synthesis.In Chapter 4,Under the catalysis of metal iron(FeCl₃ and FeTPPCl),alkynyl carbon positive ions capture active intermediates,construct multiple functional groups in one-step,constructing acyclic continuous quaternary carbon chiral centers,and quickly and efficiently constructing alkynol derivatives containing continuous quaternary carbon in one-pot.Through fine substrate regulation and catalyst screening,the reaction activity of alkynyl positive ions and diene intermediates was regulated with high chemical selectivity,to construct acyclic continuous quaternary carbon centers in one-pot under mild conditions.In the reaction,water is used as both reaction reagent and solvent.It is a kind of green,environmentally friendly,cost-effective,and non-cyclic continuous quaternary carbon construction method.In Chapter 5,we successfully developed ketimine to capture the active intermediate of onium ylide under the synergistic catalysis of metal rhodium(?)and chiral phosphoric acid,constructed multiple functional groups in one-step,constructed acyclic continuous quaternary carbon chiral centers,and quickly and efficiently constructed?-hydroxyphenylcyclobutyl-amide derivatives containing continuous quaternary carbon in one pot.This method solves the problem of poor diastereoselectivity in the previous multi-component reaction involving 3-hydroxyphenylcyclobutylamide,and provides a new idea and method for the construction of acyclic continuous quaternary carbons.