Organocatalytic Synthesis 1,4-conjugated Addition Of Vinylidene O-quinone Methide And Benzoquinone Compounds

Since the discovery of styrene type axial chirality framework in 1991,there have been few reports on the synthesis of styrene type axial chirality framework.The main reasons are presumably attributed to the relatively low-rotation energy to racemization and the difficulty to control the enantioselectivity.VQM(vinylidene o-quinone methide)is a class of compounds with high reactivity,usually in the form of reaction intermediates.Such intermediates have the characteristics of many reaction sites and high activity.As it is difficult to accurately control the reactivity and sites of this kind of intermediates,there are few reports on the asymmetric catalytic reactions of these compounds.ortho-Quinone methide(o-QMs)plays a very important role in the self-protection mechanism of biological organisms.At present,it has been reported that pyrolysis,photolysis,oxidant oxidation,tautomerism,nucleophilic addition and the addition of acid or base to promote 1,4-elimination and other methods to obtain intermediates,and o-methylene intermediates are widely used for drug target action and organic synthesis.para-Quinone methides(p-QMs)is an important class of quinone derivatives.Its structural units widely exist in natural products and bioactive organic molecules,and involve drug metabolism,biosynthesis and chemical reactions.This paper mainly deals with the asymmetric addition reactions of the above three compounds.Part Ⅰ: Organocatalytic synthesis of axial chiral styrene compoundsThis part of the work realized an organocatalytic enantioselective method for the synthesis of multiple stereoisomers bearing E,Z configurations,stereogenic carbon centers and an element of axially chiral styrenes.A series of stereochemical products with excellent E,Z selectivity,diastereoselectivity(>20:1 dr)and enantioselectivity(up to 96% ee)can be constructed by this method.At the same time,this method provides an effective and concise synthesis route of various stereoisomers and an atom economic method,which has a wide range of potential applications in organic synthesis and pharmaceutical chemistry.Part Ⅱ: Organocatalytic synthesis 1,4-conjugate addition of o-QMs and thiazolidoneIn this part of the work,an asymmetric 1,4-conjugate addition reaction of ortho-quinone methylation and thiazolidone,which was synthesized in situ by ortho-hydroxybenzyl alcohol catalyzed by chiral phosphoric acid,was studied.After analyzing the reaction results of the template substrate,through a series of optimization of the reaction conditions,the reaction conditions that can achieve the highest stereoselectivity and yields of the reaction were finally obtained.The applicability of them in the conjugate addition of o-QMs generated in situ with o-hydroxybenzyl alcohol and thiazolone was also studied.Under the optimal reaction conditions,all reactions can be performed smoothly on a variety of substrates,and a series of sulfur-containing heterocyclic compounds with high yield(76-95%),enantioselectivity(80-99% ee)and diastereoselectivity(9:1-> 20:1 dr)was obtained.What’s more,the report provides a new efficient and simple method for the synthesis of sulfur-containing heterocyclic compounds with tertiary carbon stereochiral centers.Part Ⅲ: Organocatalytic synthesis 1,4-conjugate addition of p-QMs and 5H-oxazol-4-onesThis part of the study realized the use of small organic molecules as catalysts to catalyze the synthesis of target products.In this part of the work,we used p-QMs and oxazolone as raw materials,organic small molecule tertiary amine DBU as a catalyst,and obtained a series of good to excellent yields through asymmetric conjugate addition reaction(82-99%)of a racemic heterocyclic compound.The reaction method has a small amount of catalyst(2 mol%),mild reaction conditions,high economy,and good substrate applicability.