Visible Light-promoted Isomerization Of Alkenes And Preparation Of α,β-unsaturated Ketones For The Applications In Pharmaceutical Intermediates Synthesis

Visible light is a cheap,green and inexhaustible source of energy which has been the focus of chemists in recent years.The use of visible light in organic reactions can effectively make chemical conversion more efficient,economical and environnentally friendly.With the development of organic photocatalysis technology,the strategies for visible light promoting isomerization of olefins and photoinduced stereodivergent synthesis of olefin compounds are widely applied in the construction of drug skeletons and bioactive molecules,which can possess broad application prospect.In addition,α,β-unsaturated ketone compounds are also a vital class of pharnaceutical intermediates and organic synthesis blocks with olefin structural units.Thus,seeking sustainable synthetic methods with industrial application prospects is of great practical significance.At the same time,it is also advocated by green chemistry.The experimental content of this paper mainly includes the following three parts:Firstly,we have developed a method for photocatalytic isomerization of styrenyl halides,which can be achieved by two different conditions.Then the corresponding E and Z-isomers can be obtained with high stereoselectivity respectively.Furthermore,the outstanding application value of this method is confirmed in the subsequent derivatization of various cross coupling reactions and the stereodivergent synthesis of functionalized conjugated dienes.On the other hand,the method also provides an effective way for the concise synthesis of antineoplastic drugs such as DMU-212.Secondly,we have developed a method for stereodivergent synthesis of α-aminomethyl cinnamyl ethers via photoredox-catalyzed.This reaction is earried out by an ordered radical relay reaction between hydroxylamine derivatives,alkenyl ether and arylvinylboronic acids.It can effectively construct the thermodynamically unstable Z-isomers in a one-pot manner with good functional group tolerance and yield.To some degree,this method can effectively solve the problem of regioselectivity and chemoselectivity in the preparation of α-aminomethyl cinnamyl ether derivatives,which shows a strong synthetic application value.Thirdly,the Ca(OH)2-catalyzed synthetic method of dialkylideneacetones has been developed.The method employed dilute aqueous EtOH(20%,v/v)as a green and safe solvent.The desired product with moderate to excellent yield can be obtained on a gram scale by a simple post processing and purification.It is a very reliable and practical method for the preparation of α,β-unsaturated ketones,whether in laboratory or industrial applications.