Synthesis Of Benzoxazine And Tetrahydroquinoxalines Via Transition Metal-Catalyzed Borrowing Hydrogen Methodology

3,4-dihydro-3-phenyl-2H-1,4-benzoxazine is a type of nitrogen and oxygen-containing six-membered heterocyclic compound with benzo condensate,which constitutes a variety of biologically active compounds.The structurally similar 1,2,3,4-tetrahydroquinoxaline and its derivatives have important applications in the fields of biology and pharmacology.However,there are relatively few green and affordable synthetic routes for these two types of compounds,so researchers have done a lot of researches on modern synthetic methods.Among these research methods,the most common method is the reduction of benzoxazine with hydrogen or the asymmetric reduction of quinoxaline and good results are obtained.Even so,these reduction methods are generally carried out under higher pressure hydrogen or with the addition of stoichiometric reducing agents,which is prone to generate a large amount of waste and cause serious pollution.At the same time,the raw materials used for reduction are relatively more difficult to prepare.Therefore,it is very important to develop a synthesis method with a wide range of raw materials and economical characteristics of atomic steps.Borrowing hydrogen reaction is a modern organic synthesis method that is green,high atom utilization rate,and conducive to industrialization.It uses metal catalysts to take away hydrogen from organic substrate with low activity to generate new metal hydrogen bond.Simultaneously,the organic substrate is activated and participates in the subsequent reaction to form an intermediate,and finally the metal hydrogen bond reduces the intermediate to generate a new product.Compared with the traditional hydrogenation reaction,this method avoids the danger of high-pressure hydrogen,and the by-product is only water,which has a very good application prospect.After researching a large number of documents,we have found that the currently reported borrowing hydrogen reactions are using simpler alcohols that are commercially available,but for some complex structures of target molecules.It may be necessary to use some difficultly prepared alcohol as the substrate,which limits the development of borrowing hydrogen reaction.So we strive to find a raw material that can replace alcohol.And epoxy compounds are very in line with this requiment,that is epoxy compounds can generate alcoholic hydroxyl groups in situ under acidic or alkaline conditions.Simultaneously these compounds are widely available and easy to prepare.Thence we envisage combining the reaction of catalyzing the preparation of alcohol with borrowing hydrogen reaction to overcome the difficulty of preparing alcohol and developing a one-pot multi-step research method.Therefore,we have designed two experimental schemes.The first is to successfully synthesize 3,4-dihydro-3-phenyl-2H-1,4-benzoxazine under basic conditions,using transition metal iridium catalysts,using styrene oxide and 2-aminophenol as raw materials.The second is under acidic conditions,also using transition metal iridium catalysts,using chiral epoxy compounds and 2-aminoaniline as raw materials,the successful synthesis has chiral 1,2,3,4-tetrahydroquinoxaline and its derivatives.The success of the above two strategies has important theoretical significance for the development and application of borrowing hydrogen methodology,and has important practical significance for industrial production.