| Separation and purification are key steps in organinc synthesis research and pharmaceutical industry,in order to obtain pure product.However,traditional purification progress such as column chromatography is surffering from too much waste of energy,resourse and manpower.Under such a circumstance,our group put forward to the concept of Group-Assisted Purification chemistry(GAP chemistry).By purposely introducing a well-functionalized group into the starting material,we can obtain pure product conveniently through washing the crude product with common solvents.This concept agrees with the green chemistry concept,and has a widespread prospect in organic synthesis and industry.Thus,chapter 1 reports the systematic review of GAP chemistry and summarized its application in imine chemistry,solution-phase peptide synthesis,multi-component reactions and small molecule catalysts.On the other hand,α,β-diamino acids exist widely in biologically active molecules such as natural products and peptide medicines,while controlling the vincinal chial centers still remains challenging.The second part of chapter 1 provides a general view of the recent methodologies for asymmetric syntheses of α,β-diamino acid derivatives.We found that the Mannich reaction was the most widely used reaction among all the methods,In order to extend the application of GAP chemistry,we applied it into the synthesis of α-quatemery-α,β-diamino acid derivatives.In chapter 2,we focused on the asymmetric Mannich reaction between Ni(Ⅱ)-complexed Alanine Schiff base and N-phosphonyl imines.After choosing t-BuOK as the base and DCM as the solvent,the reaction were conducted under-48 ℃ to obtain a series of syn-α-methyl-α,β-diamino acid derivatives in good to excellent yields(67-93%)and complete diastereoselectivity(dr>99:1).The reaction met the requirements of GAP chemistry,and the pure products can be obtained simply by washing the crude products with common solvents,without operating column chromatography.However,the a-group was limited to methyl group due to the steric hinderance,so we still need other methods to breakthrough the limitation.Then it comes to the third chapter,in which we chose azlactones as the nucleophile to attend the asymmetric Mannich reaction with N-phosphonyl imines.The azlactones are easy to undergo enol isomerization and have many reactive cites,so they can attend the DKR reactions,nucleophilic reactions and cycloaddition reactions under mild conditions.Meanwhile,the azlctones play an important role in the synthesis of α-quaternery amino acids.During the research,we found that azlactones can react with N-phosphonyl imines without any base or catalyst.The Mannich product can be obtained by stirring the reaction mixture in DCM under room temperature,following by the GAP washing procedure.We got 44-89%isolated yiled and excellent diastereoselectivity for a series of α-quaternery-α,β-diamino acid derivatives.Comparing with the second chapter,the condition is much milder and the substrate scopre is much broader.After the Mannich reaction,the auxiliary was cleaved and the resulting α,β-diamino ester was futher derivatized.Besides the GAP chemistry,we are also interested in exploring the new reactions.Nitrogen-containing heterocyclic compounds exsit widely in nature and living lives.The ring expiation reactions of small azo rings are important methods for synthesizing the nitrogen-containing heterocyclic compounds.While the aziriding compounds are widely explored in this field,the ring expantion reactions of 3-methyleneazetidings are not reported before.We chose diazocompounds and 3-methyleneazetidings as the starting materials to realize the new type[4+1]cycloaddition reactions succefully,leading to the synthesis of quaternary-carbon-containing 4-methyleneproline ester derivatives in good to excellent yield(up to 95%).The mechanism of this reaction differs from the common 1,2-shift reaction of the ammonium ylide,instead of a ring-opening,ring-closing tandem procedure.The carbon-carbon double bond plays an important role in forming the allyl cation intermediate.The controlling of the quaternary stereocenter is still being explored. |
