Activation And Coupling Reactions Of Alkylamines

Alkylamine is a kind of common compound that usually as a nitrogen nucleophilic reagent used in organic synthesis. Because amino group has poor leaving ability, it is not common that alkylamine as carbon electrophiles in reactions. By the use of sulfonyl-activation, we developed a nucleophilic substitution reaction of Grignard reagents with alkylamine derivatives. In the presence of acid, we reported a palladium-catalyzed cross-coupling reaction of primary allylic amines with organoboron compounds,In order to improve reaction under milder conditions, we developed an unprecedented stereo specific allylic alkylation of a-chiral primary allylic amines with malononitriles at room temperature.This dissertation includes five chapters.Chapter1:Research progress in sp3C-N bond activation of alkylamines.This chapter gives an overview of sp3C-N bond cleavage of alkylamines from two aspects:Nucleophilic substitution and transition metal catalysis. From the aspect of nucleophilic substitution, different environment in acid condition or basic condition will lead to a different mechanism and a different product. From the other aspect of transition metal catalysis, it provides another powerful method for sp3C-N bond cleavage of alkylamines. Chemists have developed so many kinds of reactions about sp3C-N bond cleavage according to oxidative addition of transition metal.Chapter2:Nucleophilic substitution of Grignard reagents with sulfonyl-activated alkylamines.In the presence of5mol%of Cul, a board range of sulfonyl-activated benzylic, allylic, and proparglic amines smoothly undergo nucleophilic substitution with Grignard reagents to afford substitution products with good yield and high selectivity. Moreover, when we use sulfonyl-activated a-chiral allylic amines to react with Grignard reagents, we can obtain the substitution products with complete transfer of chirality. And this result show that the reaction carried out through Sn2mechanism.Chapter3:Cross-coupling reaction of allylic amines with organoboron compounds.The cross-coupling reaction of allylic electrophiles with organoboron compounds is an important method for the introduction of allyl moieties to target compounds. Allylic halides, esters, and alcohols have been identified as allylic electrophiles with different problems such as low atom economy, low stereoselectivity, needing equivalent alkali and so on. In our work, we have developed an unprecedented palladium catalyzed cross-coupling reaction of primary allylic amines with organoboron compounds. The reaction has excellent atom economy, good yield, high regioselectivity and high stereoselectivity. Moreover, when we use a-chiral primary allylic amines as the allylic electrophiles, complete transfer of chirality has been achieved. With the help of this reaction, we can synthesize many kinds of a-chiral allylic compounds.Chapter4:allylic alkylation of malononitriles with allylic amines at room temperature.In chapter3, we have developed the cross-coupling reaction of allylic amines with organoboron compounds. However, the reaction could not occur only if the temperature was rose to110℃and3equivalent boronic acid was added. The next step that we focus on is how to achieve the purpose of sp3C-N bond cleavage under milder conditions. Finally, we have implemented the stereospecific allylic. alkylation of malononitriles with allylic amines in room temperature by the use of [Pd(allyl)Cl]2. In addition, any acid or basic additives were not nedded to promote the reaction. A range of a-chiral primary allylic amines smoothly react with malononitriles in good yield and an excellent a-selective fashion to give products with excellent E selectivity and complete transformation of chirality. Moreover, we can obtain derivative products such as a-chiral allylic pyrimidines, a-chiral allylic acetic acid and a-chiral allylic malonic esters which have important application value in the synthesis of drugs and natural products.