Asymmetric Mannich-Allylation Tandem Reaction

Asymmetrically catalytic allylation is a powerful and versatile method for building chiral organic molecules from achiral molecules.Under the activation of chiral catalyst,the reaction of nucleophiles containing carbon,nitrogen,oxygen,sulfur and phosphorus with allylic compounds have been developed to efficiently construct chiral carbon-carbon,carbon-nitrogen,carbon-oxygen,carbon-sulfur and carbon-phosphorus bonds.The reaction has good compatibility with various functional groups and has been successfully applied to the synthesis of a variety of natural products and synthesis of new chiral compounds.Chapter 1: The development of asymmetric allylation in recent decades from the perspective of catalytic systems and allyl reagents are summarized.The application scope of various catalytic systems and the activation methods of allyllation reagents are discussed.In particular,the joint catalytic system developed in the past two decades,which used two different catalysts to catalyze the asymmetric allylation reaction,has become an effective method to realized the reaction or prepare structure special compounds that are difficult to achieve by a single catalyst.Chapter 2: Both pyrazolone and indolone have a five-membered lactam heterocyclic structure,which has huge development potential and wide application value in medicinal chemistry and synthetic chemistry.In this chapter,pyrazolone,N-Boc derived ketimines and allenyl ether are connected in series under the action of asymmetric organocatalysts to efficiently and selectively construct the indolinone-pyrazolone-enyl ether skeleton with good to excellent yields and steroselectivities.The skeletons contain two adjacent quaternary carbon chiral centers with multiple active functional groups,which can further be converted to trispiroheterocycles with high efficiency.The structure of compound 4and 5 were elucidated by means of X-ray analysis.Furthermore,the gram-scale reaction was carried out,and the results were also obtained well.Then,the reaction was further optimized based on the analysis of the reaction mechanism,and the stereoselectivity of some reactions was further improved by the synergistic catalysis of Cat-1/PA-1,which was beneficial to the reaction.Chapter 3: Rhodanning compounds have great application value in medicines and natural products,but there are few reports on the asymmetric synthesis and transformation.In this chapter,rhodanine,N-Boc ketimines and allyl acetate occurs Mannich-allylation relay reaction to construct the indolone-Rhodanning-propene sturcture under the synergistic catalysis of chiral squaric acid and palladium.The adducts contain adjacent quaternary carbon center with nitrogen and sulfur-containing heterocycles.In addition,the multiple active functional groups can be used for various transformations and applications.In summary,this paper focuses on the three-component relay allylation reaction promoted by organocatalysts,such as chiral squaric acid and binaphthyl phosphate.A series of novel products containing two adjacent quaternary carbon chiral centers and multiple active functional groups have been constructed with high efficiency and stereoselectivity.