Study On The Palladium-catalyzed Asymmetric Allylic Amination For The Synthesis Of Chiral γ-amino Acids

Chiral amino acids and their derivatives are indispensable in chemistry,pharmacy and biology.Thus,the preparation of chiral amino acids via asymmetric synthesis is a hotspot in organic chemistry.Chiral separation is mainly used in food and drug quality detection because of its low efficiency.Many efforts have been focused on the directly synthesis of chiralα-andβ-amino acids via chemical and biological methods.On the contrary,chiralγ-amino acids were mainly synthes ized by adopting chiral auxiliaries rather than directly asymmetric catalytic synthesis.On the basis of our previous research,we designed an efficient method to obtain chiralγ-amino acids via Pd-catalyzed asymmetric allylic animation of methyl（E）-2-acetoxy-4-arylbut-3-enoate with amine.We optimized the reaction conditions by investigating the effect of solvent,base,additive,ligand and amount of catalyst on this reaction.The optimal reaction conditions were then obtained as follows:a catalytic system of[Pd（η³-C₃H₅）Cl]₂ and（R）-（-）-DTBMSEGPHOS in THF using Et₃N as a base and Cs F as an additive.After that,we explored the scope of allyl substrates and nucleophiles.Thus,a series of allyl substrates with different substituents located on phenyl ring and different nucleophiles were examined under the above optimal reaction conditions.When substrates with eletron-withdrawing groups on phenyl rings were used,the desired products were obtained with up to 97%yields and 99%ee values.Meanwhile,the use of primary amines as nucleophiles in the reaction could afford excellent catalytic behavior with the product being obtained in high yields and excellent enantioselectivities.Furthermore,we studied the application of these chiralγ-amino acids.Chiralγ-lactam,a kind of five-member nitrogenous heterocyclic skeletons,could be obtained easily via a simple transformation,which was key intermediates of many chiral medicine and difficult to obtain us ing other synthetic methods.In addition,chiralγ-amino acids could also be used a key intermediate to synthesize cis-（+）-sertraline,a drug for treating depression.