Palladium-spirophosphonazooxazoline Catalyzed Asymmetric Allyl Amination

Asymmetric catalytic are important organic synthesis methods and play an important role in the synthesis of drugs,spices and natural products.The allyl amination reaction has the advantage of mild conditions and high yield.Since Pfaltz reported the asymmetric allyl amination catalyzed by Palladium/phosphine-oxazoline ligand in 1994,the catalysis of asymmetric allyl amination has developed rapidly,asymmetric allyl amination reaction has become one of the most effective synthetic methods for the construction of chiral amines.The enantioselectivity of certain substrate reactions catalyzed by existing phosphine-oxazoline ligands are low and analyzes the spatial configuration of the ligands and their metal complexes,inspired by the structural rigidity of spirocyclic compounds this paper proposes the spiro-ring structure is used to fix the space configuration of the benzene ring skeleton and the oxazoline ring,and the chiral center on the oxazoline ring is combined with the spiro carbon,so that the oxazoline ring and the benzene ring maintain the vertical configuration,and a rigid structure is designed.and the asymmetric allyl amination reaction catalyzed by the metal palladium complex is investigated.The 7-bromo-1-indanone was synthesized from 2-bromoacetophenone by α-methylation reaction,electrophilic addition and intramolecular alkylation reaction,The key step of the 2-bromoacetophenone α-methyleneation reaction was optimized.The effects of reaction solvent,reaction temperature,reaction time and ammonium salt type on the α-methylidene reaction of o-bromoacetophenone were discussed.The optimized route and process conditions of 7-bromo-1-indanone were obtained;the 7-bromo-1-indanone was used as raw material,Three kinds of rigid structural spirophosphonazooxazoline ligands with different steric hindrance were synthesized by the reaction of Sphenylglycine chiral substrate-assisted induction,nucleophilic addition of trimethylsilyl cyanide,lead tetraacetate oxidation and borane reduction,and the optical purity of three spirooxazoline ligands reached 100% by high performance liquid chromatography.The palladium-spirooxazoline catalyzed asymmetric allyl amination was studied with the synthesis of three chiral ligands.By exploring the effects of solvent,temperature,substrate concentration,catalyst amount,and reaction time on the reaction,the optimal catalytic system and reaction conditions were determined,and different nucleophiles and different allyl acetate substrates were explored under the conditions.By comparing with known compounds,the absolute configuration of the allylated product was determined.It has been found that the yield and enantioselectivity of the reaction were low when the aromatic amine as nucleophiles,the yield and enantioselectivity of the reaction were signidicantly improved when the alkylamine as nucleophiles.The best performance of reaction ee up to 97.3% with n-butylamine as the nucleophile.Inditated that increased nucleophilic capacity of nucleophile can increase reaction yield and enantioselectivity.Studies on different substrates have found that the enantioselectivity of the substituents attached to the phenyl ring of the allyl acetate substrate was slightly reduced,and the ee was significantly decreased while the astmmetric 4-phenylbut-3-ene-2 as the substrate,indicated that the steric hindrance of the allylic substrate has a great influence on the enantioselectivity of the reaction,and the selectivity of the catalyst to the small hindered allylic substrate is low,the enantioselectivity of the reaction significantly increases when a large hindered 1,3-diphenylallyl acetate as a substrateThe results of the palladium-Spirophosphonazooxazolines catalyzed asymmetric allyl aminations were compared with those of other asymmetric allyl amination reactions catalyzed by other phosphonooxazoline-palladium complexes.The phosphineoxazoline ligands with rigid frameworks had the advantages of high catalytic activity and high enantioselectivity,which was of great significance for enriching the theory and application of these ligands.