Palladium/Sadphos Catalyzed Asymmetric Benzylations Of 2-Methyl-1-Tetralone

The enantioselective α-functional reaction of carbonyl compounds(ketones,aldehydes,esters,amides and β-dicarbonyl compounds)is an important method to construct asymmetric C-C bonds.In the past few decades,the emergence of transition metals and organic catalysis has greatly advanced the field.On this basis,palladium-catalyzed enantioselective alkylation of prochiral enolates not only enhances the scope and selectivity of the reaction,but also greatly improves the step economy and REDOX economy of this process.In this paper,a new type of tert-butyl sulfinamide phosphine ligands was prepared through structural adjustment and used in the palladium-catalyzed asymmetric benzylation of 2-methyl-1-tetralone.A series of chiral α-alkyl-α-benzyl tetralones were prepared with excellent yield and enantioselectivity.On this basis,PC-Phos have been transformed and modified from these three aspects:(1)The phenyl on P atom was modified and(S,Rs)-PC8,(S,Rs)-PC9,(S,Rs)-PC10,(S,Rs)-PC11,(S,Rs)-PC12 were synthesized respectively;(2)The alkyl substituents at position 9 of Xanthene were modified and(S,Rs)-PC13,(S,Rs)-PC14,(S,Rs)-PC15,(S,Rs)-PC16,(S,Rs)-PC17,(S,Rs)-PC18 were synthesized respectively;(3)Aryl substituents at position 2,7 of Xanthene were modified and(S,Rs)-PC19 was synthesized.The introduction of new groups at position 9 of Xanthene makes the new ligands more steric than the previous PC-Phos ligands,making it more competitive in transition metal-catalyzed asymmetric reactions.On the basis of the above work,the asymmetric benzyl alkylation of 2-methyl-1-tetralone was achieved by modifying chiral tert-butyl sulfinamide phosphine ligands(Sadphos)and using benzyl trifluoroacetate as benzyl alkylations reagent in palladiumcatalyzed reaction.In practice,the asymmetric benzylation of 2-methyl-1-tetralone which is a simple and easily synthesized substrate,can be directly achieved by avoiding the use of complicated substrates such as precomposed metallic enolates.