Design,Synthesis And Application Of Novel Multifunctional Chiral Cyclic Phosphine Catalyst Le-phos

Over the past few years,asymmetric phosphine-catalyzed reactions have emerged as powerful and versatile tools for the construction of C–C and C–X bonds,which have successfully constructed a series of chain,carbon ring,heterocycle in favor of the synthesis of the important molecular frameworks of pharmaceutical chemistry and material chemistry.Asymmetric variants of phosphine-catalyzed reactions have evolved relatively slowly due to the limitation of the kinds of chiral phosphine catalysts.In the last 20 years,with the design and synthesis of various chiral phosphine catalysts,chiral phosphine catalysis has been developed rapidly,which has provided an effective method for the asymmetric synthesis of natural products,drug molecules and other bioactive molecules.This paper is based on the design and synthesis of a novel bifunctional cyclic phosphine catalyst Le-Phos,which has been applied in highly enantioselective phosphine catalyzed?-addition of N-centered nucleophiles to allenoates.Furthermore,we also realized Le-Phos-catalyzed kinetic resolution of secondary phosphine oxides via an asymmetric allylic alkylation reaction,delivering various P-chiral tertiary phosphine oxides and P-chiral secondary phosphine oxides.The specific contents are mainly divided into the following four parts:1.IntroductionThe introduction is divided into the following two parts:in the first part,we mainly introduce the research progress of phosphine-catalyzed reactions;the second part mainly introduces the synthesis and characteristics of some chiral cyclic phosphine catalysts.2.Design and synthesis of phosphine catalyst Le-PhosStarting from the commercially available Ph PCl₂,we have a substitution reaction with the corresponding grignard reagent,and then one pot we obtain the catalyst precursor phenylcyclopentylphosphine borane complex.At the same time,commercially available chiral tert-butyl sulfonamide is dehydrated and condensed with aldehydes to obtain chiral imines.Phenylcyclopentylphosphine borane complex is lithiated,and then nucleophilic addition of the lithiated phosphine to imines obtain catalyst borane complex.Finally,chiral cyclic phosphine catalyst Le-Phos was obtained by deprotection3.Le-Phos-catalyzed asymmetric?-addition of N-centered nucleophiles to allenoates.Le-Phos exhibit good performances in enantioselective?-addition reactions ofN-centered nucleophiles and allenoates,obtaining a series of adducts?up to 98%?with good regioselectivity and enantioselectivity under mild conditions.The salient features of this reaction include high product yields,good enantioselectivity,mild reaction conditions,broad substrate scope,gram-scale scalability and easily converted to amino acids and their analogues.4.Le-Phos-catalyzed kinetic resolution?KR?of secondary phosphine oxides via an asymmetric allylic alkylation reactionWe choose second phosphine oxides and MBH esters as the substrates.We find a highly efficient phosphine-catalyzed asymmetric allylic alkylation reaction of secondary phosphine oxides with Morita-Baylis-Hillman carbonates,delivering various P-chiral tertiary phosphine oxides and P-chiral secondary phosphine oxides via kinetic resolution.The further transformations of chiral secondary phosphine oxides allowed the efficient synthesis of various tertiary phosphine oxides.Furthermore,the obtained products can be readily transformed into useful phosphine catalysts and ligands.