New Approaches Towards The Asymmetric Synthesis Of “Biaryl-Based Phosphine Ligand”

Owing to the important influence of phosphine ligands in transition metal catalyzed reactions,chemists have searched for straight forward and efficient methodologies for the synthesis of diverse phosphine ligands.Although significant progress has been made in this aspect over the past decades,the development of new phosphorus-containing ligands with properties superior to their predecessors remains a central task for chemists.Recently,biaryl monophosphine ligands have demonstrated to be highly efficient ligands for transition-metal-catalyzed organic transformations.While the synthesis of chiral biphenyl monophosphine ligands,especially whose chirality is due to biaryl axial chirality is very limited.In this paper,the author achieved the asymmetric synthesis of this kind of phosphine ligands through diastereoselective C-H functionalization and Suzuki-Miyaura cross-coupling reactions with chiral P=O as the auxiliary group.The author carried out a series of work as follows:1.The development of P=O directed C-H functionalization was introduced and also summarized our group’s work in the palladium catalyzed P=O directed C-H functionalization through seven-membered cyclopalladium pre-transition state in details.The C-H acylation reaction was mainly studied.We successfully achieved the synthesis of a series of different substituted biaryl phosphine oxides.In this reaction,the tBuPhP(O)was used as the directing group,which is a potential chiral group and provide the possibility for the asymmetric synthesis of biaryl phosphine ligands.2.We studied the palladium catalyzed P=O directed C-H functionalization through dynamic kinetic resolution in details.Different substituented axially chiral biaryl monophosphorus ligand precursors were obtained with menthyl phenylphosphinate as the auxiliary group.The menthyl phenylphosphinate being used as chiral auxiliary group has some unique features:(i)it is easy to prepare;(ii)the products contain both the axial chirality and central chirality on phosphorus atom;(iii)the menthyl group could easily be transformed into other functional groups,which is very important for the diversity of corresponding biphenyl ligands.3.Next,we synthesized a series of axially chiral monophosphine ligands through diastereoselective Suzuki-Miyaura cross-coupling reaction with menthyl phenylphosphinate as the chiral auxiliary group.The products contained both the axial chirality and central chirality on phosphorus atom.Meanwhile,this reaction was conducted under mild reaction conditions and also avoid the appliction of complicated chiral ligands.4.Finally,we developed a simple method to synthesize the axially chiral P,N-ligands(MAP).With NIS or PhI(OAc)2/I2 as the oxidants,a series of axially chiral aminophosphine compounds were obtained through radical oxidative C-H amination and dynamic kinetic resolution or desymmetrisation process.Through further reduction and ring-opening of the products,the axially chiral aminophosphine ligands were obtained.The reaction conditions were mild and the products can be synthesized in large-scale.