Metal-Catalyzed Construction Of P-Stereogenic C-P Bond

P-Stereogenic phosphines can be used as chiral ligands for metals,small molecule catalysts and biologically active molecules in a number of applications such as asymmetric catalysis and medicinal chemistry.In the past decades,the synthesis of such compounds mainly relied on the use of chiral reagents,chiral cofactors,and there was a lack of efficient synthetic methods.Until the last decade,the synthesis of P-stereogenic phosphines by asymmetric catalysis has shown more efficient advantages.In particular,the metal-catalyzed asymmetric construction of carbon-phosphine bonds for P-stereogenic phosphines has provided more possibilities for the synthesis of structurally diverse P-stereogenic phosphines compounds.The asymmetric catalytic synthesis of P-stereogenic phosphines faces challenges such as poor enantioselectivity,low reactivity and the toxic effect of phosphine centres on metals,and thus there is still much room for improvement in the current synthetic strategy.In order to address the problems of existing synthetic methods,to develop new synthetic methods and to synthesise structurally novel Pstereogenic phosphines,this thesis reports two of our research results in this area.The existing strategies for the synthesis of P-stereogenic alkynylphosphines rely on the use of chiral reagents and desymmetrization,and thus face problems such as poor substrate suitability and low synthetic efficiency.To address these problems,we have developed nickel-catalyzed asymmetric coupling reactions for the synthesis of P-stereogenic alkynylphosphines.The trivalent phosphine hydrogen reduced in situ from secondary phosphine oxides was used as a raw material for the efficient synthesis of the target products by asymmetric cross-coupling with alkynyl bromide in the Ni(COD)2/(S,S)-Et-Duphos catalytic system.By extension of the substrates,the synthesis method shows a high degree of substrate suitability.Furthermore,due to the highly reactive carbon-carbon triple bond,the alkynylphosphine can be easily transformed into structurally diverse phosphine-centred chiral compounds.In particular,we have synthesised chiral luminescent small molecules based on Pstereogenic phosphine heterocyclic structures,which exhibit significant aggregationinduced luminescence effects as well as chiral optical properties.In addition,facing problems such as the low reactivity of non-activated olefin substituents in coupling reactions,we developed a palladium-catalyzed diastereoselective synthesis of N-alkenyl phosphine oxides based on spiro-chirality and P-stereogenic in coupling reactions.The target products were synthesised diastereoselectively by cross-coupling with alkenyl trifluoromethanesulfonates with a spiro-ring structure in a Pd(TFA)2/dppb-catalyzed system using secondary phosphine oxides as raw materials.The synthesis method showed good substrate suitability through the extension of the substrate.And the synthesised Nalkenylphosphine oxides contain electron donors and hydrogen bond donors/acceptors,which may be used as small molecule catalysts or chiral ligands for metals in some asymmetric catalytic reactions.