Design,Synthesis And Application Of Novel Chiral ?-Aminephosphine Catalyst

Over the past decade,asymmetric chiral phosphines catalysis has emerged as a powerful approach to functionalized molecules and organic building blocks.Among many types of chiral phosphines,chiral ?-aminephosphines represent one of the most efficient and widely utilized catalyst.However,the traditional synthetic routines for their preparation often suffers from several drawbacks such as harsh reaction conditions,long synthetic route,low diversity etc.Thus,the development of novel strategy for the synthesis of ?-aminophosphines is highly desirable and significant.In this dissertation,a series of structurally novel chiral ?-aminophosphines were constructed in good yields with high diastereoselectivity through the nucleophilic addition of Ph2PCH2Li to chiral(Rs)-sulfinimines.Furthermore,we have evaluated their performance in the enantioselective Rauhut-Currier reaction and[3+2]cycloaddition reaction.This dissertation including the following five parts:1.Design,synthesis and application of Xiao-Phos in enantioselective Rauhut-Currier reactionsThe chiral(Rs)-sulfinimines could be obtained in good yields from commercially available aldehyde and tert-butylsulfinamide via Ti(OiPr)4 mediated condensation.The nucleophilic addition of Ph2PCH2Li to the sulfinimines furnished a set of novel chiral?-aminophosphines catalyst(Xiao-Phos)in moderate yields with good diastereoselectivity.Further investigation demonstrated that Xiao-Phos have showed good performance in the enantioselective intramolecular Rauhut-Currier reactions of cyclohexadienone derivatives and cross intermolecular R-C reaction of vinyl ketone and activated alkenes.2.Design,synthesis and application of Wei-Phos in highly enantioselective inter-molecular cross Rauhut-Currier reactionsThe nucleophilic addition of Ph2PCH2Li to the chiral sulfinimines which were obtained from 2-diarylphosphino benzaldehyde and tert-butylsulfinamide via Ti(OiPr)4 mediated condensation furnished a series of novel chiral sulfinamide bisphosphine cat-alysts(Wei-Phos)in moderate yields with good diastereoselectivity.Further investigation demonstrated that Wei-Phos have showed good performance in the enantioselective intermolecular RC reactions of vinyl ketones and 3-acyl acrylates or 2-ene-1,4-diones,leading to the RC products in high yields with up to 99%ee under 2.5-5 mol%catalyst loading.3.Peng-Phos catalysed enantioselective intermolecular cross Rauhut-Currier Reactions of activated alkenes and acrolein The nucleophilic addition of Ph2PCH2Li to the chiral sulfinimines which were obtained from 2-aryl benzaldehyde and tert-butylsulfinamide via Ti(OiPr)4 mediated condensation furnished a set of novel chiral sulfinamide bisphosphine catalysts with bulky side chain(Peng-Phos)in moderate yields with good diastereoselectivity.Further investigation demonstrated that Peng-Phos have showed good performance in the challenging enantioselective intermolecular RC reactions of active alkene with acrolein.4.Phosphine-catalyzed enantioselective[3+2]cycloadditions of terminal allenoates with ?-perfluoroalkyl enonesA set of novel chiral phosphine catalysts with different acyl protecting groups could be easily prepared from chiral sulfinamide phosphine catalysts in four steps.(S)-P3 bearing electron-withdrawing acyl protecting groups have shown excellent performance in the enantioselective[3+2]cycloadditions of allenoates with ?-perfluoroalkyl enones,leading to a wide range of trifluoromethylated cyclopentenes with two contiguous chiral centers(up to 99%yield with 99%ee).What's more,this reaction could be amenable to gram scale by utilizing only 1 mol%catalyst.5.Phosphine-catalyzed enantioselective[3+2]cycloadditions of ?-substituted allenoates with ?-perfluoroalkyl enonesCommercially available chiral phosphine(R,R)-DIPAMP have showed good performance in the enantioselective[3+2]cycloadditions of ?-aryl allenoates with ?-perfluoroalkyl enones,leading to the trifluoromethylated cyclopentenes with three contiguous chiral centers with high regioselectivity,diastereoselectivity and enantioselectivity.In contrast,our developed multifunctional phosphine(S)-P3 display-ed high performance in the asymmetric cycloaddition of ?-alkyl allenoates with trifluoromethyl enones.Additionally,control experiments demonstrated that under the catalysis of(R,R)-DIPAMP,racemic allenoate reacted with trifluoromethyl enone through a "deracemization" process,whereas a clearly kinetic resolution reaction takes place with the use of the multifunctional chiral phosphine(S)-P3 as catalyst.