Synthesis Of Chiral Phosphine Ligands And Application In Catalytical Reactions

This dissertation incudes:1) High enantioselective syntheis of3-aryl-4-phosphonobutyric acid esters via Cu-catalyzed asymmetric conjugated reduction.2)Palladium-catalyzed propargylic substitution with H-phosphonates nucleophiles:for the synthesis of1,3-dienylphosphonates.1. Syntheis of3-aryl-4-phosphonobutyric acid esters via Cu-catalyzed asymmetric conjugated reductionThe substrates3-aryl-4-phosphonobutyric acid esters was synthesized from kenones through a three-step transformation. Initially, the unsaturated esters were obtained by the Homer-Wittig reaction, in which (E)-isomers were formed predominantly. Bromination of (E)-unsaturated esters with N-bromosuccinimide in the presence of benzoyl peroxide gave the allylic bromides in high yields. The Arbusov reaction with phosphites gave the target phosphonates. And (S)-SegPhos was obtained from4-bromo-1,2-methylenedioxybenzene through a five-step transformation. Under the optimized condition((S)-Segphos as the ligand, Cu(OAc)2·H2O as the catalyst precursor, t-BuOH as the additive, PMHS as the hydride source) a wide range of3-aryl-4-phosphonobutenoates were reduced with high efficient and enantioselectivities (up to94%ee), yield up to95%. The enantioselectivities of reaction were significantly influenced by the steric effect and electronic effect. Generally speaking,substrates with an ortho-methoxy in the phenyl ring tended to be reduced with low reactivity and enantioselectivity than those with a meta-or para-methoxy group. The electronic properties of the para-substituent on the phenyl ring of the substrates also had an important influence on the enantioselectivities. The substrates with an electron-withdrawing group gave better enantioselectivities than those with an electron-donating group. However, the reduction of substrate1h with a para-nitro group on the phenyl ring required a larger catalyst loading and higher temperatures in order to reach complete conversion. Surprisingly, substrates with a meta-electron-withdrawing group on the phenyl ring were reduced with moderate ee values. In conclusion, we have developed a copper-catalyzed asymmetric conjugate reduction of3-aryl-4-phosphonobutenoates that provides an enantioselective synthesis of optically active3-aryl-4-phosphonobutyric acid esters.2. Palladium-catalyzed propargylic substitution with H-phosphonates nucleophiles:for the synthesis of1,3-dienylphosphonates.The substrates4-alkyl(aryl)-acetoxy-l-butine were synthesized from aldehyde through propargylation and esterification. Synthesis of1,3-dienylphosphonates and1,2-allenylphosphonates via Palladium-catalyzed propargylic substitution with H-phosphonates nucleophiles were also performed. Under the optimized condition(Pd2(dba)3·CHCl3as the catalyst precursor, BINAP as the ligand, Et3N as the base) the substitution of propargylic esters to H-phosphonates nucleophile produce efficiently1,3-dienylphosphonates and1,2-allenylphosphonates. The steric resistance of catalyzing to form1,3-diene phosphonate is small so that conjugated diene-type product was obtained when the No.1and No.4carbon atoms have no substituents or branch chains. While the steric resistance of catalyzing to form1,3-diene phosphonate is big so that1,2-cumulative diene phosphonate was produced when the No.1and No.4carbon atoms have substituents or branch chains. Both of the alkyl and aryl1,3-dienylphosphonates can be prepared from this transformation.