Synthesis Of New Chiral P,N,N-Ligands And Application In Copper Catalyzed Cycloaddition

Catalytic propargylic substitution represents an important C-C and C-N bond-forming reaction. Thus, the catalytic asymmetric propargylic substitution remains one of the formidable challenges in organic chemistry. In this dissertation, we have developed a new type of chiral P,N,N-ligands and successfully applied them to the Cu-catalyzed asymmetric [3+2] cycloaddition of propargylic esters with β-ketophosphates.1.(S)-DPPNH2 was prepared by the direct ortho-lithiation of(S)-phenethylamine, followed by diphenylphosphination. The resulting(S)-DPPNH2 can be easily converted into the corresponding chiral ketimine P,N,N-ligand by the reaction with 2-benzoyl-pyridine.2. The copper-catalyzed asymmetric [3+2] cycloaddition of β-ketophosphates with propargylic esters had been developed by using a chiral P,N,N-ligand. The substituent group of the ketimine in the ligand has an important influence on the reactivity and stereoselectivity.3. The reaction condition was screened by using 1-phenylprop-2-yn-1-yl acetate and dimethyl(2-oxo-2-phenylethyl)phosphonate as standard substrate and the optimal reaction condition was dentified as follow: ligand(S)-L22a(5.5 mol %), Cu(OTf)2(5 mol %), t-BuOK(1.2 eq), in MeOH at-20℃ for 24 hours. Under the optimized condition, a wide range of substitution patterns at the propargylic esters and β-ketophosphates were tolerated to the reaction, providing the corresponding chiral dihydrofuran phosphates bearing an exocyclic double bond at the 2-position in good yields(up to 95%) and moderate to excellent enantioselectivities(up to 92% ee).