Synthesis Of Chiral P,N/P,N,N-Ligands And Their Applications In Asymmetric Allylic/Propargylic Substitution Reactions

The introduction of allyl and propargyl groups in organic compounds is an important way to build carbon-carbon and carbon-heterobonds in synthesis.Moreover,asymmetric allyl substitution and asymmetric propargyl substitution reactions can generate chiral products with carbon-carbon double bonds and carbon-carbon triple bonds.These chiral products containing double bonds and triple bonds have always been the important components of chiral drugs and the important skeleton of natural products,so the unique potential value of the two types of substitution reactions has made countless researchers working for them.Although allyl substitution has acquired many breakthrough developments in the past few decades,there have been fewer and fewer reports of new ligands designed and developed for asymmetric catalytic allyl substitution in recent years.Therefore,an important and challenging task in this development field is to design and synthesize new highly effective chiral ligands.In the field of propargyl substitution,the first case of copper-catalyzed substitution reaction between propargyl and amine was successful.So far,a large number of nitrogen nucleophiles and carbon nucleophiles have been widely used in copper-catalyzed asymmetric propargyl substitution and cycloaddition reactions,but there has been no breakthrough in the asymmetric substitution reaction of propargyl with oxygen as nucleophile.Therefore,the use of oxygen-based nucleophilic reagents for the propargyl oxynucleophilic substitution reaction can further breakthrough the reaction field.This paper was carried out the following research around these two research fields.In the first part of the paper,2-(diphenyl-phosphino)benzaldehyde and 2-alkyl-1-phenylethylamine were condensed in anhydrous toluene to form Schiff base compounds,and then reacted with the methyl format the reagent or methyllithium reagent to obtain a series of P,N-phenyl skeleton ligands.Using the newly designed chiral P,N-ligand and(?-allyl)Pd Cl₂as a catalyst,Using the newly designed chiral P,N-ligand and as a catalyst,and the above catalyst was used to catalyze the asymmetric substitution reaction between(E)-1,3-dissubstituted allyl ester compounds and dimethyl malonic acid under 25?nitrogen.Finally,the product 1,3-diphenyl substituted propenyl malonate compound was obtained,and the yield of the reaction reached 98%at the best,while the best enantioselectivity reached93% ee.It has the characteristics of simple ligand synthesis,very mild reaction conditions,easy operation,cheap and easily obtained raw materials,excellent stereoselectivity,and certain universality of the substrate.In the second part of the work,Schiff base compounds obtained by condensation reaction with(S)-DPPNH₂and 2-benzoylpyridine as raw materials were used to synthesize a series newly designed chiral phenyl skeletons P,N,N-ligand.The newly designed phenyl framework P,N,N-ligand was used to generate a complex in situ with Cu(OTf)₂to catalyze asymmetric etherification of alkyne propyl acetate with aryl oxime.(S)-L1a was the preferred ligand.Methanol was used as the solvent.Diisopropylethylamine was used as the base.At atmospheric pressure,-20?reacting 12 h,the asymmetric etherification of propargyl acetate with aryl oxime was achieved at low cost.The yield of the product chiral(E)-benzaldehyde O-(1-phenylpropargyl)oxime ether was as high as 80%,and the enantioselectivity was as high as 89% ee.