The Synthesis Of Spiro Skeleton Ligands And Their Application In Asymmetric Michael Addition Reactions

The catalytic asymmetric C-H activation or functionalization to obtain the chiral compound with high selectivity has become one of the hot spots in the field of organic chemistry in recent decades.The use of transition metal to activate C-H bond of alkanes and aromatics for direct asymmetric functionalization is the most straightforward and efficient method for the synthesis of organic compounds.The design and synthesis of chiral ligands plays a very important role in the asymmetric catalytic reaction.Although metal catalysis facilitated by chiral cyclopentadienyl(Cp)ligands has emerged as a highly efficient and attractive approach,the limitations of present Cp ligands on either applicability or structural variability significantly hampered their comprehensive application.Therefore,it is of great significance to design and synthesize new chiral cyclopentadienyl ligands with simple methods.The main work of this paper is mainly to design a new route for the synthesis of chiral cyclopentadienyl ligands and apply the synthesized catalyst to an asymmetric catalytic reaction.The first part of the paper is mainly about the design and synthesis of spiro ligand.In the previously reported method,it is necessary to determine the substituents at the ortho position of cyclopentadienyl at the beginning of synthesis,which increases the difficulty,and we tend to perform ligand derivations at the last step.After we get the ligand with the-OMe at ortho position,the methyl group was removed to give the product with the-OH group,and then further derivatized to obtain a ligand with different substituents.Eventually we obtained seven different structures of spiro cyclopentadienyl ligand,and synthesized the corresponding catalyst after complexation with the rhodium salts.The second part of the paper is mainly to apply the chiral catalysts to the asymmetric catalytic reaction.We used hydroxamic acids and 1,4-benzoquinone as template substrates,and a polycyclic structure with two chiral centers which are present in many drug molecules and natural products was obtained.Through the screening of catalysts,solvents and additives,we established the optimum reaction conditions:Rh2(5 mol%),cesium acetate(30 mol%),diphenylacetic acid(1.5 eq)and the 1,4-dioxane as solvent.Under the optimum reaction conditions,a variety of reaction substrates could be tolerated and the corresponding products were generated in high yields(81%)and with enantioselectivity(94%ee).