Design,Synthesis Of Tetramethyl-1,1'-Spirobiindane-based Bisoxazoline Ligands And Their Applications In Fe-Catalyzed Asymmetric Reactions

Chiral bisoxazoline ligands occupy a significant position among nitrogen-containing ligands.These ligands have many advantages,such as simple preparation,stable properties and wide use range,which have made them exhibit excellent catalytic performance in various asymmetric reactions.So they have attracted increasing attention of chemists and have been widely used in scientific and industrial fields.In this dissertation,we firstly reviewed the development progress of chiral bisoxazoline ligands,and then reported the synthesis of novel tetramethyl-1,l'-spirobiindane-based bisoxazoline ligands,and their applications in iron-catalyzed asymmetric reactions.The details are summarized as following:1.Starting from bisphenol C,a type of new chiral bisoxazoline ligands as the desired targeted products were afforded and separated in a seven-steps reaction procedure,including cyclization,o-formylation,esterification,selective reduction,oxidation,condensation and cyclization,followed by separation by flash chromatography.Eight kinds of optically pure bisoxazoline ligands?HMSI-BOX?were obtained in a total yield of 46.9%-57.7%.Then,using the tetramethyl spiro dialdehyde as the starting materials,another type of new chiral bisoxazoline ligands were synthesized after oxidation,condensation and cyclization,and separated by flash chromatography.Eight kinds of pure chiral bisoxazoline ligands?TMSI-BOX?were prepared in a total yield of 70.3%-85.5%.The absolute configurations of these two kinds of ligands were determined by X-ray crystallographic analysis of a single crystal.2.The first enantioselective Si-H bond insertion reaction of diazoesters catalyzed by Fe/HMSI-BOX was developed.Using a-diazoesters and silanes as starting materials,the ligands,metal precursors,solvents,temperature,additives and catalyst ratio were screened,twenty-one optically active 2-aryl-2-silylacetate derivatives were obtained in high yields?up to 99%?with excellent enantioselectivities?up to 96%ee?under the optimal reaction conditions of 5 mol%Fe?OTf?2,6 mol%?R.,S,S?-2.10b and 6 mol%NaBArF in dichloromethane?2 ml.?at 40 ? for 48 hours.The kinetic isotope effect?KIE?experiment was performed.The origins of ligand-controlled enantioselectivity was explored by density functional theory?DFT?calculations and a possible quintet transition state was proposed.3.A highly enantioselective intramolecular cyclopropanation of diazoesters catalyzed by Fe/HMSI-BOX was developed.Using a-diazoester derivatives as raw materials,the ligands,metal precursors,solvents,temperature,additives and catalyst ratio were screened,sixteen optically active 3-oxabicyclo[3.1.0]hexan-2-one derivatives were synthesized in high yields?up to 96%?with excellent enantioselectivities?up to 96%ee?under the optimal reaction conditions of 10 mol%FeCl₂.4H₂O,12 mol%?R_?,S,S?-2.10b and 12 mol%NaBArF in chloroform?2 mL?at 60 ? for 24 hours.