Design,Synthesis And Application Of Novel Hexamethyl-1,1'-Spirobiindane-Based Chiral Phosphite-Olefin And Phosphoramidite Ligands

The design and synthesis of novel chiral ligands and their catalysts is one of the core contents in transition metal-catalyzed asymmetric reaction,and it is also the frontier and hotspot in current organic synthetic chemistry research.Chiral spiro structure has developed into a class of "privileged structures" for constructing ligand backbones.In particular,chiral spiro ligands derived from the spirobiindane-based skeleton have gradually become a class of "privileged ligands",which exhibit excellent catalytic activity and enantioselectivity in transition metal catalyzed asymmetric reactions.In this thesis,we firstly summed up the research progress of chiral monophosphine ligands,then,a novel hexamethyl-spirobiindane ligand skeleton was developed,and novel types of chiral phosphite-olefin Ligands and phosphoramidite ligands based on hexamethyl-spirobiindane skeleton was designed and synthesized.Furthermore,these new spiro ligands were applied in some transition metal-catalyzed asymmetric reactions.The main research contents are as follows:1.Using commercially available bisphenol C as raw material,hexamethyl-1,1'-spirobiindane-6,6'-diol?6,6'-HMSIOL?was prepared in a high yield by acid-catalyzed rearrangement reaction.Using N-Ts-L-phenylalanine acid chloride and L-menthyl chloroformate as chiral resolving reagents,respectively,successfully achieved two methods for resolution of the racemic 6,6'-HMSIOL,and the absolute configuration of some products was determined by X-ray single crystal diffraction.?R?-7,7'-HMSIOL was synthesized in a total yield of 76.3%from optically pure?R?-6,6'-HMSIOL obtained by resolution by 5-step reaction with bromination reaction,trifluoromethane sulfonylation,palladium-catalyzed selective reduction,carbonylation via bromine-lithium exchange and Baeyer-Villiger oxidative rearrangement.In addition,?R?-7,7'-HMSIOL could also be synthesized in a total yield of 64.4%from?R?-6,6'-HMSIOL by a 4-step reaction with formylation,trifluoromethane sulfonylation,palladium-catalyzed selective reduction and Baeyer-Villiger oxidative rearrangement reaction.Using?R?-7,7'-HMSIOL as a raw material,four kinds of chiral spiro phosphites?R?-2.16a-d and six kinds of chiral spiro phosphite-olefin ligands?R?-2.17a-f based on hexamethyl-spirobiindane skeleton could be prepared in a good yield.The spiro phosphoramidite ligands?S,R,R?-2.18 and?R,R,R?-2.18 based on hexamethyl-spirobiindane skeleton were also prepared by the reaction of chiral 7,7'-HMSIOL with[?+?-bis[?R?-1-phenethyl]aminophosphoric acid dichloride.These new ligand compounds were characterized by NMR,HRMS,IR,melting point and optical rotation.2.Rhodium-catalyzed asymmetric addition of arylboronic acids to N-tosylarylimines using chiral spiro phosphite-olefin ligands has been developed.The optimal P-olefin ligand could serve as an elegant chiral bidentate ligand in the Rh-catalyzed asymmetric 1,2-addition of arylboronic acids to N-tosylarylimines with a broad range of substraes leading to chiral amines with good yields and excellent enantioselectivities.It has been disclosed that spiro phosphite-olefin ligands are capable of coordinating to a rhodium?I?cation in the bidentate fashion at the phosphorus atom as well as at the olefinic double bond.Detailed stereochemical models for enantioselective induction of Rh/P-olefin catalyzed asymmetric reactions were elucidated through DFT calculations,and the origins of the higher enantioselectivity of phosphite-olefin ligands are postulated.3.Rhodium-catalyzed asymmetric addition of organoboronic acids to cyclic N-sulfonyl aldimines using chiral spiro phosphite-olefin ligands has been developed.The complex of?R?-8b and[RhCl?C₂H₄?₂]2 showed near-perfect performance.The optimal P-olefin ligand could serve as an elegant chiral bidentate ligand in the Rh-catalyzed asymmetric 1,2-addition of organoboronic acids to cyclic N-sulfonyl aldimines with a broad range of substraes leading to chiral amines with good yields and excellent enantioselectivities.It is noteworthy that styrylboronic acid reacted smoothly with various cyclic N-sulfonyl aldimines to afford the corresponding enantioselective styrylation products4.Palladium-catalyzed enantioselective alkene carboamination reaction using monodentate spiro phosphoramidite ligand was developed.After screening of reaction conditions,2 mol%Pd2?dba?3 as precursor catalyst,6 mol%?S,R,R?-2.18 as chiral ligand,two equivalent water as additives,toluene as solvent,reflux and 20h as reaction temperature and time are confirmed as optimal reaction conditions.The ligand could serve as an elegant chiral monodentate ligand in the Pd-catalyzed asymmetric alkene carboamination reactions leading to chiral imidazolidin-2-ones with good excellent enantioselectivities.Notably,nitrogen nucleophilicity on asymmetric induction had remarkable effect.The increasing electron-withdrawing ability of the p-substituent on the N-aryl moiety could increase with the level of asymmetric induction.p-Cyanophenyl-substituted substrate and p-nitrophenyl-substituted substrate could give the good results.