The Application Of Sulfinamide Phosphine Ligands In Asymmetric Metal Catalysis

Asymmetric metal catalysis is an efficient method for the synthesis of chiral compounds.Chiral ligand is the core component of asymmetric metal catalysts which is the key to stereochemistry control.Sadphos(Sulfinamide phosphine)is a novel type of chiral phosphine ligand which prepared from chiral sulfonamide and it has been successfully applied in asymmetric organic catalysis and asymmetric metal catalysis.The main work of this paper is to extend the application of chiral Sadphos ligands to more asymmetric metal catalyzed reactions because there are still many problems in asymmetric catalysis.This dissertation is divided into the following three parts:1.Pd-Catalyzed Enantioselective Heck Reaction of Aryl Triflates and Alkynes.Allene moieties with axial chirality are the key structures of a variety of natural products which have unique biological activities.As useful synthetic intermediates,allenes can be converted into other structures including the conversion from axial chirality to central chirality.The Heck reaction of alkynes to form allene lags behind due to the energetically unfavored?-hydride elimination of vinyl palladium species and there are many competitive reactions and side reactions.Although after many years of research,the reaction efficiency of the Heck reaction has been greatly improved,but no example of a Pd-catalyzed enantioselective Heck-type reaction of alkynes has been yet.Through the selection and modification of Sadphos,the first palladium catalyzed asymmetric Heck reaction between aryl triflates and alkynes was realized with novel Xu-Phos which could give axial chiral trisubstituted allenes with the highest value of96.5:3.5 er.This reaction not only had mild conditions,excellent enantioselectivity and functional group compatibility,but also achieved gram scale preparation and conversion of axial to central chirality.The key to the success is the discovery and fine-tuning of the different N-substituents of Xu-Phos,which ensure the enantioselectivity and reactivity.Without the protection group,the reaction would not be take place.The mechanism experiment shows that this reaction undergo?-hydride elimination of vinyl palladium species.2.Nickel-Catalyzed Alkyl-Alkyl Cross-Coupling Reactions of Aldehyde hydrazones with Non-activated Secondary Alkyl Bromides.The C(sp~3)-C(sp~3)bond is widely existed in organic molecules.Alkyl-alkyl cross-coupling reaction of alkyl halides is an effective synthesis method,but it is one of the most challenging reactions because of the reluctance of alkyl halides to undergo oxidative addition and reductive elimination.Alkyl metal intermediates are prone to other side reactions such as?-H elimination and protonation.In addition,this coupling reaction with secondary alkyl halides is more difficult to occur due to more electron rich and larger steric hindrance.At present,the relevant reports are mainly limited to the participation of organometallic reagents and reducing metals.Aldehydes are potential alkyl carbanions which combined with hydrazine hydrate could realize the coupling reactions with aryl halides by using the polarity reversal strategy.We further explored the application of aldehyde hydrazones in alkyl-alkyl cross-coupling reactions,and developed nickel catalyzed alkyl-alkyl cross-coupling reactions between aldehyde hydrazones and non-activated secondary alkyl bromides which could realize the coupling reaction of C site on hydrazone with high selectivity.The coupling reaction of primary and tertiary alkyl bromides could also be realized under the same condition which fills the gaps in the classical cross-coupling reactions.The experiments of free radical clock suggests that the reaction might involve a free radical process.In addition,we tried to study the asymmetric catalysis of this reaction by using the common multidentate chiral phosphine ligands and Sadphos ligands,but unsuccessful.3.Ruthenium catalyzed asymmetric addition of aldehyde hydrazones to simple ketones.Chiral tertiary alcohols are the key structures of many drug molecules and have unique biological activities.Asymmetric addition reaction of ketones is the most direct method,but there are few reports because of the small difference of steric resistance between two sides of ketone and low reactivity,especially simple ketone.Aldehydes as potential alkyl carbon anions,have achieved an asymmetric addition of simple ketones by using the polarity reversal strategy,but the enantioselectivity was not high.Through the selection and modification of Sadphos,the enantioselectivity of this reaction could be increased to 73%ee with the novel Wei-Phos as chiral ligand and methylhydrazine as additive.Through the analysis of experimental results,nitrogen ligands had a great influence on the enantioselectivity of this reaction.At present,the enantioselectivity of this reaction could be increased to 76%ee with ruthenium complexes containing chiral nitrogen ligands as catalysts and triarylphosphones as effective additive.The results have improved,but it has not reached our expectations,and our further studies on this issue will be carried out.