Modification And Application Of Sulfinamide Phosphine(Sadphos) Ligands

The process by which a reactant introduces one or more chiral elements into a reaction by using a chiral catalyst is called asymmetric catalysis.Asymmetric metal catalysis,one of the approaches to asymmetric catalysis,has been favored by chemical researchers in recent decades because of its high efficiency and practicality.Chiral ligands are an important component of asymmetric metal catalysis and play a crucial role in enhancing the reaction activity and controlling the stereoselectivity of the reaction.Based on tert-butyl sulfinamide,our group has constructed a series of new chiral phosphine ligands Sadphos(Sulfinamide phosphine),which have achieved remarkable results in both asymmetric metal catalysis and small molecule organocatalysis through unremitting efforts.This thesis is devoted to the application of Sadphos in asymmetric Heck/Cacchi tandem reactions;asymmetric coupling reactions of racemic secondary alkyl borons with aryl halides.In parallel,we have discovered the borylation cyclization process of yne-enones in the presence of boron trichloride.The specific work is divided into the following three parts:1.Palladium Catalyzed Enantioselective Tandem Heck/Cacchi Reaction of Unactivated Alkenes.2,3-dihydrobenzofuran and indole are important units in the composition of many natural products and both show excellent biological activity in medicinal chemistry.Tandem reaction,as an important means that can fuse multiple reactions in one reaction process.It improves the efficiency of the reaction and reduces the occurrence of side reactions,which is in line with the concept of green chemistry development.We developed the Heck/Cacchi tandem reaction for the construction of molecules containing multiple heterocycles.According to the screening of Sadphos ligands,we achieved a broad range of enantioenriched 2,3-dihydrobenzofuran-or indoline-substituted indoles bearing all-carbon quaternary stereocenter by palladium-catalyzed asymmetric tandem reactions of ortho-iodophenol-derived allyl ether and ortho-alkynylaniline using Xu-Phos as chiral ligand with up to 97%ee value.The reaction not only has mild conditions,good functional group compatibility,excellent chemoselectivity and enantioselectivity,but also can construct two C-C bonds and one C-N bond directly in one pot.2.Enantioselective Palladium Catalyzed Cross-Coupling Reactions of Secondary Alkylboron and Aryl Halides.Suzuki-Miyaura coupling is one of the most widely used cross coupling reactions,however,due to the slow rate of transmetallation and the occurrence of?-hydrogen elimination after transmetallation during the reaction leading to isomerization of?-alkylpalladium species and racemization of the stereocenter,asymmetric coupling of racemization secondary alkylboron with aryl halides has not been achieved yet.Consequently,we modified and screened the Sadphos ligands and found that the corresponding products were finally obtained with up to 84%ee value under the catalysis of palladium with N-allyl-Xu-Phos and N-Me-Xu-Phos with side-arm effect,but there were still have some problems such as poor substrate scope and low reactivity.In the course of our research,we have developed new ideas for modifying Sadphos and expanding the Sadphos"ligand library".3.BCl3 Mediated Borylative Cyclization of Yne-enones.Naphthalene is a privileged structural motif frequently found in numerous biologically active natural products and materials.Owing to their importance,the synthesis of multi-substituted naphthalene derivatives is significance.BCl₃ is an inexpensive electrophile that can induce borylation cyclization of various substituted alkynes,leading to regioselective synthesis of cyclic compounds containing C(sp²)-B bonds that are widely used in synthesis.BCl₃ mediated borylative cyclization of yne-enones leading to synthetic valuable multi-functionalized naphthalene boronates in one step was developed.The presence of boronic acid esters could provide more chance to synthesize multisubstituted naphthalene derivatives via functional group transformations.This strategy has the advantages of simple operation,moderate to good yields and easy to prepare on a gram scale.Meanwhile,the new synthetic applications of yne-enones have been developed.