| The charm of organic chemistry lies in the development of new methods and substances to overcome and solve the difficult synthesis of complex functional molecules.Since asymmetric metal catalysis was awarded the Nobel Prize in Chemistry in 2001,remarkable progress has made.The catalytic enantioselectiveα-functionalization of carbonyl compounds plays a crucial role in the synthesis of active drug molecules and natural products,especially in the construction of quaternary carbon stereocenters.Two main strategies can be outlined as tools forα-functionalization of carbonyl compounds in asymmetric metal catalysis:（1）Coupling reaction between enolate formed by deprotonation of carbonyl compound with electrophile.（2）Coupling reaction of halogen-containing carbonyl compounds with nucleophiles.Our group has developed a new type of novel chiral ligand sulfinamide-phosphine（Sadphos）,which has shown great performance in metal catalysis.This dissertation is dedicated to applying Sadphos to catalytic enantioselectiveα-arylation and alkenylation of carbonyl compounds to construct C（sp~3）-C（sp~2）bond while generating acyclic quaternary carbon stereocenters.In parallel,we also have developed a new type of phosphine ligand,expanding the Sadphos family.The specific work is divided into three parts:1.Palladium/Sadphos-Catalyzed Asymmetric Intermolecularα-Arylation of Aldehydes with Aryl BromidesSince 1997,the Pd-catalyzed directα-arylation of cyclic ketones was reported independently by Buchwald,Hartwig,and Miura,and this protocol has been widely extended to enantioselectiveα-arylation of other cyclic carbonyl compounds.We reported Pd catalyzed asymmetric intermolecularα-arylation reaction of disubstituted aldehydes with aryl bromides,which provides a rapid access to chiral aldehydes bearing an acyclic quaternary carbon stereocenters.The key to the success of this methodology lies on the application of electron-rich TY-Phos ligand with an allyl substituent on nitrogen atom,which makes theα-arylation occurred in good enantiocontrol at room temperature.In addition,a pair of enantiomers could be easily prepared with the use of the same ligand by exchanging the aryl groups of aldehyde and aryl bromide.2.Palladium/Sadphos-Catalyzed Asymmetric Intermolecularα-Alkenylation of Aldehydes with Alkenyl Bromideβ,γ-Unsaturated carbonyl compounds are widely existed in natural products and active pharmaceuticals.Inspired by the asymmetricα-arylation of aldehydes with aryl bromides,we synthesizedβ,γ-unsaturated carbonyl compounds by using alkenyl bromides with aldehydes as reaction partner.Regrettably,although chemical transformations can be achieved well,the enantioselectivity is poor.During the further systematic fine-tuning the structure of TY-Phos,it was founded that when a pyridine group was introduced into the substituent,better enantioselectivity and reactivity were obtained.It is not known what the role of the pyridine group is yet,and it needs to be proved by later mechanism studies.3.Design and Synthesis of a Novel Chiral Sulfinamide Phosphine Ligand-HP-PhosSince 2014,our group has synthesized Ming-Phos based on tert-butyl sulfinamide,and then Xiao-Phos,Xu-Phos,Xiang-Phos,PC-Phos and other ligand were synthesized,according to the skeleton and the electrical properties of the phosphine.Although it has shown great performance in many metal-catalyzed asymmetric reactions,there are still many problems in asymmetric catalysis that have not been solved.In view of this,we developed a novel chiral monophosphine ligand-HP-Phos,which has the characteristics of simple skeleton,short synthetic route and easy modification.Unfortunately,we have not found a suitable reaction system for this ligand. |
