Pd(?)-catalyzed Enantioselective C(sp~2)-H Activation For Synthesis Of Chiral Heterocyclics

Transition-metal-catalyzed C-H functionalization has been widely studied in recent years.However,enantioselective cleavage of inert C-H bond to construct chiral heterocyclic compounds remains one of the important challenges in the synthetic methodology.In this thesis,historical and contemporary research,in the field of transition metal-catalyzed asymmetric C-H functionalization,would be reviewed,that highlights the major achievements in diastereoselective and enantioselective C-H activation.As majorities of published results was achieved by asymmetric C-H activation/C-C coupling reaction.Our methodology was that Pd(?)-catalyzed enantioselective C-H activation/C-X coupling reactions to synthesize chiral heterocyclic compounds,in which the directing groups were also used as building blocks to synthesize heterocyclic compounds.Firstly,Pd(?)-catalyzed carboxyl group directed enantioselective C-H activation/C-O bond formation had been developed to synthesize chiral benzofuran-2-ones.The enantioselectivity was controlled by N-monoprotected amino acids(MPAA).C-O bond reductive elimination was accelerated by Pd(IV)intermediate,which characterizes high energy and instability,by using iodobenzene diacetate as oxidant.This transformation was the first example of enantioselecctive C-H functionalizations through Pd(?)/Pd(IV)redox catalysisSecondly,Pd(?)-catalyzed amide directed enantioselective C-H activation/C-N bond formation had been developed to synthesize chiral oxoindoles.Key to the successful realization of this asymmetric catalytic transformation was the identification of mono-N-protected a-amino-O-methylhydroxamic acid(MPAHA)ligands,which promote reactivity under mild conditions and control enantioselectivity.The counteranions in the solvent medium,hexafluoroacetylacetate and acetate,were also found to play key roles in stereocontrol and reactivity enhancement.