Base Metal Ni,Cu And Co-Catalyzed Regio-and Stereo-Selective Functionalizations Of Inert C-H Bonds Based On Directing Strategy

C-H bonds are ubiquitous units in organic molecules,however,the direct utilization of C-H bonds as functionalization groups?FGs?for highly regio-and stereo-selective transformation was a long-standing challenge for synthetic chemists,mainly due to the low reactivity of C-H bonds?which was caused by their high bond disassociation energy and low acidity?as well their similar chemical environments in molecules.During the past several decades,the introduction of directing groups?DGs?has emerged as a powerful method for the resolution of this problem.In this regard,the second and third row transition metals,such as Pd,Rh,Ir have dominated the past advances,however,these metals are earth-rare,cost-intensive and are generally more toxic thus limiting their sustainability.Accordingly,the development of earth-abundant,cost-effective,less toxic and more sustainable first row transition metals,such as Ni,Cu,Co as catalysts was highly desirable.Under this context,this dissertation mainly focused on base metal-catalyzed regio-and stereo-selective activation/functionalization of inert C-H bonds assisted by DGs.The main content was listed as follows:1.Ni???-Catalyzed Oxidative Alkynylation of Unactivated?Hetero?aryl C-H Bonds Using Oxygen:A User-Friendly ApproachWe have developed a Ni???-catalyzed dehydrogenative alkynylation of unactivated C?sp2?-H with terminal alkynes.This protocol features the use of catalytic amounts of nickel as the catalyst and O₂ as the sole oxidant,representing a more straightforward and environmentally-friendly method for the synthesis of aryl alkynes,this protocol also represents an advancement of the traditional Sonogashira cross-coupling reaction.Various?hetero?aryl carboxylic acids could be obtained due to the readily removal of the PIP directing group.2.Cu-Catalyzed Modular Access to N-Fused Polycyclic Indoles via Intramolecular N-H/C-H Annulation with AlkynesCu-catalyzed intramolecular N-H/C-H annulation with alkynes has been developed.Varieties of highly modular substrates consisting of tunable anilines,C,N,O-fused linkers and aryl,alkyl,silyl-terminated alkynes could be selectively converted into densely functionalized heterocycles,such as pyrrolo[1,2-a]indolones,indolo[1,2-c]quinazolinones,oxazolo[3,4-a]indolones and imid-azo[1,5-a]indolones etc.By changing the oxidant from DTBP to TEMPO,the reaction could readily be transformed to the aminooxygenation pathway.Theuse of inexpensive copper catalyst,broad substrate scope and operationally simplicity make this method attractive for efficient access to these heterocycles.Mechanistic experiments indicate that vinyl radical is involved in this reaction and an amidyl-radical-initiated radical cascade might be responsible for this transformation.3.Cp*Co?III?/MPAA-Catalyzed Enantioselective Amidation of Ferrocenes Directed by Thioamides under Mild ConditionsCp*Co?III?-catalyzed enantioselective C-H amidation of ferrocenes using monoprotected amino acid?MPAAs?as chiral carboxylic acid ligand was developed.The reaction was performed under mild conditions in high yields?up to 97%?with moderate enantioselectivity,after recrystalization,the desired product could be obtained with modest yield and excellent ee?>99%ee?,which provides a promising strategy to create planar chirality via base-metal-catalyzed enantioselective C-H activation.4.Cp*Co???/CCAs-Catalyzed Enantioselective Alkylaiton of Indoles With Simple a-AlkenesWe developed a Cp*Co???-catalyzed enantioselective alkylation of C2 position of Indoles using readily available and simple a-alkenes as alkylation reagents.In this reaction,tailor-made bulky amino acids,which were independently synthesized by a newly developed Palladium-catalyzed arylation of?L?-tert-butyl leucine derivatives,were used as effective chiral carboxylic acids?CCAs?ligands.This reaction represents a great advancement for the asymmetric hydroarylation of simple alkenes,and the newly developed bulky chiral carboxylic acids?CCAs?may enlighten the design and synthesis of other CCAs used for the asymmetric C-H activation reaction.