Highly Selective C(SP~2)-H Bond Functionalization Via Diazo Compounds

Compared to traditional coupling strategies,the C-C bond forming reactions via C?SP²?-H bond functionalizaitons don't rely on pre-functionalized staring material,showing better atom and step-economy and producing much less wastes.The more general C?SP²?-H bond functionalization approach proceeds through the insertion of a metal into a C-H bond,followed by a subsequent transformation to introduce an organic substituent.However,the C?SP²?-H bond functionalizations via diazo compounds,which server as alternative methods,remain underexplored and more researches need to be conducted to gain more insights into this reaction.My research was focused on C?SP²?-H bond functionalizations via diazo compounds and developed several novel,efficient and attractive processes,expanding our understanding on this reaction and offering a potentially efficient method for the synthesis of numerous natural products and pharmaceuticals.The content of my thesis includes four parts as the following.?1?Highly selective C-H bond functionalization of phenolPhenols are essential structural skeletons,widely found in numerous natural products,bioactive compounds,pharmaceuticals,and polymers,as well as common versatile building blocks in organic synthesis.Up to now,the number of phenols is over 4 millions.Therefore,the development of novel approach to site-selective direct C-H functionalization of unprotected phenols would be highly desirable.We realized chemoselective and para-selective functionalizations of phenols successfully utilizing specific carbophilicity of gold and strong directing ability of the hydroxyl group.The further research was conducted subsequently in order to gain more insights into gold-catalyzed highly para-selective C-H bond functionalization of phenol.The results based on DFT,control experiments and related kinetic experiments revealed that this unprecedent reaction is a two water assitanted[1,3]-H shift process.In addition,the O-H insertion is kinetic controlled process,while C-H bond functionalization is thermodynamic controlled approach.As a continuous interest in C-H bond functionalization via diazo compounds,we want to realize the intermolecular ortho-selective C-H bond functionalization of phenols with diazoesters.In general,para-substitutions are more favorable for the reactions between phenols and electrophiles due to the little differences of nucleophilicity between ortho and para positions of phenols but more steric hindrance for the ortho ones.Thus,the ortho C-H bond functionalization of phenol is a more challenging issue.We achieved it using?C₆F₅?₃ as a bifunctional catalyst,in which the hydrogen-bonding direct the diazo compound to ortho position and activate the diazoester via the strong Lewis acidity of boron.The preliminary mechanism studies shown that hydrogen bond interaction indeed played a key role in this transformation.?2?Gold-catalyzed constructions of quaternary stereocentersQuaternary carbon centers are frequently found in a broad range of biologically active molecules,natural products and pharmaceutical agents.Although numerous efforts have been devoted to this field,the efficient construction of these special units still remains vital challenge due to the steric congestion.Thus,developing novel methods to efficiently construct quaternary stereogenic carbon center has received considerable attention recently.Based on previous works,we known that active enolate gold intermediates would be generated when electron-rich aromatic compounds were treated with diazoester under a gold catalyst.We realized the construction of a series indanol and terahydronaphthalenol derivatives with two adjacent quaternary stereocenters involving a quaternary carbon stereocenter via trapping of gold enolate.?3?Highly selective C-H bond functionalization of naphthalenolAs a continuous interest in C-H bond functionalization via diazo compounds,subsequently,we want to realize the C-H bond functionalization of naphthalenol.We achieved the ortho and para C-H bond functionalization of 1-naphthalenol respectively under different ligands,utilizing the specific carbophilicity of gold carbene.Besides,we also could realized the ortho C-H bond functionalization of 2-naphthalenol.?4?Iron-catalyzed highly selectivily C-H bond functionalizationIt is always our dream that we could achieve the earth abundant metal catalyzed direct C-H bond functionalization of phenol substrates via diazo compounds.We realized the iron-catayzed ortho C-H bond functionalization of 1-naphthalenol after numerous effort.Meanwhile,we could realize the ortho C-H bond functionalization of ortho substituted phenols,which could not be obtained using?C₆F₅?3B.