Research Of Transition Metal-catalyzed Asymmetric Addition Tandem Reactions And C-H Functionalization

This dissertation focused on 3 parts: the rhodium(I)-catalyzed asymmetric 1,2-addition-tendem lactonizations of aryl boronic acid to dialdehyde to construct a series of 3-arylphthalide;asymmetric C2-H or C3-H insertion reaction of arylvinylcarbene to unprotected indole to yield a series of chiral gem-diaryl-possessing molecules with high stereo-and enantioselectivity;chiral bifunctional catalyst activated C(sp)-H insertion of hetero terminal alkyne to Cu(II)carbenes tandem 1,2-addition to isatin,to construct tetrasubstituted allenes contained both center and axis chirality.1.Rh(I)catalyzed asymmetric 1,2-addition tandem lactonization of aldehyde by aryl boronic acidsChiral lactone motif in particular chiral 3-substituted phthalide plays a significant role in natural pharmaceutical chemistry and synthetic chemistry.Based on our previous research of asymmetric arylation of carbonyl compounds,we developed an efficient method to construct a series of chiral 3-substituted phthalide,6-membered and 7-membered lactones catalyzed by rhodium(I)/chiral sulfur-olefin with good yield and ee value,which provided a novel pathway to construct drug molecules and potential leading compounds.We still discovered an unexpected kinetic resolution by arylation of bulky biphenyl dialdehyde catalyzed by the above-mentioned system,obtained asymmetric additional product with high ee and dr value.2.Rh(I)mediated asymmetric functionalization of diazocompounds to C3-H and C2-H indoles and analoguesIndole motif is an important structural fragment in natural pharmaceutical chemistry and synthetic chemistry.Chiral α-aryl-α-indole structure widely exists in drug molecules and bioactive molecules.Our team was devoted to studying the design,modification and synthesis of chiral [2.2.2]-bicycle olefin ligand,which successfully promoted a series of X-H insertion to diazo compounds.Rhodium(I)/olefin catalyst system has been first developed for asymmetric C3-H functionalization of unprotected indoles by γ-position of arylvinylcarbene,to construct high enantioselectivity and configuration remained chiral α-aryl-α-indole products.Meanwhile,asymmetric C2-H functionalization of decorated indoles and some other hetero-aromatic compounds has been realized,which can convert to heteroarylcycloalicyclic ketones,allylic alcohols,multi-substituted amino acid esters by simple application reaction.3.Small organic molecule catalyzed three component asymmetric insertion tandem rearrangement-addition reaction of C(sp)-H bond to copper(II)carbene to C(sp)-H bondChiral allenes are a class of compound based on a special structure and exist widely in many natural products.As isoelectronic species of alkyne group,the allene unit was utilized in synthesis of novel drug molecules,which was proved to possess strong pharmacological activity.Moreover,the axis chiral structure can be convert to center chiral structure easily.We developed a new strategy to construct tetrasubstituted chiral allene contained isatin skeleton through chiral bifunctional catalyzed C(sp)-H insertion of copper(II)carbene to propargylamine and analogues tandem arrangement/1,2 additional reaction to isatin,provided excellent results which was up to 82% yield,99% ee value and 99:1 dr value.Some conversions of the products constructed complex chiral spiro compounds which were difficult to form through normal synthetic routes.