Transition Metal-catalyzed Carbon-Carbon Bond Formation Based On Desymmetrization/Coupling Strategy

The construction of chiral carbon centers has always been a hot and difficult research area in organic chemistry,especially chiral quaternary carbon centers.Considering the great challenge to obtain chiral quaternary carbon centers by direct coupling reactions,we supposed that the combination of desymmetrization strategy with nickel-catalyzed couplings could provide an efficient way to achieve this target.Meanwhile,a more efficient nickel/photoredox-catalytic coupling regime was designed to realize the construction of chiral tertiary carbons,which would lay the foundation for chiral quaternary carbon centers synthesis.In this dissertation,the following three sections are focused on:（1）nickel-catalyzed intramolecular desymmetrization addition of aryl halides to 1,3-diketones;（2）dual nickel-and photoredox-catalyzed asymmetric arylation ofα-trifluoromethyl bromoalkanes;（3）molybdenum-catalyzed deoxygenative cross-coupling reactions of benzyl alcohols with benzyltrifluoroborates.1.Nickel-catalyzed intramolecular desymmetrization addition of aryl halides to1,3-diketones.In the first part,we described nickel-catalyzed intramolecular desymmetrization addition of aryl halides and 1,3-diketones.This reaction gave polycyclic products with two tetrasubstituted carbon centers with excellent diastereoselectivities and high yields.This process involved the oxidative addition of zero-valent nickel and the desymmetrization addition of a nickel species to the carbonyl group.In the meantime,the enantioselective desymmetrization of this transformation was investigated to give two stereospecific tetrasubstituted carbon centers with moderate enantioselectivies in the presence of a chiral ligand.2.Dual nickel-and photoredox-catalyzed asymmetric arylation ofα-trifluoromethyl bromoalkanes.In the second part,we reported a dual nickel-and photoredox-catalyzed regime to accomplish an enantioconvergent reductive cross-couplings of aryl halides with racemic CF₃-substituted alkyl electrophiles.The approach accommodated a broad palette of aryl iodides and alkyl bromide architectures to access a variety of enantiomerically enriched trifluoromethyl-containing compounds.The exceptionally mild conditions and without the need of metallic reductants enabled this transformation a huge potential on the application of late-stage functionalization of complex molecules.Throughradical clock experiments and light-on and light-off experiments,a trifluoromethylalkyl radical intermediate was deem to be involved in this reaction and the important role of light was demonstrated.On the basis of these experiments,a possible reaction mechanism was proposed.3.Molybdenum-catalyzed deoxygenative cross-coupling reactions of benzyl alcohols with benzyltrifluoroborates.The deoxygenative couplings of alcohols can avoid the use of haloalkanes and have many advantages,such as a wide source of substrates.Herein,an intermolecular deoxygenative cross-coupling reaction between benzyl alcohols and benzyltrifluoroborates was achieved in virtue of the special alcohol activation pattern with high-valent molybdenum-oxo catalysts.The transmetallation process between the molybdenum-oxygen bond and the nucleophilic reagent was the key to achieve this coupling.The strategy was simple to operate and had good substrate compatibility.Various alcohols including primary,secondary,and tertiary substrates can proceed efficiently under these conditions.Leveraging this strategy,several sensitive functional groups to the low-valent transition metals,such as aryl halides,can be well tolerated and the reaction can proceed smoothly in air.The mechanistic studies and DFT calculations suggested that an intramolecular concerted cyclization was involved in the reverse[2+2]-type elimination process.In summary,to achieve our goal of chiral carbon centers construction,this dissertation attempted to accomplish it from three different aspects.Firstly,combining with other strategies.Combining the desymmetrization strategy with nickel-catalyzed intramolecular addition provided a new strategy for the construction of chiral quaternary carbon centers.The second was the development of new catalytic systems.A dual nickel-and photoredox catalytic system provided a new tool for the subsequent preparation of chiral quaternary carbon in the future.Finally,the coupling partners were expanded.The deoxygenative coupling with secondary alcohols and tertiary alcohols was realized,which would provide a new way to synthesize all-carbon quaternary carbon centers.Although these results of this thesis are still far from the goal,on the basis of these works,it will provide a strong research base for accomplishing our objectives and will support subsequent research studies.