Efficient Assembly Of Polysubstituted Aromatics Via Pd/NBE Cooperative Catalysis

Polysubstituted aromatics are ubiquitously found in natural products,pharmaceuticals and organic materials.They also serve as privileged frameworks for chiral ligands and catalysts in asymmetric catalysis.As such,the rapid assembly of these motifs from readily available starting materials would be important in synthetic organic chemistry.Palladium/norbornene cooperative catalysis（namely the Catellani reaction）has become a powerful strategy for expeditious synthesis of polysubstituted arenes through simultaneous functionalization at both ortho-and ipso-positions of aryl halides.In this dissertation,a series of polysubstituted arenes were constructed based on palladium/norbornene cooperative catalysis,mainly including the following four parts.1.We have developed a dual-tasked methylation based on palladium/norbornene cooperative catalysis.Readily available（hetero）aryl iodides and inexpensive Me OTs or trimethylphosphate are utilized as the substrates and methylating reagents,respectively.Six types of ipso-terminations including Heck,Suzuki,Sonogashira,cyanation,borylation,and hydrogenation can modularly couple with this ortho C-H methylation,thereby constituting a versatile methylation toolbox for preparing diversified methylated arenes.This strategy features inexpensive methyl sources,excellent functional-group tolerance,simple reaction procedures,and scalability.Importantly,it can be uneventfully extended to isotope-labeled methylation by switching to the corresponding reagents CD₃OTs or ¹³CH₃OTs.Moreover,this toolbox can be applied to late-stage modification of biorelevant substrates with complete stereoretention.2.We have developed a palladium/norbornene cooperative catalysis promoted annulation involving an ortho C–H amination and intramolecular Heck cascade between aryl iodides and functionalized amination reagents,thereby providing a highly convergent access to the unique N-containing bridged scaffolds:hexahydro-2,6-methano-1-benzazocine.Preliminary studies underscore the feasibility of an asymmetric ortho-C–H amination/α-arylative desymmetrization cascade.3.We have developed a palladium/chiral norbornene cooperative catalysis enabled strategy for the assembly of atropisomeric o-terphenyls with 1,2-diaxes in a modular and convergent way.Readily available aryl iodides,2,6-disubstituted aryl bromides,and potassium aryl trifluoroborates are used as the building blocks,laying the foundation for diversity-oriented synthesis of these scaffolds.Other features include the unique axial-to-axial diastereoinduction mode,construction of two axes in a single operation,and step economy.DFT calculations are performed to rationalize the axial-to-axial diastereoinduction process.Synthetic utility of this method in preparation of atropisomeric oligophenyls,chiral catalysts,and ligands is demonstrated.4.We have developed the Borono-Catellani arylation strategy for chiral fluorenols synthesis,utilizing readily available potassium aryl trifluoroborates and aryl bromides as the reactants.This strategy features mild conditions,ligand-free,excellent enantioselectivities,high functional group tolerance,step economy and simple reaction procedures.