Applications Of Chiral Br?nsted Bases In Asymmetric Catalysis

Asymmetric catalysis is one of the central themes for synthesis of chiral compounds.Recently,the development of a new type of chiral Br?nsted base catalyst has received considerable attention since a range of important classes of organic reactions can be promoted with a Br?nsted base.Br?nsted bases have the functional capacity to accept a hydrogen from an acidic source or equivalent activated species.This proton transfer forms the basis of the key activation component to new-bond formation reactions.The intrinsic nature of the ion pairing complex of Br?nsted bases can become a challenge when stereoinduction comes into play.Catalysts that combine both a Br?nsted base moiety and another site with hydrogen-donating characteristics provide a bifunctional Br?nsted catalyst that can overcome the stereoinduction issues.In such way,the Br?nsted catalyst has the ability to stabilize both nucleophiles and electrophiles in the transition state to achieve high stereoselectivity.In this thesis,we introduced three kinds of chiral Br?nsted base catalysts and their applications in asymmetric catalysis.(1)Organocatalytic asymmetric synthesis of highly enantio-and diastereo-enriched six-membered dioxazinane and seven-membered dioxazepane heterocycles using a cooperative cation binding catalyst1,1’-Bi-2-naphthol(BINOL)-based cation-binding catalysts bear phenols and polyether units.The ether oxygens act as a Lewis base to coordinate metal ions such as K~+,thus generating a soluble chiral anion in a confined chiral space.Moreover,the terminal phenol groups are capable of simultaneously activating the electrophile by hydrogenbonding interaction,resulting in a well-organized transition state,leading to excellent stereoinduction.Nitrones as well as terminal-hydroxyα,β-unsaturated carbonyls serve as“amphiphilic”building units.In the presence of cation-binding catalyst,the activated chiral anion will deprotonate of hydroxyl group of terminal-hydroxyα,β-unsaturated carbonyls,thus the reaction proceeds through a tandem pathway sequence to afford the chiral six and seven-membered heterocycles.(2)Kinetic resolution of allylic alcohol with chiral BINOL-based alkoxides1,1’-Bi-2-naphthol(BINOL)is the common core skeleton of the catalyst in asymmetric synthesis.The deprotonation of BINOLs will occur at high pHs and give the phenolate anion,which can act as the Br?nsted base in many reactions.However,due to the lack of the strategy to stabilize the phenolate anion,a bifunctional binaphtholate catalyst was seldom reported.Furthermore,all the reported binaphtholate catalysts were in-situ generated with strong alkali metal bases.To overcome the drawbacks,a number of chiral BINOL derivatives-based alkoxides were synthesized by introducing a polyether units into the BINOL skeletons,ether oxygens act as a Lewis base to coordinate metal ions such as K~+,thus generating a stable and storable bifunctional binaphtholate catalyst.This kind of catalysts work successfully in resolving various secondary allylic alcohols in first time via enantioselective redox-isomerization.(3)Cinchona alkaloid catalyzed atroposelective intramolecular[4+2]cycloaddition:synthesis of axially chiral heterobiarylsCinchona alkaloid bearing a thiourea groups is a classical bifunctional Br?nsted base catalyst.In the presence of cinchona alkaloids,the highly activated vinylidene ortho-quinone methides(VQMs)which derived from 2-ethynylphenol derivatives via asymmetric hydrogen transfer can subjected to a hetero-Diels-Alder cycloaddition with alkyne to form axially chiral aryl-naphthopyran skeleton.The axially chiral aryl-naphthopyran skeleton having various functional groups can be easily transformed into valuable intermediates as either potential ligands or organocatalysts.Several chiral molecules have been synthesized using three different kinds of chiral Br?nsted base catalysts.These works showed the high importance of chiral Br?nsted base catalyst in asymmetric catalysis.