Studies On The ?-position Stereoselective Functionalization Of The Carbonyl Compounds

Carbon-carbon(C-C)bond formation is central to organic synthesis.In particular,C-C bond forming reactions involving carbonyl compounds have been playing a critical role in constructing complex valuable organic compounds.Traditionally,among various carbonyl functionalization methods,common but important approaches are that enolate and subsequently coupling,annulation or rearrangement with the electrophiles.However,from the sustainability viewpoint,these reactions have exhibited significant environmental and safety concerns.Some of the drawbacks are:1)the generation of enolates often requires stoichiometric strong metallic bases,such as LDA,and cryogenic conditions to avoid self-couplings,i.e.aldol reaction;alkyl halides employed in these reactions are generally expensive and toxic(carcinogenic),considered as "non-sustainable agents";stoichiometric metal halides and conjugate acids of the bases are formed as byproducts;2)the reduced nucleophilicity of Stork enamines versus metal enolates limited the scope of the electrophile;3)the preformed Mukaiyama silyl ether is unstable and still have atom-economic issue;and 4)control of the regioselectivity and stereoselectivity is non-trivial,and di-or tri-substituted products are often unavoidable due to the facile proton transfer.Clearly,it would be attractive if more economical and "greener" alternatives to the aforementioned reactions could be developed.A number of criteria must be met:1)use cheap and more readily available feedstocks to replace halogen-containing or stoichiometric organometallic reagents;2)realize atom-economical and byproduct-free approaches;3)enable mild,pH-and redox-neutral reaction conditions with high functional-group compatibility;and 4)achieve high site-,regio-and stereo-selectivity.Herein,we foresaw substantial advantages in the prospective use of organic and metal catalysts to achieve the a-position stereoselective functionalization of the carbonyl compounds.In this dissertation,the following three works were presented:Part 1:Pd-Catalyzed Intramolecular ?-Allylic Alkylation of Ketones with Alkynes:Rapid and Stereodivergent Construction of[3.2.1]Bicycles.We developed a palladium-catalyzed intramolecular a-allylic alkylation of unactivated ketones with alkynes.The reaction proceeds in the absence of any amine cocatalyst;both endo and exo-bridged cyclohexanone bicycles can be obtained diastereoselectively.The stereodivergency is controlled by the ligand and acid additive used.Specifically,the monodentate DTBMPP ligand favors forming the endo isomer,while the bidentate DIOP ligand prefers to give the exo isomer.A broad range of functional groups are tolerated,which provides a chemoselective approach to access[3.2.1]bicyclic skeletons.Further deuterium labeling studies support a pathway involving an alkyne/allene isomerization and Pd-?-allyl complex formationPart 2:Br(?)nsted Base Promoted[3+1]Cycloaddition/Rearrangement of C,N-cyclic Azomethine Imines with 3-Chlorooxindoles:An Efficient Synthesis of Hexahydroindeno[2,1-c]pyrazole Spirooxindole Derivatives.We disclosed an accidental discovery of bronsted base promoted[3+1]cycloaddition/rearrangement of C,N-cyclic azomethine imines with 3-chloindoles to efficiently constructed hexahydroindeno[2,1-c]pyrazole,which are ubiquitous in a number of biologically important compounds.Moreover,this method provided an efficient way to firstly accessed spirocyclic oxindoles incorporating an hexahydroindeno[2,1-c]pyrazole segment.The chiral version of this reaction also surveyed and the DFT calculation illustrated the possible mechanism and racemization process.Part 3:Catalytic Enantioselective Synthesis of 1,2,3-Trisubstituted Cyclopropanes via Ammonium Ylides.We described a discovery of chiral tertiary amine catalyzed enantioselective[2+1]annulation of 1-azadienes to synthesis 1,2,3-trisubstituted cyclopropanes.This method enables a rapid and stereoselectively synthesis of a 1,2,3-trisubstituted cyclopropanes incorporating N-sulfonyl imine motif,which is common in some nature products and drugs.We could get the amine motif selectively reduction product via hydrogen transfer strategy.The control experiments showed the reaction via the ammonium ylides pathway.