Research On The Stereoselective Synthesis Of Carbonyl Compounds Featuring Fluorinated Quaternary Carbon Center

The asymmetric construction of quaternary C-F and C-CF3 stereogenic centers is one of the most synthetically challenges,and yet not many effective methods at present can be employed for this matter.a-Fluorinated gem-diols are excellent fluorine-containing enol precursors,due to their unique nature,they attract much attentlion and research in organofluorine chemistry.It is applied to nucleophilic substitution or addition reaction,which is also a relatively effective method for asymmetrically constructing various fluorocarbon quaternary centers.This dissertation mainly focused on the studies of using a-Fluorinated ge-diols as fluorinated enol precursors to achieve efficient construction of various fluorocarbon quaternary centers.At the same time,we also explored a-CF3 indenone as a fluorine-containing building block,to construct trifluoromethyl quaternary carbon centers by direct alkylation reaction.1.Catalytic enantioselective Allylic Alkylations between in situ detrifluoroacetylatively generated 3-fluorooxindole-derived enolates and MBH Carbonates.A new type of SN2 reactivity of the Colby pro-enolates with MBH carbonates affording the corresponding products bearing two consecutive stereogenic carbons was developed.The reactions readily occurred at ambient temperatures with high chemical yields(up to 93%)and an excellent regio-(up to 50:1),diastereo-(up to 99:1 dr)and enantioselective manner(up to 97%ee).The key findings leading to successful implementation of this project were Pd2(dba)3-catalysis in combination with relatively new type of Ding-SKP chiral C2-symmteric ligands and the solvent n-propanol is the key to the reaction to achieve high regioselectivity.Simultaneously We disclose the first example of SN2' reactivity of the detrifluoroacetylatively in situ generated tertiary fluoro-enolates in the uncatalyzed reactions with Morita-Baylis-Hillman carbonates.We found that the corresponding substitution reactions readily occur at ambient temperatures in the presence of LiBr and non-nucleophilic base.Excellent chemical yields(up to 93%),high geometric selectivity and structural generality(up to 99:1 E/Z).2.Catalytic enantioselective Michael addition reactions between in situ detrifluoroacetylatively generated new Tertiary fluoro-enolates and 1-(1-(phenylsulfonyl)vinylsulfonyl)benzene.In this work we successfully developed the first example of Michael addition reactions between 1-(1-(phenylsulfonyl)vinylsulfonyl)benzene and detrifluoroacetylatively in situ generated tertiary fluoro-enolates.The reactions were found to be efficiently catalyzed by 10 mol%of Cu(OTf)2 along with C2-symmetric chiral 1,2-diamines in THF.The reactions furnishing the target products with good yields(up to 99%)and excellent stereochemical(up to 96%ee)outcomes.Furthermore,the reactions were demonstrated to be of high degree of structural generality allowing efficient synthesis of compounds featuring five-,six,seven-membered rings as well as heterocyclic 3-fluoro-2,3-dihydrochromen-4-one moiety.Finally,we conducted control experiments.We tried monofluoro-substituted benzocycloketone to react with 1-(1?(phenylsulfonyl)vinylsulfonyl)benzene under the optimal conditions,but the target product was not obtained.This indicates that the activity of the fluorine-containing enol generated in situ by detrifluoroacetylative is higher than that of the fluorine-containing enol produced by the conventional fluorine-containing block.Simultaneously we presented the first example of catalytic enantioselective Michael addition reactions between 1-(1-(phenylsulfonyl)vinylsulfonyl)benzene and detrifluoroacetylatively in situ generated 3-fluorooxindole-derived enolates.The optimal catalyst includes Cu(OTf)2 and(1S,2S)-1,2-diphenylethane-1,2-diamine featuring NHR functionalities.The reaction resulted in fluorinated quaternary stereogenic ?-fluoro ketone products with good chemical yields(up to 99%)and enantioselectivities(up to 98%).3.Asymmetric Allylic Alkylation of MBH Esters with ?-CF3 Indenone Compounds.We have developed an asymmetric allylic alkylation with high chemical selectivity and stereoselectivity of a-CF3 indene substrates.Under the action of Pd2(dba)3 and a chiral spiro ligand,we can achieve a-selective and highly efficient asymmetric allylation of a-CF3 indenone substrates with MBH esters.The substrates we extended all gave>85:15 regioselectivity,>19:1 diastereoselectivity and an average of 99%enantioselectivity,the reaction has good substrate universality.At the same time,when we reduced the amount of catalyst Pd2(dba)3 to 2 mol%,the reaction is amplified to 2.0 mmol,the reaction still gived 92:8 regioselectivity,>19:1 diastereoselectivity and 97%enantioselectivity.On the other hand,when we simply switched the ligand to the(S)-t-Bu-PHXO ligand,the regioselectivity of the reaction reversed.The reaction was carried out-30? and added 3.0 equivalents of sodium acetate,used THF as solvent,used a complex formed by Pd2(dba)3 and(S)-t-Bu-PHXO ligand as a catalyst,we can obtain 96%enantioselectivity,92:8 regioselectivity,42%yield.In this chapter,we managed to construct CF3-substituted quaternary carbon centers using ?-CF3-indenones without the assistance of chemical auxiliary.In this context,the regioselectivity of AAA reaction with MBH esters can be altered only by switching ligands in the same catalytic system,which solved the long-standing issue in a convenient manner.