| Chirality is a very common phenomenon in nature.Some molecules in creatures,such as amino acids,carbohydrates,etc.,have chirality.In the synthesis and design of drug molecules,construction of chiral molecules and the use of chiral catalysis are also often involved.According to different chiral types,chiral molecules can be divided into central chiral molecules(or point chirality molecules),that is,molecules contain chiral carbon or other asymmetric atoms.Axial chiral molecules,that is,molecules contain asymmetric axis.And planar chiral molecules,that is,molecules contain asymmetric plane.Asymmetric organocatalysts such as quinazoline,L-proline,carbene,chiral phosphoric acid,etc.,are widely used in asymmetric catalysis,because mild reaction conditions are required and they are easy to obtain and recycle.So this dissertation mainly consists of two mechanistic studies on two very different reaction systems catalyzed by organocatalysts as shown below:1.Computational studies on axial chirality control of cinchona catalyzed O-alkylationThe mechanism,especially the stereoselectivity of cinchona catalyzed O-alkylation were investigated with density functional theory(DFT)calculations.The calculation results show that chiral quinidine quaternary ammonium salt works as catalyst,alpha-H of tetrahydronaphthalene ketone substrate in basic conditions,was grabbed to form atropisomeric enolate ammonium salt,the two atropisomeric enolate ammonium salts can be converted to each other,and the isomerization process reached reversible equilibrium.The electrophilic reagent BnI reacts with enolate by O-alkylation,which is irreversible and the process of O-alkylation is the decisive step of the chirality of the product.In the dominant transition state,the non-covalent CH-0 interaction plays an important stabilizing role.The non-covalent CH-0 interaction can be analyzed by independent gradient model.2.Calculations of chiral and regioselective control mechanisms for stereoselective a-addition reaction catalyzed by sodium L-prolinateWe used DFT to study the stereoselective a-addition reaction catalyzed by L-prolinate sodium,especially the central chiral control mechanism and the regioselective control mechanism of the reaction.The cyclohexanone substrate and the sodium L-proliate molecule are intermolecular condensed to obtain an intermediate containing an enamine structure,followed by an a-addition of the enamine six-membered ring and the alkynyl amide,and undergoing a 6-exo-dig process.A double six-membered ring having an exocyclic double bonds and having a central chirality is produced.The stereoselectivity of the cycloaddition process was studied.The alkyne was subjected to a-addition from below or above the enamine six-membered ring to obtain the double six-membered ring products of different chiral centers.Transition state structure,in which the alkyne was subjected to a-addition from below the enamine six-membered ring,is favorable due to the strong electrostatic interaction between the sodium ion and the substrate carbonyl,making it a dominant transition state,the major enantiomer is generated.In addition,the calculation also studied the regioselectivity of the cycloaddition process.The alkyne was subjected to β-addition from below or above the enamine six-membered ring to obtain the seven-and six-membered ring products of different chiral centers.Similarly,the transition state structure in which the alkyne is subjected to β-addition from below the enamine six-membered ring,the transition state structure is favorable due to the strong electrostatic interaction between the sodium ion and the substrate carbonyl group,making it a dominant transition state,leading to major enantiomer.However,the transition state of seven-and six-membered ring is unfavorable comparing with the transition state of double six-membered ring.Therefore,the seven-and six-membered ring formation is disfavored due to the high ring strain in the forming bicyclic structure,and the reaction tends to form a double six-membered ring. |
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