Design And Synthesis Of Novel Organocatalysts And Studies On Their Application In Asymmetric Catalysis

Asymmetric organocatalysis has become one of the most active and attractive branch in asymmetric catalysis since the beginning of this century.Particulary,the nearly last ten years has witnessd an enormous growth concerning new catalyst design,new rection development and novel catalytic concepts.In this context,asymmetric enamine catalysis and H-bonding catalysis are two of important organocatalytic strategies that have a substantial impact on this area.Inspired by these fundermental catalytic strategies, we designed a vairety of multifunctional chiral organocatalysts,which possessed two or more reaction-promoting functionalities.Their activity and selectivity can be tuned by a simple modification of the structural motif of the catalyst.Furthermore,an elegant alignment of the steric and electronic properties of the catalyst would determine the reaction efficiency.Therefore,a variety of bifunctional L-prolinamide derivatives were prepared from commercially available L-proline and enantiopure(R,R)- or (S,S)-1,2-diaminocyclohexane.Then,we evaluated their catalytic activiteis in the direct asymmetric aldol reaction between aromatic aldehydes and cyclohexanone.High isolated yields(up to 94%), anti-diastereoselectivities(up to 99:1) and enantioselectivities(up to 97%e.e.) were obtained using our catalytic system.Particularly,our catalysts are also suitable for the asymmetric direct aldol reactions of cyclohexanone with aldehdyes in brine.Comaprable isolated yields(up to 92%) and selectivities(up to 99:1 d.r.and 96%e.e.) to the versions in organic solvents were obtained.On the basis of the success of the initial study,we then extend the use of these catalysts to the aldol reaction between hetero-cylic ketones and aldehydes.To our delight, these organocatalysts also showed excellent catalytic performances.As for the tetrahydro-4H-4-one and tetrahydro-4H-thiopyan-4-one,high isolated yields(up to 98%) and selectivities(up to 99:1 d.r.and 99%e.e.) of the corresponding aldol adducts were obtained.To furhter extend the use of our catalytic system,we developed an efficient asymmetric aldol reaction of ketones with isatins by the use of an L-proline-derived bifunctional organocatalyst.This strategy allows the enantioselective synthesis of a variety of 3-alkyl-3-hydroxyindolin-2-ones with a stereogenic quanternary carbon center in excellent yields with good to excellent enantiomeric excesses(up to 90%e.e.).On this basis,the enatioselective synthesis of(S)-convolutamydine A has been achieved(87% e.e.).Given the extraordinary capacity of the readily tunability of our bifunctional organocatalyst and the concept of "privileged chiral catalyst",we combined the stereocontrolling elements of proline and cinchona alkaloid in a single molecule and developed the 2nd generation of chiral organocatalysts.The chiral amine,prepared from L-proline and cinchonidine,has been found to be an efficient catalyst for the direct aldol reactions of acetones or 2-butanones with a wide range of aldehydes(up to 98%e.e.).The diversity of reactions catalyzed by Grubbs' ruthenium alkylidenes suggests that potential tandem processes should be achievable by using Ru catalysts.Therefore,we designed a new tandem protocol:a one-pot CM/intramolecular-hydroarylation sequence catalyzed by a single metal complex to afford diverse and structurally complex tetrahydrocarbazoles.And up to 99%overall yield was obtained.