Amino Acid-derived Br(?)nsted Base-catalyzed Highly Chemo-, Enantio- And Diastereoselective Reactions

Acyclic amino acids(AAAs) are among the most ideal chiral scaffolds to construct asymmetric organocatalysts due to the following features and advantages. They are commercially available and cheap, and can be used as chiral sources to construct bifunctional catalysts readily in high yileds; the primary amine and carboxylic acid functional groups, can be optionally transformed into the corresponding Br?nsted acids and bases to construct the target bifunctional catalysts; The reported chiral bifunctional tertiary amines, quaternary ammoniums and iminophosphoranes have clearly exhibited excellent performances in many challenging reactions.This thesis summarized these bifunctional chiral tertiary amine-promoted asymmetric transformations according to reaction patterns. Moreover, a series of asymmetric reactions mediated by AAA-derived quaternary ammoniums as phase-transfer catalysts and AAA-derived iminophosphoranes as bifunctional superbases are included.Chemoselective diversity has a pivotal position in the chemical research. The same raw materials can be used to get the different types of product by changing the reaction conditions(temperature, solvent, etc.), and this can effectively enlarge the diversity of molecules. we studied the Michael addition and [4+2] cycloaddition of asymmetric reactions between 5H-oxazol-4-ones and N-itaconimides catalysed by L-tert-leucine-derived urea-tertiary amine, the synthesis of amino acid derived thiourea-amide-tertiary amine dipeptide catalysts and their use in the cycloaddition of 5H-thiazol-4-ones and a variety of electron-deficient alkenes, including trans-4-oxo-4-arylbutenones, trans-4-oxo-4-arylbutenoates and nitroalkenes. The main contents include:A synthetic strategy for chemoselective switch and diastereo-divergent approach to asymmetric reaction between 5H-oxazol-4-ones and N-itaconimides catalysed by L-tert-leucine-derived tertiary amine-ureas. The reaction could be modulated to harness either tandem conjugate addition-protonation or [4+2] cycloaddition as major product with excellent enantio- and diastereoselectivities. Subjecting enantio-enriched cycloaddition product with basicsilica gel reagent yields the diastereomer and the product directly obtained by conditions for addition-protonation, thus opening a diastereo-divergent route for creating1,3-tertiary-hetero-quaternary stereocenters. Quantum chemical calculations provide corroborative insights into the observed stereoselectivity for [4+2] cycloaddition process.With L-tert-Leucine(S and R configuration) as the composite unit, developed a new synthetic method of acyclic amino acid derived-thiourea-amide-tertiary amine dipeptide catalyst. Through this method, chiral amino acids can be conveniently used to get a series of chiral amino acid derived-(thio)urea-amide-tertiary amine dipeptide catalysts with high yield and enantioselectivity.Developed a new family of dipeptide-based tertiary amine trifunctional organocatalysts. The first asymmetric [4+2] annulation reactions between 5H-thiazol-4-ones and a variety of electron-deficient alkenes, including trans-4-oxo-4-arylbutenones, trans-4-oxo-4-arylbutenoates and nitroalkenes, could be realized by employing a dipeptide-based tertiary amine catalyst with excellent enantioselectivities. The current strategy provides an efficient approach to significant chiral 1,4-sulfur bridged piperidinones. Through the verificative experiment, confirmed [4+2]cycloaddition is cascade Michael – mannich reaction between the 5H-thiazol-4-ones and electron-deficient alkenes. DFT mechanistic studies involving 5H-thiazol-4-one and nitroolefin catalysis offered fresh insights into the origin of enantioselectivity and chemoselectivity: in the first Michael conjugate addition step, a pronounced bifurcation in the stereoselection process occurs. It is suggested from quantum chemical modelling that major forms the S,S-configuration Michael adduct and the remaining R,R. The S,S pathway preferentially forms the kinetic [4+2]product as the major product while the R,R-route prefers the thermodynamic conjugate-protonation product, highly corroborating to experiment.