Phpsphoric Acid Catalyzed Asymmetric Synthesis Of Chiral Nitrogenous Compounds

Chiral nitrogen-containing compounds, such as nitrogenous heterocycles and amino acids, are widely distributed in natural products with a wide scope of biological and pharmaceutical activities. Five-and six-membered nitrogen-containing heterocycles appear frequently in alkloids and are used as building blocks in the total synthesis. Amino acids are basic units from which peptides and proteins are made, and play an important role in organic synthesis. The great demand for these compounds has prompted chemical community to develop new synthetic methodologies for their asymmetric synthesis.We have developed a new method to access a variety of chiral isoindoline derivatives with high enantiomeric excess from aldehydes, amino esters and quinones. This method constituting of a chiral phosphoric acid catalyzed1,3-dipolar addition of azomethines with quinones and a subsequent isomerization mediated with organic base, can be considered an enantioselective formal double-arylation of azomethines in view of the products.The organic/metallic binary catalyst systems comprise of two fundamentally different catalysts that operate cooperatively or sequentially in the same reaction solution, hold great potential in the creation of new transformations that neither type of catalyst is able to afford alone. In addition to the fundamental significance, the related reactions have some practical advantages such as highly operative efficiency, essential avoidance of additional work-up process and minimizing the pollution associated with stepwise catalytic protocols. We have designed a highly enantioselective three-component cascade reaction, consisting of an enantioseletive [4+2] cycloaddition reaction catalyzed by chiral phosphoric acid and a subsequent catalytic intramolecular hydroamination by gold(I) complex, providing a unique method for the preparation of structurally diverse and complex julolidine derivatives in high optical purity. Kinetic studies revealed that the phosphoric acid is not only a chiral catalyst for the asymmetric [4+2] cycloaddition reaction, but also an assistant to facilitate the gold complex catalyzed hydroamination reaction.31P-NMR and kinetic studies indicated that the methylgold complex easily reacts with the phosphoric acid to give gold phosphate at room temperature, which shows higher catalytic activity.We have disclosed an asymmetric dynamic kinetic resolution of azlatones through chiral phosphoric acid catalyzed alcoholisis. The structure of alcohols played an important role in the stereocontrol. This reaction provides an efficient asymmetric catalytic method to access aryl glycine derivatives in high optical purity of up96%ee and thus can be considered an efficient alternative to known procedures.