Asymmetric Mannich Reaction And Allyllic Alkylation For The Construction Of Quaternary Stereogenic Centers

Quaternary carbon stereocenters have been prevalently found in numerous natural products, biological active molecules and mutifuctional materials, as well as serving as important building blocks in organic synthesis. Catalytic asymmetric methods to access these core elements would be highly important and had attracted great interest from worldwide organic chemists. We have developed a new type of chiral bis-betaine bases for enantioselective Mannich reaction of azlactones to aldimines and chiral phosphoric acid/Palladium binary catalyst for the asymmetric allylic alkylation between pyrazolones and allyl carbonates. Both methods are highly efficient to build up quaternary carbon stereocenters.The structural motif of α,β-diamino acid is shared by many bioactive natural products and therapeutic agents including peptidesic and β-lactam antibiotics. In addition, owing to its polyfunctional nature, optically active α,β-diamino acid derivatives could be versatile building blocks for synthetic chemistry and also play an important role in modulating conformational, physicochemical and biological properties of molecules. The Mannich reaction of4-substituted azlactones for the creation of α-tetrasubstituted diamino acids has much less been investigated and most of the known variants basically favor of syn-selection. We have designed a new type of chiral bis-betaine bases for the Mannich reaction of azlactones to aldimines. The synergism among the multiple functionalities in these organobases offered high levels of enantioselectivity and yields for a wide scope of aliphatic imines and azlactones. The resultant products can be easily transformed to chiral caprolactones and α,β-diamino acids.Pyrazolin-5-ones, a class of important aza-heterocycles, have found a variety of applications as biological active molecules, ligands in coordination chemistry, agrochemical products, and scaffolds in combinatorial, photographic couplers. In particular,4-substituted-pyrazolin-5-ones are frequently found asthe core frame numerous pharmaceutically compounds. Thus, these molecules have recieved increasing interest from organic chemists in the past decades, but asymmetric catalytic approaches to access optically active4-substituted-pyrazolin-5-ones derivatives turns out to be relatively rare. In this thesis, we have described the first highly enantioselective allylic alkylation of pyrazolin-5-ones to construct quaternary carbon stereocenters by using the combined catalyst of chiral palladium complex and chiral phosphoric acid. This methodology provided high levels of enantioselectivity and yields for a wide scope of allylic carbonates and pyrazolin-5-ones.