Study On The Efficient Synthetic Methods Of Isotetronic Acids

So far, chemistry and chemical engineering have been regarded as the major contributors to economic progress over the past century, and yet the chemical industry is often taken to task for many serious environmental problems. One of the most attractive concepts for pollution protection is green chemistry. It is better to prevent waste than to treat or clean up waste after it is formed. Green chemistry is the design, development, and implementation of chemical products and processes to reduce or eliminate the use and generation of substances hazardous to human health and the enviroment.Green Chemistry is the main line of the whole thesis. In this thesis, we mainly discuss two parts of work. 1. An effective DBU-Et₃N-mediated one-pot synthesis of isotetronic acids fromα-ketoesters; 2. Preparation of P-Phos and its use in palladium-catalyzed amination of aryl halides with amines; Preparation of silica-supported Ru-P-Phos catalysts and use for enantioselective hydrogenation.First partIn chapter two, we have developed a convenient one-pot synthesis of isotetronic acids usingα-ketoesters as the starting marterial. The most satisfactory preparation involved the reaction using DBU along with Et₃N as the base. To our awareness, this represents the first one-pot synthesis of this interesting class of compounds and constitutes a novel homoaldol-based ABB' three component reaction. We have synthesized 45 isotetronic acid compounds through changing the alkylated/acrylated agents orα-ketoesters. The cross-aldol coupling is also described in the thesis. The reaction is in line with the development of green chemistry. The protocol carried several notable advantages such as the wide substrates, simple operation, exceedingly mild condition, there being no use of any expensive reagents. A further advantage is that inert atmospheric condition is not necessary. Therefor the methods we have developed may have potentiality in theory and application.In chapter three, we use the simple isotetronic acids obtained in chapter two to synthesize more complex compounds. We have synthesized a series ofβ-aryl-isotetronic acids through Suzuki reaction. Theβ-bromine isotetronic acid has been synthesized, so the Heck and Sonogashira reaction can also be used in the coupling reaction.Second partIn chapter four, the racemic ligand rac-P-Phos was synthesized using a slightly modified six-step literature method starting from 2,6-dichloropyridine. An optical reaction condition was ensured after screening several bases and solvents. We then use the air-stable dipyridylphosphine ligand rac-P-Phos in the palladium catalyzed aromatic amination of haloarenes with variable amines. The yields are generally high, demonstrating that the catalytic activity of the present system matches or exceeds that of the reported phosphine ligands reported by others. The method has common benefits in other air-stable palladium catalyzed animations, such as convenient, very efficient, wide substrate scope, low catalyst dosage. Combined with the inherent stability and easy accessibility, the present method may also facilitate the large-scale usefulness of the C-N bond forming reactions.In chapter five, we have developed and optimized a practical, efficient, and highly recyclable heterogeneous catalyst through immobilization of Ru-P-Phos onto a very cheap amorphous silica gel and mesoporous silica of SBA-15 by an easily accessible approach for the first time. The catalyst immobilized on silica gel demonstrated remarkably high catalytic activities for the heterogeneous asymmetric hydrogenation of various ketones. Particularly, the catalyst could be readily recovered and reused in multiple consecutive catalytic runs (up to 10 uses). However, the catalyst system didn't give satisfactory e.e.% values so far.