Studies On The Decarboxylative Addition Reactions Of α,α-difluoro-β-keto Acids

The introduction of difluoromethyl group into organic molecules can often bring profound changes on their physiological properties. Thus, difluoromethyl-containing compounds have received more and more attention in the field of biology, pharmaceutical and agriculture, and great interest has been attracted for their synthesis. Significant progress has been made in transition metal-catalyzed difluoromethylations in recent years, however, their industrial applications are restricted due to the harsh reaction conditions, such as the high costs of the transition metal catalysts and the requirement of air- and moisture-sensitive ligands. Therefore, it is highly significant to develop new methods for the inexpensive and efficient synthesis of difluoromethyl-containing compounds. In this dissertation,α,α-difluoro-β-keto acids and potassium α,α-difluoro-α-sulfonyl carboxylates were firstly designed and synthesized, and then their decarboxylative addition reactions with aldehydes and isatins were systematically investigated. It consists of three chapters: (1) Studies on the decarboxylative aldol reactions of α,α-difluoro-β-keto acids with aldehydes; (2) Studies on the decarboxylative addition reactions of α,α-difluoro-p-keto acids with isatins; (3) Studies on the decarboxylative aldol reactions of potassium α,α-difluoro-a-sulfonyl carboxylates with aldehydesIn chapter one, the decarboxylative aldol reactions of a,a-difluoro-β-keto acids with aldehydes were firstly investigated. The results indicated that the decarboxylative addition reactions proceed smoothly without the presence of any catalysts or bases, providing the corresponding α,α-difluoro-β-hydroxy ketones in good to high yields.In chapter two, the decarboxylative addition reactions of α,α-difluoro-β-keto acids with isatin and its derivatives were systematically investigated. The results showed that the decarboxylative addition reactions also go smoothly in the absence of any catalysts or bases,affording the corresponding 3-difluoroalkyl-3-hydroxy indolones in good to high yields.In chapter three, the decarboxylative aldol reactions between potassiumα,α-difluoro-α-sulfonyl carboxylates and aldehydes were mainly studied. It was also found that the reaction occurred without the need of any catalysts, ligands and so on, giving the difluoromethyl alcohols in good to high yields under mild reaction conditions.