Decarboxylative Alkylation Of β-Keto Acids

β-Keto acids are important intermediate in the metabolism of organism. They have been the research focus of biological chemistry since the middle of the twentieth century, but the existing reports mainly concentrated in the enzyme-catalyzed decarboxylation of β-Keto acids; The reports of such substances involved in other reactions are relatively rare, so the study for the other chemical properties of the β-keto acids has important significance.Readily available and inexpensive iron as one of the most common metallic element on earth is widespread in vivo, and at the same time its non-toxic, no pollution to the environment is also advantages in organic catalysis. Iron as a catalyst in organic reactions is belived to have great potential for development and has been reported more and more in recent years.Based on the above two points, we have developed unprecedented ferric chloride catalyzed decarboxylative alkylation of P-keto acids with sulfonamides and benzylic alcohols. This is not only conforms to the requirements of the development of green chemistry(non-toxic iron as catalyst, and harmless carbon dioxide as byproduct) but also enriched the reaction type of β-keto acids and the synthetic methods of compound that containing carbonyl functional groups. In addition, we also have developed a highly diastereoselective decarboxylative Mannich reaction of β-keto acids with N-tert-butanesulfinylα-imino esters and prepared a series of γ-oxo-α-amino esters with extremely high regioselectivity and diastereoselectivty.In order to study the reaction mechanism, the reactive intermediates of the three reactions we reported have been detected by high resolution mass spectrometer (ESI/HRMS) or nuclear magnetic resonance spectroscopy (1H NMR). All the studies indicate that reactions proceed through SN1alkylation or imine addition followed by decarboxylation.