Studies Of Chiral N-oxide Applied In Catalytic Asymmetric Cyanosilylation Of Ketoimines And Allylation Of Active Ketones

The Strecker reaction, which was reported already in 1850, is the oldest known synthesis ofα-amino acids and was regarded by many chemists. The optically pureα-amino acids have important biological activities and physiological properties. It is the precursor for medicine chemistry, agriculture chemistry and additive chemistry. In addition, it is also used in chiral asymmetric induction. The product of cyanosilylation of ketoimines is the intermediate precursor ofα,α-dialkylated amino acids. The Strecker reaction is one of the cheap and available methods. Efforts have recently culminated in efficient catalysts for the cyanation of aldimines affording a-amino acids. But it was rarely reported in the Strecker reaction of ketoimines. To the best of our knowledge, there are only three research groups have reported their works on this subject.Firstly, we synthesized a series of chiral single N-oxide and double N,N-dioxide. In the catalyst screening, we found that chiral N,N-dioxide (C67) which was generated in situ by piperidinamide and m-chloroperoxybenzoic (m-CPBA) gave the high asymmetric inductivity (72~92% ee). Attractive features of the current method include the simple in situ catalyst preparation with readily available material, mild reaction conditions and convenient procedure with the tolerance of moisture and air. Moreover, the chiral N,N'-dioxide can be easily recovered and reused at least five times without any loss in both catalytic activity and enantioselectivity. Theα-hydroxy phosphonate is the important precursor ofα-hydroxy phosphonic acid derivatives. Although their biological activities have not been extensively explored,α-hydroxy phosphonic acid derivatives have been shown to be very important enzyme inhibitors. For example, they are inhibitors of such important medicinal enzymes as renin or human immunodeficiency virus (HIV) protease and polymerase. They also show anti-virus and anti-cancer activities. The chemistry had already investigated a few asymmetric reactions ofα-keto phosphonate and obtained high eanatioselective excess, but the asymmetric allylation ofα-keto phosphonate is not reported. The ramipril derivative amide N-Oxide (C81) and In(OTf)3 catalyzed the allylation ofα-keto phosphonate and gave high reactivity and excellent eanatioselective excess (80~98% yield, 68~91% ee).Finally, mechanism study and discussion were stated in the text. With support of proper experimental phenomena, a rational catalytic cycle was proposed and a possible transition state was propounded for successful explanation of the origin of chiral induction.