Asymmetric synthesis of amino compounds by using chiral N-phosphonylimines
The great demand in life science for new molecules of biological and medicinal importance has led to an extreme significance of the development of synthetic methodologies. The asymmetric synthesis of chiral amines has long been a popular and challenging research area because chiral nitrogen-containing compounds are widely distributed in nature and many biologically important molecules. For the synthesis of chiral nitrogen-containing carbon frame works using imines as electrophiles is the most promising and convenient route. In the past two decades, chiral auxiliary based imines has drawn great attention in the asymmetric synthesis of a broad range of chiral amines such as natural products, pharmaceutical ingredients etc. In this dissertation, the development of new class of chiral phosphonyl imines and their applications in chiral amine synthesis are reported. In the first part, new chiral N-phosphonyl imines with different structure modifications were designed and synthesized. New methods were developed to reduce the reaction times and improve the reaction yields. In Particular, N-phosphonyl ketimines were obtained in good yields with the employment of a concise method which provide a general solution to the synthesis of phosphonyl imines. Six asymmetric nucleophilic addition reactions of these phosphonyl imines were discussed in the following part. Good to excellent yields and diastereoselectivities were obtained in all the cases. The resulting or amino containing compounds are extremely valuable building blocks in organic chemistry. Moreover, different coordination patterns between phosphonyl imines and nucleophiles in transition state were proposed to explain the stereochemistry of the products.