The Development Of New Reactions Based Onα-Monosubstituted Nitroacetates

C"-tetrasubstituted a-amino acids bearing a quaternary stereogenic carbon center at the a position are widely presented in natural products, drugs and pharmaceutically active compounds. The catalytic enantioselective synthesis of Cα-tetrasubstituted a-amino acid is of current research interest. This thesis focuses on the direct functionalization of a-substituted nitroacetates using different electrophiles, to furnish Cα-tetrasubstituted a-amino acid derivatives, which includes three parts:1) The first example of catalytic asymmetric amination of a-substituted nitroacetates using di-tert-butyl azodicarboxylate as the electrophile is developed. The simple and easily available bifunctional Br(?)nsted acid-base catalyst β-ICD is identified as be a highly enantioselective catalyst for the amination of a-aliphatic substituted substrates, with up to93%ee achieved using1,1,2,2-tetrachloroethane or CH2C12at-20or-40℃. Although a-phenylnitroacetates are also able to participate in this reaction with less hindered azodicarboxylates such as diethyl azodicarboxylate, the enantioselectivity of the corresponding product is not satisfactory. The amination product could be converted to tetrasubstituted chiral hydrazines.2) The first example of a highly efficient "catalyst-free" aminomethylation of both a-alkyl and aryl substituted nitroacetates in methanol is developed. A wide range of structurally diverse amines are tolerated, such as aniline derivatives and aliphatic amine. Chiral primary amines afford the corresponding products in good yields, albeit with poor diastereoselectivity. The versatility of the products is demonstrated by their facile conversion to the corresponding Cα-tetrasubstituted α,β-diamino acids-derived imidazolidinones and other useful building blocks. The high efficiency of this catalyst-free transformation is revealed by NMR spectroscopy studies and theoretical calculations.3) A highly efficient hydroxymethylation of both a-alkyl and aryl substituted nitroacetates catalyzed by only1mol%of K3PO4has been studied. The products could be further transformed to the corresponding quaternary a-substitued serine-derived oxazolidinone and aziridine. We also develop the first example of asymmetric catalytic version, and up to71%ee was achieved by using parafonn aldehyde as electrophile. In order to improve enantioselectivity, a series of newly chiral dual-core tertiary amine-phosphoramide catalysts have been synthesized from commercial available cinchona alkaloids, which are examined in this hydroxymethylation, but only moderate enantioselectivity was obtained.