Simple Synthesis Of Chiral ¦Â-amino Alcohols And Their Catalytic Asymmetric Reaction

Chiralβ-amino alcohols possess good coordination ability which can become excellent chiral catalysts by complexing with many other atoms such as B, Zn, In, etc. owing to their N and O atoms in molecules. The optical activeβ-amino alcohol is so important that it is widely used in many fields such as organic synthesis, medicine, and biology, as well as fine chemical engineering, material, etc. Based on the review of the recent synthesis methods of chiralβ-amino alcohols and their applications in the field of asymmetric catalytic synthesis, we finished the following works.In this thesis, five unreported chiralβ-amino alcohols 160a,160b,160c,161a and 161b were prepared efficiently with simple synthetic routes (referred to methoxy-carbonylated, alkylation protection and Grigard reaction or reduction) derived from D-phenylglycine through asymmetric modification of amino-group and carboxyl-group with total yields from 73% to 93%. Following the same method, another tertiary alcohol 166 was obtained.With those novelβ-amino alcohols as chiral ligands, we screened their catalytic activities on the asymmetric Barbier reaction. The screened reactions were performed with acetophenone and benzaldehyde as the substrates which react with bromopropene catalyzed by In. Among them, good enantioselectivity (61.8% e.e.) and high chemical conversion are observed when (R)-2-(benzylamino)-2-phenylethanol (161a) was used as chiral ligand. After structure-activity relationship analysis, we found that the less steric hindrance of theβ-amino alcohol, the better catalytic activity was obtained. Furthermore, we promptly extended the utility of 161a and 166 to other substituted arylaldehydes in the bromopropene-to-aldehyde addition system. Good results were also achieved with 161a as chiral ligand, which further confirmed the steric hindrance of chiral ligand plays important role in this asymmetric catalyze system.In addition, with the sameβ-amino alcohols as chiral ligands, asymmetric alkynylation of benzaldehyde was carried out and moderate-to-good enantioselectivities were observed, Among which, (S)-2-(benzyl (methyl)amino)-3-ethyl-l-phenylpentan-3-ol (166) performed the best result (60.9% e.e). Encouraged by the results, we promptly extended the utility of 166 to various substituted aldehydes in the addition system, and higher enantioselectivity (78.9% e.e) was observed when 4-bromobenzaldehyde was used as the substrate.