KINETIC RESOLUTION OF sec-ALCOHOLS WITH TWISTED AMIDES

点击翻译按钮获取中文摘要

1. Synthesis of chiral twisted amides4-alkyl-3-pivaloyl-1,3-thiazolidine-2-thiones possessing twisted amide bonds were synthesized. The structure and geometry were confirmed by 13C NMR and IR spectroscopies.2. Kinetic resolution of recemic sec-alcoholsThe twisted amides were used for the enantioselective acylation of sec-alcohols under neutral conditions. Acylations of the sec-alcohols with an amide having t-Bu group at 4-position gave the corresponding esters in 50-84% ee with (S) configuration. When methyl magnesium bromide was used as a base, the configuration of the products werereversed.3. Desymmetrization of meso-diolsEnantioselective monoacylation of meso-diols with (S)-4-t-butyl-1,3-thiazolidine-2-thione were performed to give monoesters in high yields. Very high enantioselectivity (90%ee) was obtained for cis-1,4-dihydroxytetraline. The stereochemistry at the carbon attached to the pivaloyloxy group is (S) configuration.4. Relationships between 13C-15N coupling constants and twist anglesA series of twisted amides enliched to 99% with 15N was synthesized via several steps from commercially available [15N] glycine and [15N] leucine. The C-N coupling constants were measured using 13C NMR spectroscopy. It was found that as the twist angle increase, the 1JC (O), N value decreases. This result suggests that the 13C-15N coupling constant is a useful parameter for the study of amide bond twisting.