Amino Alcohols from Asymmetric Transfer Hydrogenation of α-Amido-β-Keto Esters Possessing Olefins: Formal Total Synthesis of Sphingosine

Abstract: In this thesis a methodology to synthesize anti-β-hydroxy-α-amino esters possessing olefins has been investigated. The developed procedures originate from two already established procedures in which α-amido-β-keto esters, which do not contain olefins, has been stereoselectively reduced to the corresponding anti-β-hydroxy-α-amino alcohols via asymmetric transfer hydrogenation coupled with dynamic kinetic resolution. Both established methods, one solvent free and one emulsion procedure, have been investigated on the expanded substrate scoop. Four different α-amido-β-keto ester containing olefins were tested and it was found that the ketones were reduced to desired anti-β-hydroxy-α-amino esters in both procedures, but also side products were formed where the olefins were reduced. The ratio of the different products was dependent on the structure of the starting α-amido-β-keto ester, ligand used on the catalyst and reaction conditions such as number of equivalents of base and reaction temperature. The diastereoselectivity for the desired products was in favor of the anti stereoisomer, however, the dr was worse than in the established procedures. The usefulness of this methodology was then demonstrated by a formal total synthesis of Sphingosine.