Stereoselective synthesis of 2(S)-(1,1-dimethylethylsulfonylmethyl)-3-(1-naphthyl)-propionic acid, building block for protease inhibitors via asymmetric hydrogenation

Enantioconvergent and enantiodivergent catalytic hydrogenation of isomeric olefins

“…In the hydrogenation of (Z)-unsaturated carboxylic acids, the solvent effects are significant. 60,61 In the non-polar solvent cyclohexane, 84% ee was obtained for the (S)-product deriving from the hydrogenation of the (Z)-olefin, while the highly polar solvent TFE led to a reversed p-face selectivity generating the product with opposite configuration. By contrast, for the (E)-substrate the (S)-product was formed with low enantioselectivity in cyclohexane, but moderate in TFE (Scheme 46).…”

Asymmetric homogeneous hydrogenations at scale

“…Downstream processing improved the enantiopurity, in part by a fractional crystallisation. 178 An example of a substrate where geometric double bond isomers as well as a tautomer are present is an asymmetric hydrogenation with Rh-Josiphos (Rh-7f) of an imine/enamine mixture, which led to high enantioselectivity for the amine product 121. The product was then taken on to the HIV integrase inhibitor 122 (Scheme 36).…”

Some Synthetic Uses of Double‐Bonded Functional Groups

“…The chemical yields are high (83 99%) and the reaction occurs in up to 97% ee. This type of hydrogenation has been used as the key step in a synthesis of building blocks for protease inhibitors and has been performed on a 100 g scale 352 .…”