Gold and Biocatalysis for the Stereodivergent Synthesis of Nor(pseudo)ephedrine Derivatives: Cascade Design Toward Amino Alcohols, Diols, and Diamines
Sergio González‐Granda, Georg Steinkellner, Karl Gruber, Iván Lavandera, Vicente Gotor‐Fernández
Abstract
Abstract The combination of gold(I) and enzyme catalysis has provided access to a series of nor(pseudo)ephedrine derivatives in a regio‐ and stereoselective manner. The approach involves developing IPrAuNTf 2 ‐catalyzed hydration of 1‐phenylprop‐2‐yn‐1‐yl acetate or N ‐(1‐phenylprop‐2‐yn‐1‐yl)acetamide, followed by (dynamic) asymmetric biotransamination or bioreduction of the corresponding keto ester or keto amide intermediates. Enzyme actions were completely selective towards the modification of the methyl ketones in a highly stereoselective manner, allowing the synthesis of enantio‐ and diastereomerically enriched products using either racemic or optically active starting materials. Thus, a series of amino alcohol, diol, and diamine derivatives were produced from propargyl esters or amides (57 to 86% isolated yield), the biocatalyst of choice determining the (stereo)selectivity of the overall cascade process (70–99% diastereomeric excess and >98% enantiomeric excess), and providing access to nor(pseudo)ephedrine compounds in a straightforward manner. magnified image