Title
Gold and Biocatalysis for the Stereodivergent Synthesis of Nor(Pseudo)Ephedrine Derivatives: Cascade Design Toward Amino Alcohols, Diols, and Diamines
Author
Gonzalez-Granda, Sergio, Georg Steinkellner, Karl Gruber, Ivan Lavandera, and Vicente Gotor-Fernández
Year
2023
Journal
Advanced Synthesis & Catalysis
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 IPrAuNTf2-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.
Instrument
FT/IR-4700
Keywords
biocatalyst of choice determining ,nor(pseudo)ephedrine,