Enantioselective Carboetherification/Hydrogenation for the Synthesis of Amino Alcohols via a Catalytically Formed Chiral Auxiliary

Chiral auxiliaries
and asymmetric catalysis are the workhorses
of enantioselective transformations, but they still remain limited
in terms of either efficiency or generality. Herein, we present an
alternative strategy for controlling the stereoselectivity of chemical
reactions. Asymmetric catalysis is used to install a transient chiral
auxiliary starting from achiral precursors, which then directs diastereoselective
reactions. We apply this strategy to a palladium-catalyzed carboetherification/hydrogenation
sequence on propargylic amines, providing fast access to enantioenriched
chiral amino alcohols, important building blocks for medicinal chemistry
and drug discovery. All stereoisomers of the product could be accessed
by the choice of ligand and substituent on the propargylic amine,
leading to a stereodivergent process.