The development of asymmetric synthesis is one of the major achievements of organic chemistry. Both chiral auxiliaries and asymmetric catalysis are being used in academical and industrial settings. Particularly enantioselective catalysis has undeniable success in terms of efficiency and step-economy. However, due to the non-covalent nature of asymmetric catalysis, chirality induction can be difficult to achieve often at the expense of robustness. On the other hand, chiral auxiliaries offer high generality, but require multi-step processes and stoichiometric amount of enantiopure molecules. Recently we reported an approach that attempts to combine the best aspects from asymmetric catalysis and chiral auxiliaries. Building up on our previous expertise in molecular tethering, we developed an unprecedented Pd-catalyzed DYKAT process for enantioselective carboetherification of propargylic amines with aryl iodides (Scheme 1). In this step we install a rigid oxazolidine scaffold from non-chiral precursors. The key for success was a “one-armed” Trost-type monophosphine ligand. Then the formed CF3-containg stereocenter then acts as de facto chiral auxiliary in subsequent hydrogenation of the olefin moiety. The installed tether then can be easily removed, revealing chiral amino alcohols with various biological activities. By the choice of the absolute configuration of the ligand and the substituent on the propargylic amine, all four stereoisomers of the amino-alcohol precursors could be obtained.

Asymmetric hydrogenation via a catalytically formed chiral auxiliary: Synthesis of amino alcohols

ACS Spring Meeting 2021

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