Structural optimization of thiourea-based bifunctional organocatalysts for the highly enantioselective dynamic kinetic resolution of azlactones†
Abstract
This article describes the synthesis of a library of structurally diverse bifunctional organocatalysts bearing both a quasi-Lewis acidic (thio)urea moiety and a Brønsted basic tertiary amine group. Sequential modification of the modular catalyst structure and subsequent screening of the compounds in the alcoholytic dynamic kinetic resolution (DKR) of azlactones revealed valuable structure–activity relationships. In particular, a “hit-structure” was identified which provides e.g.N-benzoyl-tert-leucine allyl ester in an excellent enantiomeric excess of 95%.