A Catalytic Asymmetric Ugi-type Reaction With Acyclic Azomethine Imines

摘要

More than half a century ago, Ugi reported a four-component reaction consisting of an aldehyde, a primary amine, an isocyanide and a carboxylic acid. Whereas the ease of assembling a variety of complex structures in one step has prompted its widespread application in a range of organic syntheses, the realization of a catalytic asymmetric Ugi reaction still remains a largely unsolved issue, owing to its logical limitation. Namely, whereas the crucial C-C bond formation between the isocyanide and the imine is thought to be a carboxylic acid catalyzed process (Scheme 1), the carboxylic acid is then taken up in the product, thus ruling out the possibility of using a catalytic amount of chiral carboxylic acid. The only solution reported to date is the use of isocyanoacetamides in the presence of chiral phosphoric acid, a strategy that is more successful in the related Passerini reaction.