Generation and exploitation of acyclic azomethine imines in chiral Brønsted acid catalysis

Abstract

Successful implementation of a catalytic asymmetric synthesis strategy to produce enantiomerically enriched compounds requires the adoption of suitable prochiral substrates. The combination of an azomethine imine electrophile with various nucleophiles could give straightforward access to a number of synthetically useful chiral hydrazines, but is used rarely. Here we report the exploitation of acyclic azomethine imines as a new type of prochiral electrophile. They can be generated in situ by the condensation of N′-benzylbenzoylhydrazide with a variety of aldehydes in the presence of a catalytic amount of an axially chiral dicarboxylic acid. By trapping these electrophiles with alkyl diazoacetate or (diazomethyl)phosphonate nucleophiles, we produced a diverse array of chiral α-diazo-β-hydrazino esters and phosphonates with excellent enantioselectivities. Acyclic azomethine imines would be useful prochiral electrophiles in catalytic asymmetric reactions, but their generation often requires harsh conditions. Here, they are generated under mild conditions in the presence of an axially chiral dicarboxylic acid, with the chiral counterion (the conjugate base) then directing an enantioselective reaction with a diazoacetate nucleophile.

Cite this article

Hashimoto, T., Kimura, H., Kawamata, Y. et al. Generation and exploitation of acyclic azomethine imines in chiral Brønsted acid catalysis. Nature Chem 3, 642–646 (2011). https://doi.org/10.1038/nchem.1096

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