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

Nature Chemistry volume 3, pages 642–646 (2011)Cite this article

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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.

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Figure 1: Classification and reactivity of azomethine imines.
Figure 2: Influence of the catalyst structure on the reaction pathway.
Figure 3: Applications of axially chiral dicarboxylic acid catalysed reaction of acyclic azomethine imines.

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Acknowledgements

This work was partially supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan. T.H. thanks a Grant-in-Aid for Young Scientists (B).

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Authors and Affiliations

  1. Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, 606-8502, Kyoto, Japan

    Takuya Hashimoto, Hidenori Kimura, Yu Kawamata & Keiji Maruoka

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  1. Takuya Hashimoto
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  2. Hidenori Kimura
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Contributions

T.H. conceived the study and wrote the manuscript. H.K. principally performed the experiments. Y.K. assisted preliminary experiments. K.M. organized the research. All authors contributed to designing the experiments, analysing data and editing the manuscript.

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Correspondence to Keiji Maruoka.

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Crystallographic data for compound 7o (CIF 43 kb)

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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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