A Chiral Pool Strategy for the Synthesis of Enantiopure Hydroxymethyl-Substituted Pyridine Derivatives.

C. Eidamshaus, H.-U. Reissig – 2011

A simple procedure for the synthesis of enantiopure hydroxymethyl-substituted pyridine derivatives is presented. The developed method is based on TMSOTf-promoted cyclocondensations of β-ketoenamides, leading to differently substituted 4-hydroxypyridine/4-pyridone derivatives. The required β-ketoenamides were prepared by acylation ofeasily available enamino ketones with suitably protected enantiopure carboxylic chlorides. Most of the experiments were performed with D-mandelic acid as starting material. It has been shown that all steps occur essentially without racemisation. Several of the prepared 4-pyridone derivatives were transformed into the corresponding pyrid-4-yl nonaflates and subjected to a series of palladium-catalysed transformations, such as Suzuki, Heck or Sonogashira reactions. In addition, regioselective side-chain functionalisation of unsymmetrically 2,6-disubstituted pyridine derivatives was accomplished by application of Boekelheide rearrangements of the corresponding pyridine N-oxides. The presented methods allow a flexible, rapid and scalable approach to highly substituted, enantiopure pyridine derivatives.

Titel
A Chiral Pool Strategy for the Synthesis of Enantiopure Hydroxymethyl-Substituted Pyridine Derivatives.
Verfasser
C. Eidamshaus, H.-U. Reissig
Datum
2011
Kennung
10.1002/ejoc.201100681
Quelle/n
Zitierweise
Eur. J. Chem. 2011, 1162-1166.
Art
Text
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