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J Am Chem Soc. 2014 Dec 10;136(49):17302-7. doi: 10.1021/ja510163w. Epub 2014 Dec 1.

Palladium-Catalyzed Anti-Markovnikov Oxidation of Allylic Amides to Protected β-Amino Aldehydes.

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1
Stratingh Institute for Chemistry, Faculty of Mathematics and Natural Sciences, University of Groningen , 9747 AG Groningen, The Netherlands.

Abstract

A general method for the preparation of N-protected β-amino aldehydes from allylic amines or linear allylic alcohols is described. Here the Pd(II)-catalyzed oxidation of N-protected allylic amines with benzoquinone is achieved in tBuOH under ambient conditions with excellent selectivity toward the anti-Markovnikov aldehyde products and full retention of configuration at the allylic carbon. The method shows a wide substrate scope and is tolerant of a range of protecting groups. Furthermore, β-amino aldehydes can be obtained directly from protected allylic alcohols via palladium-catalyzed autotandem reactions, and the application of this method to the synthesis of β-peptide aldehydes is described. From a mechanistic perspective, we demonstrate that tBuOH acts as a nucleophile in the reaction and that the initially formed tert-butyl ether undergoes spontaneous loss of isobutene to yield the aldehyde product. Furthermore, tBuOH can be used stoichiometrically, thereby broadening the solvent scope of the reaction. Primary and secondary alcohols do not undergo elimination, allowing the isolation of acetals, which subsequently can be hydrolyzed to their corresponding aldehyde products.

PMID:
25384246
DOI:
10.1021/ja510163w
[Indexed for MEDLINE]

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