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. 2018 Nov 12;10(4):1138-1143.
doi: 10.1039/c8sc04330b. eCollection 2019 Jan 28.

The inverted ketene synthon: a double umpolung approach to enantioselective β2,3-amino amide synthesis

Mahesh Vishe  1 , Jeffrey N Johnston  1
Affiliations

The inverted ketene synthon: a double umpolung approach to enantioselective β2,3-amino amide synthesis

Mahesh Vishe et al. Chem Sci. .

Abstract

A stereocontrolled synthesis of β2,3-amino amides is reported. Innovation is encapsulated by the first use of nitroalkenes to achieve double umpolung in enantioselective β-amino amide synthesis. Step economy is also fulfilled by the use of Umpolung Amide Synthesis (UmAS) in the second step, delivering the amide product without intermediacy of a carboxylic acid or activated derivative. Molybdenum oxide-mediated hydride reduction provides the anti-β2,3-amino amide with high selectivity.

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Figures

Scheme 1
Scheme 1. β2,3-Amino amides: retrosynthesis through carbon–carbon bond-forming approaches, mapped by polarity, highlighting an unusual ‘double umpolung’ and its realization through enantioselective catalysis and Umpolung Amide Synthesis (UmAS) (this work).
Scheme 2
Scheme 2. Diastereoselective reduction of oximes to anti-β2,3-amino amides, and subsequent derivatizations.
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