10.1002/anie.201810947
Angewandte Chemie International Edition
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Scheme 7: Proposed reaction mechanism for the desired reductive
functionalization (1.), competitive reduction (2.), competitive reductive
cleavage (3.) and competitive alcoholysis (4.) of N-Py amides (1).
In conclusion, we have developed a novel method for the
reductive arylation of amides based on a stable arylboron
reactant and an alcohol, used both as reductant and solvent.
The method utilizes a Ru catalyst along with a Py DG on the
amide nitrogen to allow reaction with the unreactive carbonyl.
The DG can be easily introduced via e.g. reaction of carboxylic
acids with PyNH2. The PyNH moiety in the resulting N-Py 1-
arylalkanamine product can be readily substituted with HCl,
concomitantly generating recyclable PyNH2. The 1-aryl-1-
chloroalkane products can be further transformed via
substitution or cross-coupling reactions. This allows access to a
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wide structural variation of functionalities from
carboxylic acid.
a single
Acknowledgements
This work was supported by the Research Foundation Flanders
(FWO-Flanders), UAntwerpen (BOF), and the Hercules
Foundation.
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Ligating amides (e.g. N-Py amides) derived from acrylamides have
been used for cycloaddition and conjugate addition. For an
example, see: M. Zhang, N. Kumagai, M. Shibasaki Chem. Eur. J.
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Keywords: Ruthenium, amide, directed, three-component
reaction
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