C O M M U N I C A T I O N S
the presence of sensitive groups, such as a nitrile, nitro, azido, ester,
tertiary amide, R,ꢀ-unsaturated ester, and an alkyne (entries 2-6,
8, and 10). The nitrogen branch can also be varied without affecting
the efficiency of the reaction: a substituted N-benzyl amide and a
hindered valine-derived amide reacted smoothly, leading to the
corresponding amines in 77% and 89% yield, respectively (entries 11
and 12). Also, amides possessing alkyl substituents R to the carbonyl
reacted well under these conditions (entries 13 and 14). It is noteworthy
that all of the amines were isolated by employing a simple acid-base
extraction, thereby simplifying the purification step.
Supporting Information Available: Experimental procedures and
characterization data for each reaction. This material is available free
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a Isolated yields. b Activation of the amide was done at -78 °C for
1 h, followed by -20 °C for 1 h, and 0 °C for 10 min. c 2.0 equiv of
HEH was used instead of 1.4 equiv.
In summary, this work represents an integral and broad comple-
ment to the available and efficient tertiary amide reduction methods
(Vide supra). In that sense, general and chemoselective conditions
were developed to control the reduction outcome of secondary
amides to imine, aldehyde, and amine oxidation states. We expect
this method to be useful in the total synthesis of more complex
molecules by optimizing the step-economy in synthesis planning.
Further efforts are ongoing to apply this reduction methodology to
other carbonyl moieties, and the results will be reported in due course.
Acknowledgment. This work was supported by the Natural
Science and Engineering Research Council of Canada (NSERC),
the Canada Research Chair Program, the Canada Foundation for
Innovation, and the Universite´ de Montre´al. G.P. and W.S.B. are
grateful to NSERC, FQRNT, and Universite´ de Montre´al for
postgraduate scholarships.
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