Organic Letters
Letter
elimination of samarium selenide from II, forms iminium III.
Further reduction and protonation gives amine products 2.
For the reduction of 1n with SmI2−H2O, cyclic imine 3n was
isolated in addition to amine 2n (Scheme 5). In contrast, the
ACKNOWLEDGMENTS
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This work was realized with support of CNPq, Conselho Nacional
de Desenvolvimento Científico e Tecnologico, Brazil. We thank
Prof. J. D. Woollins (University of St Andrews) for providing the
Woollins’ reagent and EPSRC for an Established Career
Fellowship (D. J. P.) and Postdoctoral Fellowship (X. J.-B.).
́
Scheme 5. Cyclization of Selenoamide 1n Using SmI2−H2O
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reduction of 1m did not give products of cyclization (amine 2m
was the only isolated product). This is likely due to the facile
reduction of the benzyl radical intermediate to the correspond-
ing anion which outcompetes cyclization in this case.
Formation of 3n illustrates the potential to utilize radicals V
formed by SET to selenoamides in intramolecular carbon−
carbon bond forming reactions. It is also important to note that
the ability to reduce amides, activated by conversion to the
corresponding selenoamides, using SmI2−H2O should allow
radical intermediates to be intercepted that would otherwise
be readily reduced under the more reducing SmI2−H2O−NR3
conditions.
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In conclusion, we have developed the first general and
selective reduction of selenoamides to amines, including tertiary,
secondary, and primary aliphatic and aryl substrates. The SET
process employs commercially available SmI2, activated by
straightforward addition of H2O, and does not require an
additional Lewis base additive. Amides are not reduced under
these conditions; thus, transformation of amides into the
corresponding selenoamides followed by SET reduction with
SmI2−H2O represents a new strategy for amide reduction. The
potential to exploit the radical intermediates in cyclizations to
form heterocyclic imines has also been illustrated by the first
radical cyclization of a selenoamide.
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ASSOCIATED CONTENT
* Supporting Information
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S
The Supporting Information is available free of charge on the
(9) For amide reduction using SmI2, see: Szostak, M.; Spain, M.;
Eberhart, A. J.; Procter, D. J. J. Am. Chem. Soc. 2014, 136, 2268.
(10) For nitrile reduction using SmI2, see: Szostak, M.; Sautier, B.;
Spain, M.; Procter, D. J. Org. Lett. 2014, 16, 1092.
General experimental procedures, characterization de-
tails, and 1H and 13C NMR spectra of compounds (PDF)
(11) For a summary of mechanistic studies on the reduction of
carboxylic acid derivatives with SmI2, see: Szostak, M.; Spain, M.;
Eberhart, A. J.; Procter, D. J. J. Org. Chem. 2014, 79, 11988.
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derivatives, see: (a) Just-Baringo, X.; Procter, D. J. Acc. Chem. Res.
2015, 48, 1263 and references therein. (b) Shi, S.; Szostak, M. Org.
Lett. 2015, 17, 5144. (c) Shi, S.; Lalancette, R.; Szostak, M. Synthesis
2016, 48, 1825. (d) Just-Baringo, X.; Morrill, C.; Procter, D. J.
Tetrahedron 2016, 72, 7691. (e) Huang, H.-M.; Procter, D. J. J. Am.
Chem. Soc. 2016, 138, 7770. (f) Just-Baringo, X.; Clark, J.; Gutmann,
M. J.; Procter, D. J. Angew. Chem., Int. Ed. 2016, 55, 12499.
AUTHOR INFORMATION
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Corresponding Author
ORCID
Notes
The authors declare no competing financial interest.
C
Org. Lett. XXXX, XXX, XXX−XXX