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Mechanistic Study of SmI2/H2O and SmI2/Amine/H2O‑Promoted Chemoselective Reduction of Aromatic Amides (Primary, Secondary, Tertiary) to Alcohols via Aminoketyl Radicals
journal contribution
posted on 2017-06-22, 19:15 authored by Syed R. Huq, Shicheng Shi, Ray Diao, Michal SzostakSamarium(II) iodide–water
and samarium(II) iodide–water–amine
complexes have been recognized as valuable reagents for the selective
generation of aminoketyl radicals from amides and derivatives. The
resulting aminoketyl radicals can undergo reduction or reductive cyclization
pathways, providing a powerful method for (i) direct synthesis of
alcohols from amides by the challenging N–C bond scission and
(ii) synthesis of nitrogen-containing heterocycles via polarity reversal
of the amide bond. This report describes mechanistic investigation
into samarium(II) iodide–water and samarium(II) iodide–water–amine-mediated
generation of benzylic aminoketyl radicals from aromatic primary,
secondary, and tertiary amides (benzamides). The mechanistic experiments
suggest that the rate and selectivity of the reduction is closely
dependent on the water concentration and the type of amide undergoing
the reduction. The data also suggest that benzylic aminoketyl radicals
generated in the reduction of benzamides are significantly more dependent
on the electronic effects of α-substitution than the corresponding
aminoketyl radicals generated by single-electron transfer to unactivated
aliphatic amides; however, little variation in terms of steric influence
of N-substituents is observed. These observations
will have implications for the design of reductive processes involving
Sm(II)-mediated reduction of amides and reductive umpolung cyclizations
via aminoketyl radicals as a key step.