Electron Transfer Reduction of Nitriles Using SmI₂-Et₃N-H₂O: Synthetic Utility and Mechanism

Michal Szostak*, Brice Sautier, Malcolm Spain and David J. Procter*

*School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom, Email: michal.szostakrutgers.edu, david.j.proctermanchester.ac.uk

M. Szostak, B. Sautier, M. Spain, D. J. Procter, Org. Lett., 2014, 16, 1092-1095.

DOI: 10.1021/ol403668e

---

Abstract

Activation of SmI₂ (Kagan's reagent) with Lewis bases enables a mild general reduction of nitriles to primary amines under single electron transfer conditions. Activated samarium diiodide features excellent functional group tolerance and is therefore an attractive alternative to pyrophoric alkali metal hydrides. Notably, an electron transfer from Sm(II) to bench stable nitrile precursors generates imidoyl-type radicals.

see article for more examples

---

---

Procedure for the reduction of nitriles with SmI₂-Et₃N-H₂O

An oven-dried vial equipped with a stir bar was charged with a nitrile substrate (neat), placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles under high vacuum. Samarium(II) iodide (THF solution, 0.1 M, typically 6 equiv) was added followed by Et₃N (typically, 36 equiv) and H₂O (typically, 36 equiv) with vigorous stirring, which resulted in the formation of a characteristic dark brown color of the SmI₂-Et₃N-H₂O complex, and the reaction mixture was stirred for the indicated time. In some cases, a solution of nitrile substrate (1.0 equiv, stock solution in THF, 1.0 mL) was added to the preformed samarium(II) iodide/amine/H₂O complex, and the reaction mixture was stirred for the indicated time. The excess of Sm(II) was oxidized by bubbling air through the reaction mixture, and the reaction mixture was diluted with CH₂Cl₂ or Et₂O (20 mL) and NaOH (10 mL, 1 N) or KOH (10 mL, 10% aq). The aqueous layer was extracted with CH₂Cl₂ (3 x 20 mL), the organic layers were combined, washed with Na₂S₂O₃ (5 mL, aq., sat.), dried over Na₂SO₄, filtered, and concentrated. The sample was analyzed by ¹H NMR (CDCl₃, 400 or 500 MHz) and GC-MS to obtain selectivity, conversion and yield using internal standard and comparison with authentic samples. Unless stated otherwise, the crude product was purified by chromatography using a short plug of silica gel. Note that reactions involving samarium(II) can typically be followed by visual observation of the color changes of the respective reaction mixtures. In the case of Sm(II)/amine/H₂O complexes, the color changes from SmII (dark brown) to SmIII (dark to light green: oxidized, solvated; then white and yellow: fully oxidized, characteristic of SmI₂X).

---

Highly Chemoselective Reduction of Amides (Primary, Secondary, Tertiary) to Alcohols using SmI₂/Amine/H₂O under Mild Conditions

M. Szostak, M. Spain, A. J. Eberhard, D. J. Procter, J. Am. Chem. Soc., 2014, 136, 2268-2271.

---

Key Words

reduction of nitriles, samarium diiodide

---

ID: J54-Y2014