Samarium(II) Iodide

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General Characteristics

Samarium(II) iodide (SmI₂) is a mild one-electron reducing agent used for various reductive reactions of carbonyl compounds, organic halides, and electron deficient olefins.

Additional applications of SmI₂ include pinalol coupling, alkyl-carbonyl coupling, deoxygenation, the Reformatsky reaction, and free-radical mediated cyclization.

Recent studies have shed light on the effect of additives on the reactivity of SmI₂.

General References

Girard, P.; Namy, J. L.; Kagan, H. B. J. Am. Chem. Soc. 1980, 102, 2693. DOI: 10.1021/ja00528a029

Molander, G. A. Harris, C. R. Chem. Rev. 1996, 96, 307. DOI: 10.1021/cr950019y
Molander, G. A. Org. React.2004, DOI: 10.1002/0471264180.or046.03
Edmonds, D. J.; Johnston, D.; Procter, D. J. Chem. Rev.2004, 104, 3371. DOI: 10.1021/cr030017a
Nicolaou, K. C.; Ellery, S. P.; Chen, J. S. Angew. Chem. Int. Ed.2009, 48, 7140. doi: 10.1002/anie.200902151
Szostak, M.; Procter, D. J. Angew. Chem. Int. Ed.2012, 51, 9238. DOI: 10.1002/anie.201201065
Szostak, M.; Spain, M.; Procter, D. J. Chem. Soc. Rev.2013, 42, 9155. DOI: 10.1039/C3CS60223K

Reaction Mechanism

The reactivity of SmI₂ is known to vary depending on the additive. In particular, Lewis bases such as HMPA and Et₃N and proton sources like BuOH and H₂O improve the chemoselectivity and reduction potential.

(The table is extracted from Chem. Soc. Rev. 2013, 42, 9155.)

Examples

The SmI₂-amine-H₂O combination is capable of reducing esters and carboxylic acids.^[1]

Total synthesis of (+)-pleuromutilin^[2]: SmI₂ provided a highly efficient means of ester reduction, where the yield with LiAlH₄ was only 21%.

SmI₂ is a valuable reagent for mild deprotection of Ts group.^[3]

Total synthesis of maoecrystal Z^[4]: SmBr₂ led to a better result than SmI₂ in this case.

Kilo-scale synthesis of chemotherapy drug Halaven^[5]: The highly selective reduction was achieved by careful optimization of reaction conditions.

Total synthesis of atractyligenin^[6]: The directing effect of the neighboring axial ester group was utilized to achieve the highly stereoselective ketone reduction.

The deprotection of allyl ethers is another application.^[7]

Experimental Procedure

Preparation of SmI₂.^[8]

An oven-dried 100 mL round-bottomed flask equipped with a Teflon-coated magnetic stir bar and a septum was placed under vacuum and evacuated/backfilled with argon three times. In air, 1.65 g (11.0 mmol) of samarium metal and 1.55 g (5.5 mmol) of freshly washed 1,2-diiodoethane (see, below) was weighed out and added to the reaction flask. The flask was sealed with a septum, evacuated/backfilled with argon three times, and stirring was started at medium speed. 55 mL of commercial THF was added using 60 mL syringe. The flask was evacuated/backfilled with argon three times (this process removes ethylene formed during the insertion of Sm into 1,2-diiosoethane), the argon line was removed, and the septum was sealed with Parafilm. After stirring overnight, the stirring was turned off, and the solution of SmI₂ was allowed to settle for 30 min and titrated.

Purification of diiodoethane.^[8]

1,2-Diiodoethane (20 g) was dissolved in approximately 400 mL of diethyl ether, and the organic layer was washed with aqueous saturated sodium thiosulfate solution (5 x 100 mL) and water (1 x 100 mL), dried over sodium sulfate, and concentrated to give a white solid. The flask containing 1,2-diiodoethane was wrapped in aluminum foil and placed under high-vacuum for 30 min.

Experimental Tips

1) SmI₂ is air-sensitive, thus it needs to be stored in well-degassed solvents and under argon atmosphere.

2) It has been reported that the quality of SmI₂ is affected most by the quality of samarium metal, rather than water and oxygen.^[8]

The color of SmI₂ solutions looks like the following:

(a) THF solution (blue), (b) H₂O solution (wine red), (c) after being consumed by the reaction (white/yellow)

References

[1] (a) Szostak, M.; Spain, M.; Procter, D. J. Chem. Commun. 2011, 47, 10254. DOI: 10.1039/C1CC14014K (b) Szostak, M.; Spain, M.; Procter, D. J. Org. Lett. 2012, 14, 840. DOI: 10.1021/ol203361k [2] Fazakerley, N. J.; Helm, M. D.; Procter, D. J. Chem. Eur. J. 2013, 19, 6718. DOI: 10.1002/chem.201300968 [3] Ankner, T.; Hilmersson, G. Org. Lett. 2009, 11, 503. DOI: 10.1021/ol802243d [4] Cha, J. Y.; Yeoman, J. T. S.; Reisman, S. E. J. Am. Chem. Soc. 2011, 133, 14964. DOI: 10.1021/ja2073356 [5] Eisai Inc, Synlett 2013, 333. DOI: 10.1055/s-0032-1318026 [6] Singh, A. K.; Bakshi, R. K.; Corey, E. J. J. Am. Chem. Soc. 1987, 109, 6187. DOI: 10.1021/ja00254a051 [7] Dahlen, A.; Sundgren, A.; Lahmann, M.; Oscarson, S.; Hilmersson, G. Org. Lett. 2003, 5, 4085. doi:10.1021/ol0354831 [8] Szostak, M.; Spain, M.; Procter, D. J. J. Org. Chem. 2012, 77, 3049. DOI: 10.1021/jo300135v [9] Szostak, M.; Spain, M.: Procter, D. J. Nature Protocols, 2012, 7, 970. DOI:10.1038/nprot.2012.034