Reductions with samarium(II) iodide

In the presence of samarium(II) iodide, the halogen atom of alkyl, alkenyl, and aryl halides is replaced by hydrogen. In tetrahydrofuran, the mechanism of alkyl halide reduction likely proceeds through radical intermediates.[8] However, alkyl halide reductions employing HMPA as a co-solvent likely involve a large proportion of organosamarium intermediates.[9] A unified mechanistic picture is shown below. Initial electron transfer and loss of halide generate an organic radical, which may combine with a second molecule of samarium(II) iodide to form an organosamarium species. Protonation of this species then yields the reduced product. Alternatively, the intermediate organic radical may abstract a hydrogen atom from the solvent S–H.

${\displaystyle {\begin{array}{r}{}\\{\ce {R-X->[{\ce {SmI2}}][-{\ce {SmI2X}}][R.]->}}{\begin{Bmatrix}{\ce {->[{\ce {SmI2}}][{\text{R = alkyl}}]R-SmI2->[{\ce {H-X}}]}}\\{}\\{\ce {->[{\ce {Solv-H}}][{\ce {-Solv^{.}}}]}}\end{Bmatrix}}{\ce {->{R-H}+SmI2X}}\\{\text{R = aryl, alkenyl}}\end{array}}}$

(3)

Reactions of aryl and alkenyl halides involve only radical intermediates; reduction of the intermediate radicals to organosamariums is evidently slower than hydrogen atom abstraction from the solvent.[10]

If a substituent is present in the β position of the alkyl halide, reductive fragmentation to a diastereomeric mixture of alkenes may occur. β-Elimination of the intermediate organosamarium species leads to the observed products.[11]

(4)

The mechanism of reductions of aldehydes and ketones by samarium(II) iodide is based primarily on mechanisms elucidated for similar one-electron reducing agents.[12] Upon single-electron transfer, a ketyl dimer iv forms. In the absence of protic solvent, this dimer collapses to form 1,2-diols. In the presence of a proton source, however, the dimer may undergo either disproportionation to form a samarium alkoxide and carbonyl compound, or protonation to form a carbinol radical ii followed by a second reduction and protonation, yielding an alcohol.

(5)

α-Functionalized carbonyl compounds are reduced to the corresponding unfunctionalized carbonyl compounds in the presence of samarium(II) iodide. This process may be initiated by initial electron transfer to either the substituent at the α position or the carbonyl moiety, depending on the relative electron affinity of the functional groups. A second reduction immediately follows, after which either protonation or elimination-tautomerization affords the product.[13]

(6)

Nitro compounds may be reduced to either the hydroxylamine or amine oxidation level with samarium(II) iodide, depending on the conditions employed. Electron transfer, followed by proton transfer and elimination generates an intermediate nitroso compound, which undergoes two more rounds of electron transfer and protonation to afford the hydroxylamine. Further reduction of the hydroxylamine leads to the amine.[14]

(7)

Samarium(II) iodide is conveniently generated in the reaction of samarium metal with either diiodomethane or diiodoethane. The use of diiodomethane is convenient because the oxidant is a liquid (diiodoethane is a solid). Although pure SmI₂ is air sensitive, solutions of the reagent may be manipulated in air without special precautions. SmI₂ reacts very slowly with water and even more slowly with alcohols. Alcohols are commonly used as co-solvents or proton sources in SmI₂ reductions, as immediate quenching of negatively charged intermediates with a proton source has proven beneficial for reaction yields.[21] Importantly, because SmI₂ is a one-electron reductant, multiple equivalents must be used to accomplish two-electron reductions of organic substrates. In most cases, a stoichiometric amount of the reagent or slight excess is sufficient.

The polarity of the solvent has a profound effect on the course of SmI₂ reductions. Increasing the polarity of the reaction medium generally makes SmI₂ a stronger reducing agent. HMPA may be used for this purpose; however, HMPA is a known carcinogen and should be handled with extreme care.

Workup procedures may vary depending on the stability of the products. If the organic products of the reaction are stable to aqueous acid, aqueous hydrochloric acid may be used to quench the reaction. For workups involving acid-labile products, mildly basic solutions or pH 7–8 buffers may be used. Samarium salts are usually insoluble in these conditions, but do form a suspension in the aqueous phase from which the desired organic product can be extracted.[22]

(13)

To a slurry of samarium powder (0.32 g, 2.1 mmol) in 2 mL of tetrahydrofuran at room temperature was added a solution of 1,2-diiodoethane (0.56 g, 2 mmol) in 2 mL of tetrahydrofuran. The resultant olive-green slurry was stirred at ambient temperature for 1 hour, after which time the resulting dark blue slurry of samarium(II) iodide that had formed was cooled to −78° and treated with a solution of 2-acetoxy-5-iodo-1-phenyl-1-pentanone (0.35 g, 1 mmol) in 1 mL of methanol and 2 mL of tetrahydrofuran. The resultant brown mixture was stirred for 10 minutes at −78°, warmed to room temperature, and then poured into saturated aqueous potassium carbonate. The aqueous phase was extracted with diethyl ether (5 × 10 mL) and the combined extracts were dried (anhydrous magnesium sulfate). Evaporation of the solvent left a solid that was recrystallized from diethyl ether to afford 0.24 g (87%) of 5-Iodo-1-phenyl-1-pentanone, mp 72–73°. IR (CCl₄): 1690 cm⁻¹. ¹H NMR (CCl₄): δ 7.9 (m, 3H), 7.4 (m, 3H), 3.2 (t, J = 6 Hz, 2H), 2.9 (t, J = 7.5 Hz, 2 H), 1.8 (m, 4H). ¹³C NMR: δ 199.26, 136.63, 132.90, 128.21 (2 C), 127.84 (2 C), 37.09, 32.85, 24.92, 6.12. Exact mass spectral analysis, calculated for C₁₁H₁₃IO, 288.0012; found, 288.0011.[13]