Sml2 reductant

The ketyl intermediates in Sml2 reductions can be trapped by carbon-carbon double bonds, leading, for example, to cyclization of 8,e-enones to cyclopentanols. 

Reaction sequence E removed an extraneous oxygen by Sml2 reduction and installed an oxygen at C(15) by enolate oxidation. The C(l) and C(15) hydroxy groups were protected as a carbonate in Step E-5. After oxidation of the terminal vinyl group, the C-ring was constructed by a Dieckmann cyclization in Step F-4. After temporary protection of the C(7) hydroxy as the MOP derivative, the (1-ketoestcr was subjected to nucleophilic decarboxylation by phenylthiolate and reprotected as the BOM ether (Steps F-5, F- 6, and F-7). 

Reduction of acyclic a-methyl ketones. Reduction of ketones such as 1 with hydrides such as LiAlH, results in the anti or syn isomer as the predominant product. Bouvault-Blanc reduction, Birch reduction, and Sml2 reduction all favor anti Cram... 

Samarium(II) iodide smoothly reduces primary, secondaryand tertiary aliphatic as well as aromatic nitro compounds to hydroxylamines (equation 52). This reaction was found to be highly versatile although with limited scalability, since at least four equivalents of Sml2 are necessary. Most functional groups, except aldehydes and sulfones, are compatible with Sml2 reduction (equation 53). 

Keck demonstrated in 1995 that when the sodium amalgam reaction is run in MeOD as solvent, deuterium is incorporated into the product, in contrast to the absence of incorporation seen in the Sml2 reduction. Thus, the mechanism proposed above is completely consistent with the Sml2 reduction (M = Sml2). 

Tetradentate chiral proton donors have been used for the asymmetric protonation of samarium enolates formed by the Sml2 reduction of a-heteroatom-substituted carbonyl compounds. For example, Takeuchi examined the reduction of a-heterosubstituted cyclohexanone 12 using Sml2 and the BINOL-derived chiral proton source 13.41 Ketone 14 was obtained in good yield and high enantiomeric excess (Scheme 2.11). Coordination of the proton source to samarium is key to the success of the transformation.41... 

Ni, TiCl3 and Mo(CO)6. The Sml2 reduction has been shown to be selective for conjugated isoxazolines in the presence of unconjugated isoxazolines.46... 

Unexpectedly, Sml2 reduction of amides provides aldehydes in almost quantitative yield. 

Keck et al. have used the lactone annulation procedure developed in their laboratory to install the lactone moiety by reaction of the lithium enolate of methylacetate with a (3-acetoxy aldehyde [108]. The other key steps include a diastereoselective Lewis acid mediated (Z)-crotylstannane aldehyde addition, a highly selective Lewis acid promoted Mukaiyama aldol reaction and an arari-selective Sml2 reduction of a p-hydroxyketone. The preparation of the C8-C15 fragment of (-)-pironetin started with the chelation-controlled addition of (Z)-crotyl tri-n-butylstannane to the (3-benzyloxy-aldehyde 153 in the presence of TiCU [109] to give the... 

Another class of chelation-controlled reactions involves Sml2, which has been used to mediate inter- and intramolecular ketone-olefin couplings [17], Matsuda and collaborators showed that coupling erpt/ira-) -hydroxyketone with acrylonitrile led exclusively to the anti diol under Sml2 reductive conditions [18]. Chelation control model J in Scheme 6 was proposed to account for the sense of diastereo-selectivity. In this model, chelation of the Smb to both the jff-hydroxy and the... 

Review of Sml2 reduction of halides and radicals. This report (69 references) reviews various proposed mechanisms for these reactions, and suggests that both reactions may involve organosamarium(lll) intermediates."... 

Samarium iodide (Sml2) has been introduced as an efficient reducing agent for alkyl bromides and iodides in the presence of a proton source (alcohol) Alkyl chlorides are not reduced by this reagent. It has been further observed that the Sml2 reductions proceed exceedingly well in the presence of HMPA. Thus, primary, secondary and tertiary halides are reduced to alkanes under mild conditions and in very high yields (equation 44). ... 

Since the intramolecular Diels-Alder reaction and subsequent removal of acetoxyl group by Sml2 reduction have been successfully explored in the model study, we hoped to make full use of these findings in the total synthesis. Here, the strategy... 

Quantifying the Electrostatic Driving Force behind Sml2 Reductions, H. Farran, S. Hoz, Organic Letters 2008, 10, 4875 877. 

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