Reduction Using samarium iodide

The stereoselective reduction of a,a-dichloro-/3-hydroxy esters using samarium iodide yields (Z)-a-chloro-a,/3-unsaturated esters (eq 42). ... 

Evans reported an enantioselective Meerwein-Ponndorf-Verley reduction using a catalytic amount of chiral samarium complex 26 prepared from samarium (III) iodide and a chiral amino diol (Scheme 9.16) [34], Even when a partially resolved ligand (80% ee) was used, the enantiopurity of the resulting alcohol 27 reached 95% ee, which is the same value as that obtained when the enantiopure amino diol was used. 

A large number of radical reactions proceed by redox mechanisms. These all require electron transfer (ET), often termed single electron transfer (SET), between two species and electrochemical methods are very useful to determine details of the reactions (see Chapter 6). We shall consider two examples here - reduction with samarium di-iodide (Sml2) and SRN1 (substitution, radical-nucleophilic, unimolecular) reactions. The SET steps can proceed by inner-sphere or outer-sphere mechanisms as defined in Marcus theory [19,20]. 

Reduction of A,(V-di bcnzy lam i noalkyl chloromethyl ketones 133, followed by spontaneous intramolecular ring closure of the resulting 7-chloroamines 134, afforded azetidinium salts 135, which were subsequently deprotected toward chiral 3-hydroxyazetidines 136 and 137 (Scheme 29) <1997JOC1815>. In a similar approach, ct-amino aldehydes 138 were converted into 3-hydroxyazetidinium salts 139 upon treatment with diiodomethane and samarium iodide, followed by stabilization using AgBF4. Ar-Dealkylation with Pd afforded enantiopure azetidines 140 (Scheme 30) <2000TL1231>. 

Samarium iodide catalyzes the reduction of halides in damp THF120-122 and yields may be significantly improved if HMPA is added to the reaction mixture121,123. a-Halocarbonyl compounds are readily hydrodehalogenated by the use of this and similar methods124-126. Bis-cyclopentadiene complexes of samarium catalyze the reduction of benzylic and ally-lie halides via an organosamarium complex intermediate127-129. This reaction may be controlled so that monodeuteration occurs if the reaction is carried out under dry aprotic conditions followed by addition of D20 (equation 12). 

In the stereoselective synthesis of epothilone A (11), Carreira used a syn -reduction methodology in the synthesis of the key intermediate (14)9 (Scheme 4.If). Reduction of the isoxazoline 12 with samarium iodide at 0 C in THF gave the ketone 13. Narasaka reduction of the P-hydroxy ketone 13 using triethylb-orane/sodium borohydride afforded the. syn-diol 14 in high yield and with high diastereoselectivity. 

Samarium iodide has been used to bring about reductive photo-dehalogenation of 1,1-dichlorocyclopropane. The results and the efficiency of the reaction are shown in Scheme 5. The process, a Barbier reaction, is brought about using visible light. The yields of product are enhanced by the addition PhSH as a hydrogen donor. 

Apart from sodium borohydride, which is frequently used in water or water-alcohol mixtures to reduce ketones or aldehydes selectively, water is rarely used as the solvent in reductions, because of incompatibility with most reducing agents. However, samarium iodide reduction of ketones, as well as alkyl and aryl iodides is accelerated in water [99]. Likewise, the a-deoxygenation of unprotected aldonolac-tones is efficient when the SmI2-tetrahydrofuran-water system is used [100],... 

The chromium-complexed benzylic radicals are also known and were employed in a variety of useful organic reactions. One electron reductive coupling of the tricarbonylchromium complexes of o-substituted benzaldehydes and benzaldi-mines with samarium iodide gave 1,2-diols and diamines, respectively, in good yields with extremely high threo diastereoselectivity (Eq. 7) [7]. Therefore, enantiomerically pure 1,2-diols and diamines were easily obtained by using the planar chiral chromium complexes of benzaldehyde and benzaldimine. 

Samarium iodide can also be used as an alternative to sodium/ mercury amalgam for the reductive elimination of 1,2-acetoxy-sulfones in the Julia-Lythgoe olefination. The alkene is generated in a two-step process that first involves DBU or LDA treatment to generate a vinyl sulfone that is then reductively cleaved with samarium iodide (eq 44). The diastereoselectivity of both transformations is usually quite good and the method is compatible with the synthesis of monoalkenes as well as dienes and trienes. 

Tishchenko Reduction of Carbonyl Derivatives. The samarium iodide-catalyzed Tishchenko reaction has been used quite extensively in synthesis. Interesting examples include the diastereoselective synthesis of anri-l,3-diols (eq 66) and 5-lactones (eq 67). ... 

A mechanistically different stereoselective reduction of -hydroxy ketones leading to anft-l,3-diol using stoichiometric amounts of samarium iodide has been reported. ... 

There are few reports in which the 5-lactone ring is constmcted through a samarium iodide-mediated reductive cyclization of 1,5-dicarbonyl compounds. In the first example. Fang, Tsai et al. have reported the synthesis of 5-lactones using samarium... 

Imamoto et al. have reported a samarium(II) iodide promoted reductive ring opening of cyclopropane-1,1-dicarboxylie esters for the synthesis of 8-lactones [121] (Scheme 74). Treatment of various cyclopropane-1,1-dicarboxylate esters 328 with a variety of ketones 329 in the presence of samarium iodide and a catalytic amount of tris(dibenzoylmethiodo)iron(III) gave a diverse array of 2-methoxycarbonyl-5,5-disubstituted 8-lactone 330 in good yields. The use of a catalytic amount of the iron complex was imperative to accelerate the reductive ring opening of the cyclopropane. 

A useful and simple method for the one-pot preparation of highly functionalized, enanhomerically pure cyclopentanes from readily accessible carbohydrate precursors has been designed by Chiara and coworkers [73]. The procedure depends on a samarium(II) iodide-promoted reductive dealkoxyhalogenahon of 6-desoxy-6-iodo-hexopyranosides such as 7-160 to produce a 6,e-unsaturated aldehyde which, after reductive cyclization, is trapped by an added electrophile to furnish the final product. In the presence of acetic anhydride, the four products 7-161 to 7-164 were obtained from 7-160. 

Samarium(II) iodide also allows the reductive coupling of sulfur-substituted aromatic lactams such as 7-166 with carbonyl compounds to afford a-hydroxyalkylated lactams 7-167 with a high anti-selectivity [74]. The substituted lactams can easily be prepared from imides 7-165. The reaction is initiated by a reductive desulfuration with samarium(ll) iodide to give a radical, which can be intercepted by the added aldehyde to give the desired products 7-167. Ketones can be used as the carbonyl moiety instead of aldehydes, with good - albeit slightly lower - yields. 

Reductive coupling of dialdehydes may also be accomplished by use of samarium(II) iodide514. The reactions is stereoselective and has been used to prepare myo-inositol derivatives (equation 132)515. The equivalent reaction, using low-valent titanium species as catalysts, results in a mixture of products516. The production of cyclic /1-amino alcohols may be accomplished in good yields, and with a high degree of cis selectivity by the treatment of carbonyl hydrazones with samarium(II) iodide (equation 133)517. This reaction is effectively equivalent to an aza-Barbier reaction. 

Chiral induction was also observed in lanthanide(III)-alkoxide-mediated MPV reductions. The optically active ligand (Fig. 35C) was used in enantioselec-tive samarium-catalyzed MPV reductions of arylmethyl ketones (Scheme 30) [253], The resulting mixed alkoxide-iodide complex shows higher reactivity than (rBuO)SmI2. It was pointed out that the tridentate, secondary alkoxide ligand is not oxidized under the reaction conditions and that tridendate ligands... 

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