Samarium diiodide stereoselectivity

Amino alcohols like (iS )-prolinol react with nitroalkenes very rapidly with very high facia] selectivity.31 Rapid and stereoselective reduction of the nitro function is essential for the conversion of the products to 1,2-diamine derivatives with the retention of the configuration. Samarium diiodide is recommended in the stereoselective reduction of thermally unstable 2-aminonitroalkanes to give a range of useful 1,2-diamines (Eq. 4.26).32... 

A Rh-catalyzed Reformatsky reaction of chiral imine (24) led to the stereoselective preparation of the a,a-difluoro-jS-amino acid (25). 25 was converted to difluor-oalkene (26), and subsequently L-Val-i/r[(Z)CF=CH]Gly derivative (23) in greater than 82% for both steps. The samarium diiodide-mediated reductive transformation of the y,y-difluoro-a, S-enoates proceeded via successive two-electron transfers to form a dienolate species which upon kinetically controlled trapping with fert-BuOH formed 23 (Scheme 6). 

A reaction of dibromoacetic acid with different aldehydes promoted by Sml2, followed by an elimination reaction also promoted by samarium diiodide, affords ( > ,/l-unsaturalcd carboxylic acids with total stereoselectivity (Scheme 8).42 A mecha- (g) nism that involves chelation of the Sm(III) centre with the oxygen atom of the alcohol group through a six-membered chair-like transition state has been described. 

J. L. Chiara, J. Marco-Contelles, N. Khira, P. Gallego, C. Destabel, and M. Bemabe, Intramolecular reductive coupling of carbonyl-tethered oxime ethers promoted by samarium diiodide A powerful method for the stereoselective synthesis of aminocyclopentitols, J. Org. Chem., 60 (1995) 6010-6011. 

Georg, G. I. Cheruvallath, Z. S. Vander Velde, D. G. Himes, R. H. Stereoselective synthesis of 9P-hydroxytaxanes via reduction with samarium diiodide. Tetrahedron... 

A more versatile reducing agent is samarium diiodide, which promotes chemoselective cyclizations of functionalized keto aldehydes in a stereodefined manner to form 2,3-dihydrocyclopentane carboxylate derivatives in good yields and with diastereoselectivities of up to 200 1 (equation 38)7 The reaction proceeds via selective one-electron reduction of the aldehyde component and subsequent nucleophilic attack on the ketone moiety. Stereochemical control is established by chelation of the developing diol (19) with Sm " " which thereby selectively furnishes cis diols (equation 39). The stereoselective M/-cyclization of 1,5-diketones to cis cyclopentane-1,2-diols using TiCU/Zn has been used to prepare stereodefined sterically hindered acyclic 1,2-diols when a removable heteroatom, such as sulfur or selenium, is included in the linking chain (equation 40). 

Reductive deamination of pyrrolidine (3) with samarium diiodide in THF-HMPA in the presence of methanol as the proton source yielded the desired piperidone (4) stereoselectively in 90% yield (Eq. (2)), where a carbon-nitrogen bond cleavage reaction and subsequent recyclization took place simultaneously (05TL5161). 

A further, more complicated example of the stereoselective reductive ketone-alkene coupling is shown in the samarium diiodide promoted cyclization of unsaturated ji-oxo estersl2, giving 1.2,3-trialkyl-2-hydroxycyclopentanecarboxylates. The configuration of the two newly formed stereogcnic centers is determined by chelation of the intermediate radical by samarium(III). 

Other reducing agents, such as sodium/ammonia or diphenylstannane are unsatisfactory55. Since stereoselective reductions of this type have been a problem in the synthesis of milbemycins and avermectins57. the utility of the radical anion reduction via samarium diiodide/proton donor remains to be appreciated generally. For routine applications on a multigram scale, the price of samarium iodide is currently too high (1 mol of samarium costs ca. 25 times more than 1 mol of lithium). 

Since samarium diiodide is only a one electron donor, two equivalents of the metal are required in order for the reaction to proceed. The first electron donated from the samarium produces a chiral ketyl radical 30 which undergoes enantioselective addition to the acrylate according to the chelated transition state shown in 32. The second electron donation then provides a chiral samarium enolate intermediate 33 that can potentially undergo stereoselective proton transfer in the formation of a second chiral center. 

Gross S, Reissig H-U (2003) Novel stereoselective syntheses of highly functionalized benzannulated pyrrolizidines and indolizidines by samarium diiodide induced cyclizations of indole derivatives. Org Lett 5 4305 307... 

Several examples of the stereoselective formation of cyclopentane rings promoted by samarium diiodide have been reported. Thus a pinacol-like coupling of a 1,5-dialdehyde derivative produced 75 in which the newly formed hydroxyl groups R, R were in a y/z-arrangement. (See Vol. 29, p.238, ref. 95 for a related reaction). In contrast, reaction of a 5-hexenal, produced by zinc-assisted Grob fragmentation of a methyl 6-deoxy-6-iodopyranoside, produced 76 and 77 in which the exocyclic groups R, R (or R, R ) were anti to each other. ... 

Georg GI, Cheruvallath ZS, Vander Velde DG, Himes RH (1995) Stereoselective Synthesis of 9/3-Hydroxytaxanes via Reduction with Samarium Diiodide. Tetrahedron Lett 36 1783... 

The MBH adduct shown in Scheme 3.162, prepared from aromatic aldehydes and methyl acrylate, can directly undergo smooth dehydroxylation with concomitant olefin isomerization with low-valent titanium (LVT, prepared from TiCls-LAH-THF) reagent to afford the trisubstituted alkenes 364 with high ( )-selectivity. However, it is unsatisfactory in view of the low yield and the purity of products.More recently, Zhang et al. developed the samarium diiodide-promoted hydroxyl elimination of MBH adducts to form trisubstituted alkenes 364 with total ( )-stereoselectivity in good to excellent yields. This method also provided a new route to synthesizing a class of 1,5-hexadiene derivatives 365 by temperature tuning (Scheme 3.162). ... 

Another reductive coupling technique has been applied to unsaturated carbohydrate aldehydes, giving cyclopentanes with high stereoselectivity following samarium diiodide reduction, as exemplified in Scheme 12. ... 

Molander and co-workers have studied the stereoselective intramolecular addition of ketyl radicals to olefins [95JOC872]. The ketyl radicals are generated from ketone by treatment with samarium(II) diiodide. A similar reaction sequence using 61 gave only elimination products. 

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