Samarium diiodide reactions promoted

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). 

Studies by Molander et al. have demonstrated that samarium diiodide efficiently promotes the intramolecular coupling of ketones with distal epoxy olefins in the presence of HMPA, in good yields and often with high diastereoselec-tivity (Scheme 20). When tetramethylguanidine was used instead of HMPA, the desired carbocycle was obtained in good yield but the diastereoselectivity was diminished [55]. Evidence has been presented that suggests that the reaction proceeds via an initial radical cyclization route although reaction via an allyl samarium species cannot be ruled out. 

The mechanism for the transformation of 5 to 4 was not addressed. However, it seems plausible that samarium diiodide accomplishes a reduction of the carbon-chlorine bond to give a transient, resonance-stabilized carbon radical which then adds to a Smni-activated ketone carbonyl or combines with a ketyl radical. Although some intramolecular samarium(n)-promoted Barbier reactions do appear to proceed through the intermediacy of an organo-samarium intermediate (i.e. a Smm carbanion),10 ibis probable that a -elimination pathway would lead to a rapid destruction of intermediate 5 if such a species were formed in this reaction. Nevertheless, the facile transformation of intermediate 5 to 4, attended by the formation of the strained four-membered ring of paeoniflorigenin, constitutes a very elegant example of an intramolecular samarium-mediated Barbier reaction. 

Moreover, a dramatic increase of the reaction rate was observed when the coupUng of aromatic imines mediated by samariiun diiodide was carried out in the presence of both water and a tertiary amine or tetramethylethylene-diamine (TMEDA) [29], causing the almost instantaneous formation of the 1,2-diamine, although with undetermined diastereoselectivity. Similarly, the samarium diiodide promoted reductive coupling of iminiiun ions formed in situ by reacting ahphatic aldehydes with secondary amines and benzotriazole occurred at temperatures as low as - 70 °C [30]. Even in this case a mixture of diastereomers with undetermined ratio was obtained nevertheless, the item of diastereoselectivity induced by a chiral amine (auxiliary) is worthy of investigation. 

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. 

An approach based on samarium diiodide-promoted reactions of the iminoketone 279 with aldehydes provides access to a series of substituted or fused pyrroles bearing at least two phenyl groups, for instance, the system 280 (Equation 86) <2001T4881>. In an alternative lanthanide-catalyzed route, a series of pyrroles were constructed from imines and nitroalkenes in the presence of Sm(fPrO)3 <1999T13957>. A set of 1-dimethylaminopyrroles have also been obtained by TiCU-induced reactions between 2-acetoxypropanal hydrazones with silyl enol ethers <1995TL8007>. 

Samarium diiodide promotes the reaction between epoxides and imines to form oxazolidinones <2000TL3389>. 

Samarium diiodide has also been utilized as a reductant to promote pinacolic coupling reactions mediated by low-valent titanium species (equation 71). Utilizing this protocol, high diastereoselectivity can be achieved, although the yields for Ais particular process were not reported. 

Allylic halides are not as readily accessible as allylic alcohols or their ester derivatives. Thus, the requirement that allylic halides must be used as precursors for carbonyl addition reactions in conjunction with magnesium and other similar reductants is a severe restriction limiting the convenience of these routes to homoallylic alcohols. In this regard, samarium diiodide can be used to great advantage, because substrates other than allylic halides are suitable precursors for such transformations. For example, allylic phosphate esters have been reported to couple with carbonyl substrates in the presence of Smh (equation 15). Since esters and nitriles are unreactive under these conditions, the Smh-mediated process is likely to be more chemoselective than those promoted by magnesium or lithium. 

Molander, G. A., Etter, J. B. Lanthanides in organic synthesis. 8. 1.3-Asymmetric induction in intramolecular Reformatskii-type reactions promoted by samarium diiodide. J. Am. Chem. Soc. 1987, 109, 6556-6558. 

A. Chenede, E. Perrin, E. D. Rekai, and P. Sinay, Synthesis of C-disaccharides by a samarium diiodide induced intramolecular coupling reaction of tethered sugars, Synlett p, 420 (1994). P. de Poully, A. Chenede, J.-M. Mallet, and P. Sinay, Smlj-promoted chemistry at the anomeric center of carbohydrates. Reductive formation and reaction of glycosyl samarium (III) reagents Bull. Soc. Chim. Fr. 730 256 (1993). 

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. ... 

Similarly, Chiara et al. reported a cascade reaction of 6-deoxy-6-iodohexopyranosides promoted by samarium diiodide [69]. A series of 6-deoxy-6-iodohexopyranosides with different configurations and substitution patterns was treated with Sml2 in THF/HMPA to give the desired cyclopentanols. For example. 

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