Samarium ketyl radicals

The acetate function of 98 was then cleaved by treatment with samarium diiodide in methanol in high yield (81 %) [44], A potential mechanism for this transformation is shown in Scheme 3.18. Reduction of the ketone function forms a samarium ketyl radical (103). Transfer of a second electron forms a carbanion (104) which undergoes p-elimination of acetate to generate the samarium enolate 105. Protonation and tautomerization then affords the observed product 107. 

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. 

The use of samarium(II) iodide in synthesis permits the assembly of complex molecules as already shown in many examples. They profit from the electron-transfer ability of samarium(II) iodide thus, if ketones are employed as substrates the furnished ketyl-radical can react in a multitude of different ways. 

An example, where two C-C-bonds are formed and one C-C-bond is broken is the synthesis of the tricycle 3-285, which has some similarity with the eudesmane framework 3-286, developed by Kilburn and coworkers (Scheme 3.72) [113]. Thus, exposure of the easily accessible methylenecyclopropyl-cyclohexanone 3-281 to samarium(II) iodide led to the generation of ketyl radical 3-282, which builds up a six-membered ring system with simultaneous opening of the cyclopropane moiety. Subsequent capture of the formed radical 3-283 by the adjacent alkyne group afforded the tricycle 3-285 via 3-284 as a single diastereoisomer in up to 60% yield. It should be noted that in this case the usual necessary addition of HMPA could be omitted. 

Samarium diiodide has been used by Enholm and co-workers for the generation and cyclization of ketyl radicals from aldehydic substrates [Eq. (9) and (10) 33], As noted, the... 

The mechanism shown in Scheme 6-28 seems likely. The first (reversible) electron transfer generates the ketyl anion radical. It then attacks the aryl group in the ortho position. The resulting cyclohexadienyl radical is reduced to a cyclohexadienyl anion by a second electron transfer, and the anion is finally protonated. HMPA as a cosolvent can be replaced with noncarcenogenic. V-melhylpyrrolidonc (Dinesh Reissig 1999). The new reaction mode of samarium ketyls undoubtedly has a synthetic perspective. 

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. 

Samarium(H) diiodide mediated ketyl radical addition to alkyne results in the formation of an alkene after radical cyclization [95SL277]. Compound 65, a product from one such reaction, has been converted to the carbohydrate portion of miharamycin A, a nucleoside antibiotic. 

The mechanism of the intramolecular samarium-initiated Barbier reaction is still a matter of debate [80-82], One of several mechanistic possibilities is primary reductive generation of the ketyl radical anion which can subsequently initiate a second... 

Intramolecular coupling of carbonyl groups with vinylbromides after an addition-elimination sequence involves two electron-transfer steps. In the first step the ketone is reduced to the ketyl radical anion. After 5-exo-trig radical addition of the vinylbromide group, a primary radical is generated which is subsequently reduced to give an alkyl samarium species which eliminates bromide. This reaction... 

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