Samarium iodide radical cyclizations

A radical anion is involved in the samarium iodide-induced cyclization of the pyrrole derivative 58 (Scheme 19) <20030L4305>. 

Cossy has reported a synthesis of a-kainic acid that establishes the stereogenic centers on a preformed pyrrolidine ring (Eq. 20) [40], Thus, ketone 57 was prepared from L-pyroglutamic acid in 11 steps. Samarium iodide-mediated cyclization of 57 gave 58 as a mixture of stereoisomers at the carbinol carbon. Dehydration gave 59, and a 6-step sequence, starting with oxidative cleavage of the double bond, provided a-kainic acid. One notable aspect of this synthesis is the use of an enamide as a free-radical acceptor in the key cyclization. This process has been used in a number of alkaloid syntheses as will be seen in the next section. 

Scheme 3.7. Samarium(ll)iodide-induced domino radical cyclization/alkylation procedure...

Intermolecular coupling of ketones and alkenes, promoted by SmH, occurs with excellent stereochemical control. In one such reaction, samarium(II) iodide has been used to prepare cyclobutanones and cyclobutanols from chiral, 6-oxohex-2-enoates (equation 137)520. The reaction is performed in THF in the presence of HMPT and occurs in good yield with excellent stereocontrol. If appropriately located carbonyl and alkene moieties are present in a molecule, then Sml2-HMPT can be used to form cyclooctanols by a radical cyclization process in some cases there is a reasonable degree of diastereoselectivity (equation 138)521,522. 

The occurrence of the indole subunit is well established within the class of natural products and pharmaceutically active compounds. Recently, the Reissig group developed an impressive procedure for the assembly of highly functionalized in-dolizidine derivatives, highlighting again the versatility of domino reactions [8]. The approach is based on a samarium(II) iodide-mediated radical cyclization terminated by a subsequent alkylation which can be carried out in an intermolecular - as well as in an intramolecular - fashion. Reaction of ketone 3-11 with samarium(II) iodide induced a 6-exo-trig cyclization, furnishing a samarium enolate intermediate... 

Curran, D. P. Synthesis of substituted cyclooctanols by a samarium(ll) iodide promoted 8-endo radical cyclization process. On the stereoselectivity of radical 4-exo-trig-cyclization of optically active ethyl (2E)-6-oxohex-2-enoates with samarium(ll) iodide. Chemtracts Org. Chem. 1994, 7, 351-354. 

The bromoketones (94) undergo SET induced conversion into the spiro ketones (95). The electron transfer occurs on irradiation from an amine to afford the radical anion of the keto group. Loss of bromide affords the radical (96), which cyclizes to yield the products. The outcome of these photoreactions were compared with others using samarium iodide as the route to the radicals. This treatment afforded different products. ... 

A radical-mediated two-step synthesis of spiroketals has recently been reported the strategy (an example is shown in Scheme 8) involves an intramolecular radical cyclization of a ketal precursor (14), which could be easily prepared from 2-methylene-3,4-epoxyoxolanes (13). As alternative to tin-hydride mediated cyclization of alkynyl halides, samarium(II) iodide has been used to generate the alkyl radical which adds intramolecularly to the triple bond. ... 

Samarium(ir) iodide in the presence of HMPA effectively promotes the intramolecular coupling of unactivated alkenic ketones by a reductive ketyl-alkene radical cyclization process (eq 25). This protocol provides a means to generate rather elaborate carbocycles through a sequencing process in which the resulting organosamarium species is trapped with various electrophiles to afford the cyclized product in high yield. ... 

Radical Addition to Alkenes and Alkynes. Samarium(II) iodide has proven effective for initiation of various radical addition reactions to alkenes and alkynes. Typically, tin reagents are used in the initiation of these radical cyclization reactions however, the Sml2 protocol often provides significant advantages over these more traditional routes. 

Samarium(II) iodide-mediated cyclization of aryl radicals onto alkene and alkyne acceptors provides an excellent route to nitrogen- and oxygen-based heterocycles (eq 29). ... 

Di-0-benzyl-3,4-0-isopropylidene-D-mannitol was ring closed to afford a 9 1 cis/trans mixture of 189 in high yield by (Swern) oxidation and radical cyclization of the dialdehyde using samarium iodide in fcrf-butanol. The cis-diastereoisomer was selectively converted into a cis-cyclic sulfate which underwent cleavage upon treatment with potassium tert-butoxide to afford a cyclo-... 

Scheme 5.10 Samarium(ll) iodide-induced domino radical cyclization/acylation reaction.

The projected free radical cyclization proceeded as planned to give 172. Ozonolysis of the vinyl group, oxidation of the resulting aldehyde to an acid, and alkylation with diazomethane provided projected intermediate 162. Reduction of the lactone provided 173. Treatment of 173 with 6-methoxytryptamine and pivalic acid then provided a nearly equal mixture of lactams 174 (isoreserpine stereochemistry at Cg) and 175 (reserpine stereochemistry at C3). The correct C3 stereoisomer was moved forward to 176 (protection of the tertiary alcohol followed by reduction of the lactam). The silyl ethers were removed, the secondary ether was re-protected, and reaction with samarium iodide accomplished reduction of the a-hydroxy ester to provide 177. Removal of the TBS group and esterification of the alcohol completed the synthesis of reserpine. 

Condensation of resin bound ketones with hydrazines followed by cyclizative cleavage was used in a synthesis of pyrazolinones [67]. Samarium iodide induced radical cyclization of allyl aryl ethers led to benzofuran derivatives [68]. Kurth et al. have reported a two reaction iterative process for the construction of polyisoxazolines [69] and polyisoxazoles [70]. An intramolecular Heck reaction has been employed to prepare 2-oxindole derivatives [71]. 

The reductive cleavage of the proximal cyclopropane bond in bicyclo[3.1.0]heptan-2-ones with samarium(II) iodide involves a one-electron transfer and formation of a radical intermediate which can undergo intramolecular cyclization reactions. ... 

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