Samarium diiodide radical cyclizations

Aurrecoechea, J.M., Lopez, B., Fernandez, A., Arrieta, A., and Cossio, F.P., Diastereoselective synthesis of cycloalkylamines by samarium diiodide-promoted cyclization of a-amino radicals derived from a-benzotriazolylalkenylamines, 7. Org. Chem., 62, 1125, 1997. 

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). 

Figure 4.11. Examples of redox-initiated radical reactions. Samarium diiodide reduction of the bromide gives a radical that cyclizes faster than the second reduction reaction. Manganese triacetate oxidation of the P-keto ester gives an enol radical that is not further oxidized by the manganese reagent. The IBX oxidizes anilides to the corresponding radicals. Hexamethylphosphoramide = HMPA and Tetrahydrofuran = THE.

A similar process is possible using samarium diiodide. With this reagent carbohydrate radicals are generated through a one-electron reduction of, for example, anomeric phenyl sulfones. The so-induced cyclization of the tethered sugar 59 gives compound 60, which has been transformed to a C-disaccharide [31]. 

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... 

Intramolecular addition of vinyl radicals to olefins as a method for heterocycle synthesis has been examined. The vinyl radicals can be conveniently generated from vinyl bromides and samarium(II) diiodide [95JOC7424], The intermediate radical after cyclization undergoes a further electron transfer from samarium to furnish a carbanion which is quenched at the end of the reaction. A samarium(II) diiodide mediated aryl radical cyclization onto a dihydrofuran has been reported [95T8555],... 

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. 

Ni(0) catalyst. A radical 5-exo cyclization to the potentially zinc or nickel-complexed ketone provides an alkoxyl radical that combines with the co-produced Ni(I) species. A transmetalation to a zinc alkoxide regenerates the catalyst and forms the zinc cyclopentoxide, from which products 79 are liberated on hydrolysis. A bimetallic Cu(I)-Mn(II) system provided similar results (see Sect. 8.4). Analogous samarium diiodide-mediated reactions require in contrast stoichiometric amounts of the reducing agent and are less diastereoselective [26, 27],... 

There exists also a synthesis of cyclopentadecanone (VII/81) and ( )-mus-cone, based on a three-carbon annulation of cyclic ketones followed by the regioselective radical cleavage of the zero bridge of the so formed bicyclic system [44], The synthesis of cyclopentadecanone is summarized in Scheme VII/16. The cyclization of VII/78 to the bicyclic alcohol VII/79 proceeds best (94 % yield) with samarium diiodide in the presence of hexamethylphosphoric acid triamide and tetrahydrofuran [45], The oxidative cleavage of VII/79 to the ring expanded product VII/80, was performed by treatment with mercury(II)-oxide and iodine in benzene, followed by irradiation with a 100 Watt high pressure mercury arc. Tributyltinhydride made the de-iodination possible. 

Samarium diiodide-promoted 5-exo radical cyclization and further transformation lead only to the C-analog derivative 21 of methyl isomaltoside. 

Compared with the numerous efficient syntheses based on nucleophilic/electrophilic or concerted (c/. Section 4.2.4) cyclization reactions of carbonyl derivatives, very little synthetic applications have been described that rely on radical-induced ring closure reactions, such as the reductive cyclization of 8-un-saturated iminium salts like (129) using samarium diiodide, which affords (132) as the only bicyclic product (Scheme 62). 2 The reaction is believed to proceed by single electron transfer, going through the a-amino radical (130), which cyclizes in an exocyclic mode to give the denoted product (132) via the benzylic carbon radical (131). 

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. 

Samarium diiodide-induced ketyl couplings are of significant synthetic interest, and Reissig el al. have reported an elegant application of the reaction in the case of the precursor 18. Reaction of 18 with 2 equivalents of samarium diodide and HMPA gave the 2-benzazepine 19 from an S-endo-dig cyclization reaction of the ketyl radical from the... 

Cyclobutadiene iron tricarbonyl complexes also stabilized carbocations on an adjacent carbon. The cation reacts with silyl enol ethers to afford alkylated complexes such as (127) (Scheme 187). A samarium diiodide-mediated intermolecular radical cyclization of iron tricarbonyl complex (128) is depicted in Scheme 188. An excellent stereocontrol at three contiguous centers is observed. 

Our first specific Wessely oxidation approach is outlined in Scheme 2. Following an aldol-type reaction between an appropriately protected resorcinol fragment and an aldehyde, we expected the Wessely oxidation to selectively dearomatize at the ortho position of both phenols. The intramolecular Diels-Alder cycloaddition reaction was then expected to form the tricyclic core, which could then be converted to the critical tetracyclic cage via a samarium diiodide(II)-type 6-exo-trig ketyl radical cyclization reaction. 

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