Ketyl radicals, generation

Alcohols are not only source of ketyl radicals generated by hydrogen abstraction from the a-C-H position (Eq. (7), Table 1). Oxidation of alcohols with Pb(OAc)4, PhI(OAc)2, and S2082 with Ag(I) as catalyst produces alkoxy radicals (RO-) which may further undergo /3-scission (Eq. 13), intramolecular hydrogen abstraction, or intra- and intermolecular addition to alkenes, generating a nucleophilic carbon-centered radical useful for heteroaromatic substitution (Scheme 6) [2]. 

In parallel the cocatalysis of cobalt compounds with A7-hydroxyphthalimide 398 was developed extensively for oxidative radical reactions [434]. Ishii and colleagues showed that these conditions can be used in radical additions (Fig. 92). Ketyl radicals generated by hydrogen abstraction from secondary alcohols 396 add to a.p-unsaturated esters 397 affording 2,4-dihydroxy esters, which cyclized to lactones 399 under the reactions conditions [435]. Using 0.1 mol% of Co(OAc)2, 1 mol% of Co(acac)3, and 10 mol% of 398 under 1 atm of oxygen, the cyclic products 399 were isolated in 14—90% yield. As observed for similar reactions, Co(III) alone needs an induction period (see below). 

It is highly significant that the naphthalene system is susceptible to an intramolecular attack by a ketyl radical generated from a ketone. 

Few examples of what might be described as an intermolecular coupling reaction on inactivated alkenes has appeared [62], Thus ketyl radicals generated from aromatic aldehydes and ketones underwent intermolecular addition to the para position of another aldehyde. Cross-coupling reactions are not feasible in these systems and typically yields are quite low. 

Interestingly, the ketyl radicals generated from the carbonyl group at the side chain of 6-7-dimethoxy tetraline chromium complex 15 attacked on the chromi-um-complexed arene ring with loss of the methoxyl group to afford the cycliza-tion chromium complex 16 as a single diastereomer (Eq. 12) [12]. 

The mechanism of the photoreduction of azoxybenzene to azobenzene in the presence of benzophenone was rationalized by Monroe and Wamser to involve the transfer of a proton from the ketyl radical, generated from excited benzophenone via hydrogen abstraction from the solvent to azoxybenzene, followed by dehydration (chemical sensitization). ... 

The above-mentioned multi-component catalytic systems are of synthetic potential in radical reactions. The generated ketyl radicals are able to undergo the inter- and intra-molecular coupling with a variety of radical acceptors. 

The transformation of2-734 involves an initial generation of an organosamarium species 2-735 with subsequent nucleophilic addition to the lactone carbonyl. Presumably, a tetrahedral intermediate 2-736 is formed that collapses to yield the ketone 2-737. This reacts with Sml2 to give a ketyl radical 2-738, which undergoes an intramolecular S-exo radical cyclization reaction with the alkene moiety. The resultant... 

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. 

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 previous chapter covered radical cation cyclization reactions that were a consequence of single-electron oxidation. In the following section, radical anion cyclization reactions arising from single-electron reduction will be discussed. In contrast to the well documented cyclization reactions via carbon-centered free radicals [3, 4], the use of radical anions has received limited attention. There are only a few examples in the literature of intramolecular reductive cyclization reactions via radical anions other than ketyl. Photochemi-cally, electrochemically or chemically generated ketyl radical anions tethered to a multiple bond at a suitable distance, have been recognized as a promising entry for the formation of carbon-carbon bonds. 

Apart from PET-reductive cyclization, chemical reduction has also been applied to the total synthesis of natural products such as capnellenediol 186 [184]. Naphthalene sodium is shown to be a suitable oxidant for generating ketyl radical anions which cyclize efficiently in a 5-exo-dig mode. In contrast, electroreductive cyclization of 184 does not lead to 185, but exclusively to the thermodynamically preferred 5-exo isomer with a remaining double bond in the endocyclic position [185] (Scheme 35). The steroid precursor 4.5-secocholes-tan-5-one 187, in which the lOa-side chain is varied, has been cyclized under the same conditions [186-188] (Scheme 36). Reduction with naphthalene sodium or sodium in ether exclusively produces the A B-cis steroid 188 with an exo double... 

We may be left to wonder how the rate of formation for the ketyl radical from benzophenone could get faster by adding 1,7-octadiene, or any other invisible substrate. The answer is simple, the rate is not faster, but rather, the rate constant for the signal growth is larger. In fact, the actual initial rate (see Eq. 10) is the same, as long as the same concentration of RO is generated initially in the presence or absence of XH. At any other time the rate will be lower in the presence of XH than in its absence, since XH will cause a decrease in RO concentration at aU times except at zero time. 

Electron paramagnetic resonance studies have shown that the biacetyl ketyl radical (3) and the radical derived from dioxane are formed when biacetyl is irradiated in dioxane solution.51 Nonphotochemically generated radicals derived from dioxane and cyclohexane add to biacetyl to yield acylated product.56 If cleavage were occurring in addition to or instead of hydrogen abstraction, one would expect to find at least moderate yields of acylated products in all solvents instead of just those which produce the least stable solvent radical. 

Photoreduction was quenched by high concentrations of biacetyl, slightly retarded by iodonaphthalene, but not affected by azulene or anthracene.113 These observations led to the unsatisfying conclusion that reduction proceeded via a triplet state which could be only selectively quenched. However, later work114 using flash photolysis showed that the benzophenone ketyl radical was generated upon irradiation of solutions of benzophenone and acridine, and that its predominant mode of disappearance was by reaction with... 

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... 

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