A-keto radical

Mattay et al. examined the regioselective and stereoselective cyclization of unsaturated silyl enol ethers by photoinduced electron transfer using DCA and DCN as sensitizers. Thereby the regiochemistry (6-endo versus 5-exo) of the cyclization could be controlled because in the absence of a nucleophile, like an alcohol, the cyclization of the siloxy radical cation is dominant, whereas the presence of a nucleophile favors the reaction pathway via the corresponding a-keto radical. The resulting stereoselective cis ring juncture is due to a favored reactive chair like conformer with the substituents pseudoaxial arranged (Scheme 27) [36,37]. 

The utility of tandem oxidative cyclizations is clearly demonstrated in substrates in which both additions are to double bonds [12]. Oxidative cydization of 20 with two equivalents of Mn(OAc)3 and of Cu(OAc)2 in acetic acid at 25 °C affords 86 % bicyclo[3.2.1]octane 25. Oxidation affords the a-keto radical 21, which cyclizes exclusively 6-endo in the conformation shown to afford the tertiary radical 22 with... 

It is widely believed that enone-alkene photoadditions proceed through an exciplex (excited complex). For cyclopentenone and 7, the exciplex forms from the photoexcited enone in its triplet state and the glycal in its ground-state. The regiochemistry of addition probably reflects a preferred alignment of the addends in the exciplex. Because a photoexcited enone probably has considerable diradical character, it is reasonable to assume that the more electrophilic a-keto radical would prefer to bind to the more nucleophilic portion of the alkene, since this would maximise attractive interactions within the complex. The reaction of 7 with cyclopentenone would thus favour the formation of diradical 22, which would then ring-close to cyclobutane 14 (Scheme 6.7). 

We can also find examples of fragmentation of cation radicals in photochemical reactions (see section a-Keto Radicals from a-Stannyl Carboxylates ). Here, one example is presented illustrating the cleavage of cation radical CR13 of dimethyl(trimethylsilyl-methyl)amine (13) in a photochemical reaction described by Mariano and co-workers (Scheme 8). ... 

This vanadium method enables the cross-coupling only in combinations of silyl enol ethers having a large difference in reactivity toward radicals and in their reducing ability. To accomplish the crosscoupling reaction of two carbonyl compounds, we tried the reaction of silyl enol ethers and a-stannyl esters based on the following consideration. a-Stannyl esters (keto form) are known to be in equilibrium with the enol form such as stannyl enol ethers, but the equilibrium is mostly shifted toward the keto form. When a mixture of an a-stannyl ester such as 45 and a silyl enol ether is oxidized, it is very likely that the stannyl enol ether will be oxidized preferentially to the silyl enol ether. The cation radical of 45 apparently cleaves immediately giving an a-keto radical, which reacts with the silyl enol ether selectively because of the low concentration of the stannyl enol... 

Salts of other transition metals including vanadium, cerium, chromium and manganese have been used for a-oxygenation, although rarely applied in synthesis. Manganese triacetate has been used for the efficient a -oxidation of enones (Section 2.3.2.2.1.i), but appears not to have been used for the a-hydrox-ylation of saturated ketones des]Hte its known ability to form the corresponding a-keto radicals. Similarly the use of Lewis acid assisted enolization in the oxidative process appears to have been limited to the LTA-mediated examples. 

Most organic free radicals are nucleophilic and will react with electrophilic centers. Lewis acids have been used to activate aj3-unsaturated carbonyl compounds towards addition of free radicals and also to stabilize a-keto radicals [67]. The first report of the use of a chiral Lewis acid to effect an asymmetric free-radical reaction was that of Urabe, Yamashita, Suzuki, Kobayashi, and Sato in 1995 [68]. They found that if the BINOL aluminum catalyst 313 is stoichiometrically complexed with lactone 323 and then treated with butyl iodide and tributylstannane in the presence of triethylborane the alkylated lactone 324 can be isolated in 47 % yield with 23 % ee (Sch. 40). 

Reactions with other radicals, namely, photochemically generated a-keto radicals and alkyl thiyl radicals exhibit results similar to those of PhS. 

It is noteworthy that this Cl reagent can be applied to a wide range of organic radicals involving rather stable radicals such as a-keto radical, a-alkoxyalkyl radical, and the benzyl radical for which the aforementioned radical formylation system with CO cannot be applied. The high reactivity of phenyl sulfonyl oxime ether is supported by kinetic studies [29]. The approximate rate constants for the addition of a primary alkyl radical to this phenyloxime ether was determined to be k=9.6xl0 M s at 25 °C, which is 1.8 times faster than the addition to aery-... 

The oxidation of 1-methoxycyclopropanol with iron(IIl) nitrate in methanol in the presence of but-3-en-2-one gives the 6-oxo ester in 30% yield.The mechanism may involve addition of a 2-(methoxycarbonyl)ethyl radical, obtained via iron(III) induced oxidation, to but-3-en-2-one resulting in an a-keto radical. A more effective and practical intermolecular addition of cyclopropanols to alkenes was recently performed in the presence of manganese(III) pyridine-2-carboxylate (Table 4)T 32 -phe reaction may proceed by way of (i) generation of 8-acylalkyl... 

Within the past decade, diastereosolective radical reactions have become feasible and the factors contolling selectivity defined. Chiral auxiliaries for radical reactions have been recently developed in analogy to those developed for carban-ion chemistry in the 1970s and 1980s. The first example of stoichiometric use of a chiral ligand for enantioselective radical additions was recently reported by Porter and coworkers [59,60,61]. Reaction of the amide 14 with allyltrimethyl-silane at -78 °C, initiated by triethylborane, in the presence of 1 equiv. each of zinc triflate and the chiral bidentate ligand 15, provided the allylated product in a yield up to 88% and ee of 90%, Eq. (18). The presumed intermediate is the a-keto radical complexed to the chiral Lewis acid. 

Two resonance structures, in which the odd electron is localized on carbon (54) or on oxygen (55), may be written for a semidione radical. Based on the conclusion 135), mentioned earlier, that the odd electron of a-keto radicals is mainly localized on carbon, the canonical form 55... 

Mn(OAc)3 in AcOH at 60 °C oxidizes aldehydes RCH2CHO to RCH-CHO. These radicals add to alkenes to give radicals that abstract a hydrogen, or are oxidized to acetates or alkenes affording mixtures of limited synthetic utility [11a]. Similarly, Mn(OAc)3 in AcOH at 40-80 °C oxidizes acetophenone, acetone, cyclo-pentanone, cyclohexanone or other simple symmetrical ketones to a-keto radicals that add to alkenes leading to modest yields of coupled products [11a]. 

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