Radical anions ketyls

Since products from the 1,6-addition reactions are formed in much larger amounts than those from the 1,2-addition reaction (38 72), and since no cyclization takes place in the latter reaction, the conclusion was made that the 1,2-addition reaction product results from a collapse of a radical anion (ketyl)-radical cation (RMgX pair in which the group R of the Grignard is still tightly bound to the magnesium. 

A mechanistic scheme for the titanium-mediated coupling of two carbonyl groups involves an initial one-electron transfer from titanium metal to the aldehyde or ketone carbonyl group to produce radical anions (ketyl species), which then dimerize to a Ti-pinacolate. Hydrolysis of the pinacolate generates the vicinal diol. 

The halogenated biphenyls represent a class of compounds where reductive conditions [51] (solvated electron, aromatic radical anions, ketyl radicals) answer the purpose much better than the OH radical. However, this is to be seen in the context that the toxicity of the halogenated biphenyls exceeds that of biphenyl itself by such a wide margin that the latter compound is considered as relatively harmless. Complete removal of the pollutant would still have to rely on the oxidative pathway. A similar situation exists with respect to nitro-aromatics [52] which are also subject to reductive attack, indirectly by the OH radical via a-hydroxyethyl radical generated from the additive ethanol [53]. 

Conversion of the iV-methylamide of linoleic acid into a mixture of conjugated 9,11- and 10,12-iV-methyloctadecadienamides (cisjrans- after short reaction, trans,trans- after prolonged treatment), and reduction of aj8-unsaturated ketones and lactones to their radical anions (ketyls), are brought about by an alkali-metal methylsulphinylmethylide. 

Rapid purification Check for peroxides (see Chapter 1 and Chapter 2 for test under ethers). Pre-dry with CaCl2 or better over Na wire. Then reflux the pre-dried solvent over Na (1 % w/v) and benzophenone (0.2% w/v) under an inert atmosphere until the blue colour of the benzophenone ketyl radical anion persists. Distil, and store over 4A molecular sieves in the dark. 

Two classes of charged radicals derived from ketones have been well studied. Ketyls are radical anions formed by one-electron reduction of carbonyl compounds. The formation of the benzophenone radical anion by reduction with sodium metal is an example. This radical anion is deep blue in color and is veiy reactive toward both oxygen and protons. Many detailed studies on the structure and spectral properties of this and related radical anions have been carried out. A common chemical reaction of the ketyl radicals is coupling to form a diamagnetic dianion. This occurs reversibly for simple aromatic ketyls. The dimerization is promoted by protonation of one or both of the ketyls because the electrostatic repulsion is then removed. The coupling process leads to reductive dimerization of carbonyl compounds, a reaction that will be discussed in detail in Section 5.5.3 of Part B. 

When saturated steroidal ketones are reduced in ammonia, an alcohol is usually present to act as a proton donor and high yields of steroidal alcohols are obtained. Under these conditions, reduction probably proceeds by protonation of the radical-anion (or ketyl) (61), which results from a one electron addition to the carbonyl group, followed by addition of a second electron and proton. Barton has proposed that reduction proceeds via protonation of the dianion (62) arising from addition of two electrons to the carbonyl group. This proposal implies that the ketyl (61) undergoes addition of a second electron in preference to undergoing protonation by the... 

Allyl (27, 60, 119-125) and benzyl (26, 27, 60, 121, 125-133) radicals have been studied intensively. Other theoretical studies have concerned pentadienyl (60,124), triphenylmethyl-type radicals (27), odd polyenes and odd a,w-diphenylpolyenes (60), radicals of the benzyl and phenalenyl types (60), cyclohexadienyl and a-hydronaphthyl (134), radical ions of nonalternant hydrocarbons (11, 135), radical anions derived from nitroso- and nitrobenzene, benzonitrile, and four polycyanobenzenes (10), anilino and phenoxyl radicals (130), tetramethyl-p-phenylenediamine radical cation (56), tetracyanoquinodi-methane radical anion (62), perfluoro-2,l,3-benzoselenadiazole radical anion (136), 0-protonated neutral aromatic ketyl radicals (137), benzene cation (138), benzene anion (139-141), paracyclophane radical anion (141), sulfur-containing conjugated radicals (142), nitrogen-containing violenes (143), and p-semi-quinones (17, 144, 145). Some representative results are presented in Figure 12. 

Figure 3.20. TR spectra of fluoranil in 2-propanol obtained (after band fitting and deconvolution) at various time delays (Ap nip 355 nm, Apj bs 416 nm) (a) 10 ns, (b) 50ns, (c) 100ns, (d) 150ns, (e) 250ns, (f) 500 ns, (g) 1.3 ps, (h) 3.0 ps, [a] dots - original spectra and line-fitted spectra, [b] after the deconvolution of each band - the bands indicated as lines belong to the ketyl radical and the bands indicated as dots belong to the radical anion. See text for more details. (Reprinted from reference [91]. Copyright (1997), with permission from Elsevier.)...

The resnlts from the TR experiments presented in Fignres 3.19-3.21 above were used to determine single exponential rate constants of 5.1 X 10 s for the decay of the ketyl radical, 1.6 X 10 s for the formation of the flnoranil anion and 8.4 X 10" s for the decay of the flnoranil radical anion. These rate constants snggest that the flnoranil radical anion is forming from the ketyl radical. A reaction mechanism for the intermo-lecular abstraction reaction can be described as follows ... 

Reaction step 5 in Scheme 3.1 can be rnled ont becanse the flnoranil ketyl radical (FAH ) reaches a maximum concentration within 100 ns as the triplet state ( FA) decays by reaction step 2 while the fluoranil radical anion (FA ) takes more than 500 ns to reach a maximum concentration. This difference snggests that the flnoranil radical anion (FA ) is being produced from the fluoranil ketyl radical (FAH ). Reaction steps 1 and 2 are the most likely pathway for prodncing the flnoranil ketyl radical (FAH ) from the triplet state ( FA) and is consistent with the TR resnlts above and other experiments in the literatnre. The kinetic analysis of the TR experiments indicates the fluoranil radical anion (FA ) is being prodnced with a hrst order rate constant and not a second order rate constant. This can be nsed to rnle ont reaction step 4 and indicates that the flnoranil radical anion (FA ) is being prodnced by reaction step 3. Therefore, the reaction mechanism for the intermolecular hydrogen abstraction reaction of fluoranil with 2-propanol is likely to predominantly occur through reaction steps 1 to 3. 

Comparison of the TR spectra of the fluoranil ketyl radical (FAH ), the triplet state ( FA) and the fluoranil radical anion (FA ) to the results of density functional theory (DFT) calculations for these intermediates provides additional insight into... 

Scheme 3.1 Possible reaction steps in the hydrogen abstraction reaction of fluoranil with 2-propanol. Note FA= fluoranil, (CH3)2CHOH = 2-propanaol, FAH = fluoranil ketyl radical, FA = fluoranil radical anion.

ESR spectroscopy, however, revealed that 75, which one may call a ketyl radical, was not present in alkaline solutions of 77 in absence of oxidizing agents. The signal actually observed was that of 9-hydroxy-N,N -dimethyl-9,9 -biacridan radical 76. It was suggested that this radical was formed by one-electron transfer from N-methyl-acridone radical anion 75 to lucigenin monocarbinol 77, or by addition of hydroxide ion to lucigenin radical cation 78 (formed from lucigenin by one-electron transfer by the ketyl 75). 

Reductive Cross-Coupling of Nitrones Recently, reductive coupling of nitrones with various cyclic and acyclic ketones has been carried out electrochem-ically with a tin electrode in 2-propanol (527-529). The reaction mechanism is supposed to include the initial formation of a ketyl radical anion (294), resulting from a single electron transfer (SET) process, with its successive addition to the C=N nitrone bond (Scheme 2.112) (Table 2.9). 

After formation of an O-coordinated ketyl radical anion and a cis coordinated tyrosin via hydrogen abstraction, a rapid intramolecular one-electron redox reaction occurs with release of the product aldehyde and formation of the fully reduced active site containing a Cu(I) ion, which then reacts with 02 to give H202 and the active enzyme. The above sequence represents Nature s mechanistic blueprint for coordination chemists. 

Scheme 11.16 Diastereocontrol via chelate effect stereoselective 5-exo-trig cyclization on to a cumulated Jt-bond of a chelated ester-substituted ketyl radical anion 50 [74]. a 94 6 mixture of diastereomers.

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. 

The electroreductive cyclization reaction of 6-heptene-2-one 166, producing CIS-1,2-dimethylcyclopentanol 169, was discovered more than twenty years ago [166]. In agreement with Baldwin s rules, the 5-exo product is obtained in a good yield. Since that time, the mechanism of this remarkable regio- and stereoselective reaction has been elucidated by Kariv-Miller et al. [167-169]. Reversible cyclization of the initially formed ketyl radical anion 167 provides either the cis or the trans distonic radical anion. Subsequent electron transfer and protonation from the kinetically preferred 168 leads to the major cis product 169. The thermodynamically preferred 170 is considered as a source of the trace amounts of the trans by-product 171 (Scheme 32). 

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... 

The first (reversible) electron transfer generates the ketyl anion-radical. The ketyl moiety 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... 

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