Radical Ketyl intermediate

The following mechanism can be assumed. Initially, the ketyl intermediate 3-159 is formed, which leads to 3-160 by a radical epoxide opening. Reaction with the second molecule of Sml2 gives samarium-chelated hydroxy-ketyl 3-161, which cyclizes to afford the products 3-157 and 3-158. 

Although one can equally well envision a mechanism whereby a tin radical adds to the carbonyl oxygen to furnish a ketyl radical, this intermediate would have to eliminate a phenylsulfonyl radical and form... 

A particularly stable ketyl radical is derived from benzophenone (cf. Figure 17.52). This is why additions of the Grignard reagents R2Mg2Hal2 to this substrate proceed more frequently via radicals as intermediates than others. An example in which the occurrence of such a radical intermediate is documented by the typical radical cyclization 5-hexenyl —> cyclopentyl-carbinyl (cf. Section 1.10.2) is the following ... 

Fig. 17.49. Reductions of a-heterosubstituted ketones to a-unsubstituted ketones (see Figures 15.34 and 17.59 for the preparation of compounds A and B, respectively). Here, a ketyl is formed as a radical anion intermediate (for more details about ketyls see Section 17.4.2). The ketyl obtained from A releases a chloride ion, the ketyl resulting from B releases a hydroxide ion. In each case, an enol radical is formed thereby which picks up an electron. This leads to the formation of a zinc enolate from which the final product is generated by protonation.

In a detailed kinetic study, Flowers showed that the rate of ketone reduction is directly related to the pof the alcohol proton source used in the reaction and that the proton source must be sufficiently acidic to protonate the ketyl radical anion intermediate 3.11 Interestingly, when H20 is used as a proton... 

The ketyl radical anion intermediates can be exploited in carbon-carbon bond-forming reactions. Intermolecular and intramolecular pinacol couplings between the carbonyl groups of ketones and aldehydes are well known (Chapter 5, Section 5.1), as are intermolecular and intramolecular carbonyl-alkene couplings (Chapter 5, Section 5.2). 

Hence, a quick analysis might use LUMO energies from semi-empirical calculations for the analysis of the reduction of 3 (Scheme 3). Because the LUMO energy of acetone as model for site (a) in 3 is the lowest within the three electrophores, one must expect that an electron will be accepted at this site. This is indeed demonstrated in the PET reduction of 3 to a ketyl radical anionic intermediate using tri-ethylamine as sensitizer [8]. 

Direct evidence for the formation of radical ion intermediates in the benzophenone-amine system was also obtained by Peters et al. [153-156]. Picosecond laser-flash photolysis studies have indicated the formation of ketyl radical anions concomitant with the decay of the benzophenone triplet. For 1.0 M dime-thylaniline and diethylaniline the rate of electron transfer to the benzophenone triplet was 3.6 x 10 and 4.2 x 10 m s , respectively. On the basis of their studies Peters et al. proposed a mechanism in which a solvent-separated ion pair... 

Figure 13 Chemical models for the radical isomerization process in the action of DDH. At the top is a base-catalyzed mechanism by way of a ketyl radical as the key intermediate. At the bottom is an acid-catalyzed mechanism by way of a radical cationic intermediate.

Reactions herein significantly differ from most standard nBu SnH-mediated radical transformations that employ a variety of well-known precursors for carbon-centered radicals, including halides, thioacyl moieties, olefins, selenides and sulfides. Most of these potentially useful precursors are sacrificed and lost during the radical reaction and are not available for subsequent manipulations [7]. However, O-stannyl ketyl intermediates conserve the carbonyl oxygen for further functionalization. 

Studies by Hou and coworkers were initiated to compare and contrast the ability of different ligands to stabilize ketyl intermediates and showed that the (-N(SiMe3)2) ligand behaved somewhat different than the Cp ligand upon the reduction of a ketone (Hou et ah, 1998). The reaction of [(Me3Si)2N]2Sm(THF)2 with one equivalent of fluorenone in THF produced a brown solution with a UV-vis spectrum consistent with the formation of a ketyl radical. Upon removal of solvent however the pinacolate was isolated as the major product in 79% yield (eq. (135)). This finding is in contrast to the... 

The initial step of the coupling reaction is the binding of the carbonyl substrate to the titanium surface, and the transfer of an electron to the carbonyl group. The carbonyl group is reduced to a radical species 3, and the titanium is oxidized. Two such ketyl radicals can dimerize to form a pinacolate-like intermediate 4, that is coordinated to titanium. Cleavage of the C—O bonds leads to formation of an alkene 2 and a titanium oxide 5 ... 

The mechanism for the transformation of 5 to 4 was not addressed. However, it seems plausible that samarium diiodide accomplishes a reduction of the carbon-chlorine bond to give a transient, resonance-stabilized carbon radical which then adds to a Smni-activated ketone carbonyl or combines with a ketyl radical. Although some intramolecular samarium(n)-promoted Barbier reactions do appear to proceed through the intermediacy of an organo-samarium intermediate (i.e. a Smm carbanion),10 ibis probable that a -elimination pathway would lead to a rapid destruction of intermediate 5 if such a species were formed in this reaction. Nevertheless, the facile transformation of intermediate 5 to 4, attended by the formation of the strained four-membered ring of paeoniflorigenin, constitutes a very elegant example of an intramolecular samarium-mediated Barbier reaction. 

Another mechanism, involving addition of the ketyl to another molecule of ester (rather than a dimerization of two ketyl radicals), in which a diketone is not an intermediate, has been proposed Bloomfield, J.J. Owsley, D.C. Ainsworth, C. Robertson, R.E. J. Org. Chem., 1975, 40, 393. 

In order to extract the contributions and dynamics of the ketyl radical and fluoranil anion from the TR spectra obtained with the 416 nm probe wavelength, a deconvolution of the Raman bands were done using a fitting procedure employing a Lorentzian lineshape for the Raman bands of the two intermediates. Figure 3.20 shows a comparison of the best-fit (lines) to the experimental TR spectra (dots) in the left-side spectra and the deconvolution extracted from this best fit for the ketyl radical spectra... 

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... 

Reduction of Ketones and Enones. Although the method has been supplanted for synthetic purposes by hydride donors, the reduction of ketones to alcohols in ammonia or alcohols provides mechanistic insight into dissolving-metal reductions. The outcome of the reaction of ketones with metal reductants is determined by the fate of the initial ketyl radical formed by a single-electron transfer. The radical intermediate, depending on its structure and the reaction medium, may be protonated, disproportionate, or dimerize.209 In hydroxylic solvents such as liquid ammonia or in the presence of an alcohol, the protonation process dominates over dimerization. Net reduction can also occur by a disproportionation process. As is discussed in Section 5.6.3, dimerization can become the dominant process under conditions in which protonation does not occur rapidly. 

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... 

Kim, J., Darley, D.J., Buckel, W., and Pierik, A.J. 2008. An Allylic ketyl radical intermediate in clostridial amino-acid fermentation. Nature 452 239-242. 

The enthalpy changes associated with proton transfer in the various 4, -substituted benzophenone contact radical ion pairs as a function of solvent have been estimated by employing a variety of thermochemical data [20]. The effect of substituents upon the stability of the radical IP were derived from the study of Arnold and co-workers [55] of the reduction potentials for a variety of 4,4 -substituted benzophenones. The effect of substituents upon the stability of the ketyl radical were estimated from the kinetic data obtained by Creary for the thermal rearrangement of 2-aryl-3,3-dimethylmethylenecyclopropanes, where the mechanism for the isomerization assumes a biradical intermediate [56]. The solvent dependence for the energetics of proton transfer were based upon the studies of Gould et al. [38]. The details of the analysis can be found in the original literature [20] and only the results are herein given in Table 2.2. 

The major product of the keto olefin cyclizations often corresponds to what one would predict, assuming the intermediate ketyl behaves like the corresponding monoradical (Eq. 34). For example, given an option between a 5-exo and a 6-endo-trig cyclization, the former predominates in radical cyclizations [51], and constitutes the exclusive cyclization path in the electrochemical counterpart, 110 - 112 [47]. In addition, the stereochemical outcome parallels that of the radical... 

The process can be interrupted at the stage of ketyl 171, thereby providing access to an acyl radical synthon. The radical character of the intermediate is... 

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