Intermediate ketyl

The other type of mechanism is a SET process" " with a ketyl intermediate " ... 

The ketyl intermediates in Sml2 reductions can be trapped by carbon-carbon double bonds, leading, for example, to cyclization of 8,e-enones to cyclopentanols. 

Another reagent that has found use in pinacolic coupling is prepared from VC13 and zinc dust.264 This reagent is selective for aldehydes that can form chelated intermediates, such as (3-formylamides, a-amidoaldehydes, a-phosphinoylaldehydes,265 and 8-ketoaldehydes.266 The vanadium reagent can be used for both homodimerization and heterodimerization. In the latter case, the reactive aldehyde is added to an excess of the second aldehyde. Under these conditions, the ketyl intermediate formed from the chelated aldehyde reacts with the second aldehyde. 

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 the method has been supplanted for synthetic purposes by the use of hydride donors, the reduction of ketones to alcohols by alkali metals in ammonia or alcohols provides some 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 intermediate formed by a single-electron transfer. The intermediate, depending on its structure and the reaction medium, may be protonated, disproportionate, or dimerize.137 In hydroxylic solvents such as liquid ammonia or in the presence of an alcohol, the protonation process dominates over dimerization. As will be discussed in Section 5.5.3, dimerization may become the dominant process under other conditions. 

Dimethyl-2,3-butanediol (pinacol) (2.12) on treatment with H2SO4 generates 3,3-dimethyl-2-butanone, commonly known as pinacolone (2.13). Pinacol itself is produced by magnesium reduction of acetone, probably by way of a ketyl intermediate. 

Reduction of benzophenone in liquid ammonia gives both alcohol and pinacol products. The ketyl intermediate in this reaction is stabilized by phenyl substituents, and competitive carbon atom protonation and dimerization generate alkoxide salts that remain in solution until hydrolyzed prior to product isolation. Benzophenone (diphenyl ketone) forms a deep blue ketyl which is stable in solvents that lack acidic hydrogens such as hydrocarbons and ethers. It is widely used as an indicator of oxidizing or acidic impurities during the purification of such solvents. 

Williams and Blann developed a route to cyclobutanols starting from carbohydrate-derived precursors [59]. The ketyl intermediates formed on treatment of precursors 35 with SmU in THF/HMPA underwent 4-exo-ketyl-olefin cyclisations to afford cyclobutanols 36 as isomer pairs (major isomer shown). Good yields were obtained for R = t-butyldimethylsilyl and trityl (triphenylmethyl), but for R = pivaloyl the reaction was diverted into an elimination pathway. 

It has been known since the early part of this century that reduction of benzophenone with sodium in liquid ammonia affords diphenylmethanol via a ketyl intermediate, and Hall et al. have shown more recently that aromatic aldehydes and ketones can be reduced with lithium in liquid ammonia to the corresponding methylene derivatives (equations 1-3). 

This reaction is called the pinacol synthesis, and is of general applicability. It works best for symmetrical aromatic ketones, because of the high stability of the aromatic ketyl intermediate, which incidentally is blue in colour. 

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. 

Reaction of ketyls. The coupling between ketones and nitriles to afford a-ketols likely involves ketyl intermediates. Conjugate addition of the ketyl derived from a-ketols shows stereoselectivity owing to chelation effects. ... 

The reduction of ketones with Sm(II) reductants to ketyls constitutes the first step in a number of important reactions including reductions, pinacol couplings and ketyl-olefin couplings. In spite of this, little was known about the nature of the intermediates in these reactions. To study these systems in detail, Hou et al. exposed Sm(Cp )2(THF)2 in THE to an equimolar amount of fiuorenone in an attempt to isolate the ketyl intermediate (Hou et al., 1998). Evaporation of the solvent provided a crystalline product that was dissolved in toluene, which after concentration of the solvent produced (Cp )2Sm(biphenyl-2,2 -diyl ketyl)(THF) in an overall 87% yield (eq. (128)). 

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... 

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