Ketones, aromatic pinacols

Samarium diiodide is another powerful one-electron reducing agent that can effect carbon-carbon bond formation under appropriate conditions.257 Aromatic aldehydes and aliphatic aldehydes and ketones undergo pinacol-type coupling with Sml2 or SmBr2. 

REDUCTION WITH ALUMINUM AMALGAM Reduction of Aliphatic-Aromatic Ketones to Pinacols [144]... 

The hydrodimerization of aromatic or aliphatic aldehydes and ketones yields pinacols (.100) (Eq. (184) ). 

Electrolytic formation of carbon bonds during formation of heterocyclic compounds occurs in the reduction of ketones to pinacols, in the hydrodimerization reaction, in some radical coupling reactions, and in the oxidative coupling of activated aromatic systems. 

Manganese. Li and Chan [34] and Rieke [35] have independently reported that manganese reagents can accomplish the pinacol coupling of aromatic carbonyl compounds. In the Li/Chan study, reaction of an array of aromatic aldehydes proceeded in good to excellent yield in the presence of Mn/Ac0H/H20, albeit with poor diastereoselectivity (Eq. 3.15). Under these conditions, aliphatic aldehydes are reduced to the corresponding alcohol, and ketones (aromatic or aliphatic) do not react. 

Aromatic aldehydes and ketones undergo pinacol coupling in solid state by Zn-ZnCl reagent to give a mixture of the reduced product (0-2%) along with major amount (45-80%) of the coupled product (glycol) (Scheme 32). 

Diols (pinacols) can be synthesized by reduction of aldehydes and ketones with active metals such as sodium, magnesium, or aluminum. Aromatic ketones give better yields than aliphatic ones. The use of a Mg—Mgl2 mixture has been called the Gomberg-Bachmann pinacol synthesis. As with a number of other reactions involving sodium, there is a direct electron transfer here, converting the ketone or aldehyde to a ketyl, which dimerizes. 

Purely aromatic ketones generally do not give satisfactory results pinacols and resinous products often predominate. The reduction of ketonic compounds of high molecular weight and very slight solubility is facilitated by the addition of a solvent, such as ethanol, acetic acid or dioxan, which is miscible with aqueous hydrochloric acid. With some carbonyl compounds, notably keto acids, poor yields are obtained even in the presence of ethanol, etc., and the difficulty has been ascribed to the formation of insoluble polymolecular reduction products, which coat the surface of the zinc. The adffition of a hydrocarbon solvent, such as toluene, is beneficial because it keeps most of the material out of contact with the zinc and the reduction occurs in the aqueous layer at such high dilution that polymolecular reactions are largdy inhibited (see Section IV,143). 

Preparative conversion of ketones (particularly aromatic ones) into pinacols can also be effected photochemically by u.v. irradiation in the presence of a hydrogen donor, e.g. Me2CHOH. 

Termination is principally via radical coupling forming hexabutylditin, or to a lesser degree via the coupling of ketyl radicals. In the case of the mr ketones a different mechanism is proposed. The rate of abstraction of H from the tributyltinhydride by benzylic radicals is slower than the corresponding abstraction by alkyl radicals. Since the rate at which the tributyltin radical will add to aromatic carbonyls is similar to the addition rate to aliphatic carbonyls, the dominant radical species for the tttt systems is the ketyl radical. The primary termination process involves the coupling of the predominant radical species resulting in pinacol formation. 

Titanium-mediated pinacol coupling reactions have been reviewed until 2000.80 81 Since then, various intermole-cular pinacol couplings have been reported with aldehydes, - ketones, a-ketoesters, and imines, as well as asymmetric versions thereof.101-104 Scheme 29 shows one example of an asymmetric pinacol coupling of aromatic aldehydes, promoted and catalyzed by the new chiral titanium complex (A)-75, that has been developed by Riant and co-workers.101 Yields for pinacol products 76 are generally high. Under catalytic conditions, ee is moderate (up to 63%), while stoichiometric conditions allow to obtain up to 91% ee. 

Pinacol coupling. Yb(0) metal can effect pinacol reduction of aromatic, but not aliphatic ketones.1 However, it can effect cross-coupling of benzophenone with aliphatic ketones, often in high yield (equation I). 

Aldehydes and ketones can be hy-drodimerized to pinacols (Eq. 2) [34-37]. With aromatic carbonyl compounds, the yields and selectivities are mostly higher than with aliphatic ones. The reaction has been extended to imines (Eq. 2, X = NAr, N-Bn) [38-41] and to heterohydrodimerizations affording, for example, y-lactones (Eq. 3) [42-44]. 

For further contributions on the dia-stereoselectivity in electropinacolizations, see Ref. [286-295]. Reduction in DMF at a Fig cathode can lead to improved yield and selectivity upon addition of catalytic amounts of tetraalkylammonium salts to the electrolyte. On the basis of preparative scale electrolyses and cyclic voltammetry for that behavior, a mechanism is proposed that involves an initial reduction of the tetraalkylammonium cation with the participation of the electrode material to form a catalyst that favors le reduction routes [296, 297]. Stoichiometric amounts of ytterbium(II), generated by reduction of Yb(III), support the stereospecific coupling of 1,3-dibenzoylpropane to cis-cyclopentane-l,2-diol. However, Yb(III) remains bounded to the pinacol and cannot be released to act as a catalyst. This leads to a loss of stereoselectivity in the course of the reaction [298]. Also, with the addition of a Ce( IV)-complex the stereochemical course of the reduction can be altered [299]. In a weakly acidic solution, the meso/rac ratio in the EHD (electrohy-drodimerization) of acetophenone could be influenced by ultrasonication [300]. Besides phenyl ketone compounds, examples with other aromatic groups have also been published [294, 295, 301, 302]. 

The electroreductive coupling of the hindered aromatic ketones (367) has been achieved in a DMF-BU4NBr-(Hg) system by the aid of CrCh or MnCl2 as the electrocatalyst (Scheme 134) [484, 485]. The reductive coupling proceeds at a less negative potential [ 1/2 —1.44 —1.53 V (SCE)] than the reduction of the ketone (—1.63 —2.01 V). In some cases, Mn electrocatalysts favor the reduction to the carbinol (369), whereas a Cr catalyst promotes the formation of the pinacol (368). 

An interesting deoxygenation of ketones takes place on treatment with low valence state titanium. Reagents prepared by treatment of titanium trichloride in tetrahydrofuran with lithium aluminum hydride [205], with potassium [206], with magnesium [207], or in dimethoxyethane with lithium [206] or zinc-copper couple [206,209] convert ketones to alkenes formed by coupling of the ketone carbon skeleton at the carbonyl carbon. Diisopropyl ketone thus gave tetraisopropylethylene (yield 37%) [206], and cyclic and aromatic ketones afforded much better yields of symmetrical or mixed coupled products [206,207,209]. The formation of the alkene may be preceded by pinacol coupling. In some cases a pinacol was actually isolated and reduced by low valence state titanium to the alkene [206] (p. 118). 

Good yields of pinacols from aromatic aldehydes and ketones are obtained by adding catechol to the TiCl3-Mg reagent prior to the coupling.164... 

I, 5-dithioniabicyclo[3.3.0]octane bis(trifluoromethanesulfonate) 7 in acetonitrile at 50°C. The salt promotes pinacol coupling of aromatic ketones even at —40 °C. In addition, the diastereoselectivity dl meso) of the coupling reaction of acetophenone in acetonitrile at —40°G is 94 6. "... 

Nil2 or Fe(acac)3 in a catalytic amount also accelerates the pinacol coupling in pivalonitrile. The system can be applied to the coupling reactions of aromatic and aliphatic ketones (Equation (33)). ... 

Pinacol reduction.1 In a strongly basic medium (pH 11-12), TiCl3 effects pinacol reduction of aromatic ketones, ArCOCH3 or C6H5COR, previously effected with a Ti(II) species (7, 373-374). Both the dl- and meso-pinacols are formed with marked preference for the former isomer. 

Several studies have been made of the effect of added metal ions on the pinacol/alcohol ratio. Addition of antimony(m) chloride in catalytic amounts changes the product of the electrochemical reduction of acetophenone in acidic alcohol at a lead electrode from the pinacol in the absence of added metal salt to the secondary alcohol in its presence53. Antimony metal was suspected to be an intermediate in the reduction. Conversely, addition of Sm(in) chloride to DMF solutions of aromatic aldehydes and ketones54 and manganese(II) chloride to DMF solutions of hindered aromatic ketones55 results in selective formation of pinacols in excellent yields. When considering these results one should keep in mind the fact that aromatic ketones tend to form pinacols in DMF even in the absence of added metal ions1,29,45. 

The pinacol-type coupling of aliphatic aldehydes, in the presence of niobium(IH) salts, occurs, with a high anti diastereoselectivity (equation 131)512. In the case of aromatic aldehydes and ketones the alkene product is sometimes formed513. In both cases the cyclic acetals may also be formed. 

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