Ketones from pinacols

The Grignard reagents prepared from the activated magnesium appear to react normally with electrophiles. Thus reactions with proton donors, ketones, and carbon dioxide afford hydrocarbons, alcohols, and carboxylic acids, respectively. The reductive coupling of ketones to pinacols had also been accomplished with the activated magnesium. ... 

We have seen similar radical anions generated from ketones in pinacol reduction with sodium or magnesium (p. 218), and also from esters with sodium in the acyloin condensation (p.218). 

In the conversion that gave its name to this reaction, the acid-catalyzed elimination of water from pinacol give s r-butyl methyl ketone. 

In fact, diketones in a medium sized ring give several transannular reactions such as pinacol coupling [equation (i)] or aldolization [equation The later reaction also occurs during hydrogenation of aliphatic monoketones under favorable conditions (Pd-on-carbon, zeolite, 200°C, 4 X 10 kPa) to produce methyl isobutyl ketone from acetone (in 96%) -... 

Rearrangements of pinacol, l,l -dihydroxy-l,l -dicyclopentyl, and 1,1 -dihydroxy-1,1 -dicyclohexyl to the corresponding ketones, with negligible alkene formation, occurred in superheated D2O in 60 min at 275 °C [103]. Although a classical method for the pinacolone from pinacol required boiling in 25%... 

Ketones which contain a tertiary alkyl group are formed as the result of the elimination of water from pinacols. When pinacol is heated with an aqueous solution of an acid, it loses water and forms a ketone, named pinac-oliUy which is the first member of a series of substances known as pinac-olins. In the transformation a molecular rearrangement evidently takes place. The probable course of the reaction is expressed by the formulas,—... 

The conclusion that pinacolin has the constitution assigned to it here, has been reached as the result of the study of the reactions of the compound. Its formation as the result of the elimination of water from pinacol would lead to the view that it is an ether, and has the structure represented by the middle formula in the series above. Pinacolin, however, shows the reactions which are characteristic of ketones. The intermediate product in the transformation of a pinacol to a pinacolin has been isolated in certain cases. 

Pinacol upon dehydration with acid catalysts e.g., by distillation from 6A sulphuric acid or upon refluxing for 3—4 hours with 50 per cent, phosphoric acid or hydrated oxalic acid) is transformed into methyl ter<.-butyr ketone or plnacolone ... 

Selective hydroxylation with osmium tetroxide (one equivalent in ether-pyridine at 0 ) converts (27) to a solid mixture of stereoisomeric diols (28a) which can be converted to the corresponding secondary monotoluene-sulfonate (28b) by treatment with /7-toluenesulfonyl chloride in methylene dichloride-pyridine and then by pinacol rearrangement in tetrahydrofuran-lithium perchlorate -calcium carbonate into the unconjugated cyclohepte-none (29) in 41-48 % over-all yield from (27). Mild acid-catalyzed hydrolysis of the ketal-ketone (29) removes the ketal more drastic conditions by heating at 100° in 2 hydrochloric acid for 24 hr gives the conjugated diketone (30). 

The study of optical isomers has shown a similar development. First it was shown that the reduction potentials of several meso and racemic isomers were different (Elving et al., 1965 Feokstistov, 1968 Zavada et al., 1963) and later, studies have been made of the ratio of dljmeso compound isolated from electrolyses which form products capable of showing optical activity. Thus the conformation of the products from the pinacolization of ketones, the reduction of double bonds, the reduction of onium ions and the oxidation of carboxylic acids have been reported by several workers (reviewed by Feokstistov, 1968). Unfortunately, in many of these studies the electrolysis conditions were not controlled and it is therefore too early to draw definite conclusions about the stereochemistry of electrode processes and the possibilities for asymmetric syntheses. 

Unsymmetrical alkenes can be prepared from a mixture of two ketones, if one is in excess. " The mechanism consists of initial coupling of two radical species to give a 1,2-dioxygen compound (a titanium pinacolate), which is then deoxygenated. " ... 

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. 

Trimethylsilylation of enolizable carbonyl compounds and alcohols has also been accomplished by the fluoride ion promoted reaction with hexamethyldisilane and ethyl trimethylsilylacetate [48, 49], with high stereospecificity giving Z-enol ethers from ketones [50]. l-Trimethylsilyl-(l-trimethylsilyloxy)alkanes, produced from the reaction of aldehydes with hexamethyldisilane, undergo acid-catalysed hydrolysis during work up to yield the trimethylsilylcarbinols [51]. In the case of aryl aldehydes, the initially formed trimethylsiloxy carbanion produces the pinacol (Scheme 3.1). 

Pinacol formation from ketones and aldehydes by cathodic reduction has been enhanced in the presence of Cr(II) complexes. Electrolysis of a mixture of ben-zophenone (364) and chromium chloride hexahydrate in a DMF-NaCl04 system... 

Probably the most familiar radical reactions leading to 1,2-D systems are the so called acyloin condensation and the different variants of the "pinacol condensation". Both types of condensation involve an electron-transfer from a metal atom to a carbonyl compound (whether an ester or an aldehyde or a ketone) to give a radical anion which either dimerises directly, if the concentration of the species is very high, or more generally it reacts with the starting neutral carbonyl compound and then a second electron is transferred from the metal to the radical dimer species (for an alternative mechanism of the acyloin condensation, see Bloomfield, 1975 [29]). 

---