Pinacol reduction

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). 

Intramolecular pinacol reduction. Sml2 can promote intramolecular reductive conpling of keto aldehydes to provide 2,3-dihydroxycyclopentanecarboxylates with marked diastereoselectivity.2... 

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). 

The Clemmensen reduction of j8-diketones (1,3-diketones) is rather complicated. The first step in the reaction of 2,4-pentanedione with zinc amalgam is an intramolecular pinacol reduction leading to a cyclopropanediol. Next the cyclopropane ring is opened in the acidic medium, and a rearrangement followed by a reduction gives the final product, a ketone, with a changed carbon skeleton [924, 925]. The ketone is usually accompanied by small amounts of the corresponding hydrocarbon [924] or an a-hydroxy ketone [925]. 

Reactions reminiscent of pinacol reduction take place if esters are treated with sodium in aprotic solvents. The initially formed radical anion dimerizes and ultimately forms an a-hydroxy ketone, an acyloin. Such acyloin conden-... 

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. 

Metal-ammonia reduction of ketones. Swiss chemists have reported a detailed study of the mechanism of this reaction, using for the most part (-l-)- 3,3-D2] camphor as substrate. The conclusions drawn have some useful practical applications. The choice of metal (Li, Na, or K) has little effect on the course of reduction to the thermodynamically more stable diastereoisomeric alcohol. The most important conclusion is that pinacol reduction can be suppressed completely in Na-NH3 reductions by use of ammonium chloride as the proton source, a finding first reported by Murphy and Sullivan.2 This salt also partially suppresses pinacol formation in Li-NHj reductions. It also suppresses reduction of enolates, and thus should decrease racemization in reduction of chiral ketones. 

Pinacol reductive coupling.1 A couple prepared by sonication of zinc dust and CuCl2 in acetone-water (4 1) promotes coupling of enones and acetone to a, 3-unsaturated vic-diols. The reaction is slow in the absence of sonication. 

Symmetrical diols can be made by a radical reaction. Radical reactions are rarely much use in carbon-carbon bond formation as they often give poor yields and many products. They are of course useful in some FGI reactions in things like allylie bromination and in functionalising remote carbon atoms. If you want to read more about this see Tedder, Part 2, Chapter 11 or Carruthers, Chapter 4. One useful radical reaction is the pinacol reduction ... 

Due to the inherent dissymmetry of monosubstituted triquinacenes, dimerization of such compounds will generate a pair of coupling products (meso and dl) if the monomer is racemic. Only when bonding between optically pure triquinacenes of the same chirality results can it be guaranteed that the formation of meso dimer will be precluded. In their study of the pinacolic reduction of <2/-2,3-dihydrotriquinacen-2-one, Paquette and co-workers showed that approximately equal amounts of the dl diol 458 and meso isomer 459 resulted.405 When enantiomerically pure (+)-380 was used, 458 was the exclusive reductive coupling product because of enforced enantio-... 

Hydroxymethylation of carbonyl compounds. Alkyl chloromcthyl ethers reaet in the presence of Smh (2 equiv.) with ketones in THE to give adducts in 50-80% yield. The reaction with aldehydes is conducted in tetraethylcne glycol dimethyl ether, which suppresses pinacol reduction. Hydroxymethylation of carbonyl compounds can be effected by use of benzyl chloromcthyl ether followed by hydrogenolysis of the adduct. 

Allylic pinacols. Reduction of ketones bearing an electron-withdrawing group with TiCli in the presence of a,p-enals results in coupling to allylic pinacols in 45 85% yield. Example ... 

The reaction with zinc is most efficient in pyridine containing a trace of water, although piperidine, dimethyl-formamide, and other bases may replace pyridine, or ethane did may be used (zinc in acidic media gives bis-steroidal products resulting from a pinacolic reduction— see below). 

Crawford and co-workers " discovered a surprising combination for effecting dehydrogenation palladium charcoal and sulfur. The Diels-Alder adduct (3) was obtained by pinacol reduction of the tetralone (1), dehydration to (2) by refluxing... 

Phthalic acid, 259 Phthalic anhydride, 104 a-Picoline, 161 a-Picoline N-oxide, 161 Picolinic acid, 16 Picramic acid, 271 Picric acid, 271 Pinacol reduction, 7 Pinosylvin, 31 Piperazines, 322 Piperidine, 33, 291 2-Piperidone, 194 Pivaldehyde, 105 Podophyllotoxin, 337 Podophyllotoxone, 337 Polonovski reaction, 308 Polyisoprenoids, 300-301 Polymethoxybenzophenones, 30—31 Polymethylhydrosiloxane, 294 Polyphosphate ester (PPE), 229-230 Polyphosphoric acid, 227, 231—232 Potassium, 232, 233 Potassium acetate, 96 Potassium amide, 232—233, 310 Potassium azodicarboxylate, 100 Potassium r-butoxide, 26, 45, 47, 77-78, 85, 133, 188, 212, 222, 225, 233-234, 236, 246... 

Pinacol reduction. Pinacol reduction is generally carried out with amalgamated magnesium or aluminum in benzene. Schreibmann1 reports that higher yields are obtained with amalgamated aluminum in either methylene chloride or THF, in which the aluminum pinacolates are very soluble. They are thus easily separated from excess metal before hydrolysis to the pinacol. 

This section is concerned with radical dimerisations of this kind (22-23), mostly to make 1,2-difunctionalised compounds. Thus a 1,2-diol (24) could be made from two radicals (25) and this is indeed how it is made. The radicals (25) are generated by metal catalysed reduction of acetone. The product (24) is known as pinacol and the reaction is sometimes called pinacol reduction. The reaction works for most ketones, including enolisable ketones. 

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