Diols from pinacol reaction

Diols, via Pinacol reaction, 10, 529 a-Diones, from Grignard reagents, 9, 55 DIOP, and chiral bisphosphane ligands, 10, 7 Diorganoditellurides halogenolysis, 9, 595... 

The conversion of pinacol (Expt 5.35) to t-butyl methyl ketone (pinacolone, Expt 5.98) under acid conditions exemplifies a general reaction of 1,2-diols (the pinacol-pinacolone rearrangement). The mechanism, formulated below, involves loss of water from the protonated 1,2-diol accompanied by a 1,2-nucleophilic shift of a methyl group. 

The same idea allows us to make symmetrical 1,2-diols 33 by the pinacol reaction. Again we avoid cations and anions by making both halves radicals. These are generated by addition of electrons from metals to aldehydes and ketones. So an electron from sodium adds to acetone to give a radical anion 35 that might dimerise to give 33. 

But how else might they have done it Perhaps equally obvious is to use the pinacol reaction to make the diol 68 and oxidise both alcohols. We shall now broaden the discussion by writing Ar for the substituents as many of the reactions have not in fact been done with o-tolyl substituents. Two of the best yielding methods are Mg in the presence18 of Me3SiCl and samarium iodide where the colour change from blue Sm(III) to yellow Sm(IL) is characteristic.19... 

Titanium can be used as the metal source of electrons in the pinacol reaction and, provided the reaction is kept cold and no tie ft for too long, diols can be isolated from the reaction (see the example at the end of the previous section). However, unlike magnesium or aluminium, titanium reacts... 

Eight-membered heterocyclic diols were prepared from acyclic dicarbonyls via pinacol reactions (Scheme 81 <2004TL253>). The cis- or trans-diol stereoselectivity was controlled by the low-valent metal catalyst used. For instance, when using Sml2, the cis-trans ratio 193 194 was 3 1 (Scheme 28 <2004TL579, 2004T10385>). This method is a viable alternative to the metathesis-dihydroxylation strategy presented earlier. 

The evidence for carbocation intermediates in the pinacol rearrangement is compelling for some substrates and conditions. Bunton" found that pinacol itself that was recovered from O-enriched aqueous sulfuric acid had incorporated an appreciable amount of solvent oxygen. Under these conditions the reaction goes to completion, i.e. the incorporation cannot be due to reversible formation of diol from pina-... 

Thus, it would seem that the chiral phosphoric acid s reinforcement (and potential acceleration) of this preferential reactivity profile ensured that virtually none of the undesired diastereomer of 36 was formed under the reaction conditions. It seems appropriate, therefore, in an enpirical sense to conclude that this increase in selectivity can be attributed to specific interactions between the diol moiety of the substrate and the chiral acid. Significandy, this notion may be applicable to other systems where such opportunities may exist. And, as a side note, the pinacol reaction process here may have biogenetic relevance as well, considering the structures of related natural products that are presumed to arise via acid-catalyzed processes from various oxidized forms of 38-40. In this case, starting diol 34 is the Mly oxidized version of these substrates (38-40) in terms of the double bond. 

Along with their work on the nickel-catalyzed Suzuki-Miyaura coupling of neopentylglycol boronic esters, Percec and coworkers examined the speed of transesterification of a cyclic arylboronic ester with a diol under anhydrous conditions. In both assays in Scheme 3.2, some transesterification had taken place after 10 h (equilibrium was not reached). This result shows that transesterification of cyclic boronic esters is always possible, even starting from pinacol esters. This should be kept in mind when considering reactions in the presence of alcohol solvents and water. 

Lithium bromide and lithium chloride can also enhance the reactivity of Sml2 in THF (Fuchs et ah, 1997 Miller et ah, 2000). Addition of anhydrous LiCl and LiBr to Sml2 resulted in rate enhancement and better yields in pinacol coupling of cyclohexanone. In the Barbier type reaction of 1-iodobutane with 2-octanone, the presence of LiBr and LiCl resulted in the formation of pinacol coupling product (diol from 2 moles of 2-octanone) as the major product rather than the nucleophilic addition of halide to ketone (eq. (52), table 8). 

The chiral diol 17 derived from tartaric acid is exploited in the titanium-catalyzed asymmetric pinacol coupling in the presence of Zn and MesSiCl to give the corresponding diol in 11-71 ee % [44], The chiral salen ligands 18-20 are used in the titanium-catalyzed enantioselective coupling reaction, which achieves the higher selectivity [45-47]. The chromium complex with TBOxH (21) efficiently catalyzes the asymmetric coupling reaction of both aromatic and aliphatic aldehydes [48]. 

Cross-coupling reactions of ArCOAr. Reaction of Yb(0) with diaryl ketones changes the reactivity of the carbonyl group from electrophilic to nucleophilic. Thus in the presence of this lanthanoid metal, diaryl ketones couple with other ketones, nitriles, and epoxides to give pinacols, a-hydroxy ketones, and 1,3-diols, respectively, via the intermediate a. 

The first total synthesis of ( )-sarcophytol B (5) from S./i-famesal (92), which was reported by McMurry et al. in 1989, used a low-temperature titanium-induced pinacol coupling reaction of 1,14-dialdehyde as the key step. They concluded that the natural sarcophytol B has the stereochemistry of a trans diol (Scheme 6-5). Li et al. reported on a concise total synthesis of ( )-sarcophytol B (5) from /i./i-famesol (91) by a low-valent titanium-mediated intramolecular McMurry... 

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