Pinacols unsymmetrical

The pinacol rearrangement is frequently observed when geminal diols react with acid. The stmcture of the products from unsymmetrical diols can be predicted on the basis of ease of carbocation formation. For example, l,l-diphenyl-2-metltyl-l,2-propanediol rearranges to... 

Unsymmetrical diols typically give a mixture of pinacol products. For example, the diol shown below might give eight distinct products (counting cis and tmns diastereomers as distinct products). In fact, it gives only the two shown. 

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. " ... 

Product 117 is a convenient starting compound for the subsequent modification of photochromes. Publication (09TL1614) gives an efficient synthetic route to both symmetrical 118 and unsymmetrical 119 phenyl-substituted dihetarylethenes bearing amino, hydroxy, or carboxy groups based on a Suzuki reaction of dichloride 117 with commercially available substituted boronic acids (or their pinacol esters) in a dimethyl ether (DME)-H20 mixture (4 1). For the symmetrical products, the yields are 85-95% for the unsymmetrical products, they are 60%. 

The limitation of the pinacol is the need for symmetry. This section and the next suggest ways of avoiding this problem. Unsymmetrical epoxides are easily made from alkenes and open with Lewis acid catalysis to give the more substituted of the two possible cations.9 Even such a weak Lewis acid as LiBr opens the epoxide 51 to give the tertiary cation 52 which rearranges by ring contraction to the aldehyde 53. The authors prefer to have the bromocompound 54 as an intermediate.10... 

Fig. 14.15. Regioselectivity of the pinacol rearrangement of an unsymmetrical glycol. The more stable carbenium ion is formed under product development control. Thus, the benz-hydryl cation B is formed here, while the tertiary alkyl cation D is not formed.

Stepwise double coupling of two different arylboronic acids with a dihaloarene afforded one-pot, two-step method for synthesizing unsymmetrical teraryls, quateraryls, and other higher order polyaryls.882 The first total synthesis of dragmacidin D involved a sequential double coupling of two different pinacol 3-indoleboronic esters (ArBpin Equation (207)).882... 

Tetraalkyl- and tetraatyl-ethylene glycols (pinacols) are made by reduction of ketones with active metals such as sodium, magnesium, and aluminum. The reaction is only fair for aliphatic and alicyclic ketones. Acetone, methyl ethyl ketone, cyclopentanone, and cyclohexanone all give less than 0% yields of pinacols. Mixtures of ketones are reduced to unsymmetrical pinacols. An active zinc-copper couple has been employed in the reduction of several simple olefinic aldehydes to dieodiols, e.g., crotonaldehyde to dipropenyl glycol,... 

Indeed, it has been found that unsymmetrical pinacols can be generated in surprisingly high yields by treating 1 equiv. of a diaryl ketone with 1 equiv. of ytterbium metal, and subsequently quenching the resultant reaction mixture with a variety of aldehydes and ketones (equation 100). Yields in most cases are high, and this particular transformation represents one of the very few ways in which such a process can be accomplished efficiently. Reaction of benzophenone/ytterbium with 2-cyclohexen-l-one provides mixtures of 1,2- and 1,4-addition products, together with some benzhydrol. 

The enantioselective total synthesis of the polysubstituted tetrahydrofuran (-)-citreoviral, the unnatural enantiomer, was synthesized by L.E. Overman et al. The Prins-pinacol rearrangement of an allylic 1,2-diol with an unsymmetrical ketone proceeded with high stereoselectivity. The jb/s(trimethylsilyl)-1,2-diol was condensed with the dimethyl acetal of the unsymmetrical ketone in the presence of catalytic amounts of TMSOTf, which yielded a nearly 1 1 mixture of the corresponding acetal and rearrangement product. The acetal was converted to the desired tetrahydrofuran product upon exposure to tin tetrachloride. 

Other unsymmetrical diols, prepared (inefficiently) by the coupling of mixtures of ketones, have been studied. The preferred cation argument is also found to be applicable to mixed medium-ring analogs, i.e. the kinetically favored pinacol rearrangement product is that predicted by consideration of the relative stabilities of the two possible, initially formed, carbocations. ° Earlier work with these compounds may have given misleading results due to product instability. To illustrate, Mundy observed that (24) is converted to (25) as the temperature is increased. 

Although its utility appears to be limited, Mukaiyama et al. found that the chloropyrimidinium fluo-rosulfate (53) can effect both functionalization and subsequent pinacol rearrangement in a one-pot procedure. Unsymmetrical secondary-tertiary diols give the products expected of derivatization at the secondary hydroxy group. A major side reaction is elimination. 

In the pinacol coupling, two ketones are reductively coupled to give a 1,2-diol. (Compare the photochemical pinacol coupling discussed in Section 5.3.1.) The two ketones are usually identical, but intramolecular dimerizations can give unsymmetrical 1,2-diols. The reaction proceeds by electron transfer to the ketone to give a ketyl radical anion. This compound dimerizes to give the 1,2-diol. 

It is interesting that with the unsymmetrical pinacols (XXIII) these migrational aptitudes not only do not agree at all with experiment but also it is difficult even to predict the major product of the reaction.19,20... 

UNSYMMETRICAL, 11, 88 Picryl chloride, 13, 37 Pimelic acid, 11, 43 Pinacol hydrate, 13, 111 Pinacolone, 14, 88 Piperonal, 10, 82 Piperonylic ACID, 10, 82 Pivaloin, 13, 26... 

Laude and Wiemann155 reported the reduction of mixtures of ketones to unsymmetrical pinacols. 

Ligands 5 and 6 are particularly efficacious for the borylation of aryl chlorides to pinacol boronate esters, thus allowing the direct one-pof synthesis of unsymmetrical biaryls from two aryl chlorides (Equation 2.23) [41]. Due to the wide breadth and scope that this family of biaryldialkylphosphine Hgands offers for palladium-catalyzed couplings of aryl chlorides, many are commercially available and aU are highly crystalline, air-stable solids, and hence easy to use. 

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