Reviews and Accounts ARKIVOC 2012 (i) 134-151
The 1,2-diol unit is one of the most ubiquitous functional groups in bioactive substances and the pinacol coupling has been playing an important role in the synthesis of pharmacologically
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important agents (e.g. taxol,cotylenol,HIV-I protease). Other important approaches to vicinal diols, such as epoxide ring opening and olefin dihydroxylation, require the preexistence of the central carbon-carbon bond in the starting materials.
Since its first report, a number of reproducible and high yielding protocols were described.4 Virtually all of them involve the use of metals in a low oxidation state acting in single electron transfer (SET) processes.
The recognition of the basic factor that influences the stereochemical outcome of the reaction permitted a high level of control in the distribution of diasteroisomeric adducts. More recently, enantioselective approaches have been developed for the successful dimerization of carbonyl compounds. Efficient catalytic methodologies have also been proposed. All these developments however, are to much of an extent, limited to intramolecular coupling or to homocoupling of an intermolecular reaction. These aspects are very properly discussed in an
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excellent recent reviews.
Comparatively, there is many fewer reports of intermolecular cross coupling pinacol reaction. Despite of the introduction of some promising methodologies developed for this aim, the efficient and wide scoping cross fashion of the reaction remains a great challenge. This account concerns to the efforts, advances and challenges involved in pinacol cross coupling reaction of two different carbonyl components.
2. Seminal Work Scheme 2 shows the basic accepted mechanism of pinacol coupling promoted by low-valent metals. The first step consists in the formation of a ketyl radical by the electron transfer from the metal to carbonyl compound. The subsequent C-C bond forming step could takes place from two metal-bonded ketyl radicals or through a pseudo-bridged intermediate in an intramolecular fashion. When the dimerization of two such radicals operates through a pseudo-bridged metal atom, the threo selectivity in the product predominates, due to steric reasons. On the other hand, when two such species couple through a non-bridged intermediate, the formation of the erythro product is favoured.5
Under these mechanistic backgrounds, the efficiency of cross coupling of two different carbonyls with similar reduction potentials is intrinsically limited. Thus, good yields of desired mixed 1,2-diols could not be expected unless in cases where one of the two carbonyls components is electronically activated or when an excess of one of them is employed.
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