Alkenes pinacol coupling reactions

Curiously, the relative stereochemistry between the carboxylate and the adjacent hydroxy group in the Sml2-mediated intramolecular pinacolic coupling reaction is opposite to that observed in the intramolecular Barbier reactions and ketone-alkene reductive coupling reactions discussed previously (compare... 

The initial step of the coupling reaction is the binding of the carbonyl substrate to the titanium surface, and the transfer of an electron to the carbonyl group. The carbonyl group is reduced to a radical species 3, and the titanium is oxidized. Two such ketyl radicals can dimerize to form a pinacolate-like intermediate 4, that is coordinated to titanium. Cleavage of the C—O bonds leads to formation of an alkene 2 and a titanium oxide 5 ... 

The ketyl radical anion intermediates can be exploited in carbon-carbon bond-forming reactions. Intermolecular and intramolecular pinacol couplings between the carbonyl groups of ketones and aldehydes are well known (Chapter 5, Section 5.1), as are intermolecular and intramolecular carbonyl-alkene couplings (Chapter 5, Section 5.2). 

In 1977, McMurry and Kees [152] developed a titanium-induced intramolecular coupling procedure to form cycloalkenes from dicarbonyl compounds. Mechanistically, as shown in Scheme 85, the coupling reaction proceeds by an initial pinacol dimerization of the dicarbonyl 253 to 254, followed by titanium-induced deoxygenation to afford alkene 255. 

From a synthetic point of view, bond forming steps are the most important reactions of radical ions [202]. Several principle possibilities have been described in Section 8.1 and are summarized in Scheme 52. Many carbo- and heterocyclic ring systems can be constructed by (inter- and intramolecular) radical addition to alkenes, alkynes, or arenes. Coupling of carbonyl radical anions leads to pinacols either intra-or inter-molecular which can be further modified to give 1,2-diols, acyloins or alkenes. Radical combination reactions with alkyl radicals afford the opportunity to synthesize macrocyclic rings. These radical ion-radical pairs can be generated most efficiently by inter- or intramolecular photoinduced electron transfer. 

Formation of the alkene is thought to proceed via initial formation of a Ti-pinacolate followed by its deoxygenation to produce the double bond. In support of the proposed mechanistic scheme are the facts that (1) pinacol intermediates can be isolated when the coupling reaction is carried out at 0 °C rather than at solvent reflux temperature and (2) treatment of isolated pinacols with low-valent titanium at 60 °C deoxygenates them to the corresponding alkenes. 

The reductive coupling of carbonyl compounds, especially ketones, to give pinacols is an important method for the formation of vicinally functionalized C—C bonds. In addition, the related coupling of carbonyls to give alkenes, the McMurry reaction, provides a complementary route for C=C bond elaboration." ... 

Carbon-Carbon Bond Formation - A number of anodic and cathodic coupling reactions are known. The Kolbe oxidation of carboxylate salts and pinacol formation from ketone reduction are familiar examples. Somewhat less well known is the reductive coupling of activated alkenes. 

One of the most powerful methods for constructing a carbon-carbon bond is the reductive coupling of carbonyl compounds giving olefins and/or 1,2-diols [71]. Of these methods, the pinacol coupling [72], which was described in 1859, is still a useful tool for the synthesis of vicinal diols. The corresponding products of this reaction can be used as intermediates for the preparation of ketones and alkenes [73]. More importantly, this methodology has been applied to the synthesis of biologically active natural compounds [74]. 

The McMurry coupling reaction generally leads to three alkenes, two symmetrical products and one asymmetrical. However, depending on the reaction conditions, especially changes in temperature and medium, other secondary compounds are also formed, in particular, the transposition product and pinacol [129]. These two new species were synthesized and studied by orienting the reaction more specifically in their favor. The IC50 values of these compounds are collected in Table 42.7. 

The effects of a number of additives on the TiCU- and TiCls-reducing agent systems have been considered with a view to enhancing the formation of the alkene products of the coupling reaction or, on the contrary, to stop it at the pinacol stage. 

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