Pinacol coupling reaction

 A pinacol coupling reaction is an organic reaction in which a carbon-carbon covalent bond is formed between the carbonyl groups of an aldehyde or a ketone in presence of an electron donor in a free radical process ^[1]. The reaction product is a vicinal diol. The reaction is named after the product of this reaction with acetone, pinacol (also 2,3-dimethyl-2,3-butanediol or tetramethylethylene glycol). The reaction is usually a homocoupling but intramolecular cross-coupling reactions are also possible. Pinacol was discovered by Wilhelm Rudolph Fittig in 1859.

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Reaction mechanism

The first step in the reaction mechanism is one-electron reduction of the carbonyl group by a reducing agent such as magnesium to a ketyl radical anion species. Two ketyl groups react in a coupling reaction yielding a vicinal diol with both hydroxyl groups deprotonated. Addition of water or another proton donor gives the diol. With magnesium as an electron donor, the initial reaction product is a 5-membered cyclic compound with the two oxygen atoms coordinated to the oxidized Mg²⁺ ion. This complex is also broken up by addition of water with formation of magnesium hydroxide. The pinacol coupling can be followed up by a pinacol rearrangement. The alternative McMurry reaction with titanium trichloride gives deoxygenation of the vicinal diol to an alkene.

Scope

The Pinacol coupling of benzaldehyde can be carried out in water with vanadium trichloride and aluminium as co-reductant in order to maintain the catalytic cycle ^[2]. This heterogeneous reaction in water at room temperature yields 72% after 3 days with 56:44 dl:meso composition. In another system with benzaldehyde, Montmorillonite K-10 and zinc chloride in aqueous THF under ultrasound the reaction time is reduced to 3 hours (composition 55:45) ^[3]. On the other hand certain tartaric acid derivatives can be obtained with high diastereoselectivity in a system of samarium(II) iodide and HMPA ^[4].

Two examples of pinacol coupling used in total synthesis are the Mukaiyama Taxol total synthesis and the Nicolaou Taxol total synthesis.

References

1. ^  R. Fittig. Justus Liebigs Ann. Chem. 110, 23–45 (1859).
2. ^  Vanadium-Catalyzed Pinacol Coupling Reaction in Water Xiaoliang Xu and Toshikazu Hirao J. Org. Chem.; 2005; 70(21) pp 8594 - 8596 doi:10.1021/jo051213f
3. ^  Pinacolization of aromatic aldehydes using Zn/montmorillonite K10-ZnCl2 in aqueous THF under ultrasound Zang Hongjun, Li Jitai, Bian Yanjiang, Li Tongshuang Chemical Journal on Internet Jan. 1, 2003 Vol.5 No.1 Online Article
4. ^  Asymmetric synthesis by stereocontrol Yong Hae Kim, Sam Min Kim, and So Won Youn Pure Appl. Chem., Vol. 73, No. 2, pp. 283–286, 2001. Online Article