View source for Chemistry:Pinacol coupling reaction

{{Short description|Organic chemical reaction}}
{{Reactionbox|Type=Coupling reaction|NamedAfter=[[Chemistry:Pinacol|Pinacol]]|Section1={{Reactionbox Identifiers|OrganicChemistryNamed=pinacol-coupling-reaction}}}}
[[Image:Pinacol coupling of benzaldehyde.png|right|425px|thumb|The Pinacol coupling reaction]]
A '''pinacol coupling reaction''' is an [[Chemistry:Organic reaction|organic reaction]] in which a carbon–carbon bond is formed between the carbonyl groups of an [[Chemistry:Aldehyde|aldehyde]] or a [[Chemistry:Ketone|ketone]] in presence of an electron donor in a [[Biology:Radical|free radical]] process.<ref>{{cite journal | vauthors = Fittig R | journal = Justus Liebigs Annalen der Chemie | volume = 110 | pages = 23–45 | year = 1859 | doi = 10.1002/jlac.18591100103 | title = Ueber einige Producte der trockenen Destillation essigsaurer Salze | trans-title = On some products of the dry distillation of acetate salts | language = German | url = https://zenodo.org/record/1427129 }}</ref> The reaction product is a [[Chemistry:Vicinal|vicinal]] [[Chemistry:Diol|diol]]. The reaction is named after [[Chemistry:Pinacol|pinacol]] (also known as 2,3-dimethyl-2,3-butanediol or tetramethylethylene glycol), which is the product of this reaction when done with [[Chemistry:Acetone|acetone]] as reagent. The reaction is usually a homocoupling but intramolecular cross-coupling reactions are also possible. Pinacol was discovered by Wilhelm Rudolph Fittig in 1859.

==Reaction mechanism==
The first step in the [[Physics:Reaction mechanism|reaction mechanism]] is a [[Chemistry:One-electron reduction|one-electron reduction]] of the carbonyl group by a [[Chemistry:Reducing agent|reducing agent]] —such as [[Chemistry:Magnesium|magnesium]]— to a [[Chemistry:Ketyl|ketyl]] radical anion species. Two ketyl groups react in a [[Chemistry:Coupling reaction|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 Mg<sup>2+</sup> ion. This complex is broken up by addition of water with formation of [[Chemistry:Magnesium hydroxide|magnesium hydroxide]]. The pinacol coupling can be followed up by a [[Chemistry:Pinacol rearrangement|pinacol rearrangement]]. A related reaction is the [[Chemistry:McMurry reaction|McMurry reaction]], which uses [[Chemistry:Titanium(III) chloride|titanium(III) chloride]] or [[Chemistry:Titanium(IV) chloride|titanium(IV) chloride]] in conjunction with a reducing agent for the formation of the metal-diol complex, and which takes place with an additional deoxygenation reaction step in order to provide an [[Chemistry:Alkene|alkene]] product.

:[[Image:Pinacol reaction mechanism.svg|600px]]

==Scope==
Benzophenone may undergo the pinacol coupling photochemically.<ref>{{OrgSynth | prep = cv2p0071 | title = Benzopinacol | vauthors =  Bachmann WE | collvol = 2 | collvolpages = 71 | year = 1943}}</ref> Benzaldehyde may also be used as a substrate with the use of catalytic [[Chemistry:Vanadium(III) chloride|vanadium(III) chloride]] and [[Chemistry:Aluminium|aluminium]] metal as the stoichiometric reductant.<ref>{{cite journal | vauthors = Xu X, Hirao T | title = Vanadium-catalyzed pinacol coupling reaction in water | journal = The Journal of Organic Chemistry | volume = 70 | issue = 21 | pages = 8594–8596 | date = October 2005 | pmid = 16209617 | doi = 10.1021/jo051213f }}</ref> This heterogeneous reaction in water at [[Physics:Room temperature|room temperature]] yields 72% after 3 days with 56:44 [[Chemistry:Diastereomer|dl]]:[[Chemistry:Meso compound|meso]] composition.

In another system with benzaldehyde, [[Chemistry:Montmorillonite|Montmorillonite]] K-10]] and [[Chemistry:Zinc chloride|zinc chloride]] in aqueous THF under [[Physics:Ultrasound|ultrasound]] the reaction time is reduced to 3 hours (composition 55:45).<ref>{{cite journal | title = Pinacolization of aromatic aldehydes using Zn/montmorillonite K10-ZnCl<sub>2</sub> in aqueous THF under ultrasound | vauthors = Hongjun Z, Jitai L, Yanjiang B, Tongshuang L | journal = Chemical Journal on Internet | year = 2003 | volume = 5 | issue = 1 | pages = 8 | url = http://www.chemistrymag.org/cji/2003/051008ne.htm | archive-url = https://web.archive.org/web/20021121001218/http://www.chemistrymag.org/cji/2003/051008ne.htm | url-status = dead | archive-date = 2002-11-21 }}</ref> On the other hand, certain [[Chemistry:Tartaric acid|tartaric acid]] derivatives can be obtained with high diastereoselectivity in a system of [[Chemistry:Samarium(II) iodide|samarium(II) iodide]] and [[Chemistry:Hexamethylphosphoramide|HMPA]].<ref>{{cite journal | title = Asymmetric synthesis by stereocontrol | vauthors = Kim YH, Kim SM, Youn SW | journal = Pure and Applied Chemistry | volume = 73 | issue = 2 | pages = 283–286 | year = 2001 | doi = 10.1351/pac200173020283| doi-access = free }}</ref>

A titanium-catalyzed [[Physics:Photoredox catalysis|photocatalytic]] approach was also developed: the use of catalytic [[Chemistry:Titanocene dichloride|titanocene dichloride]] in the presence of a red-absorbing organic dye as the [[Physics:Photosensitizer|photosensitizer]], and [[Chemistry:Hantzsch ester|Hantzsch ester]] as the terminal reducing agent, enabled the homocoupling reactions of a wide variety of aromatic aldehydes in [[Chemistry:Trifluorotoluene|trifluorotoluene]] under orange-light irradiation, with high yields and diastereoselectivities (more than 20:1 dl:meso). An enantioselective version (up to 92% [[Chemistry:Enantiomeric excess|e.e.]]), using catalytic amounts of a chiral titanium [[Chemistry:Salen ligand|salen]], was also developed.<ref>{{cite journal | vauthors = Calogero F, Magagnano G, Potenti S, Pasca F, Fermi A, Gualandi A, Ceroni P, Bergamini G, Cozzi PG | display-authors = 6 | title = Diastereoselective and enantioselective photoredox pinacol coupling promoted by titanium complexes with a red-absorbing organic dye | journal = Chemical Science | volume = 13 | issue = 20 | pages = 5973–5981 | date = May 2022 | pmid = 35685797 | pmc = 9132033 | doi = 10.1039/D2SC00800A }}</ref>

Two examples of pinacol coupling used in [[Chemistry:Total synthesis|total synthesis]] are the [[Chemistry:Mukaiyama Taxol total synthesis|Mukaiyama Taxol total synthesis]] and the [[Chemistry:Nicolaou Taxol total synthesis|Nicolaou Taxol total synthesis]].

''p''-Hydroxy[[Chemistry:Propiophenone|propiophenone]] is used as the substrate in the synthesis of [[Chemistry:Diethylstilbestrol|diethylstilbestrol]].

An unsymmetrical pinacol coupling reaction between para-chloro-acetophenone and acetone was employed to give [[Chemistry:Phenaglycodol|phenaglycodol]] in a 40% yield.

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
*{{OrgSynth | prep = cv1p0459 | title = Pinacol Hydrate | | collvol = 1 | collvolpages = 459 | year = 1941 | vauthors  = Adams R, Adams EW }}
{{refend}}

[[Category:Addition reactions]]
[[Category:Free radical reactions]]
[[Category:Carbon-carbon bond forming reactions]]

{{Sourceattribution|Pinacol coupling reaction}}