Does a Grignard reagent react with enones to give the 1,2- or 1,4- product?

[![Reaction of phenylmagnesium bromide with cyclohex-2-en-1-one](https://i.stack.imgur.com/TlOsu.png)](https://i.stack.imgur.com/TlOsu.png)


Cyclohexenone, an α,β-unsaturated ketone, is electrophilic at both the carbonyl carbon, as well as the β-carbon. So, it can either undergo 1,2-addition to give the allylic alcohol **1**, or 1,4-addition to give the ketone **2**.


Where does the Grignard reagent add to?




The correct answer is the 1,2-addition product (i.e. the allylic alcohol **1**). In general, Grignard reagents and organolithium reagents add directly to the carbonyl carbon, while organocuprates (organocopper reagents) add to the beta-position of an unsaturated ketone.


This exact transformation was reported by Akai and coworkers recently ([*Org. Lett.* **2010,** *12,* 4900](https://doi.org/10.1021/ol102053a)) and they obtained compound **1** in 95% yield (the supplementary information [(PDF)](http://pubs.acs.org/doi/suppl/10.1021/ol102053a/suppl_file/ol102053a_si_001.pdf) is free).


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The Grignard reaction, although very well examined, there are still arguments about the mechanism and the overall process. The reagent is usually best described via the [Schlenk equilibrium](https://en.wikipedia.org/wiki/Schlenk_equilibrium), but that is not only dependent on $\ce{X}$, but also on the solvent:


$$\ce{2RMgX <=> R2Mg + MgX2}$$


There also have been some dimeric structures reported, i.e. the symmetrical, the asymmetrical, and the alkyl bridging dimer. According to Milton Orchin[1] (and references therein) the latter is responsible for the formation of the above equilibrium.


[![Grignard dimers](https://i.stack.imgur.com/QyvYo.png)](https://i.stack.imgur.com/QyvYo.png)


There are many mechanism possible, two of them following a non-radical pathway are depicted below. In both cases, the 1,2-addition leads to the major product. The six-membered transition state (top route) has been proposed many times and employs the alkyl bridging dimer.[2] 


The bottom route considers only the monomeric Grignard reagent. Whichever pathway is taken, the result is the same: 1,2-addition, resulting in a tertiary alcohol, with the C=C double bond retained.


[![Mechanism](https://i.stack.imgur.com/d2jrF.png)](https://i.stack.imgur.com/d2jrF.png)




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**Notes and References**


It has been correctly pointed out by ron that Grignard agents cannot coexist with acid, as my previous draft suggested. Even water poses a big threat to the stability, as pointed out by yasir. I was a little confused about this, because adding a $\ce{Cu(I)}$ co-catalyst will result in the 1,4-product,[3] and I assumed the same would happen with an acid.


1. [M. Orchin, *J. Chem. Educ.*, **1989**, *66* (7), 586.](https://doi.org/10.1021/ed066p586)
2. See for example: [E. C. Ashby. *A detailed description of the mechanism of reaction of Grignard reagents with ketones*. International Conference on Organometallic Chemistry, ICOMC, Organometallic Chemistry, IX, University of Dijon, France, 1979-09-03–1979-09-07.](https://doi.org/10.1351/pac198052030545) Also available for free at [iupac.org](https://www.iupac.org/publications/pac/1980/pdf/5203x0545.pdf).
3. [M. S. Kharasch, and P. O. Tawney, *J. Am. Chem. Soc.*, **1941**, *63* (9), 2308–2316.](https://doi.org/10.1021/ja01854a005)


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