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For my organic chemistry exam I needed to synthesize cylcohexanone and in one of the steps a Diels-Alder reaction was required. I chose to use vinyl alcohol followed by an elimination reaction to get the desired product.

My professor said that this could not work because a dienophile needs to be electron deficient and that vinyl alcohol is electron rich. Is there any argument I can make as to why the reaction would actually work? It was a reaction of diene + vinyl alcohol to yield cyclohexanol.

The actual answer he said was to use two dienes, one as the diene and the other as the dienophile followed by a few subsequent reactions ending with ozonolysis to get cyclohexanone.

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    $\begingroup$ You professor is correct for common setting. Inverse electron demand is possible, but requires strongly electron-deficient dienes, which are not all that abundant and usually imply nitrogen or oxygen participating in -ene part. $\endgroup$ – permeakra Dec 13 '16 at 15:21
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    $\begingroup$ Vinyl alcohol does not exist in appreciable concentration under normal conditions. It exists in a keto-enol tautomeric equilibrium, with the equilibrium lying far, far to the keto isomer (acetaldeyde) side. However, you could use a vinyl alcohol "equivalent" such as vinyl acetate. Vinyl acetate behaves like a typical dienophile in the Diels-Alder reaction. After the Diels-Alder step you would need to simply hydrolyze the product to obtain the desired cyclohexenol. $\endgroup$ – ron Dec 13 '16 at 16:04
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Firstly, your Diels-Alder products are missing the double bond in the ring (formed between what was formerly C-2 and C-3 of the diene). You could always simply hydrogenate it down to the alkane, but I feel like this would present some selectivity issues in your professor's suggested synthetic route, especially since a terminal double bond is more likely to be hydrogenated than an internal double bond (sterics), and an internal double bond more prone to ozonolysis than a terminal double bond (more electron-rich).

Anyway, ron pretty much said what there is to say about "vinyl alcohol". It doesn't exist in any appreciable quantity, since the keto form acetaldehyde is much more stable (see another of ron's answers here):

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Apart from what ron suggested (vinyl acetate), another alternative is to use 2-chloroacrylonitrile as the dienophile. The cyano group is electron-withdrawing, so the the usual requirement for an electron-poor dienophile is met. Treatment with hydroxide will unmask the ketone functionality, see for example the second and third steps in Corey's prostaglandin synthesis. (For a possible mechanism, see Mechanism for basic hydrolysis of α-chloronitrile to ketone?.) You can then hydrogenate the C=C bond chemoselectively to get the desired product, cyclohexanone.

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2-Chloroacrylonitrile is what is called a "masked ketene". Ketenes don't undergo [4+2] cycloadditions such as the Diels-Alder reaction because they have a much greater propensity to react in a [2+2] fashion (even cyclopentadiene, an excellent diene in the Diels-Alder, reacts with ketenes via a [2+2]). So, these reagents are essentially surrogate ketenes: with one additional step (hydrolysis in this case), you can access what is formally a ketene+diene Diels-Alder adduct. There's a nice review of masked ketene reagents here.

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  • $\begingroup$ Just wondering, how exactly does hydroxide unmask the ketone functionality? Two substitutions, substituting CN and Cl with OH, then the hydrate converts to ketone? $\endgroup$ – Tan Yong Boon Nov 29 '18 at 3:40
  • $\begingroup$ @TanYongBoon, there’s a link in the answer. $\endgroup$ – orthocresol Nov 29 '18 at 9:27

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