# Synthesis of 2-benzylcyclohexan-1-ol from cyclohexanone

There are no conditions given and a mechanism is required.

I first thought it could be along the lines of Claisen rearrangement but that needs an aromatic ring. Since the Claisen rearrangement can't be used I considered a ($\mathrm{S_N2}$) reaction of benzyl bromide by the alpha carbon followed by reduction of the carbonyl.

Making a carbon-carbon bond at the alpha position of a carbonyl suggests using some kind of enolate chemistry. In contrast to an SN2 type reaction with an alkyl halide (which can give over-alkylation and competitive O-alkylation), an aldol condensation is a reliable way to construct the requisite C-C bond. Here cyclohexanone reacted with benzaldehyde under basic conditions gives an enone. Two subsequent reduction steps, hydrogenation followed by hydride addition to the ketone, give the target compound.

• However you would probably have to be concerned about dialdol here.
– Jan
Jan 7 '16 at 20:52
• @Jan Yes, I would... SciFinder had lots of examples of mono-aldol, and there's probably enough of a reactivity difference between cyclohexanone and the mono-aldol product to get good enough selectivity here. Way better than alkylation at least. Jan 7 '16 at 21:07
• Hmm, wouldn't NaBH4 probably produce the saturated alcohol directly from the α,β-unsaturated carbonyl? Jan 3 '17 at 18:33
• @orthocresol You might be right... I thought NaBH4 was pretty selective for the ketone, but quick Google searches support what you're suggesting. Looking thru SciFinder for similar transformations, it looks like more commonly people reduce the ketone first with hydride (NaBH4 or LAH) and then follow up with hydrogenation. I'm guessing that hydride will give a mixture of the fully reduced and the allylic alcohol. In practice, you're right. Try NaBH4 first, and if it goes all the way, great. If not, hydrogenation is easy and will finish it off. Jan 3 '17 at 19:43
• ...or hydrogenate enone over PtO2 or Ni(R) to get double reduction. Apr 8 '18 at 18:38

Ok so I found an answer:

• Deprotonate at the alpha carbon using LDA which gives a negative charge.
• This then attacks $\ce{BrCH2Ph}$ at the $\ce{CH2}$ and kicks off the bromine in the process ($\mathrm{S_N2}$).
• Then to form the alcohol the ketone is reduced using $\ce{LiAlH4}$ using THF as a solvent.
• Alkylation of an enolate is not a reliable reaction. You have to be concerned about over-alkylation and O-alkylation. There are better approaches to this target. Dec 9 '15 at 15:44
• How would one prevent over alkylation? Should I have introduced a protecting group first like a ketal for the carbonyl? How would I protected the other alpha carbon? @jerepierre Dec 9 '15 at 17:30
• You can treat cyclohexanone with dimethyl carbonate (THF, NaH) to give the anion of a beta-ketoester. Now alkylate with benzyl bromide followed by aqueous acid hydrolysis and decarboxylation. Extra step but more selective than direct alkylation. One might consider an enamine alkylation. Apr 8 '18 at 18:44