SolutionsProtection of carbonyl groups
Exercise 1
How would you convert ethyl 4-oxocyclohexanecarboxylate into 4-(hydroxydiphenylmethyl)cyclohexanone? Say when protection and deprotection take place.
1) Ethylene glycol, TsOH, refluxing toluene with a Dean–Stark trap: the ketone becomes a dioxolane. 2) Excess PhMgBr (two equivalents add to the ester) and neutral aqueous work-up: tertiary alcohol. 3) Dilute aqueous acid (HCl, acetone): the acetal is hydrolysed. The acid should be mild so as not to dehydrate the tertiary alcohol.
Exercise 2
A compound has an aldehyde and a ketone. How would you reduce only the ketone? Propose one strategy with protection and one without.
With protection: the more reactive aldehyde selectively forms the acetal with one equivalent of ethylene glycol (or the dimethyl acetal with trimethyl orthoformate); the ketone is reduced with NaBH4 and the acetal hydrolysed. Without protection: the Luche reduction (NaBH4, CeCl3 in methanol) reduces ketones in the presence of aldehydes, because cerium promotes formation of the aldehyde hemiacetal with methanol, which masks it.