12.13:
Protecting Groups for Aldehydes and Ketones: Introduction
The carbonyl functional group in different compounds like aldehydes, ketones, esters, acids, and acid chlorides can be reduced to the hydroxyl group to give corresponding alcohols.
However, what happens if a compound has multiple reducible functional groups and selective reduction of one group over the other is desired?
While reducing a polyfunctional compound, for instance, a compound containing an ester and a ketone, the more reactive ketone gets preferentially reduced to an alcohol.
Consequently, selective reduction of the ester becomes difficult to accomplish in a single step.
The selective transformation of ester to alcohol can be achieved by protecting the more reactive ketone carbonyl group, then reducing the ester, and, finally, removing the protecting group to regenerate the ketone.
This selective protection is similar to protecting a car's windows with tapes to prevent them from getting painted when spray-painting a car's body.
Acetals and thioacetals are the preferred protecting groups for aldehydes and ketones because they can be easily formed and selectively removed under mild conditions, and they pull through several diverse reaction conditions.
12.13:
Protecting Groups for Aldehydes and Ketones: Introduction
Protecting groups are compounds that can bind to a specific functional group in the presence of other functional groups to protect them from undesired chemical reactions. These compounds can selectively bind to particular functional groups and advance chemoselective reactions in polyfunctional systems (Figure 1). After the functional group has served its purpose, it is removed by reacting it with specific compounds.
The aldehydes and ketones can be selectively protected in the presence of other carbonyl groups such as esters or acids based upon their reactivity. This is important for the manipulation of one functional group over the other.
For instance, when carrying out a reduction reaction in the presence of an ester and a ketone, the ketone will always be preferentially reduced to alcohol. In order to achieve the selective reduction of an ester to an alcohol while keeping the ketone unaffected, the ketone group needs to be protected (Figure 2, first step). After the ketone is protected, the ester is reduced to an alcohol using LiAlH4 (Figure 2, second step). Finally, the ketone is regenerated by removing the protecting group (Figure 2, third step).
Acetals and thioacetals are the most commonly used protecting groups for aldehydes and ketones and can be easily removed. In addition, they are resistant to chemical species such as nucleophiles, or reducing and oxidizing agents.