A. Which of the following tertiary alcohols cannot be...

a. Which of the following tertiary alcohols cannot be prepared from the reaction of an ester with excess Grignard reagent?
b. For those alcohols that can be prepared by the reaction of an ester with excess Grignard reagent, what ester and what Grignard reagent should be used?

Key Concepts

Strategic Selection of Ester and Grignard Reagent

The overall strategy involves selecting an ester and a Grignard reagent whose alkyl (or aryl) groups combine to afford the desired tertiary alcohol. The choice is dictated by the need to have one alkyl group in the ester and the remaining two groups contributed by the Grignard reagent. This concept underscores the importance of retrosynthetic planning and reagent selection to ensure that, after two sequential nucleophilic additions, the desired tertiary alcohol is obtained.

Mechanistic Limitations and Steric Considerations

Some tertiary alcohols cannot be prepared using this method due to steric hindrance or incompatibility in the reaction pathway. If the intended tertiary alcohol would require the formation of extremely congested centers or would form from an ester whose structure is not amenable to double addition of a Grignard reagent, then the reaction may not proceed effectively. Understanding these limitations is critical when planning a synthesis route involving Grignard reactions with esters.

Nucleophilic Acyl Substitution Mechanism

At the heart of the reaction is the nucleophilic attack performed by the Grignard reagent on the electrophilic carbonyl carbon of the ester, leading to a tetrahedral intermediate. The intermediate then collapses, ejecting a good leaving group (generally an alkoxide from the ester), which sets the stage for further nucleophilic addition. This two-step addition process is key in generating tertiary alcohols when using a Grignard reagent with esters.

Grignard Reaction with Esters

This concept covers the mechanism by which esters are converted to tertiary alcohols using Grignard reagents. In this reaction, an ester reacts with an excess of a Grignard reagent; the first equivalent adds to the carbonyl to form a ketone intermediate after the departure of a leaving group, and a second equivalent then adds to that ketone to form a tertiary alkoxide. Upon acidic workup, the alkoxide is protonated to yield the final tertiary alcohol.

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