Protecting groups, functionalized Grignard

With the alcohol protected, preparation of the Grignard reagent can proceed, and this can then react with the ketone carbonyl in a nucleophilic addition. The protecting group can then be removed by treatment with acid, to restore the hydroxyl function. This also involves a tertiary carbocation that is subsequently quenched with water. 

In aromatic systems, oxazolines can have three different functions (Fig. 4). Firstly, they can be used as protecting groups for carboxylic acids. Secondly, they activate even electron-rich aromatic systems for nucleophilic substitution. Fluorine or alkoxy groups in the ortho position can be substituted by strong nucleophiles such as Grignard reagents. Thirdly, when biaryl compounds with axial chirality are synthesized in these reactions, oxazolines can induce the formation of only one atropisomer with excellent selectivity. These three qualities were all used in the synthesis of 20, a precursor of the natural product isochizandrine [10]. 

Meyers Al, Temple DL et al (1974) Oxazolines. XL Synthesis of functionalized aromatic and aliphatic acids. Useful protecting group for carboxylic acids against Grignard and hydride reagents. J Org Chem 39 2787-2793... 

By protecting sensitive functional groups like ketones it becomes possible to make reagents that would otherwise be unstable. In a synthesis of the natural product porantherine, a compound based on the structure in the margin was needed. As it s a symmetrical secondary alcohol (see p. 216), a good way to make it is to add a Grignard reagent twice to ethyl formate. 

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