Ortholithiation mechanism

Af,Af-Dimethylcarbamates are unstable once ortholithiated, and rearrange rapidly by a carbamoyl transfer mechanism known as the anionic ortfio-Fries rearrangement . With Af,Af-diethylcarbamates, this rearrangement can be controlled the ortholithiated carbamate 64 is stable at —78°C but, on warming to room temperamre, rearranges to give a 2-hydroxybenzamide 65 (Scheme 33) °. ... 

Alkyl aryl ethers have a long history in lithiation reactions, and there are detailed reports on the mechanism (see section 2.3.1) and relative efficiency135 of the lithiation of anisole and its derivatives. Methyl aryl ethers are often lithiated in Et20, but THF can be just as effective. The stabilisation afforded to an ortholithiated anisole relative to a /rara-lithiated anisole can be judged from their relative heats of protonation by s-BuOH.233... 

The Reimer-Tiemann reaction used to be an important way of making ortho-substituted phenols, but the yields are often poor, and modern industly is wary of using large quantities of chlorinated solvents. On a small, laboratory scale it has largely been superseded by ortholithiation (Chapter 9) and by modern methods outside the scope of this book. The mechanism probably goes something like this. 

Mechanisms and catalysis ch12 special about aromatic compounds Regioselectivity and ortholithiation ch24... 

The mechanism of Bu Li/TMEDA mediated arene ortholithiation has been studied by B3LYP/6-31G optimisations of reactants and proposed transition structures. Activation energies using MeLi as a computational model for Bu Li have been obtained for different proposed mechanisms including transition structures based upon triple ions of the form [RiLi]" [Li(TMEDA)2]. It is shown that alkoxy-lithium interactions are of only minor importance. 

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