Chemoselectivity thermodynamic control

The relative reactivity of the alcohol and amine in the example just given could be overturned by conducting a reaction under thermodynamic control. In kinetically controlled reactions, the idea that you can conduct chemoselective reactions on the more reactive of a pair of functional groups— carbonyl-based ones, for example—is straightforward. But what if you want to react the less reactive of the pair There are two commonly used solutions. The first is illustrated by a compound needed by chemists at Cambridge to study an epoxidation reaction. They were able to make the following diol, but wanted to acetylate only the more hindered secondary hydroxyl group. 

Among the methods for their preparations, two reactions described by House have been employed widely 7 a thermodynamically controlled sil-ylation with chlorotrimethylsilane/triethylamine in hot dimethylformam-ide or a kinetically controlled reaction which involves lithiation with a lithium dialkylamide followed by quenching with the chlorosilane. Each method has its own merits and drawbacks with respect to three important factors regio-, stereo-, and chemoselectivities. 

There are two problems of chemoselectivity in this synthesis. How do we cleave one double bond in (22) without cleaving the other, and how do we control the cyclisation of (20) Epoxidation of (22) selectively attacks the more substituted double bond to give (23) which can be opened to (20) in two steps.The cyclisation of (20) can be controlled by conditions strong base gives (19) by thermodynamic control and weak base enolises only the aldehyde (kinetic control) to give (21). 

The thermodynamic driving force notwithstanding, the coupling of two different radicals is not an especially practical preparative method to form a new bond. This is because the preparation of precursors that directly decompose to radicals is rarely convenient, because disproportionation can often compete effectively with recombination, and especially because chemoselectivity (that is, the selective-coupling of two different radicals to the exclusion of self-coupling) is difficult to achieve if all coupling reactions occur at the same rate (the diffusion-controlled limit). 

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