Strategy II Chemoselectivity

Background Needed for this Chapter References to Clayden, Organic Chemistry Chapter 8 Acidity, Basicity, and pKa. 

If a molecule has two reactive groups and we want to react one of them and not the other we need chemoselectivity. Under this heading we can consider  

The relative reactivity of two different functional groups, such as NH2 and OH. 

The reaction of one of two identical groups we might want to make the monoether 5. 

The reaction of a group once when it might react twice as in thiol synthesis. 

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Ideally, a metal catalyst should be able to perform a chemoselective substrate oxidation followed by direct reoxidation with molecular oxygen. Due to the extreme difference in required reactivity of the metal catalyst for each of these processes, cocatalysts are frequentiy necessary. Two distinct strategies will be discussed (i) modification of the metal-based oxidant with a coreductant allowing oxygenase activity (Section 5.2.1) or (ii) inclusion of another catalyst which is directly oxidized by O2 and is responsible for reoxidation of the substrate catalyst (Section 5.2.2). The following sections describe specific examples of each approach. 

The total synthesis of (-l-)-anatoxin-a was achieved by Martin et al. 12a, b and Mori et al. [12c, d] by using the same strategy. The key step is the constraction of an azabicyclo[4.2.1]nonene ring system. For that purpose, the 2,5-ds-disubstituted pyrrolidine derivative 34 was synthesized from (-l-)-pyroglutamic acid. Ene-yne metathesis appHed to 34 was carried out using second-generation catalyst [Ruj-II to form the azabicychc compound 35 [12a, b], which was chemoselectively dihy-droxylated to provide 36. From the latter compormd, anatoxin-a was synthesized (Scheme 6.9). 

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