Chapter 9: Chemoselectivity

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Chapter 9 is in a portable document file (pdf) and can be viewed by clicking the blue Chapter 9 button. The drawing below the button illustrates the importance of electron-withdrawing ability of double-bond substituents in determining chemoselectivity in radical cyclization. Beside and below the drawing is a summary of Chapter 9.

This drawing shows the chemoselectivity of two radical cyclization reactions.
Summary of Chapter 9

Chemoselectivity refers to ability of a reagent or intermediate (e.g., a radical) to react with one group in a molecule in preference to a different, but potentially reactive, group present in the same molecule. Since most carbohydrate radicals trace their beginnings to reactions involving either the tri-n-butyltin radical [Bu3Sn·] or tris(trimethylsilyl)silyl radical [(Me3Si)3Si·], chemoselectivity in the reactions of these radicals plays a central role in carbohydrate radical formation. In many reactions a second opportunity for chemoselectivity arises when an initially formed, carbon-centered radical reacts selectively with another molecule present in solution.

The tri-n-butyltin radical adds to carbon–carbon, carbon–oxygen, and carbon–sulfur multiple bonds in a reversible fashion; consequently, for chemoselec-tive reaction to occur, the reverse reaction must be blocked in some manner. Preventing reversal of radical addition usually is achieved by hydrogen-atom abstraction, addition to a multiple bond, or fragmentation of the adduct radical. Silicon–carbon bonds tend to be stronger than tin–carbon bonds so addition of some silyl radicals to unsat-urated compounds is not reversible at normal reaction temperatures. The tris(trimethyl-silyl)silyl radical, however, does add reversibly to unsaturated com-pounds.

Carbon-centered radicals tend to be quite chemoselective intermediates. They add readily to electron-deficient, carbon–carbon, multiple bonds but are less reactive in group and atom replacement reactions than are (Me3Si)3Si· and Bu3Sn·.