V. Summary

Halogen-atom abstraction by a tin-centered radical is a com­mon reaction in carbohydrate chem­is­try. Ample evidence supporting radical intermediates in this type of reaction comes from chem­ical reactivity and from direct radical observation by ESR spectroscopy. Iodides are the most reac­tive of the halogenated carbo­hy­drates. Bromides are slightly less so, but the reactivity of chlorides is con­sid­erably reduced. Fluorides are essentially unreactive. In dehalogenation reac­tions the transition-state struc­ture is thought to involve partial tin–halogen and carbon–halogen bonds.

Simple reduction (replacement of a halogen atom with a hydrogen atom) occurs under mild reaction conditions. The halogen atom being abstracted can be attached to any carbon atom in the carbohydrate framework. Although the primary role of simple reduction is in the synthesis of deoxy sugars and deoxy nucleosides, this reaction also can be used to modify the reactivity of halogenated protecting groups. Replacement of halogen atoms with hydrogen atoms can convert a group that is difficult to hydrolyze into one that does so more easily.

Simple reduction of anomeric halides must compete with group migration when there is an acyloxy group at C-2. This migration, which is useful in the synthesis of 2-deoxy sugars, is most likely to occur when the concentration of the hydrogen-atom transfer (e.g., tri-n-butyltin hydride) is held at a very low level.

Halogen-atom abstraction often is the first step in the addition of a carbo­hydrate radical to a compound containing a multiple bond. Such addition will occur in an intra­molec­ular fashion if the multiple bond is electron-deficient because under the proper conditions a nucleophilic carbo­hy­drate radical adds to an electron-deficient multiple bond more rapidly than it abstracts a hydrogen atom. ­When the radical center and the multiple bond are in the same molecule and easily come within bonding distance, cyclization takes place so readily that it will occur even if the multiple bond is not electron-deficient. A charac­ter­istic of cyclization reac­tions is that formation of the new carbon–carbon bond often occurs in a highly stereoselective fashion.

Halogenated carbohydrates participate in a variety of less common reactions. These include double bond formation, internal hydrogen-atom abstrac­tion, addition to molecular oxygen, cyclo­pro­pane ring opening, and radical anion formation.

Free-radical bromination produces several types of brominated carbo­hy­drates. Bromination of benzylidene acetals leading to formation of bromo­deoxy benzoates is a standard reaction in carbohydrate synthesis. Modi­fi­cations of this reaction also are known; thus, the cation produced following benzylidene acetal bromination can be intercepted by water to give a hydroxy benzoate. Carbohydrates protected as benzyl ethers react with bromine to produce unstable bromides that, in turn, react with water to give benz­alde­hyde and the deprotected carbohydrate. Reaction with bromine of carbo­hydrates that do not contain benzyl or benzylidene protection regioselectively replaces a hydrogen atom on one of the carbon atoms attached to the ring oxygen atom.