Radical Reactions of Carbohydrates

Volume II: Radical Reactions in Carbohydrate Synthesis

Chapter 5: Acetals and Ethers

Chapter 5 is in a portable document file (pdf) and can be viewed by clicking the blue, Chapter 5 button below. The drawing underneath the button pictures the formation and reaction of a carbohydrate radical produced by hydrogen-atom abstraction from an acetal. Beside the drawing is a description of the reaction. Below the drawing and its description is a summary of Chapter 5.

Chapter 5: Acetals and Ethers

This drawing shows a radical epimerization of a cyclic acetal.

Drawing Description

If in a pair of equilibrating acetals one is substantially more stable than the other, the less stable structure can be converted essentially completely into the more stable one by radical reaction. The basic idea behind such an epimerization process, which is illustrated by the conversion shown on the left (Scheme 8 of Chapter 5), is to create a strained ring system and then relieve the strain by radical reaction.

Summary of Chapter 5

The free-radical bromination of a benzylidene acetal is a standard procedure in carbohy­drate chemistry for ring opening that results in the formation of bromodeoxy sugars. Ring opening in the absence of bromine occurs when 4,6-O-benzylidene acetals react with peroxides in the presence of a thiol catalyst. Hydrogen-atom abstraction by an electrophilic, thiyl radical is the first step in this reaction. This is also the first step in reactions of other acetals leading to epimerization and deoxygenation.

Ethers, like acetals, serve as protecting groups during carbohydrate synthesis, but this pro­tection is not total because both ethers and acetals undergo hydrogen-atom abstraction in the presence of reactive, electrophilic radicals. These radicals can be sulfur-, oxygen-, or bromine-centered. When hydrogen-atom abstraction by an alkoxy radical is intramolecular, it typically is highly regioselective and can lead to formation of a new ring system.

Acetals and ethers, including silyl ethers, have a connective role in radical cyclization reac­tions. The radical center and the multiple bond involved in a cyclization reaction are often joined together by an acetal or ether linkage.