Radical Reactions of Carbohydrates

Volume II: Radical Reactions in Carbohydrate Synthesis

Chapter 17: Oxime Ethers and Related Compounds

Chapter 17 is in a portable document file (pdf) and can be viewed by clicking the blue, Chapter 17 button below. The drawing underneath the button pictures a radical cyclization reaction involving an oxime ether. Beside the drawing is a description of the reaction. Below the drawing and its description is a summary of Chapter 17.

Chapter 17: Oxime Ethers and Related Compounds

This drawing pictures a stereoselective cyclization of an oxime radical.

Drawing Description

An O-isopropylidene group that is close to the reactive centers in a cyclization reaction has a pronounced effect on stereoselectivity. This effect is illustrated by the reaction shown in the Scheme on the left (Scheme 5 in Chapter 17), where the sole product has the NHOBn substituent on the side of the newly formed ring that is opposite to the O-isopropylidene group. In this reaction the chair-like conformation 17 of the intermediate radical is greatly favored over its boat-like counter­part 18 due, in large measure, to destabilizing steric interactions that involve the O-isopropylidene group.

Summary of Chapter 17

Carbon-centered radicals add to carbon–nitrogen double bonds in oxime ethers, hydrazones, ketonitrones, and protonated heteroaromatics. These reactions are regiospecific with addition occurring to the carbon atom in the double bond. The majority of such reactions involve oxime ethers and usually result in formation of a new ring. These cyclization reactions often are quite stereoselective. This is particularly true if an O-isopropylidene group is near the reactive center, in which case the nitrogen-containing substituent and the O-isopropylidene group in the product are on opposite sides of the new ring. Radical addition to protonated hetero-aromatics is different from addition to other compounds containing carbon–nitrogen multiple bonds because addition is always followed by hydrogen-atom abstraction that rearomatizes the ring.