Radical Reactions of Carbohydrates

Volume II: Radical Reactions in Carbohydrate Synthesis

Chapter 11: Synthesis of O-Thiocarbonyl Compounds

Chapter 11 is in a portable document file (pdf) and can be viewed by clicking the blue, Chapter 11 button below. The drawing underneath the button pictures the formation of a common, O-thiocarbonyl, carbohydrate derivative. Beside the drawing is a description of the reaction. Below the drawing and its description is a summary of Chapter 11.

Chapter 11: Synthesis of O-Thiocarbonyl Compounds

This drawing shows reactions leading to the formation of a (thiocarbonyl)imidazolide.

Drawing Description

There are scattered reports of (thiocarbonyl)imidazolides forming more slowly than might be expected under typical reaction conditions. One such report concerns the methyl glycoside 5 in the drawing on the left (Scheme 3 in Chapter 11). This glycoside (5) reacts so slowly that prior activation with bis(tributyltin)oxide is necessary to increase its nucleophilicity to the point that (thiocar-bonyl)imidazolide formation proceeds at an acceptable rate.

Summary of Chapter 11

Synthesis of O-thiocarbonyl compounds [(xanthates, (thiocarbonyl)imidazolides, aryl thi­onocarbonates, cyclic thionocarbonates, thionoesters)] is the first step in using them to generate carbon-centered radicals.

Xanthates usually are prepared by deprotonating a partially protected carbohydrate and then reacting the resulting alkoxide ion with carbon disulfide and methyl iodide. The primary limitation of this approach is that it involves conditions in which base-sensitive compounds are unstable. Xanthate synthesis by phase-transfer reaction or by reaction with phenyl chlorodithioformate avoids this difficulty.

(Thiocarbonyl)imidazolides are formed by reacting a partially protected carbohydrate with N,N-thiocarbonyldiimidazole. The conditions for synthesis are much less basic that those used for preparing xanthates.

Aryl thionocarbonates typically come from reaction of a partially protected carbohydrate with phenoxythiocarbonyl chloride in the presence of DMAP (4-dimethylaminopyridine). Side reactions are rare and tend to arise when DMAP promotes base-catalyzed reactions that compete with thionocarbonate formation. Phenyl thionocarbonates also can be prepared in reactions catalyzed by N‑hydroxysuccinimide (NHS). This alternative procedure normally is implemented to improve product yields or avoid side reactions caused by DMAP. An additional option for phenyl thionocarbonate preparation consists of reacting a partially protected sugar with thiophosgene and treating the product with a phenol. This procedure is useful in preparing phenyl thionocarbonates with groups, usually electron-withdrawing ones, in the aromatic ring.

If a partially protected carbohydrate has vicinal, cis-related hydroxyl groups, reaction with N,N-thiocarbonyldiimidazole will form a cyclic thionocarbonate. A second procedure for syn­thesis of these compounds consists of formation of a stannylene complex of a carbohydrate, and then reaction of this complex with thiophosgene or phenoxythiocarbonyl chloride.

Thionoesters are less frequently used in deoxygenation reactions than other O-thiocarbonyl compounds, in part, due to the difficulty in their preparation. The only thionoesters used to a significant extent in deoxygenation are thionobenzoates.

When O-thiocarbonyl compounds are unable to form under the standard reaction conditions, sometimes they can be synthesized by converting the partially protected carbohydrate reactant into its corresponding alkoxide ion. Forming an alkoxide ion also increases the possibility that group migration will compete with formation of an O-thiocarbonyl, carbohydrate derivative.