Radical Reactions of Carbohydrates

Volume II: Radical Reactions in Carbohydrate Synthesis

Chapter 3: Compounds with Carbon-Sulfur Single Bonds

Chapter 3 is in a portable document file (pdf) and can be viewed by clicking the blue, Chapter 3 button below. The drawing underneath the button shows an addition of a thiyl radical to an unsaturated carbohydrate. Beside the drawing is a more detailed description of the reaction. Below the drawing and its description is a summary of Chapter 3.

Chapter 3: Compounds with Carbon-Sulfur Single Bonds

This drawing describes addition of a thiol to an unsaturated carbohydrate.

Drawing Description

Thiyl radicals add readily to unsat-urated carbohydrates. In the reaction pictured in the drawing on the left (Scheme 21 in Chapter 3) the thiyl radical 23 adds to the unsaturated carbohydrate 21 to produce the S-di-saccharide 22. Both the overall reaction and the propagation steps are shown in this drawing.

Summary of Chapter 3

         Tin-centered radicals react with carbohydrates that contain methylthio, ethylthio, or phenylthio groups to produce carbon-centered radicals. Two mechanisms have been proposed for such a reaction. The first is a concerted SH2 process, and the second is a stepwise reaction that forms an intermediate with a hypervalent sulfur atom. Molecular orbital calculations favor the concerted process.

Radical reaction of a compound with an alkylthio or arylthio group breaks the C–S bond that produces the more stable, carbon-centered radical. This means that when fragmentation takes place in a carbohydrate containing a methylthio, ethylthio, or phenylthio substituent, a carbohydrate radical forms rather than an alkyl or aryl radical. Reactions that begin with carbon–sulfur bond cleavage often lead to either simple reduction or radical cyclization. Similar reactions occur when the sulfur atom is part of a dithioacetal, thiocarbonate, or dithiocarbonate.

         When the carbon–sulfur bonds in a carbohydrate are part of a sulfone and when an electron-donor (usually SmI2) is present, bond cleavage occurs via an electron-transfer reaction. When SmI2 is present, the resulting, carbon-centered radical combines rapidly with a molecule of SmI2 to produce an organosamarium intermediate that undergoes reactions typical of an organometallic compound (e.g., proton abstraction, β elimination, addition to an aldehyde or ketone). Radical cyclization is one of the few reactions fast enough to occur before a carbon-centered radical can react with SmI2.

         If a compound has a hydrogen–sulfur bond, the major reaction pathway usually is hydrogen-atom abstraction to form a sulfur-centered radical. This radical adds readily to a carbon–carbon double bond.