Participation by Sulfur Groups

Eliel, E. L. Knox, D. E. Neighboring group participation by sulfur involving four-mem-bered-ring intermediates./. Am. Chem. Soc. 1985, 107, 2946-2952. 

In both cases, intramolecular displacement of the chloride leaving group by the sulfur atom—or, as we should call it, participation by sulfur (see Chapter 37)—gives a three-membered cyclic sulfonium ion intermediate (an episulfonium or thiiranium ion). Nucleophilic attack on this electrophilic sulfonium ion, either by water or by the structural proteins of the skin, is very fast. Of course, mustard gas can react twice in this way. You will see several more examples of reactions in which a sulfonium ion intermediate acts as an electrophile in the next section. 

The type of orbitals involved in sulfur-bond formation varies considerably by structure and can be represented as involving orbitals which have p, sp hybrid or d character. The role of the sulfur d orbitals has been a matter of some debate but at least in compounds containing unsaturated bonds and/or electron-withdrawing groups the d orbitals are credited with conferring enhanced stability on the ground state of the molecules as a result of resonance interaction. In photochemical rearrangements of thiophene derivatives for example (vide infra) the transition states proposed all involve d-orbitals participation by sulfur. 

Participation by sulfur has also been noted in attempts to hydrolyze the imino chloride functionality of penicillin intermediates, e.g., as in (66), to amide groups. Treatment of (66) with silver nitrate or aqueous acid resulted in the formation of three products, (67)-(69). Their formation can be rationalized as shown in Eq. (20). ... 

Step 1 Make a new bond between a nucleophile and an electrophile and simultaneously break a bond to give stable molecules or ions. The reason for the extremely rapid hydrolysis of the sulfur mustards is neighboring group participation by sulfur in the ionization of the carbon-chlorine bond to form a cyclic sulfonium ion. This is the rate-determining step of the reaction although it is the slowest step, it is much faster than reaction of a typical primary chloroalkane with water. At this point, you should review halogenation of alkenes (Sections 6.3D and 6.3F) and compare the cyclic halonium ions formed there with the cyclic sulfonium ion formed here. 

FIGURE 9.82 Mechanism of neighboring group participation by sulfur. 

Neighboring-group participation reactions by sulfur and nitrogen functions have also been observed for deoxyhalogeno sugars. An example is the formation of the anhydride 146, which possesses an oxathiabicyclo[2.2.2]octane ring-system constrained in a boat-like conformation, on treatment of methyl 4-0-benzoyl-2-S-benzoyl-6-bromo-6-deoxy-2-thio-Q -D-altropyranoside (145) with methanolic... 

Phenylthio-3-trimethylsilylalkanols lose the element of trimethylsilanol on treatment with an acid [208]. Ionization of the hydroxyl group is participated by the sulfur atom and the episulfonium intermediates then undergo desilylation. The Si-C-C-S segment is conjoint and its fragmentation proceeds upon activation by episulfonium ion formation. 

---