Sulfur–, Selenium–, Silicon–, and Phosphorus–Containing Reagents in Organic Synthesis
Textbooks
Clayden, chapters 17 (Mitsunobu, pp. 431–433), 31 (Julia and Wittig, pp. 810–818), 46 (sulfur), and 47 (boron, silicon, tin)
Sulfur and oxygen nucleophiles compared
Sulfur's more diffuse, polarisable lone pairs make sulfur nucleophiles softer than their oxygen counterparts.
| Reaction | Relative rate |
|---|---|
| MeOH + MeI → Me2O | 1 |
| Me2S + MeI → Me3S+ I− | 347 000 |
| MeO− Na+ + MeI → Me2O | 1 950 000 |
| HS− Na+ + MeI → MeSH | 100 000 000 |
Ester cleavage with thiolate anions
Sulfur (and selenium) electrophiles
Diphenyl disulfide (PhSSPh) and benzenesulfenyl chloride (PhSCl) are sulfur electrophiles that behave as sources of PhS+. PhSSPh is attacked by lithium enolates to give α-(phenylthio)ketones. Similarly, trimethylsilyl enol ethers are attacked by PhSCl to give the same product.
These reagents also add to π bonds, initially yielding episulfonium ions. They subsequently undergo nucleophilic ring-opening attack.
PhSX reagents are useful for synthesising enones from ketones. The ketone is deprotonated to its enolate by LDA; the enolate then reacts with PhSSPh. The α-(phenylthio)ketone is oxidised by H2O2 (or mCPBA) to the sulfoxide. Upon heating, benzenesulfenic acid (PhSOH) is syn-eliminated via a five-membered cyclic transition state.
Julia olefination
A connective double bond synthesis. A sulfone with an α hydrogen is deprotonated by BuLi, and then adds to an aldehyde or ketone. The resulting sulfonyl alkoxide is esterified, usually to a benzoate or acetate. Two diastereomers are sometimes possible, but they both later form the same product. Sodium-mercury amalgam is used as a one-electron reducing agent to eliminate benzenesulfinate (PhSO2−) and the carboxylate (RCO2−).