1. Nucleophilicity of Sulfur Compounds

Sulfur analogs of alcohols are called thiols or mercaptans, and ether analogs are called sulfides. The chemical behavior of thiols and sulfides contrasts with that of alcohols and ethers in some important ways.

Since hydrogen sulfide (H₂S) is a much stronger acid than water (by more than ten million fold), we expect, and find, thiols to be stronger acids than equivalent alcohols and phenols. Thiolate conjugate bases are easily formed, and have proven to be excellent nucleophiles in S_N2 reactions of alkyl halides and tosylates.

Although the basicity of ethers is roughly a hundred times greater than that of equivalent sulfides, the nucleophilicity of sulfur is much greater than that of oxygen, leading to a number of interesting and useful electrophilic substitutions of sulfur that are not normally observed for oxygen.

Sulfides, for example, react with alkyl halides to give ternary sulfonium salts (equation # 1) in the same manner that 3º-amines are alkylated to quaternary ammonium salts. Although equivalent oxonium salts of ethers are known, they are only prepared under extreme conditions, and are exceptionally reactive.

Remarkably, sulfoxides (equation # 2), sulfinate salts (# 3) and sulfite anion (# 4) also alkylate on sulfur, despite the partial negative formal charge on oxygen and partial positive charge on sulfur.

2. Reactions of Ylides

The most important use of ylides in synthesis comes from their reactions with aldehydes and ketones, which are initiated in every case by a covalent bonding of the nucleophilic alpha-carbon to the electrophilic carbonyl carbon.

Alkylidenephosphorane ylides react to give substituted alkenes in a transformation called the Wittig reaction. This reaction is illustrated by the first three equations below. In each case the new carbon-carbon double bond is colored blue, and the oxygen of the carbonyl reactant is transferred to the phosphorus.

The Wittig reaction tolerates epoxides and many other functional groups, as demonstrated by reaction # 1. The carbanionic center may also be substituted, as in reactions # 2 & 3. A principal advantage of alkene synthesis by the Wittig reaction is that the location of the double bond is absolutely fixed, in contrast to the mixtures often produced by alcohol dehydration. With simple substituted ylides Z-alkenes are favored (reaction # 2).

The fourth equation shows a characteristic reaction of a sulfur ylide. Again, the initial carbon-carbon bond is colored blue, but subsequent steps lead to an epoxide product rather than an alkene.