Alkyl sulfonates with active hydrogen

This reaction was initially reported by Eisleb in 1941. It is the alkylation of compounds of active hydrogen with alkyl halide via the treatment of sodium amide. The compounds with active hydrogens include deoxybenzoin, diphenylmethane, phenylacetonitrile, fluorene, " benzyl phenyl sulfone, and 2-pyridyl acetonitrile. This reaction normally gives a satisfactory yield of introducing A/, A/ -dialkylamino alkyl group to compounds with an active proton. ... 

Activating an alcohol by converting it to an alkyl halide with a hydrogen halide followed by reaction with a nucleophile forms a substitution product with the same conhguration as the alcohol, whereas activating an alcohol by converting it to a sulfonate ester followed by reaction with a nucleophile forms a substitution product with a conhguration opposite that of the alcohol. 

The clinical and commercial success of the antidepressant compound fluoxetine (Chapter 2 Prozac) engendered considerable work in other laboratories. A benzo-dioxan based compound that shows similar activity shares only a few stmctural features with the prototype. The benzodioxan nucleus (68-3) is formed by an alkylation reaction between the fluorocatechol (68-1) and the derivative (68-2) from meso, and hence achiral, butanetetrol. The benzyl protecting groups are then removed by hydrogenation over palladium, and the thus-obtained diol is converted to the fiii-toluene-sulfonate (68-4) by reaction with toluenesulfonyl chloride. Treatment of that intermediate with benzylamine leads to fiw-alkylation on the same nitrogen to form a pyrrolidine ring and thus the tricyclic compound (68-5). A second hydrogenolysis step then leads to fluparoxan (68-6) [70]. 

Electrophilic N-aminations have been performed with hydroxylamine-O-sulfonic acid (HOSA)," O-(2,4-dinitrophenyl)hydroxylamine and C>-mesitylenesulfonylhydroxylamine. The use of HOSA is mainly restricted to aqueous reaction media. Imide sodium salts of some heterocycles such as theobromine (88) can be converted to hydrazine derivatives by treatment with 0-(diphenylphosphinyl)hydroxylamine (equation 35)." This reaction has been extended to synthesis of N-arylhyd ines, where R and R are hydrogen, alkyl or aryl (equation 36)." Similarly, trisubstituted hydrazines can be prepared by the use of N-aryl-O-acetylhy oxylamines and secondary amines." A recent publication" concerning the synthesis of l-acyl-2-dkylhydrazines from hydroxamic acids and amines in the presence of activating agents has been found to be erroneous no N—N bond formation occurs under these conditions." ... 

The sulfone is a versatile functional group comparable to the carbonyl functionality in its ability to activate molecules for further bond construction, the main difference between these two groups being that the sulfone is usually removed once the synthetic objective is achieved. The removal most commonly involves a reductive desulfonylation process with either replacement of the sulfone by hydrogen (Eq. 1), or a process that results in the formation of a carbon-carbon multiple bond when a P-functionalized sulfone, for example a (3-hydroxy or (3-alkoxy sulfone, is employed (Eq. 2). These types of reactions are the Julia-Lythgoe or Julia-Paris-Kocienski olefination processes. Alkylative desulfonylation (substitution of the sulfone by an alkyl group, Eq. 3), oxidative desulfonylation (Eq. 4), and substitution of the sulfone by a nucleophile (nucleophilic displacement, Eq. 5) are also known. Finally, p-eliminations (Eq. 6) or sulfur dioxide extrusion processes (Eqs. 7, 8 and 9) have become very popular for the... 

A Cr(VI) sulfoxide complex has been postulated after interaction of [CrOjtClj] with MejSO (385), but the complex was uncharacterized as it was excessively unstable. It was observed that hydrolysis of the product led to the formation of dimethyl sulfone. The action of hydrogen peroxide on mesityl ferrocencyl sulfide in basic media yields both mesityl ferrocenyl sulfoxide (21%) and the corresponding sulfone (62%) via a reaction similar to the Smiles rearrangement (165). Catalytic air oxidation of sulfoxides by rhodium and iridium complexes has been observed. Rhodium(III) and iridium(III) chlorides are catalyst percursors for this reaction, but ruthenium(III), osmium(III), and palladium(II) chlorides are not (273). The metal complex and sulfoxide are dissolved in hot propan-2-ol/water (9 1) and the solution purged with air to achieve oxidation. The metal is recovered as a noncrystalline, but still catalytically active, material after reaction (272). The most active precursor was [IrHClj(S-Me2SO)3], and it was observed that alkyl sulfoxides oxidize more readily than aryl sulfoxides, while thioethers are not oxidized as complex formation occurs. 

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