Sulfones, alkylation from alkyl halides

Sulfonate esters are subject to the same limitations as alkyl halides Competition from elimination needs to be considered when planning a functional group transforma tion that requires an anionic nucleophile because tosylates undergo elimination reactions just as alkyl halides do... 

An advantage that sulfonate esters have over alkyl halides is that their prepara tion from alcohols does not involve any of the bonds to carbon The alcohol oxygen becomes the oxygen that connects the alkyl group to the sulfonyl group Thus the configuration of a sulfonate ester is exactly the same as that of the alcohol from which It was prepared If we wish to study the stereochemistry of nucleophilic substitution m an optically active substrate for example we know that a tosylate ester will have the same configuration and the same optical purity as the alcohol from which it was prepared... 

Sulfonate esters are especially useful substrates in nucleophilic substitution reactions used in synthesis. They have a high level of reactivity, and, unlike alkyl halides, they can be prepared from alcohols by reactions that do not directly involve bonds to the carbon atom imdeigoing substitution. The latter aspect is particularly important in cases in which the stereochemical and structural integrity of the reactant must be maintained. Sulfonate esters are usually prepared by reaction of an alcohol with a sulfonyl halide in the presence of pyridine ... 

TABLE 3. Sulfones from sulfinates R1S02M and alkyl halides... 

Alkylation of carbanions derived from allyl aryl sulfones 236 with alkyl halides is known... 

Formation of Alkyl Halides from Esters of Sulfuric and Sulfonic Acids... 

Another general process involves the reaction of Pd(0) species with halides or sulfonates by oxidative addition, generating reactive intermediates having the organic group attached to Pd(II) by a ct bond. The oxidative addition reaction is very useful for aryl and alkenyl halides, but the products from saturated alkyl halides often decompose by (3-elimination. The a-bonded species formed by oxidative addition can react with alkenes and other unsaturated compounds to form new carbon-carbon bonds. The... 

The main advantages of preparation of hydroxylamines through Af-alkylation of other hydroxylamines are versatility and predictable stereochemical outcome that allow the introduction of the hydroxyamino group at advanced stages of multistep syntheses. The use of nucleophilic displacement is however problematic for sterically hindered alkyl halides and sulfonates. Apart from several examples mentioned below, alkylation of hydroxylamines with tertiary alkyl halides does not take place. 

Alkylation of hydroxylamines with secondary alkyl halides and alkyl sulfonates like 10 (equation 7) is one of the most frequently used synthetic approaches, especially to enantiomerically pure hydroxylamines such as 11 (equation 7). The reaction proceeds with inversion of configuration and does not produce appreciable amounts of diaUcyla-tion products. Both hydroxylamine as well as N- and O-alkylhydroxylamines have been successfully used. Alkyl trillates are probably the most useful substrates for these transformations since they can be prepared from a large pool of commercially available enantiomerically pure chiral secondary alcohols. 

The metalated hydrazones are alkylated by alkyl halides, dialkyl sulfates or alkyl sulfonates at low temperatures in tetrahydrofuran (—95°C) or diethyl ether (— 110°C) to form the a-sub-stituted hydrazones in nearly quantitative yields. The ambident azaenolates react exclusively at the C-terminus side products resulting from N-, di-, or polyalkylation are not observed. The crude alkylated hydrazones can be purified by distillation or silica gel chromatography (diethyl ether/pentane) without epimerization. However, in most cases, they are pure enough to be directly cleaved to the desired alkylated carbonyl compound. 

Problem 13.17 How does sulfonate ester formation from suifonyl chloride resemble nucleophilic displacements of alkyl halides "d... 

The alkyl sulfonic acid is made by oxidizing the thiol, which in turn comes from the halide. 

The Grignard reagents used in the reaction may be either those derived from aryl halides or those formed from alkyl halides. Phenyllithium reacted with the tosylate to give sulfones rather than azoxy compounds. 

Literature procedures for the synthesis of hydroperoxides include the preparation from hydrogen peroxide (via reaction with alkyl halides, -phosphites, -sulfonates, alkenes,... 

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