Configuration halides from alcohols

Halides from alcohols via iminoesters with inversion of configuration s. 11, 619 OH Hal... 

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... 

One of the most important reasons for using tosylates in S j2 reactions is stereochemical. The S]s]2 reaction of an alcohol via an alkyl halide proceeds with hvo inversions of configuration—one to make the halide from the alcohol and one to substitute the halide—and yields a product with the same stereochemistry as the starting alcohol. The SN2 reaction of an alcohol via a tosylate, however, proceeds with only one inversion and yields a product of opposite stereochemistry to the starting alcohol. Figure 17.5 shows a series of reactions on the R enantiomer of 2-octanol that illustrates these stereochemical relationships. 

Koenigs-Knorr synthesis. Formation of glycosides from acetylated glycosyl halides and alcohols or phenols in the presence of silver carbonate or silver oxide. The reaction proceeds with inversion of configuration. 

A popular reaction type in recent years has been the conversion of alcohols into other compounds by use of an organophosphorus compound in the presence of a source of a nucleophile [reaction (8)]. PhsP plus diethyl azodicarboxylate has been a particularly popular form of organophosphorus reagent, and the product is formed with inversion of configuration. In 1977 there appeared a number of variations on this general theme, for the synthesis of halides, thiocyanates, thio-ethers, azides, and esters from alcohols.Similar systems have been used to convert amides and thioamides into nitriles. ... 

An advantage that sulfonates have over alkyl halides is that their preparation from alcohols does not involve any of the bonds to carbon. The alcohol oxygen becomes the oxygen that coimects the alkyl group to the sulfonyl group. Thus, the configuration of a... 

Preparation.—From Alcohols or other Halides. Factors affecting the formation of isomerically and optically pure alkyl halides from saturated aliphatic alcohols have been discussed by Hudson and co-workers. - Reactions with thionyl chloride give reduced amounts of rearrangement products if pyridine hydrochloride is added, and isomerically pure chlorides RCl from almost all alcohols ROH if HMPT or DMF is the solvent. In the latter medium (58) is a presumed intermediate, as is the case in the reaction of alcohols with Vilsmeier reagents (59, X = Cl or Br). Such species produce halides via inversion of configuration from secondary alcohols, presumably according to Scheme 24. In the related reaction of PCI3 with unhindered primary alcohols in DMF to produce alkyl... 

The reactions of alcohols with hydrogen halides to give alkyl halides (Chapter 4) are nucleophilic substitution reactions of alkyloxonium ions m which water is the leaving group Primary alcohols react by an 8 2 like displacement of water from the alkyloxonium ion by halide Sec ondary and tertiary alcohols give alkyloxonium ions which form carbo cations m an S l like process Rearrangements are possible with secondary alcohols and substitution takes place with predominant but not complete inversion of configuration... 

Evidence for this mechanism is as follows The addition of pyridine to the mixture of alcohol and thionyl chloride results in the formation of alkyl halide with inverted configuration. Inversion results because the pyridine reacts with ROSOCl to give ROSONC5H5 before anything further can take place. The Cl freed in this process now attacks from the rear. The reaction between alcohols and thionyl chloride is second order, which is predicted by this mechanism, but the decomposition by simple heating of ROSOCl is first order. ... 

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 formation of an alkanethiol by reaction of an alkyl halide or alkyl /Moluenesulfonatc with thiourea occurs with inversion of configuration in the step in which the carbon-sulfur bond is formed. Thus, the formation of (R)-2-butanethiol requires (.S Kvcc-butyl /Moluenesulfonatc, which then reacts with thiourea by an SN2 pathway. The /Moluenesulfonatc is formed from the corresponding alcohol by a reaction that does not involve any of the bonds to the stereogenic center. Therefore, begin with (.S )-2-bulanol. 

Because the reaction proceeds mainly by an S 2 mechanism, the alkyl halide produced from an optically active alcohol will have the opposite relative configuration from the alcohol from which it was formed. 

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