Alkyl halides, enantiomeric purity

The ester was cleaved by reduction with DIBAL (Ml AlH) and an achiral version of the normal protecting group put in place. It would obviously be silly to create unnecessary diastereo meric mixtures in these reactions. Then the tin could be exchanged first with lithium and then with an elec-tuophile, even an alkyl halide, with retention of configuration and without loss of enantiomeric purity. The intermediate organolithium compound must have had a stable configuration. 

The analysis of isothiouronium salts, which are conveniently formed by reacting alkyl halides with thiourea, provide a way to study alkyl halides . The H NMR spectrum of s-butylisothiouronium chloride and bromide exhibited enantiomeric discrimination in the presence of [Eu(tfc)3(fod)] The enantiomeric purity of several alkyl methyl phenyl sulfonium ions (73) under conditions of slow inversion was determined using either [Eu(tfc)3(fod)] or [Eu(tfc)4] It was possible to study the inversion barrier by variable-temperature studies in the presence of the shift reagent. 

Reactions.—Kinetic resolution of secondary alkyl bromides and iodides can be achieved by reaction of two molar equivalents of the halide with the chiral lithio-oxazoline (69) and isolation of excess halide (Scheme 33). The lithio derivative (69) reacts preferentially with (S )-halide [as in (70) with smaller than R J leaving enriched (R)-halide of 30-50% enantiomeric purity. 

A procedure for enantioselective synthesis of carboxylic acids is based on sequential alkylation of the anion of the oxazoline 9 via its lithium anion. Chelation by the methoxy group leads preferentially to the transition state in which the lithium is located as shown. The lithium acts as a Lewis acid in directing the approach of the alkyl halide. This is reinforced by a steric effect of the phenyl substituent. As a result, alkylation occurs predominantly from the lower face of the anion. The sequence in which the groups R and R are introduced determines the chirality of the product. The enantiomeric purity of disubstituted acetic acids obtained after hydrolysis is in the range of 70-90%. ... 

Enantiomerically pure a-acyloxy ketones were readily prepared by reacting alkyl, alkenyl, alkynyl and arylmanganese halides with chiral a-acyloxy carbocyclic acid chlorides (Scheme 13.22) [25]. The reaction takes place under mild conditions in ether or in TH F to give the expected ketones in high yields with an excellent enantiomeric purity. 

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