Chiral compounds alcohol-amine conversion

The major application of the Mitsunobu reaction is the conversion of a chiral secondary alcohol 1 into an ester 3 with concomitant inversion of configuration at the secondary carbon center. In a second step the ester can be hydrolyzed to yield the inverted alcohol 4, which is enantiomeric to 1. By using appropriate nucleophiles, alcohols can be converted to other classes of compounds—e.g. azides, amines or ethers. 

A closely related method does not require conversion of enantiomers to diastereomers, but relies on the fact that (in principle, at least) enantiomers have different NMR spectra in a chiral solvent, or when mixed with a chiral molecule (in which case transient diastereomeric species may form). In such cases, the peaks may be separated enough to permit the proportions of enantiomers to be determined from their intensities.Another variation, which gives better results in many cases, is to use an achiral solvent but with the addition of a chiral lanthanide shift reagent such as fn5[3-trifluoroacetyl-(i-camphorato]europium(III). ° Lanthanide shift reagents have the property of spreading NMR peaks of compounds with which they can form coordination compounds, for example, alcohols, carbonyl compounds, and amines. Chiral lanthanide shift reagents shift the peaks of the two enantiomers of many such compounds to different extents. 

A typical example that illustrates the method concerns the lipase- or esterase-catalyzed hydrolytic kinetic resolution of rac-1-phenyl ethyl acetate, derived from rac-1-phenyl ethanol (20). However, the acetate of any chiral alcohol or the acetamide of any chiral amine can be used. A 1 1 mixture of labeled and non-labeled compounds (S)- C-19 and (f )-19 is prepared, which simulates a racemate. It is used in the actual catalytic hydrolytic kinetic resolution, which affords a mixture of true enantiomers (5)-20 and (J )-20 as well as labeled and non-labeled acetic acid C-21 and 21, respectively, together with non-reacted starting esters 19. At 50% conversion (or at any other point of the kinetic resolution), the ratio of (5)- C-19 to (1 )-19 correlates with the enantiomeric purity of the non-reacted ester, and the ratio of C-21 to 21 reveals the relative amounts of (5)-20 and (J )-20 (98). 

The hydrogenolysis of chloroform to hydro n chloride has been used in the production of labile amines catalytic reduction of azides, nitriles, oximes, and nitro-compounds in a solvent containing a small amount of chloroform results in the trapping of the produced amine as its hydrochloride. Sodium sulphide smoothly reduces nitroxides to amines. The utility of chiral a-phenylethylamine-borane complexes for the conversion of ketones into alcohols or amines has been studied whereas chemical yields are good, optical yields are poor. ... 

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