Diastereomer derivatives

Intramolecular cycloadditions of alkenyl-substituted nitrile oxides produce bicyclic isoxazolines. When monocyclic olehns are used, tricyclic structures are obtained. This approach was pioneered by both Kozikowski s and Curran s groups. A typical case involves the cycloaddition of nitro compound 191 [mixture of diastereomers derived from pentenose pyranoside 190], which produced a diaster-eomeric mixture of isoxazolines that contain cis-fused rings (i.e., 192) in near quantitative yield (326) (Scheme 6.85). Further elaboration of this mixture led to epoxycyclopentano-isoxazoline 193, which was then converted to the aldol product in the usual manner. The hydrogenation proceeded well only when rhodium on alumina was used as the catalyst, giving the required p-hydroxyketone 194. This... 

As stated earlier, this technique relies essentially on the formation of covalently bonded diastereomers derived from a pair of chiral analytes (SAs pair of enantiomers) which have been converted to a pair of diastereomers using an optically pure chiral derivatizing agent (CDA) which, in this case, serves as a chiral selector (SO). In this context the definition of " optical purity of the CDA is critical (see Section 3.2.1.2.) and has to be evaluated by complementary methods. 

Combination of a nonracemic isocyanate and a l,3-disul)sliluted distannoxane has provided a new method for determination of the optical purity of chiral alcohols (Scheme 12.174) [316]. When a chiral alcohol was reacted with commercially available (l )-l-(l-naphthyl)efhyl isocyanate in the presence of 1,3-disubstituted distannoxane, formation of the desired carbamates occurred rapidly, with acid-labile functional groups such as ester, THP and /Miydroxyketone remaining intact. Subsequent HPLC analysis of the resulting carbamate revealed a pair of well-separated peaks of diastereomers derived from both enantiomeric alcohols. 

Currently, several hundred reagents are available for the preparation of diastereomer derivatives, and this list continues to grow. In consequence, any type of comprehensive coverage is impossible here. As well as the nature of the reactive group, cost, reactivity, stability, and availability are important selection criteria, since in advance of trial experiments, success cannot be guaranteed for analytes not studied previously. For trace analysis, the choice of a more selective and sensitive detector for the analysis may minimize the number of options to reagents with suitable characteristic detector properties. 

Van Renshurg H, van Heerden PS, Bezuidenhoudt BCB, Ferreira D. Enantiose-lective synthesis of the four catechin diastereomer derivatives. Tetrahedron Lett 1997 38 3089 3092. 

The last step towards the three-component Ugi-type coupling envisaged in the ret-rosynthesis is described below. The, commercial amine 27 was oxidized to imine 26 (94% ee) by MAO-N, as previously described [20], which was then combined with 25 and 28 give the advanced intermediate 40. Finally, cleavage of the acetate followed by Dess-Martin oxidation gave Telaprevir (24) as a 83 13 4 mixture of diastere-omers, with one minor diastereomer derived from the incomplete stereoinduction of the Ugi-type 3CR and the other from the minor enantiomer of imine 26. Flash chromatography allowed straightforward separation of the diastereomers to afford pure Telaprevir (24) in 80% yield over the last two steps (Scheme 15.11). 

The method of partial dedoubling of Horeau (28-35) was applied to establish the absolute configuration of the four enol ethers 74-77. Since diastereomers, derived from reaction of a racemate with an optically active compound, are formed at a different rate, an excess of one enantiomer will be found in the remaining part of the original racemate. If the absolute configuration of the enantiomer in excess and, consequently, also that of the other enantiomer, which has reacted preferentially, are known, the absolute configuration of the optically active component can be derived. It is accepted that the least hindered diastereomer is formed preferentially. 

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