Threo diastereomers

Doublet observed (ca. 0.1 ppm separation) due to the presence of erythro and threo diastereomers. 

Enol lactones are assumed to form from iV-methylisoquinolinium salts as a result of a Hofmann-type degradation process. This P elimination is a highly stereospecific reaction in which Z isomers are produced from precursors of erythro configuration and isomers from threo diastereomers(5,97). This fact seems to suggest that syn rather than the more usual anti elimination takes place. Examination of models indicates, however, that there is a preferred conformation in which the C-8 hydrogen is in the syn and coplanar position to the quaternary nitrogen. This hypothesis was proved correct in experiments carried out in vitro (5,14,15,91-94). 

It would be highly desirable to be able to correlate metal ion structure as well as the individual steric requirements of the specific substituents Ri, R2, and Ra with the equilibration studies cited above. Because of the numerous uncertainties associated with the data, however, only qualitative generalizations can be made. The higher-valent metal aldolate complexes (M = ZnL, MgL, AIL2), upon equilibration, appear to favor the threo diastereomer to a greater extent than the monovalent metal aldolates (M = Li, Na). With regard to... 

The full potential of this C-H activation process, as a surrogate Mannich reaction, was realized in the direct asymmetric synthesis of threo-methylphenidate (Ritalin) 217 (Eq. 28) [140]. C-H insertion of N-Boc-piperidine 216 using second-generation Rh2-(S-biDOSP)2 and methyl phenyldiazoacetate resulted in a 71 29 diastereomeric mixture, where the desired threo-diastereomer was obtained in 52% yield with 86% enantiomeric excess. Winkler and co-workers screened several dirhodium tetracarboxami-dates and found Rh2(R-MEPY)4 to be the catalyst that gives the highest diastereoselec-tivity for this reaction [142]. 

Organic chemists use an informal nomenclature system based on Fischer projections to distinguish between diastereomers. When the carbon chain is vertical and like substituents are on the same side of the Fischer projection, the molecule is described as the erythro diastereomer. When like substituents are on opposite sides of the Fischer projection, the molecule is described as the threo diastereomer. Thus, as seen in the... 

Whatever the explanation for the stereocontrol, these processes are quite useful synthetically, enabling one to prepare nearly pure erythro or threo diastereomers in high yield. A number of groups have shown that by using a chiral auxiliary in the enamine, ester or amide unit, products of very high enantiomeric excess can be obtained.69... 

The reaction of methyl phenyldiazoacetate with N-Boc-piperidine (36) is a good illustration of the potential of this chemistry because it leads to the direct synthesis of f/ireo-methylphenidate (37) [27]. The most efficient rhodium car-boxylate catalyst for carrying out this transformation is Rh2(S-biDOSP)2 (2), which results in the formation of a 71 29 mixture of the readily separable threo and erythro diastereomers. The threo diastereomer 37 is produced in 52% isolated yield and 86% ee [Eq. (19)]. Other catalysts have also been explored for this reaction. Rh2(R-DOSP)4 gives only moderate stereoselectivity while Rh2(R-MEPY)4 gave the best diastereoselectivity in this reaction (94% de) [29]. 

The erythro/threo diastereomers of a larger variety of 4,5-disubstituted 1,3-dioxanes (chiral conformationally restricted arachidonic acid analogs 54-59) proved to be of enantiomerically pure stereochemistry (cf. Scheme 17) (99TA139) the epimers were clearly identified by the coupling patterns of the protons in positions 4, 5, and 6, reflecting the ax,equ (threo) and equ,equ (erythro) relationships of the two substituents. 

For example, syn dihydroxylation of frans-crotonic acid gives the two enantiomers of the threo diastereomer of 2,3-dihydroxybutanoic acid. The same reaction with m-crotonic acid gives the erythro diastereomer of the product. 

The terms erythro and threo are used with dissymmetric molecules whose ends are different. The erythro diastereomer is the one with similar groups on the same side of the Fischer projection, and the threo diastereomer has similar groups on opposite sides of the Fischer projection. The terms meso and ( ) [or (4,/)] are preferred with symmetric molecules. 

The problem of diastereoselective aldol addition has been largely solved48,108). Under kinetic control Z enolates favor erythro adducts and E enolates the threo diastereomers, although exceptions are known. This has been explained on the basis of a six-membered chair transition state in which the faces of the reaction partners are oriented so as to minimize 1,3 axial steric interactions 481108). This means that there is no simple way to prepare erythro aldols from cyclic ketones, since the enolates are geometrically fixed in the E geometry. 

Separate the isomers by flash column chromatography on silica gel (ethyl acetate then acetone as eluant). The first diastereomer eluted from the column is the erythro adduct, with further elution affording the corresponding threo isomer. The diastereomers are recrystallized separately from ethyl acetate to afford the erythro diastereomer (1/ S,2S/ )-2-diphenylphosphinoyl-1-phenylbutan-1-ol (1.05 g, 73%) and the threo diastereomer (1/ S,2/ S)-2-diphenylphosphinoyl-1-phenylbutan-1-ol (180 mg, 13%) as needles. 

The deamination of 3-phenyl-2-butylamines,(J57), X=NH2, differs strongly from the solvolysis of the corresponding tosylates (Table 13)200. As pointed out previously, these reactions are conformationally controlled (Section 6.2). With the erythro diastereomer, the tram orientation of phenyl and amino (diazonium) groups is conformationally favored. A high yield of optically active erythro product results. With the threo diastereomer, phenyl participation is conformationally disfavored. Threo and erythro products are obtained in comparable quantities, and with partial race-mization, indicating the dominance of the kc pathway. 

Our interest in the effect of fluorine substitution on polyglutamate metabolism arose from the observation that the DL-threo diastereomer of 4-fluoroglutamate... 

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