Diastereomers erythro/threo

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. 

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

By this concept, a reversible enzymatic aldol reaction generates a mixture of l-threo/erythro aldol diastereomers (133) from which the i-threo isomer is preferentially decomposed by an irreversible decarboxylation to furnish aromatic aminoalcohol (R)-(134) vhth 78% ee in high yield. 

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). 

C=X bonds The stereochemistry of the reduction of carbonyl compounds has been intensely studied with regard to synthetic and mechanistic aspects. The reduction of 1,2-diphenyl-l-propanone at a Hg cathode in aqueous EtOH and pH 8 affords the erythro alcohol as the major diastereomer (erythro threo = 5 to 1.4 1) [332]. This selectivity is in accord with a protonation of the intermediate anion, formed in an ECE sequence, from the least hindered side (Fig. 61). 

Catalyst Substrate Diastereomer ratio erythro/threo (%) C-2 2S-2R C-3 3R-3S ... 

A related strategy was used to prepare D-allosamine (134). Cycloaddition of the dipole derived from nitroacetal (129) to (S )-vinyl dioxolane (74) afforded a mixture of erythro/threo isoxazolines 130 131 (Scheme 6.72). The erythro isoxazoline was subjected to hydroxylation as described above, to give 4-hydroxyisoxazoline 132 with high diastereoselectivity. Lithium aluminium hydride reduction furnished a single diastereomer of aminodiol 133, which could be deprotected to give the hydrochloride salt of D-allosamine (134) (141). 

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]. 

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. 

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