Enantiomeric substituted

Rotation about the 1,1 -bond is resisted by van der Waals interactions between the hydrogens shown in the structures. These hydrogens crowd each other when the two naphthyl groups are coplanar, and the racemization process requires tjie hydrogens to move past each other. The existence of enantiomeric substituted biphenyls also depends on steric interactions between substituents. The relationship between the rate of racemization and... 

Within a series of related peptides, retention time on RP-HPLC can be used as an indicator of the peptide s structure. For example, in a homologous series of GS14 diastereomers in which each peptide contains a different enantiomeric substitution within the GSM (2) framework, each peptide possesses a unique retention time on RP-HPLC as shown in Figure 3J12 ... 

The position of the enantiomeric substitution is shown for each peak on the chromatogram. 

Tsuji, H. and Okumura, A. (2009) Stereocomplex formation between enantiomeric substituted polydactide)s blends of poly[(S)-2-hydroxybutyrate] and poly[(R)-2-hydroxybutyrate]. Macromolecules, 42, 7263-7266. 

Enantiomeric substitution products can be obtained with the corresponding enantiomeric ligands with the same rate of selectivity. In general, this is true in most cases, but sometimes different enantiomeric excess values are observed, depending on the ligand or the leaving group used. This memory effect can only be explained if the substitution does not proceed via a fully symmetrical it-allyl complex, but via a close ion pair [45]. 

Ac-E-L-E-K-L-L-X-E-L-E-K-L-L-K-E-L-E-K-amide, an amphipathic a-helical peptide, where X is substituted by leucine (LL7), valine (LV7), threonine (LT7), or serine (LS7), i.e., substitutions are made in the hydrophilic face of the helix cyclo-V-X-L-Y-P-V-X-L-Y-P), where X is substituted by diaminopropionic acid (Dap), diaminobutyric acid (Dab), ornithine (Orn), lysine (Lys), arginine (Arg), or histidine (His) Cyclo-(V-K-L-K-V-Y-P-L-K-V-K-L-Y-P), where 14 analogues were produced by single enantiomeric substitutions at each residue around the ring an extra two analogues were produced by double or quadruple enantiomeric substitutions of the lysine (K) residues... 

Although unsynunetrically substituted amines are chiral, the configuration is not stable because of rapid inversion at nitrogen. The activation energy for pyramidal inversion at phosphorus is much higher than at nitrogen, and many optically active phosphines have been prepared. The barrier to inversion is usually in the range of 30-3S kcal/mol so that enantiomerically pure phosphines are stable at room temperature but racemize by inversion at elevated tempeiatuies. Asymmetrically substituted tetracoordinate phosphorus compounds such as phosphonium salts and phosphine oxides are also chiral. Scheme 2.1 includes some examples of chiral phosphorus compounds. 

Since most often the selective formation of just one stereoisomer is desired, it is of great importance to develop highly selective methods. For example the second step, the aldol reaction, can be carried out in the presence of a chiral auxiliary—e.g. a chiral base—to yield a product with high enantiomeric excess. This has been demonstrated for example for the reaction of 2-methylcyclopenta-1,3-dione with methyl vinyl ketone in the presence of a chiral amine or a-amino acid. By using either enantiomer of the amino acid proline—i.e. (S)-(-)-proline or (/ )-(+)-proline—as chiral auxiliary, either enantiomer of the annulation product 7a-methyl-5,6,7,7a-tetrahydroindan-l,5-dione could be obtained with high enantiomeric excess. a-Substituted ketones, e.g. 2-methylcyclohexanone 9, usually add with the higher substituted a-carbon to the Michael acceptor ... 

In 1896, the German chemist Paul Walden made a remarkable discovery. He found that the pure enantiomeric (+)- and (-)-malic acids could be intercon-veited through a series of simple substitution reactions. When Walden treated (-)-malic acid with PCl5, he isolated (4-)-chlorosuccinic acid. This, on treatment with wet Ag20, gave (+)-malic acid. Similarly, reaction of (+)-malic acid with... 

Especially in the early steps of the synthesis of a complex molecule, there are plenty of examples in which epoxides are allowed to react with organometallic reagents. In particular, treatment of enantiomerically pure terminal epoxides with alkyl-, alkenyl-, or aryl-Grignard reagents in the presence of catalytic amounts of a copper salt, corresponding cuprates, or metal acetylides via alanate chemistry, provides a general route to optically active substituted alcohols useful as valuable building blocks in complex syntheses. 

Besides simple alkyl-substituted sulfoxides, (a-chloroalkyl)sulfoxides have been used as reagents for diastereoselective addition reactions. Thus, a synthesis of enantiomerically pure 2-hydroxy carboxylates is based on the addition of (-)-l-[(l-chlorobutyl)sulfinyl]-4-methyl-benzene (10) to aldehydes433. The sulfoxide, optically pure with respect to the sulfoxide chirality but a mixture of diastereomers with respect to the a-sulfinyl carbon, can be readily deprotonated at — 55 °C. Subsequent addition to aldehydes afforded a mixture of the diastereomers 11A and 11B. Although the diastereoselectivity of the addition reaction is very low, the diastereomers are easily separated by flash chromatography. Thermal elimination of the sulfinyl group in refluxing xylene cleanly afforded the vinyl chlorides 12 A/12B in high chemical yield as a mixture of E- and Z-isomers. After ozonolysis in ethanol, followed by reductive workup, enantiomerically pure ethyl a-hydroxycarboxylates were obtained. 

The a-substitution of enantiomerically enriched (-)-sparteine complexes of lithioalkenyl carbamates with methyl chloroformate76 or carbon dioxide77, in a manner contrary to a former assumption 76, proceeds with inversion of the configuration 131 131, leading to optically active 3-alkenoic acid esters. 

An extremely attractive feature of the route outlined at the beginning of this section for the transformation of boronates 3 or 4 to a-substituted allylboron compounds 5 is that reagents with very high enantiomeric purity (> 90% ee) may be prepared when precursors such as 3 and 4, and therefore also ate complex 1, contain a suitable diol chiral auxiliary17. The following syntheses of (S)-68, lib9, and 1310 illustrate this feature. 

Chiral, nonracemic allylboron reagents 1-7 with stereocenters at Cl of the allyl or 2-butenyl unit have been described. Although these optically active a-substituted allylboron reagents are generally less convenient to synthesize than those with conventional auxiliaries (Section 1.3.3.3.3.1.4.), this disadvantage is compensated for by the fact that their reactions with aldehydes often occur with almost 100% asymmetric induction. Thus, the enantiomeric purity as well as the ease of preparation of these chiral a-substituted allylboron reagents are important variables that determine their utility in enantioselective allylboration reactions with achiral aldehydes, and in double asymmetric reactions with chiral aldehydes (Section 1.3.3.3.3.2.4.). 

Optically active (Z)-l-substituted-2-alkenylsilanes are also available by asymmetric cross coupling, and similarly react with aldehydes in the presence of titanium(IV) chloride by an SE process in which the electrophile attacks the allylsilane double bond unit with respect to the leaving silyl group to form ( )-s)vr-products. However the enantiomeric excesses of these (Z)-allylsilanes tend to be lower than those of their ( )-isomers, and their reactions with aldehydes tend to be less stereoselective with more of the (E)-anti products being obtained74. 

The synthesis of enantiomerically enriched vinyl carbamates is described in Section 1.3.3.3.8.2.2. by applying this procedure, these were also obtained efficiently in the racemic form. Some further examples of substituted carbamates are collected below ... 

Another route to enantiomcrically pure iron-acyl complexes depends on a resolution of diastereomeric substituted iron-alkyl complexes16,17. Reaction of enantiomerically pure chloromethyl menthyl ether (6) with the anion of 5 provides the menthyloxymethyl complex 7. Photolysis of 7 in the presence of triphenylphosphane induces migratory insertion of carbon monoxide to provide a racemic mixture of the diastereomeric phosphane-substituted menthyloxymethyl complexes (-)-(/ )-8 and ( + )-( )-8 which are resolved by fractional crystallization. Treatment of either diastereomer (—)-(/J)-8 or ( I )-(.V)-8 with gaseous hydrogen chloride (see also Houben-Weyl, Vol 13/9a, p437) affords the enantiomeric chloromethyl complexes (-)-(R)-9 or (+ )-(S)-9 without epimerization of the iron center. 

When /V-arenesulfonyl-a-amino acid derived boranes 13 and 14 are used in substoichiometric amounts in order to mediate enantioselective aldol additions of a,a-dimethyl substituted ketcnc acetal 15, /J-hydroxycarboxylic esters 16 are obtained in enantiomeric excess of 84 to > 99 %3fi. 

Metalated SAMP- or RAMP-hydrazones derived from alkyl- or arylethyl ketones 3 add to arylaldehydes both diastereo- and enantioselectively. Substituted / -hydroxy ketones with relative syn configuration of the major diastereomer are obtained with de 51-80% and 70-80% ee. However, recrystallization of the aldol adducts, followed by ozonolysis, furnishes diastereo- and enantiomerically pure (lS, S )-. yn-a-mcthyl-/3-hydroxy ketones 5 in 36-51% overall yield. The absolute configuration of the aldol adducts was established by X-ray crystallographic analysis. Starting from the SAMP- or RAMP-hydrazone either enantiomer, (S,S) or (R,R), is available using this methodology16. 

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