Enantiomerically enriched

Further, peak overlap results in nonlinear detector response vs concentration. Therefore, some other detection method must be used in conjunction with either of these types of detection. Nevertheless, as can be seen from Figure Ilf, chiroptical detection can be advantageous if there is considerable overlap of the two peaks. In this case, chiroptical detection may reveal that the lea ding and tailing edges of the peak are enantiomerically enriched which may not be apparent from the chromatogram obtained with nonchiroptical detection (Fig. He). 

In a novel approach, enantiomerically enriched (R)-pantolactone (9) is obtained in a enzymatic two-step process starting from racemic pantolactone. 

Preparation of enantiomerically enriched materials by use of chiral catalysts is also based on differences in transition-state energies. While the reactant is part of a complex or intermediate containing a chiral catalyst, it is in a chiral environment. The intermediates and complexes containing each enantiomeric reactant and a homochiral catalyst are diastereomeric and differ in energy. This energy difference can then control selection between the stereoisomeric products of the reaction. If the reaction creates a new stereogenic center in the reactant molecule, there can be a preference for formation of one enantiomer over the other. 

Whereas the barrier for pyramidal inversion is low for second-row elements, the heavier elements have much higher barriers to inversion. The preferred bonding angle at trivalent phosphorus and sulfur is about 100°, and thus a greater distortion is required to reach a planar transition state. Typical barriers for trisubstituted phosphines are BOSS kcal/mol, whereas for sulfoxides the barriers are about 35-45 kcal/mol. Many phosphines and sulfoxides have been isolated in enantiomerically enriched form, and they undergo racemization by pyramidal inversion only at high temperature. ... 

As was the case for kinetic resolution of enantiomers, enzymes typically exhibit a high degree of selectivity toward enantiotopic reaction sites. Selective reactions of enaiitiotopic groups provide enantiomerically enriched products. Thus, the treatment of an achiral material containing two enantiotopic functional groups is a means of obtaining enantiomerically enriched material. Most successful examples reported to date have involved hydrolysis. Several examples are outlined in Scheme 2.11. 

Chiral chemical reagents can react with prochiral centers in achiral substances to give partially or completely enantiomerically pure product. An example of such processes is the preparation of enantiomerically enriched sulfoxides from achiral sulfides with the use of chiral oxidant. The reagent must preferential react with one of the two prochiral faces of the sulfide, that is, the enantiotopic electron pairs. 

The acetolyses of both ero-2-norbomyl brosylate and e do-2-norbomyl brosylate produce exclusively exo-2-norbomyl acetate. The exo-brosylate is more reactive than the endo isomer by a factor of 350. Furthermore, enantiomerically enriched exo-brosylate gave completely racemic ero-acetate, and the endo-brosylate gave acetate that was at least 93% racemic. 

The application of the AE reaction to kinetic resolution of racemic allylic alcohols has been extensively used for the preparation of enantiomerically enriched alcohols and allyl epoxides. Allylic alcohol 48 was obtained via kinetic resolution of the racemic secondary alcohol and utilized in the synthesis of rhozoxin D. Epoxy alcohol 49 was obtained via kinetic resolution of the enantioenriched secondary allylic alcohol (93% ee). The product epoxy alcohol was a key intermediate in the synthesis of (-)-mitralactonine. Allylic alcohol 50 was prepared via kinetic resolution of the secondary alcohol and the product utilized in the synthesis of (+)-manoalide. The mono-tosylated 3-butene-1,2-diol is a useful C4 building block and was obtained in 45% yield and in 95% ee via kinetic resolution of the racemic starting material. 

Enantioselective desymmetrization of achiral or meso compounds with formation of enantiomerically enriched products, among them heterocycles 99JCS(P1)1765. 

The 1,2-cyclohexanediamine-derived sulfonamide is not unique in its ability to afford enantiomerically enriched cyclopropanes. The efforts at improving the original protocol led not only to higher selectivity, but to a deeper understanding of the nature of the catalytic process. 

Apart from tertiary amines, the reaction may be catalyzed by phosphines, e.g. tri- -butylphosphine or by diethylaluminium iodide." When a chiral catalyst, such as quinuclidin-3-ol 8 is used in enantiomerically enriched form, an asymmetric Baylis-Hillman reaction is possible. In the reaction of ethyl vinyl ketone with an aromatic aldehyde in the presence of one enantiomer of a chiral 3-(hydroxybenzyl)-pyrrolizidine as base, the coupling product has been obtained in enantiomeric excess of up to 70%, e.g. 11 from 9 - -10 ... 

On that basis, crystallization is often used in combination with other enantiose-lective techniques, such as enantioselective synthesis, enzymatic kinetic resolution or simulated moving bed (SMB) chromatography [10, 11]. In general, when referring to crystallization techniques, the aim is to obtain an enantiomeric enrichment in the crystallized solid. However, the possibility of producing an enrichment in the mother liquors [12, 13], even if this is not a general phenomenon [14], must be taken into account. 

In another example of enantioselective distillation, it was the enantiomeric mixture to resolve itself which contributed to create a chiral environment. Thus, non-racemic mixtures of a-phenylethylamine were enantiomerically enriched by submitting to distillation different salts of this amine with achiral acids [199]. 

Following Uskokovic s seminal quinine synthesis [40], Jacobsen has very recently reported the first catalytic asymmetric synthesis of quinine and quinidine. The stereospecific construction of the bicyclic framework, introducing the relative and absolute stereochemistry at the Cg- and expositions, was achieved by way of the enantiomerically enriched trans epoxide 87, prepared from olefin 86 by SAD (AD-mix (3) and subsequent one-pot cyclization of the corresponding diol [2b], The key intramolecular SN2 reaction between the Ni- and the Cg-positions was accomplished by removal of the benzyl carbamate with Et2AlCl/thioanisole and subsequent thermal cyclization to give the desired quinudidine skeleton (Scheme 8.22) [41],... 

The addition of an achiral organometallic reagent (R M) to a chiral carbonyl compound 1 (see Section 1.3.1.1.) leads to a mixture of diastercomers 2 (syn/anti) which can be either racemic, or enantiomerically enriched or pure, depending on whether the substrates are race-mates or pure enantiomers. This section incorporates only those reactions starting from optically pure a-amino aldehydes, however, optical purity of the starting material has not been demonstrated in all cases. 

A convenient route to highly enantiomerically enriched a-alkoxy tributylslannanes 17 involves the enanlioselective reduction of acyl stannanes 16 with chiral reducing agents10. Thus reaction of acyl stannanes with lithium aluminum hydride, chirally modified by (S)-l,l -bi-naphthalene-2,2 -diol, followed by protection of the hydroxy group, lead to the desired a-alkoxy stannanes 17 in optical purities as high as 98 % ee. 

When using enantiomerically enriched aldehydes, precautions should be taken in order to avoid their racemization prior to addition. It is recommended not to use reagents of high... 

Allylmetal reagents which hear alkyl or aryl groups at both termini are stereogenic and usually add aldehydes w ith a high degree of reagent-induced stereoselectivity (Section D.3.3.1.5.1.). Some of these reagents have been prepared in enantiomerically enriched form and used in enantioselective synthesis. Table 4 collects some representative examples. 

Table 2. Enantiomerically Enriched [l-(Diisopropylaminocarbonyloxy)-2-alkenyl]lithium-TMF.DA Complexes by Deprotonation of Optically Active Precursors...

I-(Diisopropylaminocarbonyloxy)-2-alkenyllithium-TMEDA Complexes (Enantiomerically Enriched or Racemic) General Procedure19,6S. 

Enantiomerically Enriched 4-Acetoxy-l,3-diphenyl-2-alkanones General Procedure120 ... 

With 1,3-Chirality Transfer from Enantiomerically Enriched Allyllithium Derivatives... 

Enantiomerically enriched l-(diisopropylaminocarbonyloxy)allyllithium derivatives (Section 1.3.3.3.1.2.) add to carbonyl compounds with syn-l,3-chirality transfer21, giving good evidence for a pericyclic transition state in the main reaction path (Section 1.3.3.1.). However, since the simple diastereoselectivity and the degree of chirality transfer are low, for synthetic purposes a metal exchange with titanium reagents or trialkyltin halides (Section D.1.3.3.3.8.2.3.) is recommended. 

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. 

Enantiomerically enriched formyl irimclhyleiiemethane -irontricarbonyl complexes add to allylzinc bromides with high stereoselectivity. This was used, after photochemical deprotection, in an enantioselcctive synthesis of the insect pheromone (-)-ipsdienol4s. 

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 ... 

Good chemical yields were obtained with the lithium derivative whereas very high diastereose-lectivities were obtained with the titanium derivative. These adducts were readily hydrolyzed with 0.1 N hydrochloric acid to enantiomerically enriched nitro amino acids, methyl 2-amino-3-methyl-4-nitrobutanoates. 

The preparation of enantiomerically enriched a-ketosulphoxides 272 was also based on a kinetic resolution involving the reaction of the carbanion 273 derived from racemic aryl methyl sulphoxides with a deficiency of optically active carboxylic esters 274334, (equation 151). The degree of stereoselectivity in this reaction is strongly dependent on the nature of both the group R and the chiral residue R in 274. Thus, the a-ketosulphoxide formed in the reaction with menthyl esters had an optical yield of 1.3% for R = Et. In the... 

A kinetic resolution of racemic sulphoxides was observed in the reduction by chiral polyiminoalanes. The efficiency of this process depends on the molecular structure of the polyiminoalane. With open pseudo-cubic tetra [JV-(l-phenylethyl)]imidoalane, unreacted sulphoxides were isolated in enantiomeric enrichment up to 75%. Optical purity was shown to increase with increasing the reaction temperature, a maximum enrichment being observed between 55 and 70 °C336. 

Enantiomers (M)- and (P)-helicenebisquinones [32] 93 have been synthesized by high pressure Diels-Alder reaction of homochiral (+)-(2-p-tolylsulfo-nyl)-l,4-benzoquinone (94) in excess with dienes 95 and 96 prepared from the common precursor 97 (Scheme 5.9). The approach is based on the tandem [4 + 2] cycloaddition/pyrolitic sulfoxide elimination as a general one-pot strategy to enantiomerically enriched polycyclic dihydroquinones. Whereas the formation of (M)-helicene is explained by the endo approach of the arylethene toward the less encumbered face of the quinone, the formation of its enantiomeric (P)-form can be the result of an unfavourable interaction between the OMe group of approaching arylethene and the sulfinyl oxygen of 94. 

It is well known that certain microorganisms are able to effect the deracemization of racemic secondary alcohols with a high yield of enantiomerically enriched compounds. These deracemization processes often involve two different alcohol dehydrogenases with complementary enantiospedficity. In this context Porto ef al. [24] have shown that various fungi, induding Aspergillus terreus CCT 3320 and A. terreus CCT 4083, are able to deracemize ortho- and meta-fluorophenyl-l-ethanol in good... 

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