Enantiofacial discrimination

The above interesting approach to the asymmetric allyltitanation reaction does, however, have a limitation. Thus, L-glucose is much more expensive that the D-form and, consequently, homoallylic alcohols of the opposite configuration cannot easily be obtained by this method. In an attempt to induce the opposite si face selectivity, other acetonide derivatives of monosaccharides from the xylose, idose, and allose series were tested [42b,42c], The enantiofacial discrimination was, however, much lower than that with DAGOH and both re and si face selective additions to aldehydes were observed. 

The success of bis(oxazoline)-copper(II) catalyzed Diels-Alder reactions involving acryloylimides as dienophiles has been extended to the Michael reaction, Eqs. 204 and 205. The observed enantiofacial discrimination in the Diels-Alder reactions was expected to translate well to Michael reactions involving enolsilanes as nucleophiles. Indeed, fumarate-derived imides afford Michael adducts of enolsilanes in high enantioselectivity (240). Diastereoselectivity in these reactions may be regulated by judicious choice of thioester and enolsilane geometry to provide either diastereomer in high selectivity (>99 1 syn or 95 5 anti). 

Cinnamate salts and cinnamic amides react with low regioselectivity to yield mixtures of the 2- and 3-alkylated products . orflzo-Substituted aryllithium-(-)-sparteine complexes 468 add with good enantiofacial discrimination to orf/zo-substituted ferf-butyl cinnamates 467 to give 469 (equation 128) ". The ehiral additive (i ,i )-l,2-dimethoxy-1,2-diphenylethane in some cases gave improved ee values. 

The last incorporated stereocenter is now responsible for the enantiofacial discrimination, as was the case for tin-aUcoxides, which was shown by detailed... 

The new aldolase differs from all other existing ones with respect to the location of its active site in relation to its secondary structure and still displays enantiofacial discrimination during aldol addition. Modification of substrate specificity is achieved by altering the position of the active site lysine from one /3-strand to a neighboring strand rather than by modification of the substrate recognition site. Determination of the 3D crystal structure of the wild type and the double mutant demonstrated how catalytic competency is maintained despite spatial reorganization of the active site with respect to substrate. It is possible to perturb the active site residues themselves as well as surrounding loops to alter specificity. 

We designed and prepared the structurally rigid, chiral spiro ammonium salts 32 as a new C2-symmetric chiral phase-transfer catalyst (Fig. 4.1), and successfully applied this to the highly efficient, catalytic enantioselective alkylation of 28 under mild conditions [24]. A key finding was the significant effect of an aromatic substituent at the 3,3 -position of one binaphthyl subunit of 32 (Ar) on the enantiofacial discrimination, and (S,S)-32e was revealed as the catalyst of choice for preparing a variety of essentially enantiopure a-amino acids by this transformation (Table 4.3). 

Siering C, Grimme S, Waldvogel SR (2005) Direct assignment of enantiofacial discrimination on single heterocyclic substrates by self-induced CD. Chem-Eur J 11 1877-1888... 

Enantiofacial discrimination of achiral enolates by chiral electrophiles is also possible. Duhamel and co-workers reported that the reaction of the... 

The asymmetric induction in the formation of 214 stems from an eiiantiodifferentiation of two double bonds. The intramolecular jr-enantiofacial discrimination (cf. Scheme 3-49 for the intermolecular version) has also been successful, as shown by the asymmetric construction of quaternary carbon centers in the preparation of spirooxindoles 217 from 216 (Scheme 3-51). It is amazing that each product enantiomer was obtained selectively by careful choice of reaction conditions and, remarkably, by applying exactly the same enantiomer of the chiral phosphane ligand [122]. 

As pointed out in an earlier section, the ees for the asymmetric hydroxylation of acyclic enolates derived from a-branched carbonyl compounds is often low because of the difficulty in generating a specific enolate geometric isomer as well as poor enantiofacial discrimination between the re and si faces of the enolate (Scheme 25). In one example of a double stereodifferentiation process, the asymmetric oxidation of a chiral enolate, was successfully employed to circumvent these difficulties <87JOC5288>. For the matched pair, (—)-(179) and oxaziridine (—)-(114), the de was 88-91% (Equation (43)) whereas with the mismatched pair, (—)-(179) and (+)-(114), the de dropped to 48.4%. The pyrrolidine methanol chiral auxiliary in (180) was removed without racemization by basic hydrolysis affording nonracemic atrolactic acid in 70-89% yield. 

The secondary binding group y to the olefin is typically a carbonyl group and is necessary for chelation of the substrate to the rhodium atom to provide an intermediate of the type 5 (Fig. 3). This ordered transition state orientates the substrate so that the hydrogen adds predominantly onto only one face of the olefin, providing high enantiofacial discrimination in the formation of the product. 

Of special importance is a mixed lithium-magnesium complex, since the individual metal enolates show much lower enantiofacial discrimination. (2/l,3/ )-Dipivaloyltartaric acid is not a useful proton source, however, tert-butyl alcohol, 3,4-dimethyl-5-phenyl-2-imidazolidinone and 2-(Ar-isopropyl-Ar-methylamino)-l-phenylpropanoI (9-H) yield highly enantiomerically enriched (R)- or (S )-oc-damascone (11), especially in the presence of lithium (+)- or (-)-2-(Ar-iso-propyl-A -methylamino)-1 -phenylpropanolate (9-Li) as an auxiliary. 

Higher enantioselectivities are obtained in tetrahydrofuran as solvent compared to diethyl ether. However, the enantiofacial discrimination is improved if diethyl ether with 5-10% tetrahydrofuran is used. The strength of this effect depends on the nature of the proton source. 

Northrup and MacMillan extended the iminium-mediated Diels-Alder reactions to a,p-unsaturated ketones using a new chiral amine catalyst (Schane 1.43) [66]. They found that cycloaddition of a,P-unsaturated ketones was unsuccessful with the chiral amine salts previously identified as excellent catalysts for enal activation. In contrast, the 2-(5-methylfuryl)-derived imidazolidinone 118 afforded good levels of enantiofacial discrimination while maintaining high reaction efficiency (89% yield, 25 1 endo/exo, 90% ee). 

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