Chiral auxiliary strategy

The conceptual complement to the chiral modification of the catalyst is the temporary modification of the substrate. Unlike the chiral auxiliary strategy, temporary substrate modification has greater latitude in introducing the kind of groups... 

With the improved route to prepare the triazole fragment 3 and the one-pot method to access keto amide 25 demonstrated, we set out to explore the chiral auxiliary strategy that had been demonstrated previously from keto ester 10. 

Many chiral auxiliaries that fulfill all of these requirements are currently available from the chiral pool and from synthetic and semisynthetic sources. A very limited collection of this type of stereoselective syntheses is presented in Fig. 3 to illustrate the fundamental principles of the chiral auxiliary strategy. 

Finally comes the step which shows the power of chiral auxiliary strategy we just remove the chiral auxiliary from the product by treating with a nucleophile. The auxiliary can in principle be used again, but most importantly of all, the product obtained is just one of the two enantiomers we made in the racemic version of this reaction. This isn t a resolution—all... 

This is what we mean by a chiral auxiliary strategy... 

The synthesis of 8 is a very rare example that utilizes diastereoselective pathways to achieve chiral calixarenes. In most cases chiral groups are simply attached to the macrocyclic ring. Here, the stereogenic centers were introduced on an imine-calixarene scaffold using a chiral auxiliary strategy. 

Apart from the above chiral auxiliary strategy, several additional asymmetric methods have been developed for the synthesis of chiral warfarin, such as asymmetric hydro-genation and enantioselective hetero-Diels-Alder... 

Upon removal of the auxiliary, an enantioenriched product could be obtained. The application of chiral auxiliary-based methods to Simmons-Smith cyclopropanation not only provided a useful synthetic strategy, but it also served to substantiate earlier mechanistic hypotheses regarding the directing influence of oxygen-containing functional groups on the zinc reagent [6dj. 

The retrosynthetic analysis presented in Scheme 6 (for 1, 2, and 16-19) focuses on these symmetry elements, and leads to the design of a strategy that utilizes the readily available enantiomers of xylose and tartaric acid as starting materials and/or chiral auxiliaries to secure optically active materials.14 Thus by following the indicated disconnections in Scheme 6, the initially generated key intermediates 16-19 can be traced to epoxide 23 (16,19 =>23),... 

To date, direct asymmetric synthesis of optically active chiral-at-metal complexes, which by definition leads to a mixture of enantiomers in unequal amounts thanks to an external chiral auxiUary, has never been achieved. The most studied strategy is currently indirect asymmetric synthesis, which involves (i) the stereoselective formation of the chiral-at-metal complex thanks to a chiral inductor located either on the ligand or on the counterion and then (ii) removal of this internal chiral auxiliary (Fig. 4). Indeed, when the isomerization of the stereogenic metal center is possible in solution, in-... 

Among the various strategies [34] used for designing enantioselective heterogeneous catalysts, the modification of metal surfaces by chiral auxiliaries (modifiers) is an attractive concept. However, only two efficient and technically relevant enantioselective processes based on this principle have been reported so far the hydrogenation of functionalized p-ketoesters and 2-alkanons with nickel catalysts modified by tartaric acid [35], and the hydrogenation of a-ketoesters on platinum using cinchona alk oids [36] as chiral modifiers (scheme 1). 

Figure 1-31. Strategy for generation of new chiral centers on a chiral substrate. A and B must be homochiral. A-C(x), chiral substrate B-C(y), chiral reagent I, desired transformation II, double asymmetric induction III, removal of the chiral auxiliary. Reprinted with permission by VCH, Ref. 88.

The epoxidation of enones with poly-D-leucine is complementary to other strategies. Enders et u/.[8] introduced a new method for the asymmetric epoxidation of a-enones using diethylzinc, oxygen and (1R, lR)-or (IS1, 2S)-N-methylpseudoephedrine as chiral auxiliary. 

Gerard Uhommet was born in 1945 in Paris (France). He obtained his M.Sc. from the University of Paris in 1969. He carried out his Ph.D. studies under the supervision of Profs Pierre Maitte and Henri Sliwa at UPMC (P. and M. Curie University), Paris between 1970 and 1975. After a postdoctoral position at the East Anglia University in Norwich, UK, with Prof A.R. Katritzky (1976-1977), he accepted a position as Assistant Professor at UPMC, Paris. In 1985, he became Full Professor at the same university. His research interests include the development of new strategies sparing chiral auxiliaries for use in asymmetric and natural product synthesis. 

Finally, another possibility is to design enantioselective syntheses by using external chiral auxiliaries either in catalytic or in stoichiometric quantities [21], Since these strategies are nowadays of great interest in organic synthesis, we will consider here some of the most recent results achieved in enantioselective aldol condensations, as well as in the asymmetric epoxidation and hydroxylation of olefmic double bonds. 

The diastereomerically related keto esters 53 and 55, activated for removal of the chiral auxiliary, were obtained from 5 and 9. The requisite nitrogen atom was introduced by an azide displacement of chloride and at an opportune stage of the synthesis an intramolecular aminolysis of the carboxylic ester provided the enantiomerically related keto lactams 54 and 56. Although shorter routes to these popular synthetic targets have been reported in recent years, the conversion of 9 to (—)-iso-nitramine (ten steps, 50% overall yield) clearly illustrates the efficiency of the asymmetric Birch reduction-alkylation strategy for construction of the azaspiroundecane ring system. 

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