External chirality induction

The internal and the external chiral induction each activate the same proton they are matched [72] and enforce each other. 

The photochemical behaviour of 7 OEt is the first example in which the reaction of achiral molecules in an achiral crystal packing does not occur at random but stereospecifically, resulting in a syndiotactic structure. As no external chiral catalyst exists in the reaction, the above result is a unique type of topochemical induction , which is initiated by chance in the formation of the first cyclobutane ring, but followed by syndiotactic cyclobutane formation due to steric repulsions in the crystal cavity. That is, the syndiotactic structure is evolved under moderate control of the reacting crystal lattice. 

SRURC is such an interesting example of the facile formation of chiral induction from racemic mixtures in the absence of any external symmetry-breaking agent that it deserves special attention. One of the best studied examples is the crystallization of bromofluoro-l,4-benzodiazepinooxazole (Fig. 11.3), which possesses a single asymmetric carbon atom at C14 and a potentially asymmetric bridgehead nitrogen atom at N4. 

If stoichiometric quantities of the chiral auxiliary are used (i.e., if the chiral auxiliary is covalently bonded to the molecule bearing the prochiral centres) there are in principle three possible ways of achieving stereoselection in an aldol adduct i) condensation of a chiral aldehyde with an achiral enolate ii) condensation of an achiral aldehyde with a chiral enolate, and iii) condensation of two chiral components. Whereas Evans [14] adopted the second solution, Masamune studied the "double asymmetric induction" approach [22aj. In this context, the relevant work of Heathcock on "relative stereoselective induction" and the "Cram s rule problem" must be also considered [23]. The use of catalytic amounts of an external chiral auxiliary in order to create a local chiral environment, will not be considered here. 

We turn now to a presentation of our own research on the use of built-in or internal chiral auxiliaries for asymmetric induction in photochemical reactions in the crystalline state [28]. This work is a natural outgrowth of the work of Toda and coworkers on the use of external chiral host compounds for the same purpose discussed in Sect. 2.2. In both cases, the primary role of the chiral auxiliary is to guarantee the presence of a chiral space group for the ensuing solid-state photochemical reaction. 

If the carbamate already contains a stereogenic centre, the internal chiral induction will either oppose or enforce the external induction exerted by the chiral base. In the (5 )-A,A-dibenzylphenylalaninol carbamate 89 (equation 19), i-BuLi/TMEDA removes preferently the pro-R-H to form the (25, 17 )-configured lithium compound 90a besides few 91a, ratio 90 10. However, when i-BuLi/(—)-sparteine (11) is applied, due to its high preference for /jro-i -protons, the ratio 90b/91b is inverted (10 90). The intermediates had been applied to the synthesis of several dipeptide isostere spacers. ... 

External Asymmetric Induction with Chiral Auxiliaries or Catalysts... 

Seebach and Naef1961 generated chiral enolates with asymmetric induction from a-heterosubstituted carboxylic acids. Reactions of these enolates with alkyl halides were found to be highly diastereoselective. Thus, the overall enantioselective a-alkyla-tion of chiral, non-racemic a-heterosubstituted carboxylic acids was realized. No external chiral auxiliary was necessary in order to produce the a-alkylated target molecules. Thus, (S)-proline was refluxed in a pentane solution of pivalaldehyde in the presence of an acid catalyst, with azeotropic removal of water. (197) was isolated as a single diastereomer by distillation. The enolate generated from (197) was allylated and produced (198) with ad.s. value >98 %. The substitution (197) ->(198) probably takes place with retention of configuration 196>. 

Intramolecular oxidative cyclizations in the appropriately substituted phenols and phenol ethers provide a powerful tool for the construction of various practically important polycyclic systems. Especially interesting and synthetically useful is the oxidation of the p-substituted phenols 12 with [bis(acyloxy)iodo]-arenes in the presence of an appropriate external or internal nucleophile (Nu) leading to the respective spiro dienones 15 according to Scheme 6. It is assumed that this reaction proceeds via concerted addition-elimination in the intermediate product 13, or via phenoxenium ions 14 [18 - 21]. The recently reported lack of chirality induction in the phenolic oxidation in the presence of dibenzoyltar-taric acid supports the hypothesis that of mechanism proceeding via phenoxenium ions 14 [18]. The o-substituted phenols can be oxidized similarly with the formation of the respective 2,4-cyclohexadienone derivatives. 

Thorough investigation of nitrogen substituents of phenylalanine for asymmetric induction disclosed that A-MOM-A-lloc derivative 40 gives a-methylated product in 81% ee and in 96% yield without the aid of any external chiral... 

Chiral synthesis, also called asymmetric synthesis, is synthesis which preserves or introduces a desired chirality. Principally, there are three different methods to induce asymmetry in reactions. There can be either one or several stereogenic centres embedded in the substrate inducing chirality in the reaction (i.e. substrate control) or an external source providing the chiral induction (i.e. reagent control). In both cases the obtained stereoselectivity reflects the energy difference between the diastereomeric transition states. 

According to the general principles of asymmetric synthesis, chiral induction can be effected via substrate, reagent, or external (catalyst) control. Effective substrate control in the sense of induced diastereoselectivity requires a preformed stereogenic center within the substrate. For organometallic catalytic conversions a stereospecific reaction course and simple diastereoselectivity, as outlined above, is prerequisite. 

Three photoreactions produced unstable intermediates (10 secstrong interactions with external chiral additives, have led to interesting asymmetric inductions. 

In the presence of (-)-sparteine, efficient enantiotopic differentiation is caused by this chiral external ligand (Sect. 2.5). In the current section we deal with internal chiral induction in chiral alkyl carbamates. 

In 123, the internal chiral induction can be overridden by the external ligand (-)-sparteine (Sect. 2.5.4) [78]. 

On the other hand the external asymmetric induction strongly depended on the chiral auxiliary. The careful analysis of the hypothetical zwitterionic intermediates c-a and c-fi indicated the formation of a stereogenic ammonium center. In terms of the well-known 1,3 chirality transfer of 3,3sigmatropic rearrangements, the... 

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