Enantio-induction

There are three main criteria for design of this catalytic system. First, the additive must accelerate the cyclopropanation at a rate which is significantly greater than the background. If the additive is to be used in substoichiometric quantities, then the ratio of catalyzed to uncatalyzed rates must be greater than 50 1 for practical levels of enantio-induction. Second, the additive must create well defined complexes which provide an effective asymmetric environment to distinguish the enantiotopic faces of the alkene. The ability to easily modulate the steric and electronic nature of the additive is an obvious prerequisite. Third, the additive must not bind the adduct or the product too strongly to interfere with turnover. 

The intramolecular Claisen-Schmidt addition rate of 6-keto-6-p-r-butylphenyl hexanal in the presence of p-CD is minimal at neutral pH but is strongly accelerated in alkaline medium [12]. p-CD molecules bearing one or two imidazole groups catalyze the cyclization by a factor of 20-50 at pH 7, but the enantio-induction is minimal. 

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

The complexation procedure included addition of an equimolar amount of R,R-DBFOX/Ph to a suspension of a metal salt in dichloromethane. A clear solution resulted after stirring for a few hours at room temperature, indicating that formation of the complex was complete. The resulting solution containing the catalyst complex was used to promote asymmetric Diels-Alder reactions between cyclopen-tadiene and 3-acryloyl-2-oxazolidinone. Both the catalytic activity of the catalysts and levels of chirality induction were evaluated on the basis of the enantio-selectivities observed for the endo cycloadduct. 

Fluoboric acid is also an efficacious promoter of cyclic oxo-carbenium ions (Scheme 4.24) bearing an activated double bond which, in the presence of open-chain and cyclic dienes, rapidly undergo a Diels-Alder reaction [91]. Chiral a, -unsaturated ketones bearing a -hydroxy substituents, protected as acetals, react with various dienes in the presence of HBF4, affording Diels-Alder adducts that were isolated as alcohols by hydrolysis of the acetal group by TsOH. Some examples of reactions with isoprene are reported in Table 4.23. The enantios-electivity of the reaction is dependent on the size of the substituent R on the of-carbon high levels of asymmetric induction were observed with R = z-Pr (90 1) and R = t-Bu (150 1) and low levels with R = Me (2.7 1) and R = Ph (3.0 1). Scheme 4.24 shows the postulated reaction mechanism. 

In this section, various types of topochemical behaviour such as the even-numbered degree of polymerization mechanism, topochemical induction into the syndiotactic structure, stereo- and enantio-selective reactions, and the formation of highly strained cyclophanes are described. 

The first report to use diphosphite ligands in the asymmetric hydroformylation of vinyl arenes revealed no asymmetric induction [46]. An important breakthrough came in 1992 when Babin and Whiteker at Union Carbide patented the asymmetric hydroformylation of various alkenes with ee s up to 90%, using bulky diphosphites 2a-c derived from homochiral (2R, 4R)-pentane-2,4-diol (Scheme 4) [17]. Their early results showed that (a) bulky substituents are required at the ortho positions of the biphenyl moieties for good regio- and enantio-selectivity and (b) methoxy substituents in the para positions of the biphenyl moieties always produced better enantio-selectivities than those observed for the corresponding ferf-butyl-substituted analogues. 

SE.3.1.2. Desymmetrization of gem-Dwarboxylates An equivalent of asymmetric carbonyl addition can be achieved by the alkylation of gem-dicarboxylates (Scheme 8E.17). The alkylation of gem-dicarboxylates, which are easily prepared by the Lewis acid-catalyzed addition of acid anhydrides to an aldehyde, converts the problem of differentiating the two enantiotopic 7t-faces of a carbonyl group into that of asymmetric substitution of either enantiotopic C-O bond of the gem-dicarboxylate. Although asymmetric induction may be derived from enantio-discrimination in the ionization step or in the alkene coordination step, the fast and reversible nature of alkene coordination suggests that the ionization step is more likely to be the source of enantio-discrimination. 

Unless asymmetric induction is complete, it is necessary to remove the undesired enantiomer from the product mixture. Whereas in conventional diastereoselective asymmetric syntheses this removal can typically be readily accomplished by crystallization or chromatography, the separation of enantiomeric products can be problematic. Often, though, with enantio-enriched samples it is possible to recrystallize either the racemate from the pure enantiomer or, preferably, one enantiomer from the other [I2a,16,17], Another very effective method to produce enan-tiopure compounds is by enzymatic resolution of the enantio-enriched product from chiral PTC [16,18]. These methods are illustrated by examples in the alkylation section of this chapter (Chart 10.6). 

Buffer catalysis has been applied to induce chiral induction by enantio-selective protonation remarkable enantiomeric excess was achieved in the photodeconjugation of a,/3-unsaturated ketones and esters by using chiral catalysts for the ketonization of photoenols in aprotic solvents.29... 

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