Chirality regeneration

The reaction is limited to allylic alcohols other types of alkenes do not or not efficiently enough bind to the titanium. The catalytically active chiral species can be regenerated by reaction with excess allylic alcohol and oxidant however the titanium reagent is often employed in equimolar amount. 

Alkaline hydrolysis of the adducts 6 and 7, which is fairly mild in the case of the imide adducts, liberates 3-hydroxycarboxylic acids 8 or ent-8 and simultaneously regenerates the chiral auxiliary reagent. Furthermore, both enantiomers of the 3-hydroxycarboxylic acid are available in almost optically pure form depending on which reagent is chosen as the starting material. 

An example that refers to the third method additives can be employed is described below. Markedly enhanced enantioselectivity was reported for P. cepacia lipase and subtilisin Carlsberg with chiral substrates converted to salts by treatment with numerous Bronsted-Lowry adds or bases [63]. This effect was observed in various organic solvents but not in water, where the salts apparently dissociate to regenerate... 

Enantioenriched alcohols and amines are valuable building blocks for the synthesis of bioactive compounds. While some of them are available from nature s chiral pool , the large majority is accessible only by asymmetric synthesis or resolution of a racemic mixture. Similarly to DMAP, 64b is readily acylated by acetic anhydride to form a positively charged planar chiral acylpyridinium species [64b-Ac] (Fig. 43). The latter preferentially reacts with one enantiomer of a racemic alcohol by acyl-transfer thereby regenerating the free catalyst. For this type of reaction, the CsPhs-derivatives 64b/d have been found superior. 

As oxidation also converts the original chiral terpene-derived group to an alcohol, it is not directly reusable as a chiral auxiliary. Although this is not a problem with inexpensive materials, the overall efficiency of generation of enantiomerically pure product is improved by procedures that can regenerate the original terpene. This can be done by heating the dialkylborane intermediate with acetaldehyde. The a-pinene is released and a diethoxyborane is produced.204... 

Kitamura and Noyori have reported mechanistic studies on the highly diastere-omeric dialkylzinc addition to aryl aldehydes in the presence of (-)-i-exo-(dimethylamino)isoborneol (DAIB) [33]. They stated that DAIB (a chiral (i-amino alcohol) formed a dimeric complex 57 with dialkylzinc. The dimeric complex is not reactive toward aldehydes but a monomeric complex 58, which exists through equilibrium with the dimer 57, reacts with aldehydes via bimetallic complex 59. The initially formed adduct 60 is transformed into tetramer 61 by reaction with either dialkylzinc or aldehydes and regenerates active intermediates. The high enantiomeric excess is attributed to the facial selectivity achieved by clear steric differentiation of complex 59, as shown in Scheme 1.22. 

The production of enantiomerically pure products is of great importance in chemical industry. The most desirable way to obtain these products is by chiral catalysis. Homogeneous complexes can often be used as chiral catalysts however, because of their difficult regenerability, the development of heterogeneous chiral catalysts by immobilization of these complexes is difficult but highly desired. 

An electron-rich metal can deprotonate the dicarbonyl derivative, affording the hydridopalladium intermediate 23, which can undergo a Tr-allyl 24 formation through diene insertion (which can be assimilated to a hydridopalladation of olefin) (Scheme 7). The attack of the enolate to the -jr-allyl species occurs with good enantioselectivity in the presence of the chiral ligand. The final product 21 is released and the palladium(O) complex 22 is regenerated. 

LA represents Lewis acid in the catalyst, and M represents Bren sled base. In Scheme 8-49, Bronsted base functionality in the hetero-bimetalic chiral catalyst I can deprotonate a ketone to produce the corresponding enolate II, while at the same time the Lewis acid functionality activates an aldehyde to give intermediate III. Intramolecular aldol reaction then proceeds in a chelation-controlled manner to give //-keto metal alkoxide IV. Proton exchange between the metal alkoxide moiety and an aromatic hydroxy proton or an a-proton of a ketone leads to the production of an optically active aldol product and the regeneration of the catalyst I, thus finishing the catalytic cycle. 

More recently, Kobayashi and co-workers reported on Zr-catalyzed additions of ketene and thioketene acetals to a range of aromatic and aliphatic aldehydes (Scheme 6.25) [83], As in the Erker study, the presence of protic additives proved critical here as well. As the example in Scheme 6.25 illustrates, the addition of larger amounts of iPrOH improved the yield and ee it was reported that in the absence of the alcohol additive much lower yield and enantioselectivities" were attained. The proposed catalytic cycle, depicted in Scheme 6.25, provides a plausible rationale for the role of the additive Si transfer is facilitated by iPrOH to regenerate the chiral catalyst. Finally, it is worthy of mention... 

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