Addition enantioselectivity

Navarre L, Martinez R, Genet JP, Darses S. Access to enantioenriched a-amino esters via rhodium-catalyzed 1,4-addition/enantioselective protonation. J. Am. Chem. Soc. 2008 13 6159-6169. 

Silyl groups, which are non-polar electropositive groups without lone pairs, tolerate many chemical reactions that would not be possible in presence of hydroxy groups. The Fleming-Tamao Oxidation permits silyl groups to be used as masked hydroxy groups , which has found broad application in total syntheses. In addition, enantioselective hydrosilylation of alkenes followed by Fleming-Tamao oxidation allows the preparation of chiral alcohols. 

Tandem Asymmetric Conjugate Addition. Enantioselective conjugate addition of an organometallic reagent to a prochiral... 

Despite the obvious potential of cinchona alkaloids as bifunctional chiral catalysts of the nucleophilic addition/enantioselective protonation on prochiral ketenes, no further contribution has appeared to date and only a few papers described this asymmetric reaction with other catalysts [13], When the reaction is carried out with soft nucleophiles, the catalyst, often a chiral tertiary amine, adding first on ketene, is covalently linked to the enolate during the protonation. Thus, we can expect an optimal control of the stereochemical outcome of the protonation. This seems perfectly well suited for cinchona analogues and we can therefore anticipate successful applications of these compounds for this reaction in the near future. 

Despite the importance of the Michael addition in organic synthesis, the tandem conjugate addition/enantioselective protonation has been little explored [14] and only a few publications have involved cinchona alkaloids as bifunctional catalysts B for controlling the configuration of the chiral carbon created during protonation (Scheme 7.9). 

Pracejus and coworkers reported the first Michael addition/enantioselective protonation mediated by cinchona alkaloids [15]. The authors put a special emphasis on the requirement of using chiral P-N,N-dialkylamino alcohol to achieve significant inductions. The addition of benzyl thiol 16 on 2-phthalimidoacrylate 17 catalyzed by 5 mol% of quinidine 3 gave the best selectivity (Scheme 7.10). 

Scheme 7.11 Tandem thiophenol addition/enantioselective protonation on a-phenylacrylates [16].

Scheme 7.15 Deng s tandem Michael addition/enantioselective protonation [19].

Scheme 7.16 Deng s Michael addition/enantioselective protonation with acyclic cyanoacetates [19].

Then, the same group extended this strategy to transfer hydrogenation of 3 substituted quinolines with up to 86% ee (Scheme 10.25) [27]. They thought the transfer hydrogenation of 3 substituted quinolines was also a cascade reaction involving 1,4 hydride addition, enantioselective isomerization, and... 

Other additions. 4-Substituted dihydropyridines are usually synthesized by addition reactions on activated pyridines. Derivatization of 3-pyridinecarbalde-hyde into a C2-symmetrical imidazolidine enables the addition enantioselective by using soft nucleophiles, the attack of which is preceded by coordination to the chiral auxiliary. 

Dihydrofuran (10.137) has also proved to be a popular substrate for the asymmetric Heck reaction. Hayashi has reported that using a Pd/BINAP catalyst not only is the initial addition enantioselective, but that the diastereomeric intermediates, i.e. of structure (10.119) preferentially give different regioisomeric products (10.138) and (10.139). This effect is similar to that of a kinetic resolution (see Section 4.1). ... 

The first asymmetric direct intermolecular aldol reaction catalyzed by L-proline was disclosed by List, Lemer, and Barbas III in 2000 [5]. Other amino acids possessing secondary amine groups were also screened but at best exhibited the same activity [14]. Both functional groups present on an amino acid are essential for good catalytic activity. Additionally, enantioselectivity is dependent on the distance between the amino and carboxylic groups, with (3-amino acids exhibiting lower enantioselectiv-ities [8f, 15]. 

The introduction of a phosphate moiety into a polyhydroxy compound by classic chemical methods is tedious since it usually requires a number of protection and deprotection steps. Furthermore, oligophosphate esters as undesired byproducts arising from overphosphorylation are a common problem. Employing enzymes for the regioselective formation of phosphate esters can eliminate many of these disadvantages thus making these syntheses more efficient. Additionally, enantioselective transformations are also possible involving the desymmetrization of prochiral or weso-diols or the resolution of racemates. 

Nifrilases catalyze the conversion of organonitriles directly to the corresponding carboxylic acids. Synthetic hydrolysis of nitriles into the corresponding amides and carboxylic acids requires severe reaction conditions. A typical synthetic approach would require the use of 70% H2SO4 and heat (13). Such a reaction condition is not compatible when selectivity and the conservation of other hydrolysable functional groups in a substrate are desired. Biotransformation of nitrites can be accomplished under mild conditions, in an aqueous environment (13). Additionally, enantioselectivity of the biocatalytic conversion of nitriles to chiral acids has been demonstrated (14-16). Therefore, nifrilases provide an alternative route for synthetic processes that require conversion of nitriles to corresponding acids. 

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