Asymmetric reactions alkylation, catalytic

Pd-catalyzed asymmetric allylic alkylation is a typical catalytic carbon-carbon bond forming reaction [ 126 -128]. The Pd-complex of the ligand (R)-3b bearing methyl, 2-biphenyl and cyclohexyl groups as the three substituents attached to the P-chirogenic phosphorus atom was found to be in situ an efficient catalyst in the asymmetric allylic alkylation of l-acetoxy-l,3-diphenylprop-2-en (4) with malonate derivatives in the presence of AT,0-bis(trimethylsilyl)acetamide (BSA) and potassium acetate, affording enantioselectivity up to 96% and quantitative... 

The catalytic enantioselective addition of vinylmetals to activated alkenes is a potentially versatile but undeveloped class of transformations. Compared to processes with arylmetals and, particularly alkylmetals, processes with the corresponding vinylic reagents are of higher synthetic utility but remain scarce, and the relatively few reported examples are Rh-catalysed conjugate additions. In this context, Hoveyda et al. reported very recently an efficient method for catalytic asymmetric allylic alkylations with vinylaluminum reagents that were prepared and used in Thus, stereoselective reactions... 

Bayardon and Sinou have reported the synthesis of chiral bisoxazolines, which also proved to be active ligands in the asymmetric allylic alkylation of l,3-diphenylprop-2-enyl acetate, as well as cyclopropanation, allylic oxidations and Diels-Alder reactions. [62] The ligands do not have a fluorine content greater than 60 wt% and so are not entirely preferentially soluble in fluorous solvents, which may lead to a significant ligand loss in the reaction system and in fact, all recycling attempts were unsuccessful. However, the catalytic results achieved were comparable with those obtained with their non-fluorous analogues. 

As the examples in Scheme 2 illustrate, the emergence of catalytic RCM proved instrumental in rendering the Zr-catalyzed C-C bond-forming reaction a more viable method in asymmetric synthesis [5d]. Catalytic RCM of dienes 4 and 7, effected by 2 mol% of Ru catalyst la, leads to the formation of 5 and 8 in high yield. Subsequent Zr-catalyzed alkylation of the resulting heterocycles in the presence of 10 mol% 3b delivers unsaturated amides 6 and 9 in the optically pure form (>98% ee) and in 76% and 77% isolated yield, respectively (Scheme 2). 

Acrylonitrile, polymerization, 120 Activity of phase-transfer catalysts Sjj2 reactions, 170-175 weak-nucleophile Sj.Ar reactions, 175-182 Acyltetracarbonyl cobalt compound, cleavage in the carboxyalkylation of alkyl halides, 150 Addition reactions, Michael, catalytic asymmetric, 69,70f... 

The transition metal based catalytic species derived from hydrogen peroxide or alkyl hydroperoxides are currently regarded as the most active oxidants for the majority of inorganic and organic substrates " An understanding of the mechanism of these processes is therefore a crucial point in the chemistry of catalytic oxidations. This knowledge allows one to predict not only the nature of the products in a given process, but also the stereochemical outcome in asymmetric reactions. 

With 1-alkoxyallenes as proelectrophiles, the palladium-catalysed asymmetric allylic alkylation proceeds with 1,3-dicarbonyl compounds as pronucleophiles with excellent regioselectivity good enantioselectivity (82-99% ee) was obtained with the Trost lig- and. The pH of the medium proved crucial for the reactivity and selectivity. By using the more acidic Meldrum s acids, the reactions required a co-catalytic amount of a Brpnsted acid, such as CF3CO2H. On the other hand, the less acidic 1,3-diketones failed to react under these conditions but the reaction proved to occur in the presence of the weaker benzoic acid, suggesting the need for general base catalysis. Indeed, a mixture of Et3N and PhCOiH proved to be optimal (93-99% ee). A mechanistic model to rationalize these results has been developed.88... 

Muzart and coworkers have reported a new catalytic enantioselective protonation of prochiral enolic species generated by palladium-induced cleavage of p-ketoesters or enol carbonates of a-alkylated 1-indanones and 1-tetralones [21 ]. Among the various (S)-p-aminocycloalkanols examined, 17 and 18 were effective chiral catalysts for the asymmetric reaction and (J )-enriched a-alkylated 1-indanones and 1-tetralones were obtained with up to 72% ee. In some cases, the reaction temperature affected the ee. 

The obtained amino functionalised imidazolium salts could be used to generate the corresponding palladium(ll) carbene complexes using the silver(l) complexes as carbene transfer agents. Application of these palladium(ll) complexes (predominantly in situ) in asymmetric allylic alkylation reactions between ( )-l,3-diphenylprop-3-enyl acetate and dimethyl malonate (a standard reaction for this catalytic process [145]) gave up to 80% ee,... 

In an extension of this methodology, it has been demonstrated that in some cases the enantioselective alkylation of lithium enolates can be achieved by means of a catalytic amount of 1. As in the stoichiometric version (vide supra), the reaction conditions play a crucial role in determining the yield and % ee. One fundamental modification in the catalytic version is the addition of two equiv of an achiral bidentate amine [e.g. tetramethylethylenediamine (TMEDA) or Al,lV,7V, A -tetramethy-Ipropylene diamine (TMPDA)] to trap the large excess of lithium bromide present at the beginning of the reaction. This catalytic asymmetric variant is illustrated by the reaction of the lithium enolate of 1-tetralone with a variety of electrophiles (eq 7). In this example, the optimal reaction conditions were determined to be 0.05 equiv of 1,2.0 equiv of TMPDA, and 10.0 equiv of the alkyl halide. 

The rate of catalytic ethylmagnesation in the terminal alkenes of the reaction products is sufficiently slower, so that unsaturated alcohols and amines can be isolated in high yield (the second alkylation is not generally diastereoselective). Zr-catalyzed asymmetric olefin alkylation thus affords non-racemic reaction products that bear an alkene and a carbinol unit, functional groups that are readily amenable to a wide range of subsequent derivatization procedures. 

Katritzky and Harris reported in 1992 the use of diethylzinc for the chiral amino alcohol-mediated enantioselective addition to the C=N bond in these compounds (Scheme 12) [34]. These substrates act as masked activated N-acylimines. Of the large variety of Hgands available for the catalytic asymmetric reactions of dialkylzinc reagents,the sterically constrained P-dialkylamino alcohol, (-)-N,N-dibutylnorephedrine (DBNE) 18, prepared by alkylation of commercially available norephedrine, was selected for this study. Some preliminary experiments conducted with the use of -(aminobenzyl)benzotriazoles gave the ethylated product, but with no enantioselectivity. Diethylzinc (Et2Zn) was found to react even in the absence of a chiral promoter. The behavior of the less reactive N-(amidobenzyl)benzotriazoles 19a-g was then investigated. 

---