Ketones asymmetric catalysis

Keywords Aldol, Direct, Ketone, Asymmetric catalysis, Enantioselective reaction, Diastereo-selectivity, 1,2-Diol, Aldehyde, Enamine, Lewis acid, Bronsted base, Organocatalysis, Bimetal-... 

The past thirty years have witnessed great advances in the selective synthesis of epoxides, and numerous regio-, chemo-, enantio-, and diastereoselective methods have been developed. Discovered in 1980, the Katsuki-Sharpless catalytic asymmetric epoxidation of allylic alcohols, in which a catalyst for the first time demonstrated both high selectivity and substrate promiscuity, was the first practical entry into the world of chiral 2,3-epoxy alcohols [10, 11]. Asymmetric catalysis of the epoxidation of unfunctionalized olefins through the use of Jacobsen s chiral [(sale-i i) Mi iln] [12] or Shi s chiral ketones [13] as oxidants is also well established. Catalytic asymmetric epoxidations have been comprehensively reviewed [14, 15]. 

The complex Pd-(-)-sparteine was also used as catalyst in an important reaction. Two groups have simultaneously and independently reported a closely related aerobic oxidative kinetic resolution of secondary alcohols. The oxidation of secondary alcohols is one of the most common and well-studied reactions in chemistry. Although excellent catalytic enantioselective methods exist for a variety of oxidation processes, such as epoxidation, dihydroxy-lation, and aziridination, there are relatively few catalytic enantioselective examples of alcohol oxidation. The two research teams were interested in the metal-catalyzed aerobic oxidation of alcohols to aldehydes and ketones and became involved in extending the scopes of these oxidations to asymmetric catalysis. 

R. Noyori and T. Ohkuma, Asymmetric Catalysis by Architectural and Functional Molecular Engineering Practical Chemo- and Stereoselective Hydrogenation of Ketones , Angew. Chem. Int. Ed. Engl, 2001, 40, 40. 

Noyori, R. and Okhuma, T. (2001) Asymmetric catalysis by architectural and functional molecular engineering practical chemo- and stereoselective hydrogenation of ketones. Angewandte Chemie-International Edition, 40 (1), 40-73. 

Abstract In the first part of this mini review a variety of efficient asymmetric catalysis using heterobime-tallic complexes is discussed. Since these complexes function at the same time as both a Lewis acid and a Bronsted base, similar to enzymes, they make possible many catalytic asymmetric reactions such as nitroal-dol, aldol, Michael, Michael-aldol, hydrophosphonyla-tion, hydrophosphination, protonation, epoxide opening, Diels-Alder and epoxi-dation reaction of a, 3-unsaturated ketones. In the second part catalytic asymmetric reactions such as cya-nosilylations of aldehydes... 

TABLE 12. The asymmetric reduction of prochiral ketones under catalysis of chiral urea derivative 8173 (in all reactions 5% catalyst was used)... 

For these and similar reactions recently a variety of Lewis acidic aluminium, rare earth metals, and titanium alkoxides have been applied. Alkoxides have the additional advantage that they can be made as enantiomers using asymmetric alcohols which opens the possibility of asymmetric catalysis. Examples of asymmetric alcohols are bis-naphtols, menthol, tartaric acid derivatives [28], Other reactions comprise activation of aldehydes towards a large number of nucleophiles, addition of nucleophiles to enones, ketones, etc. 

In 2008, the same group employed chiral dicarboxylic acid (R)-5 (5 mol%, R = 4- Bu-2,6-Me2-CgHj) as the catalyst in the asymmetric addition of aldehyde N,N-dialkylhydrazones 81 to aromatic iV-Boc-imines 11 in the presence of 4 A molecular sieves to provide a-amino hydrazones 176, valuable precursors of a-amino ketones, in good yields with excellent enantioselectivities (35-89%, 84-99% ee) (Scheme 74) [93], Aldehyde hydrazones are known as a class of acyl anion equivalents due to their aza-enamine structure. Their application in the field of asymmetric catalysis has been limited to the use of formaldehyde hydrazones (Scheme 30). Remarkably, the dicarboxylic acid-catalyzed method applied not only to formaldehyde hydrazone 81a (R = H) but also allowed for the use of various aryl-aldehyde hydrazones 81b (R = Ar) under shghtly modified conditions. Prior to this... 

Cyanation of carbonyl compounds has one of the richest histories of any transformation in the field of asymmetric catalysis, and intensive research efforts have continued unabated since the editorial deadline for the first edition of Comprehensive Asymmetric Catalysis in 1998. This chapter will summarize all efforts in this area from 1998 to date, highlighting the most important catalytic systems from a synthetic and/or mechanistic standpoint. Significant advances in both the cyanation of aldehydes (formation of secondary cyanohydrins Section 28.2.1) and the cyanation of ketones (formation of tertiary cyanohydrins Section 28.2.2) will be addressed [1,2]. 

The chemoenzymatic synthesis of chiral alcohols is a field of major interest within biocatalytic asymmetric conversions. A convenient access to secondary highly enan-tiomerically enriched alcohols is the usage of alcohol dehydrogenases (ADHs) (ketoreductases) for the stereoselective reduction of prochiral ketones. Here, as in many other cases in asymmetric catalysis, enzymes are not always only an alternative to chemical possibilities, but are rather complementary. Albeit biocatalysts might sometimes seem to be more environmentally friendly, asymmetric ketone reduction... 

Asymmetric catalysis undertook a quantum leap with the discovery of ruthenium and rhodium catalysts based on the atropisomeric bisphosphine, BINAP (3a). These catalysts have displayed remarkable versatility and enantioselectivity in the asymmetric reduction and isomerization of a,P- and y-keto esters functionalized ketones allylic alcohols and amines oc,P-unsaturated carboxylic acids and enamides. Asymmetric transformation with these catalysts has been extensively studied and reviewed.81315 3536 The key feature of BINAP is the rigidity of the ligand during coordination on a transition metal center, which is critical during enantiofacial selection of the substrate by the catalyst. Several industrial processes currently use these technologies, whereas a number of other opportunities show potential for scale up. 

First tests of the ligand in the hydrosilylation of ketones catalyzed by [(41)RhI(COD)] only yielded racemic mixtures of the secondary alcohols, and no further application in asymmetric catalysis of 41 has been reported to date. 

Microbial Asymmetric Catalysis - Enantioselective Reduction of Ketones"... 

Labande et al. tested the rhodium(I) complexes of diphenylphosphinoferrocenyl functionalised NHC ligands (Cp,Cp and Cp,Cp substitution) in the hydrosilylation of ketones finding these complexes of only moderate activity [186]. As no attempt was made for the chiral resolution of the catalysts prior to use in catalysis, the prochiral acetophenone could not be tested in asymmetric catalysis. 

Experiments conducted in the mid-1980s by Agami indicated a small nonlinear effect in the asymmetric catalysis in the Hajos-Parrish-Wiechert-Eder-Sauer reaction (Scheme 6.7). Agami proposed that two proline molecules were involved in the catalysis the first proline forms an enamine with the side chain ketone and the second proline molecule facilitates a proton transfer. Hajos and Parrish reported that the proline-catalyzed cyclization shown in Scheme 6.7 did not incorporate when run in the presence of labeled water. While both of these results have since been discredited—the catalysis is first order in catalyst and is incorporated into... 

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