Ketones chiral catalysts

Apart from tertiary amines, the reaction may be catalyzed by phosphines, e.g. tri- -butylphosphine or by diethylaluminium iodide." When a chiral catalyst, such as quinuclidin-3-ol 8 is used in enantiomerically enriched form, an asymmetric Baylis-Hillman reaction is possible. In the reaction of ethyl vinyl ketone with an aromatic aldehyde in the presence of one enantiomer of a chiral 3-(hydroxybenzyl)-pyrrolizidine as base, the coupling product has been obtained in enantiomeric excess of up to 70%, e.g. 11 from 9 - -10 ... 

Keywords acrylates, acrylamides, fumarates, a, -unsaturated ketones, vinyl ethers, vinyl sulphoxides, chiral dienophiles, chiral dienes, chiral catalysts polymer-supported chiral Lewis acids... 

Other S/N ligands have been investigated in the enantioselective catalytic reduction of ketones with borane. Thus, Mehler and Martens have reported the synthesis of sulfur-containing ligands based on the L-methionine skeleton and their subsequent application as new chiral catalysts for the borane reduction of ketones." The in situ formed chiral oxazaborolidine catalyst has been used in the reduction of aryl ketones, providing the corresponding alcohols in nearly quantitative yields and high enantioselectivities of up to 99% ee, as shown in Scheme 10.60. 

Catalytic Enantioselective Reduction of Ketones. An even more efficient approach to enantioselective reduction is to use a chiral catalyst. One of the most developed is the oxazaborolidine 18, which is derived from the amino acid proline.148 The enantiomer is also available. These catalysts are called the CBS-oxazaborolidines. 

Hu, A.G., Yee, G.T. and Lin, W.B. (2005) Magnetically recoverable chiral catalysts immobilized on magnetite nanopartides for asymmetric hydrogenation of aromatic ketones. Journal of the American Chemical Society, 127 (36), 12486-12487. 

Catalytic enantioselective nucleophilic addition of nitroalkanes to electron-deficient alke-nes is a challenging area in organic synthesis. The use of cinchona alkaloids as chiral catalysts has been studied for many years. Asymmetric induction in the Michael addition of nitroalkanes to enones has been carried out with various chiral bases. Wynberg and coworkers have used various alkaloids and their derivatives, but the enantiomeric excess (ee) is generally low (up to 20%).199 The Michael addition of methyl vinyl ketone to 2-nitrocycloalkanes catalyzed by the cinchona alkaloid cinchonine affords adducts in high yields in up to 60% ee (Eq. 4.137).200... 

As outlined in Section II,E, ketone and imine groups are readily hydrogenated via a hydrosilylation-hydrolysis procedure. Use of chiral catalysts with prochiral substrates, for example, R,R2C=0 or R,R2C=N— leads to asymmetric hydrosilylation (284, 285 Chapter 9 in this volume) and hence optically active alcohols [cf. Eq. (41)]. 

A chiral catalyst consisting of Irans-RuC]2(xy]binap)(daipen) and (CH3)3COK in 2-propanol effects asymmetric hydrogenation of a-, / -, and y-amino aromatic ketones [128]. Hydrogenation of 2-(dimethylamino)acetophenone catalyzed by the (R)-XylBINAP/(R)-DAIPEN-Ru complex [(R,R)-31D] gives the R amino alcohol in 93% ee (Fig. 32.36). The optical yield is increased up to 99.8%, when... 

Cyanohydrins are starting materials of widespread interest for preparing important compounds such as a-hydroxy acids/esters, a-amino acids, / -amino alcohols, a-hydroxy aldehydes, vicinal diols, and a-hydroxy ketones. Cyanohydrin compounds can be synthesized using various chiral catalysts such as cyclic... 

In Scheme 8 40, the reaction of 9-anthryl trifluoromethyl ketone 103 and mesityl trifluoromethyl ketone 104 with catecholborane 106 in the presence of 10 mol% of chiral catalyst 107 (CBS) provides (R)-carbinol 108 and 109 with 94% and 100% ee, respectively. When methyl ketone instead of trifluoromethyl ketone is used in the reaction, product 110 is obtained with ( -configuration in 99.7% ee with over 95% yield. 

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. 

Among many other methods for epoxidation of disubstituted E-alkenes, chiral dioxiranes generated in situ from potassium peroxomonosulfate and chiral ketones have appeared to be one of the most efficient. Recently, Wang et /. 2J reported a highly enantioselective epoxidation for disubstituted E-alkenes and trisubstituted alkenes using a d- or L-fructose derived ketone as catalyst and oxone as oxidant (Figure 6.3). 

Asymmetric catalytic reduction reactions represent one of the most efficient and convenient methods to prepare a wide range of enantiomerically pure compounds (i.e. a-amino acids can be prepared from a-enamides, alcohols from ketones and amines from oximes or imines). The chirality transfer can be accomplished by different types of chiral catalysts metallic catalysts are very efficient for the hydrogenation of olefins, some ketones and oximes, while nonmetallic catalysts provide a complementary method for ketone and oxime hydrogenation. 

One of the fundamental operations in organic synthesis remains the stereoselective reduction of carbonyl groups1241. In a process related to that reported by Hosomi et u/.[25], using hydrosilanes as the stoichiometric oxidant and amino acid anions as the catalytic source of chirality, a variety of ketones were reduced in good to excellent yield and with good stereoselectivity1261. This process reduces the amount of chiral catalyst needed and utilizes catalysts from the chiral pool that can be used directly in their commercially available form. 

Using methyl vinyl ketone as Michael acceptor, it was found (42) that a variety of donors gave optically active products when quinine was used as the chiral catalyst. Figure 7 lists the donors. Unfortunately in none of these cases... 

Reductive metallation of aldehydes (but not ketones) by tri-n-butyl-(trimethyisilyl)stannane to yield a-hydroxystannanes is catalysed by tetra-n-butylammonium cyanide [15]. Other phase-transfer catalysts are not as effective and solvents, other than tetrahydrofuran, generally give poorer conversions. Use of a chiral catalyst induced 24% ee with 3-phenylpropanal. 

The regio- and diastereo-selectivity of the Michael addition of 2-phenylcyclo-hexanone with a,p-unsaturated ketones are dependent on the reaction conditions. Mixtures of all six diastereoisomers resulting from reaction at either the 2- or 6-position of the cyclohexanone ring can be obtained using solid potassium hydroxide with tetra-n-butylammonium or A-benzylephcdrinium bromide catalysts. At 20°C with tetra-n-butylammonium bromide, the ratio of the 2,2- and 2,6-disubstituted cyclohexanones is ca. 3 2, but at higher temperatures with solid potassium f-butoxide the kinetically formed 2,6-isomer predominates (ca. 5 1) with the (2S,6R, R )-stereoisomer dominant, whereas greater amounts of the thermodynamically preferred 2,2-(2S,lR )-isomer are obtained with the chiral catalyst [61]. 

Asymmetric induction using catalytic amounts of quininium or A-methyl-ephedrinium salts for the Darzen s reaction of aldehydes and ketones with phenacyl halides and chloromethylsulphones produces oxiranes of low optical purity [3, 24, 25]. The chiral catalyst appears to have little more effect than non-chiral catalysts (Section 12.1). Similarly, the catalysed reaction of sodium cyanide with a-bromo-ketones produces epoxynitriles of only low optical purity [3]. The claimed 67% ee for the phenyloxirane derived from the reaction of benzaldehyde with trimethylsul-phonium iodide under basic conditions [26] in the presence of A,A-dimethyle-phedrinium chloride was later retracted [27] the product was contaminated with the 2-methyl-3-phenyloxirane from the degradation of the catalyst. 

Several early reports of high asymmetric induction during the hydride reduction of ketones under the influence of chiral catalysts [e.g. 1,2] have been discredited [3-6]. 

TABLE 11.2. Reduction of ketones by BH3 with chiral catalyst 3 (derived from (+)-2)... 

Table 5.5 Asymmetric transfer hydrogenation of aromatic ketones catalyzed by preformed chiral catalysts and KO Bu system in 2-propanol. ...

Attempts to achieve optical induction during the reduction of aromatic ketones to the secondary alcohol by immobilising a single layer of chiral catalyst on a solid electrode surface have been much less successful. The preparation of such coatings... 

The asymmetric hydrogenation of unfunctionalized ketones is a much more challenging task than that of functionalized ketones [3 j, 115]. Many chiral catalysts which are effective for functionalized ketones do not provide useful levels of enantioselectivity for unfunctio-nalized ketones, due to a lack of secondary coordination to the metal center. Zhang demonstrated the enantioselective hydrogenation of simple aromatic and aliphatic ketones using the electron-donating diphosphane PennPhos, which has a bulky, rigid and well-defined chiral backbone, in the presence of 2,6-lutidine and potassium bromide [36]. 

Aliphatic Ketones The asymmetric hydrogenation of simple aliphatic ketones remains a challenging problem. This may be attributed to the difficulty with which the chiral catalyst differentiates between the two-alkyl substituents of the ketone. Promising results have been obtained in asymmetric hydrogenation of aliphatic ketones using the PennPhos-Rh complex in combinahon with 2,6-lutidine and potassium bromide (Tab. 1.11) [36]. For example, the asymmetric hydrogenation of tert-butyl methyl ketone affords the requisite secondary alcohol in 94% ee. Similarly, isopropyl, Butyl, and cyclohexyl methyl ketones have been reduced to the corresponding secondary alcohols with 85% ee, 75% ee, and 92% ee respectively. 

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