Ketones chiral 3-hydroxy

Aldol-type condensation of chiral a-sulfinyl hydrazones with aldehydes also provides a route leading to chiral 3-hydroxy ketones. - This is exemplified by the synthesis of (-)-(/ )-[6]-gingerol (98 equation 24). ... 

Menche recently established an effective two step strategy for synthesizing chiral 1,3 amino alcohols [26]. The first step, an enantioselective aldol reaction, provides chiral (3 hydroxy ketones, which are then reductively aminated under the conditions ofp anisidine (2.0 equiv), Ti(Oi Pr), (1.4 equiv), CH3CN ( 20 °C), in the presence of polymethylhydrosilane (2.2 equiv) over 48 h. A variety of examples are shown in Figure 7.4. 

The diastereofacial preferences of keto ethers (192) are summarized in equation (116) and Table 21. The (Z)-lithium enolate of (192), prepared by reaction of the keto ether with lithium hexamethyldisila-zane, reacts with isobutyraldehyde to give syn aldols (193) and (194), along with small amounts of an anti aldol of undefined stereochemistry (195). - The results of this investigation demonstrate that the facial preference of a chiral 3-hydroxy ketone can be affected to some extent by the hydroxy-protecting group,... 

Furthermore, both (E)- and (Z)-enolborinates add to aldehydes in a stereoconvergcnt manner, giving predominantly, syn-/J-hydroxycarbonyl compounds49. In contrast, only moderate induced diastereoselectivity is obtained in the reaction of achiral aldehydes with C2-symmetric enolborates, whereby the chiral information is located in the ligand at the metal atom50. The ee of the product /1-hydroxy ketones ranges from 4 to 72%. 

A combination of substrate-induced and auxiliary-induced stereoselectivity is provided by the diisopinocampheylborinates 11a and lib derived from the chiral ketone (S)-l-benzyloxy-2-mcthyl-3-pentanone52. Whereas this ketone provides no significant diastereoselectivity when converted into the dibutylboron enolate and, subsequently, added to aldehydes, use of the diisopinocampheyl reagents 11a and lib leads to the jS-hydroxy ketones 12 and 13 in a stereoselective manner. The chiral information which is located in the carbon chain of the starting ketone 10 is incorporated into the products ... 

Chiral oxazolidines 6, or mixtures with their corresponding imines 7, are obtained in quantitative yield from acid-catalyzed condensation of methyl ketones and ( + )- or ( )-2-amino-l-phcnylpropanol (norephedrine, 5) with azeotropic removal of water. Metalation of these chiral oxazolidines (or their imine mixtures) using lithium diisopropylamide generates lithioazaeno-lates which, upon treatment with tin(II) chloride, are converted to cyclic tin(II) azaenolates. After enantioselective reaction with a variety of aldehydes at 0°C and hydrolysis, ft-hydroxy ketones 8 are obtained in 58-86% op4. 

In theory, the chiral center can be anywhere in the molecule, but in practice, reasonable diastereoselectivity is most often achieved when it is in the a position. For examples of high diastereoselectivity when the chiral center is further away, especially in reduction of P-hydroxy ketones, see Narasaka, K. Pai, F. Tetrahedron, 1984, 40, 2233 Hassine, B.B. Gorsane, M. Pecher, J. Martin, R.H. Bull. Soc. Chim. Belg., 1985, 94, 597 Bloch, R. Gilbert, L. Girard, C. Tetrahedron Lett., 1988, 53, 1021 Evans, D.A. Chapman, K.T. Carreira, E.M. J. Am. Chem. Soc., 1988, 110, 3560. 

The conversion of 27 to chiral hydroxy acid 26 was envisioned to arise via a sequential reduction protocol where the ketone moiety of 27 would enantioselectively be reduced to give chiral allylic cyclopentenol 46 (Scheme 7.11). Subsequent 1,4-addition of hydride to the a,/J-unsaturated ester of 46, presumably assisted by... 

This finding is also in agreement with another three-component Michael/aldol addition reaction reported by Shibasaki and coworkers [14]. Here, as a catalyst the chiral AlLibis[(S)-binaphthoxide] complex (ALB) (2-37) was used. Such hetero-bimetallic compounds show both Bronsted basicity and Lewis acidity, and can catalyze aldol [15] and Michael/aldol [14, 16] processes. Reaction of cyclopentenone 2-29b, aldehyde 2-35, and dibenzyl methylmalonate (2-36) at r.t. in the presence of 5 mol% of 2-37 led to 3-hydroxy ketones 2-38 as a mixture of diastereomers in 84% yield. Transformation of 2-38 by a mesylation/elimination sequence afforded 2-39 with 92 % ee recrystallization gave enantiopure 2-39, which was used in the synthesis of ll-deoxy-PGFla (2-40) (Scheme 2.8). The transition states 2-41 and 2-42 illustrate the stereochemical result (Scheme 2.9). The coordination of the enone to the aluminum not only results in its activation, but also fixes its position for the Michael addition, as demonstrated in TS-2-41. It is of importance that the following aldol reaction of 2-42 is faster than a protonation of the enolate moiety. 

Hydroxynitrile lyases (HNLs or oxynitrilases) catalyze C—C bond-forming reactions between an aldehyde or ketone and cyanide to form enantiopure cyanohydrins (Figure 1.15), which are versatile building blocks for the chiral synthesis of amino acids, hydroxy ketones, hydroxy acids, amines and so on [68], Screening of natural sources has led to the discovery of both... 

Palladium-catalyzed bis-silylation of methyl vinyl ketone proceeds in a 1,4-fashion, leading to the formation of a silyl enol ether (Equation (47)).121 1,4-Bis-silylation of a wide variety of enones bearing /3-substituents has become possible by the use of unsymmetrical disilanes, such as 1,1-dichloro-l-phenyltrimethyldisilane and 1,1,1-trichloro-trimethyldisilane (Scheme 28).129 The trimethylsilyl enol ethers obtained by the 1,4-bis-silylation are treated with methyllithium, generating lithium enolates, which in turn are reacted with electrophiles. The a-substituted-/3-silyl ketones, thus obtained, are subjected to Tamao oxidation conditions, leading to the formation of /3-hydroxy ketones. This 1,4-bis-silylation reaction has been extended to the asymmetric synthesis of optically active /3-hydroxy ketones (Scheme 29).130 The key to the success of the asymmetric bis-silylation is to use BINAP as the chiral ligand on palladium. Enantiomeric excesses ranging from 74% to 92% have been attained in the 1,4-bis-silylation. 

In the hydrogenation of diketones by Ru-binap-type catalysts, the degree of anti-selectivity is different between a-diketones and / -diketones [Eqs (13) and (14)]. A variety of /1-diketones are reduced by Ru-atropisomeric diphosphine catalysts to indicate admirable anti-selectivity, and the enantiopurity of the obtained anti-diol is almost 100% (Table 21.17) [105, 106, 110-112]. In this two-step consecutive hydrogenation of diketones, the overall stereochemical outcome is determined by both the efficiency of the chirality transfer by the catalyst (catalyst-control) and the structure of the initially formed hydroxyketones having a stereogenic center (substrate-control). The hydrogenation of monohydrogenated product ((R)-hydroxy ketone) with the antipode catalyst ((S)-binap catalyst) (mis-... 

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... 

M. Masui, A. Ando, T. Shioiri, Asymmetric Synthesis of a-Hydroxy Ketones Using Chiral Phase Transfer Catalysts , Tetrahedron Lett. 1988, 29, 2835-2838. 

Two-step asymmetric hydrogenation of (3-diketones shows that the overall stereochemistry is determined by the catalyst and by the chirality of the intermediate hydroxy ketone. Thus partial hydrogenation of acetylacetone (2) catalyzed by Ru-... 

Epoxidations of chiral allenylsilanes are also highly stereoselective, especially if the silyl group is spatially demanding (Eq. 9.54) [60]. A bis-epoxide intermediate is formed which rearranges to an a,/8-unsaturated a -hydroxy ketone. Such products are of interest as branched carbohydrate analogues. 

Acyloxy-l-cyanoalkanes [45, 46], which can be used as precursors for ketones [47], a-hydroxy ketones [48] and 1,4-dicarbonyl compounds [47], are prepared in one pot from the appropriate aldehyde, sodium or potassium cyanide, and the acylating agent under phase-transfer catalytic conditions [47-49]. Attempts to synthesize chiral cyanhydrins using chiral phase-transfer catalysts have been unsuccessful (see Section 12.3). 

Chiral cyanohydrins are versatile intermediates in the synthesis of a-hydroxy acids, /3-amino alcohols, amino nitriles, a-hydroxy ketones and aziridines. For the synthesis of enantiopure cyanohydrins, the use of hydroxynitrile lyases is currently the most effective approach.Application of an organic-solvent-free system allows thermodynamically hindered substrates to be converted with moderate to excellent yields. With the use of the highly selective hydroxynitrile lyase from Manihot esculenta, the syntheses of several acetophenone cyanohydrins with excellent enantioselectivities were developed (Figure 8.2). (5)-Acetophenone cyanohydrin was synthesized on a preparative scale. ... 

Kalaitzakis, D., Rozzell, J.D., Kambourakis, S. and Smonou, I., Synthesis of valuable chiral intermediates by isolated ketoreductases application in the s3mthesis of -alkyl—hydroxy ketones and 1,3-diols. Adv. Synth. Catal, 2006, 348, 1958-1969. 

Furthermore, this reaction was applied to the aldol reaction of 3-pentanone. When the chiral oxazolidine was prepared from 3-pentanone and the aldol reaction was carried out by the same procedure, the a, 6-anti 6-hydroxy ketones were produced predominantly over the syn-isomer 8i with excellent optical purities.(5) (See Table 2.)... 

Microbial reduction of prochiral cyclopentane- and cyclohexane-1,3-diones was extensively studied during the 1960 s in connection with steroid total synthesis. Kieslich, Djerassi, and their coworkers reported the reduction of 2,2-dimethylcyclohexane-l,3-dione with Kloeokera magna ATCC 20109, and obtained (S)-3-hydroxy-2,2-dimethylcyclohexanone. We found that the reduction of the 1,3-diketone can also be effected with conventional baker s yeast, and secured the hydroxy ketone of 98-99% ee as determined by an HPLC analysis of the corresponding (S)-a-methoxy-a-trifluoromethylphenylacetate (MTPA ester).(S)-3-Hydroxy-2,2-dimethy1cyc1ohexanone has been proved to be a versatile chiral non-racemic building block in terpene synthesis as shown in Figure 1. 

These reagents exhibit good stereoselectivity toward chiral substrates, such as acylox-azolidines.187 Chiral oxaziridine reagents, such as A-C, have been developed, and these can achieve enantioselective oxidation of enolates to a-hydroxy ketones.188... 

More recently, the same group achieved a simple, highly stereocontrolled total synthesis of (+)-hirsutic acid (Scheme LXXIX) ". This chirally directed effort developed subsequent to reaction of dl-728 with (+)-di-3-pinanylborane, alkaline hydrogen peroxide oxidation, chromatography, PCC oxidation, and hydrogenolysis. The dextrorotatory hydroxy ketone 729 was nicely crafted into keto aldehyde 730 from which 720 was readily obtained. Once again, the Wacker oxidation played an instrumental role in annulation of the third five-membered ring. The remainder of the asymmetric synthesis was completed as before. 

Fluoral hydrate and hemiacetals are industrial products. They are stable liquids that are easy to handle, and they react as fluoral itself in many reactions. Thus, in the presence of Lewis acids, they react in Friedel-Crafts reactions. They also react very well with organometallics (indium and zinc derivatives) and with silyl enol ethers.Proline-catalyzed direct asymmetric aldol reaction of fluoral ethyl hemiac-etal with ketones produced jS-hydroxy-jS-trifluoromethylated ketones with good to excellent diastereo- (up to 96% de) and enantioselectivities. With imine reagents, the reaction proceeds without Lewis acid activation. The use of chiral imines affords the corresponding 8-hydroxy ketones with a 60-80% de (Figure 2.49). ° ... 

The project encompassed the comparative characterization of pyruvate decarboxylase from Z. mohilis (PDC) and benzoylformate decarboxylase from P. putida (BED) as well as their optimization for bioorganic synthesis. Both enzymes require thiamine diphosphate (ThDP) and magnesium ions as cofactors. Apart from the decarboxylation of 2-ketoacids, which is the main physiological reaction of these 2-ketoacid decarboxylases, both enzymes show a carboligase site reaction leading to chiral 2-hydroxy ketones (Scheme 2.2.3.1). A well-known example is... 

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