Meso-ketone, enantioselective

SCHEME 170. Pt-catalyzed enantioselective Baeyer-Villiger oxidation of cyclic meso-ketones with H2O2 using chiral diphosphine hgands... 

Honda et al. have utilized acid-catalyzed lactonization of a 5-hydroxy ester in an enantioselective synthesis of the lactone moiety of HMG CoA reductase inhibitor [52] (Scheme 15). An enantioselective deprotonation reaction of meso-ketone 75 with lithium (5,5)-a,a -dimethyldibenzylamide as the chiral base in the presence of... 

Enantioselective deprotonations of meso substrates such as ketones or epoxides are firmly entrenched as a method in asymmetric synthesis, although the bulk of this work involves stoichiometric amounts of the chiral reagent. Nevertheless, a handful of reports have appeared detailing a catalytic approach to enantioselective deprotonation. The issue that ultimately determines whether an asymmetric deprotonation may be rendered catalytic is a balance of the stoichiometric base s ability... 

Enantioselective C-H insertion is still a virgin area in dioxirane chemistry, but its feasibility has been demonstrated in the kinetic resolution of racemates and in the desymmetrization of meso 1,2-diols and their acetals. Moderately good enan-tioselectivity has been achieved by use of Shi s ketone 9 as the precursor to the dioxirane (Scheme4) [27, 28],... 

The Ni/tartaric acid/NaBr catalyst system has been extensively studied. A variety of ketone substrates have been reduced with Ni/tartaric acid/NaBr catalysts with variable enantioselectivities, but the highest (>85% ee) are obtained for the reductions of P-keto esters and P-diketones (Schemes 12.60 and 12.61).5 Asymmetric reduction of diketones results in the formation of mesa and chiral diols. The highest meso chiral diol ratio of 2 98 and enantioselectivities of 98% ee are obtained with modified Raney nickel catalysts treated by sonication.5... 

Enolboration of Ketones and Opening of meso-Epoxides. Methyl alkyl ketones have been successfully enolized by IpciBX (X = OTf or Cl) in the presence of a tertiary amine. The corresponding enolborinates have been used in asymmetric aldol condensations (eq 5). The reagent has also been applied to the enantioselective opening of mcj o-epoxides to form the corresponding nonracemic chlorohydrins (eq 6). ... 

For the enantioselective reduction of cyclic meso-imides and 1 -siloxy-2-alkanones, 1,2-reduction of other enones,the prototypal chiral bicyclic oxazaborolidine is adequate, although 81 has been used to reduce a-phenylthio-p-phenyl ketones to obtain precursors of a-hydroxy thioesters. The enantiomer of 81 mediates reduction of enediones to the corresponding chiral diols. ... 

Oxidation of Meso Diols. Asymmetric induction of meso and prochiral diols by lipases is very successful in the field of organic synthesis. Also it is well known that selective oxidation of prochiral or meso diols by HLADH provides oxidized products with a significant degree of enantioselectivity. However, it has not been reported that alcohol oxidases were applied to such types of oxidation. The microbial oxidation of meso diols by Candida boidinii SA051 was carried out and gave optically active hydroxy ketones (Figure 8). 

Interligand asymmetric induction. Group-selective reactions are ones in which heterotopic ligands (as opposed to heterotopic faces) are distinguished. Recall from the discussion at the beginning of this chapter that secondary amines form complexes with lithium enolates (pp 76-77) and that lithium amides form complexes with carbonyl compounds (Section 3.1.1). So if the ligands on a carbonyl are enantiotopic, they become diastereotopic on complexation with chiral lithium amides. Thus, deprotonation of certain ketones can be rendered enantioselective by using a chiral lithium amide base [122], as shown in Scheme 3.23 for the deprotonation of cyclohexanones [123-128]. 2,6-Dimethyl cyclohexanone (Scheme 3.23a) is meso, whereas 4-tertbutylcyclohexanone (Scheme 3.23b) has no stereocenters. Nevertheless, the enolates of these ketones are chiral. Alkylation of the enolates affords nonracemic products and O-silylation affords a chiral enol ether which can... 

Ketones [60], P-fimetionalized ketones [61] [62] and meso eylic imide [63] have been enantioselectively redueed using polymer-supported chiral sulfonamides in presence of boranes (NaBH4/Me3SiCl or BH3.SMe2), leading in situ to the eorresponding oxazaborolidine polymer-supported chiral sulphonamide 70 (Scheme 32). 

Worthy of mention is that catalysts based on Co, Cu, Pd, P 20,60 and Al are all active towards meso or chiral cyclobutanone substrates, which are intrinsically much more reactive than larger cychc ketones. Some representative examples are reported in Scheme 23.29. However, only biocatal3dic BV oxidations performed with isolated enzymes, or whole cells containing cyclohexanone monooxygenases (CHMOs) or BV monooxygenases (BVMOs) showed good conversions as well as enantioselectivity above 95% ee with cyclohexanone as the substrate. " ... 

Scarso and Strukul observed that anionic micelles based on sodium dodecyl-sulfate (SDS) efficiently solubilized Pt bis-cationic complexes and ketones in the apolar core of the micelles. This favored the contact between substrate and catalyst and, more importantly, led to a higher steric control of the asymmetric reaction thanks to the more ordered nano-environment present in the micelles compared to bulk organic solvents. Each substrate required the dedicated optimization of the catalyst, the surfactant and the experimental conditions since the distribution of the substrates and catalysts is greatly affected by the kind of surfactant and aggregate considered (Scheme 23.42). Overall, in all the cases tested, an increase in enantioselectivity was observed for the asymmetric BV oxidation of meso-4-substituted cyclohexanones with bis-diphenylphoshinobinaphthyl (BINAP) as the hgand and SDS as the surfactant. A different scenario was present in the kinetic resolution of chiral cyclobutanones or with meso cyclobutanones where an increase of enantioselectivity was observed with the neutral polyoxyethanyl-a-tocopheryl sebacate (PTS) surfactant (Scheme 23.42). 

Paneghetti, C., Gavagnin, R., Pinna, R, et al. (1999). New Chiral Complexes of Platinum(II) as Catalysts for the Enantioselective Baeyer-Villiger Oxidation of Ketones with Hydrogen Peroxide Dissymmetrization of Meso-Cyclohexanones, Organometallics, 18, pp. 5057-5065. 

Scheme 4.4 Desymmetrization of meso cyclic ketones and kinetic resolntion of racemic 2-arylcyclohexanones by enantioselective Baeyer—VUliger oxidation.

Zhou, L., Liu, X., Ji, J., Zhang, Y, Hu, X., Lin, L., Feng, X. (2012). Enantioselective Baeyer-Villiger oxidation desymmetrization of meso cyclic ketones and kinetic resolution of racemic 2-arylcyclohexanones. Journal of the American Chemical Society, 134, 17023-17026. 

Transition metals can be eliminated from the catalytic systems. Thus, a quinine-derived urea organocatalyst is effective in the enantioselective oxidation of a wide range of diaryl-substituted meso-1,2-diols using bromi-nation reagents as oxidants (Scheme 31). " The method is simple, operates at ambient temperature and utilizes available reagents to yield a-hydroxy ketones in good yields (up to 94%) and enantioselectivities (up to 95% ee). 

Paneghetti C, Gavagiun R, Piima F, Strukul G. New chiral complexes of platinum(II) as catalysts for the enantioselective Baeyer-Villiger oxidation of ketones with hydrogen peroxide dissymmetrization of meso-cyclohexanones. Organometallics 2001 18 5057 5065. 

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