Oxidative ketones, asymmetric hydrogenation

Keywords Alcohols Alkenes Asymmetric transfer hydrogenation C-alkylation Imines Ketones W-aUcylation Oxidation Reduction Transfer hydrogenation... 

As already mentioned, the secondary alcohols that are obtained are optically active. It should be stressed that the reduction of ketones to carbinols by means of fermenting yeast is completely different from the method of resolution of racemic alcohols by treatment with living microorganisms (Pasteur). In the latter case one of the enantiomorphs is removed by oxidation during metabolism in the former it is produced by true asymmetric hydrogenation, without the intermediate formation of the inactive form, (Cf. Mayer and Levene and Walti. )... 

Considerable advances have been made in catalytic methodologies to perform asymmetric oxidations.1 3 Although no large-scale processes for commercial chiral pharmaceuticals currently use the technology, the methods are relatively new compared to catalytic asymmetric hydrogenation. The approach, however, is now in the synthetic arsenal, and it is surely just a matter of time before it comes to fruition as many drug candidates use asymmetric oxidations. An example of an up and coming asymmetric oxidation is the epoxidation method based on carbohydrate ketones (Chapter 10). 

A similar selective oxidation can be carried out with tetrakis(triphenylphosphine)ihoditun(I) hydride and an a, >unsaturated ketone as hydrogen acceptor, in this case the use of an optically active phosphine provided an enantioselective synthesis, although the levels of asymmetric induction were rather low (Scheme 10). ... 

The efficiency of a Raney nickel catalyst for hydrogenation of carbonyl groups is much diminished if the catalyst is treated with 0.1% acetic acid or an amino acid, particularly dibasic amino acids or L-phenylalanine but the efficiency for hydrogenation of C=C double bonds remains unaffected. Thus mesityl oxide was hydrogenated to isobutyl methyl ketone selectively and in good yield but cinnamaldehyde could not be reduced in this way.161 For asymmetric hydrogenation with Raney nickel modified by optically active 2-hydroxy carboxylic acids see Tatsumi et al.162... 

KRs based on the oxidation of a chiral secondary alcohol to a prochiral ketone has been of considerable interest as the later can be usually recycled into the racemic starting material by simple hydride reduction [2d, 55]. The first broadly applicable method for this purpose was reported by Noyori et al. [56], under catalytic hydride transfer conditions similar to those employed for the asymmetric hydrogenation of ketones. For example, excellent results (s>50) have been reported for the KR of benzyhc alcohols by using a chiral diamine-ruthenium complex in the... 

Colladon, M., Scarso, A. and Strukul, G. (2006). TaUoring Pt(ll) Chiral Catalyst Design for Asymmetric Baeyer-Villiger Oxidation of CycUc Ketones with Hydrogen Peroxide, Synlett, 20, pp. 3515-3520. 

In addition methyl isobutyl ketone, which could be regarded as a hydrogenation intermediate, does not give an optically active alcohol. Furthermore, the authors were able to find traces of 2-methyl-2 pentene-4-ol in the reaction mixture. Consequently, the authors concluded that a bidentate coordination of both and groups is essential for the asymmetric hydrogenation of mesityl oxide. 

Yamamoto et al. have reported the synthesis of optically active 8-lactones by Baeyer-Villiger oxidation of chiral cyclopentanones [77] (Scheme 34). Asymmetric hydrogenation of enones 175 and 176 in the presence of 0.01 equivalent of Ru2Cl4[(5)-p-Tolyl-Binap]2NEt3 catalyst afforded chiral ketones 177 and 178 in good yield and with excellent enantioselectivity. These chiral ketones were found to show a fundamentally jasmine-like floral odor. Chiral ketones 177 and 178 were then transformed to 8-lactones 179 and 180 by Baeyer-Villiger oxidation with... 

Colladon M, Scarso, A, Strukul G. Tailoring Pt(II) chiral catalyst design for asymmetric Baeyer-Villiger oxidation of cyclic ketones with hydrogen peroxide. Synlett 2006 3515 3520. 

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

Chan has discovered a completely atropdiasteroselective synthesis of a biaryl diphosphine by asymmetric intramolecular Ullmann coupling or Fe(m)-promoted oxidative coupling. A chiral atropisomeric biaryl bisphosphine ligand 2 was synthesized through this central-to-axial chirality transfer.38 Recently, a xylyl-biaryl bisphosphine ligand, Xyl-TetraPHEMP, was introduced by Moran, and is found to be effective for the Ru-catalyzed hydrogenation of aryl ketone.39... 

The asymmetric synthesis of allenes via enantioselective hydrogenation of ketones with ruthenium(II) catalyst was reported by Malacria and co-workers (Scheme 4.11) [15, 16]. The ketone 46 was hydrogenated in the presence of iPrOH, KOH and 5 mol% of a chiral ruthenium catalyst, prepared from [(p-cymene) RuC12]2 and (S,S)-TsDPEN (2 equiv./Ru), to afford 47 in 75% yield with 95% ee. The alcohol 47 was converted into the corresponding chiral allene 48 (>95% ee) by the reaction of the corresponding mesylate with MeCu(CN)MgBr. A phosphine oxide derivative of the allenediyne 48 was proved to be a substrate for a cobalt-mediated [2 + 2+ 2] cycloaddition. 

In the early 1980 s Julia and Colonna published a series of papers which, to some extent, filled the gap left by the natural biocatalysts. The Spanish and Italian collaborators showed that a, -unsaturated ketones of type 1 underwent asymmetric oxidation to give the epoxide 2 using a three-phase system, namely aqueous hydrogen peroxide containing sodium hydroxide, an organic solvent such as tetrachloromethane and insoluble poly-(l)-alanine, (Scheme 1) [12]. The reaction takes place via a Michael-type addition of peroxide anion (the Weitz-Scheffer reaction). 

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