Unsaturated ketones, asymmetric hydrogenation

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). ... 

Asymmetric syntheses of warfarin <96TL8321> and the axially chiral bicoumarin, isokotanin A <96TL3015> have been reported. The former is based on a Rh-catalysed asymmetric hydrogenation of a 3-(a,P-unsaturated ketone) substituted coumarin, whilst the key steps of the latter are an asymmetric Ullmann coupling and a selective demethylation. The stereochemistry of the fused dihydrocoumarin resulting from Li/NHs reduction of... 

Use of RuCl2(PPh3)3 with a glucofuranose derivative (61) as donor solvent leads to asymmetric hydrogenation of prochiral a,/3-unsaturated ketones to the saturated ketones, with up to 34% ee in the case of a cyclohexene-3-one (497). 

Complexes containing one binap ligand per ruthenium (Fig. 3.5) turned out to be remarkably effective for a wide range of chemical processes of industrial importance. During the 1980s, such complexes were shown to be very effective, not only for the asymmetric hydrogenation of dehydroamino adds [42] - which previously was rhodium s domain - but also of allylic alcohols [77], unsaturated acids [78], cyclic enamides [79], and functionalized ketones [80, 81] - domains where rhodium complexes were not as effective. Table 3.2 (entries 3-5) lists impressive TOF values and excellent ee-values for the products of such reactions. The catalysts were rapidly put to use in industry to prepare, for example, the perfume additive citronellol from geraniol (Table 3.2, entry 5) and alkaloids from cyclic enamides. These developments have been reviewed by Noyori and Takaya [82, 83]. 

The Stereochemistry of Hydrogenation of , -Unsaturated Ketones Robert L. Augustine Asymmetric Homogeneous Hydrogenation J. D. Morrison, W. F. Masler, and M. K. Neuberg... 

Iridium-Catalyzed Asymmetric Hydrogenation of Olefins with Chiral N,P and C,N Ligands 53 Table 2 Enantioselective hydrogenations of linear a,(3-unsaturated ketones... 

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). 

R)-BINAP/l,2-diphenylethylenediamine ruthenium(II) complexes covalently attached to polystyrene (Scheme 4.32) promote the asymmetric hydrogenation of aromatic ketones and of a, yS-unsaturated ketones [125]. The catalysts (52) and (53) were reused at high substrate/catalyst molar ratio (S/C) of 2470 in 14 experiments. Remarkably, the enantiopurity of the products remained high after each run, constantly being in the range of 97 to 98% ee. 

Subsequently, List reported that although the method described above was not applicable to the reduction of a,P-unsaturated ketones, use of a chiral amine in conjunction with a chiral anion provided an efficient and effective procedure for the reduction of these challenging substrates [210]. Transfer hydrogenation of a series of cyclic and acyclic a,P-unsaturated ketones with Hantzsch ester 119 could be achieved in the presence of 5 mol% of valine tert-butyl ester phosphonate salt 155 with outstanding levels of enantiomeric control (Scheme 64). A simple mechanistic model explains the sense of asymmetric induction within these transformations aUowing for reliable prediction of the reaction outcome. It should also be noted that matched chirality in the anion and amine is necessary to achieve high levels of asymmetric induction. 

The Julia - Colonna asymmetric epoxidation of electron-deficient unsaturated ketones to the corresponding epoxides with high yields and high ee is well known. This technique produces chiral chemical entities from the clean oxidant, hydrogen peroxide, without the use of a toxic or water sensitive transition metal additive. 

SCHEME 45. Ir(I)-catalyzed asymmetric hydrogenation of a,/3-unsaturated ketones. 

The majority of recent publications still deal with the chiral hydrogenation of ketones containing other functional groups as well. The general characteristics of these reactions are illustrated by the asymmetric hydrogenation of a./f-unsaturated ketones. In addition, the purpose of the present review is to summarize the latest results of the chiral hydrogenation of ketones which do not contain other functional groups (dialkyl ketones and alkyl aryl ketones). 

Optically active 4-alkoxycarbonyl-3-hydroxycyclohexanones (formed in highly enantio- and diastereoselective organocatalytic asymmetric domino Michael aldol reaction of / -keto esters and a,/ -unsaturated ketones) are transformed into corresponding chiral oxepanones under the action of urea-hydrogen peroxide and trifluoroacetic anhydride <2004AGE1272>. 

PhanePhos-ruthenium-diamine complexes catalyze the asymmetric hydrogenation of a wide range of aromatic, heteroaromatic, and cx,P-unsaturated ketones with high activity and excellent enantioselectivity (Burk, 2000). 

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