Enones, asymmetric hydrogenation

Phosphite compounds, which have been discussed in the context of their application in asymmetric hydrogenation reactions (see Section 6.1.2.6), can also be used to effect the copper salt-mediated asymmetric conjugate addition of diethylzinc to enones.74 As shown in Scheme 8-33, in the presence of diphosphite 92 and copper salt [Cu(OTf)2], the asymmetric conjugate addition proceeds smoothly, giving the corresponding addition product with high conversion and ee. In contrast, the monophosphite 93 gave substantially lower ee. 

Reactions where NLE have been discovered include Sharpless asymmetric epoxi-dation of allylic alcohols, enantioselective oxidation of sulfides to sulfoxides, Diels-Alder and hetero-Diels-Alder reactions, carbonyl-ene reactions, addition of MesSiCN or organometallics on aldehydes, conjugated additions of organometal-lics on enones, enantioselective hydrogenations, copolymerization, and the Henry reaction. Because of the diversity of the reactions, it is more convenient to classify the examples according to the types of catalyst involved. 

Asymmetric Hydrogenation of Alkenes, Enones, Ene-esters and Ene-Acids... 

Carbonyl-selective asymmetric hydrogenation of 2-cyclohexenone - a simple cyclic conjugated enone - is stdl difficult, but some substituted 2-cydohexenones such as 2,4,4-trimethyl-2-cyclohexenone, (R)-carvone, a chiral dienone, and (R)-pule-gone, an s-cis chiral enone have been used successfully [66, 68, 81b, 107]. 

Nucleophilic oxidation of electron-deficient alkenes is another route to epoxides. For example, reaction of enones with hydrogen peroxide and sodium hydroxide provides epoxides in good yield. The first attempt to turn this into an asymmetric transformation utilised the benzylchloride salt of quinine as a chiral phase transfer catalyst but only moderate enantioselectivity was obtained (55% with... 

Hirata, T, K. Shimoda, and T. Gondai, 2000. Asymmetric hydrogenation of the C-C double bond of enones with the reductases from Nicotiana tabacum. Chem. Lett.. 29 850-851. 

The sense of enantioselection in other reactions can be also analyzed using the conclusions made above. Thus, the structurally rigid Rh complex of (R, R)-QuinoxP ligand (147) always has the bulky tert-hutyl substituent in the upper left quadrant, and the sense of enantioselection of asymmetric hydrogenation (stereoselection in octahedral Rh(III) complexes) is consistent with that of asymmetric addition of arylboronic acids to enones (stereoselection in square planar Rh(I) complexes) (Scheme 1.35). ... 

In contrast, as shown above, the asymmetric environment around the Rh atom changes when the geometry of the Rh-(S)-BINAP complex (148) transforms from octahedral to square planar. Accordingly, whereas the sense of enantioselection of asymmetric hydrogenation catalyzed by 147 is the same as in the case of 148, an opposite sense of enantioselection is observed in the asymmetric addition of phenylboronic acid to cyclic enones catalyzed by 147 and 148. ... 

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... 

As highlighted earlier, one of the issues with carrying out high pressure hydrogenations on scale is the need for specialised plant reactors which many companies do not have as standard. Scientists at Lilly faced this problem when looking to scale up asymmetric hydrogenation of tetra-substituted enone 88, an intermediate in the synthesis of LY500307 (Scheme 14.31). The conditions developed for this transformation... 

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