Ketones enantiospecific

Finally, (S )-coriolic acid (a metabolite of hnoleic acid) has been synthesized, in an enan-tiospecific fashion, by the use of the alcohol dehydrogenase enzyme from baker s yeast in the presence of NADPH. In the key step of this synthesis, the supported enzyme/NADPH was used to reduce a bromovinyl ketone enantiospecifically (equation 71)291. 

Aromatics occur as ligands in ruthenium complexes that are used for hydrogen transfer reaction, i.e. two hydrogen atoms are transferred from a donor molecule, e.g. an alcohol, to a ketone, producing another alcohol. Especially the enantiospecific variant has become important, see Chapter 4.4. The substitution pattern of the aromatic compound influences the enantioselectivity of the reaction. 

Kinetic resolution relies on enantiospecific conversion of one enantiomer present in a racemic mixture while the other remains unchanged (except for parallel kinetic resolution in which both enantiomers are transformed but to different products). For secondary alcohols enantiospecific conversion might consist in oxidation of one enantiomer to a ketone while the other remains unchanged (Scheme 12.20). 

Many of the above-described examples highlight the diastereoselectivity of the solid-state reaction. Cyclic ketones with cis- or trans-a,a -substituents give the ring-contraction product with the same relative stereochemistry. Examples include 2-indanones 157 and 159 (Scheme 2.38), cyclohexanones 162 and 164—167 in Scheme 2.39, and ketones 177 and 179 in Scheme 2.43. The diastereospedfidty and enantiospecificity of linear ketones was also tested with the pentasubstituted acetone derivative 187 in its racemic and enantiomerically pure forms (Scheme 2.45). Notably, both samples reacted efficiently and in a completely diastereo-specific manner when reactions were carried out to 60% conversion. Sample of ( I )-(2R,4S)-187 gave the corresponding combination product in 100% ee and... 

The first enantiospecific total synthesis of (+)-ajmaline [(+)-17] was developed by Cook et al. 161). D-(+)-Tiyptophan methyl ester (126) was converted enantiospecifically, via intermediate 127, to the optically active )-N -benayltetracyclic ketone (-) 107, which was then transformed into the ot,P-unsaturated aldehyde (-)-128. When compound (-)-128 was stirred with 3-bromo-4-hq>tene in die Barbier Grignard process conditions the 1,4-addition products 129a,b... 

Bromocamphor has been employed as the chiral starting material in an enantiospecific synthesis (ref. 146) which involved the formation of an indanone (CD moiety) related structurally to that used by Hoffmann-La Roche and led finally to (-)-estrone. Attempts to alkylate the a,p-unsaturated ketone with 2-(3-methoxyphenyl)ethyl iodide failed, not surprisingly, due to an elimination rather than the desired substitution reaction and accordingly the use of an a-methylenic derivative of the ketone and 3-methoxybenzyl chloride were obligatory. By the use of (-)-3-bromocamphor, which is readily available from (-)-borneol by oxidation to (-)-camphor and bromination, natural (+)-estrone could be obtained. 

Halenaquinone (134) and Halenaquinol (135) are novel pentacyclic polyketides that were isolated from tropical marine sponge [60]. They have attracted much attention because of their interesting antibiotic and cardiotonic activity. Harada61 utilized the Wieland-Miescher ketone (1) as starting material for the enantiospecific synthesis of this interesting natural product with novel pentacyclic polyketide skeleton, and this is described in "Fig (11)". 

The enantiospecific synthesis of anhydromacrosalhine-methine (344) commenced with the tetracyclic ketone 343 which was converted into alstonerine (347) as described previously (227). Reduction of alstonerine, followed by dehydration of the resultant allylic alcohol, provided (—)-anhydromacrosalhine-methine (344), identical with material prepared from natural (+ )-ajmaline (Scheme 25) 228,230). In the context of a synthesis of talpinine and talcarpine, an improved synthesis of (—)-anhydromacrosalhine-methine was also achieved from improved routes to the tetracyclic ketones 348 and the enol ether 349, key intermediates in the talpinine/talcarpine synthesis (233). 

The application of rhodium-diphosphonite catalysts (where diphosphonites are Reetz s ligands with BINOL and ferrocene subvmits) for alkene, ketone, and ketoester hydrogenation resulted in practically enantiospecific reaction (ee higher than 99.5%) (173,223). 

Gusso, A., Baccin, C., Pinna, F., et al. (1994). Platinum-Catalyzed Oxidations with Hydrogen Peroxide Enantiospecific Baeyer-Villiger Oxidation of Cyclic Ketones, Organometallics, 13, pp. 3442-3451. 

When a-heterocyclic substituted ketones have been subjected to yeast-mediated reductions, yields and enantiospecificity were low for 2-acylthiazoles [149], ketoisox-azoles [160], and 5-acetyl-2-isoxazolines [161]. 

Oren, J., Vardi, M., Viskin, R., Abramson, S., and Fuchs, B., Homoconjugated ketones with extended unsaturation wavelength selective, diastereoselective and enantiospecific photochemical transformations of methyl 7-oxospiro[5.5]undeca-l,3-and 2,4-diene-2-carboxylate, Helv. Chim. Acta, 76, 1182, 1993. 

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