Cyclic ketones, determining

TMM cycloadditions to cyclic and conjugated ketones have also been reported (Scheme 2.22) [31]. The steric nature of the substrate does play a critical role in determining product formation. Thus the cyclic ketone (73) produced 55% yield of the tetrahydrofuran, but no cycloadduct could be obtained from the cyclic ketone (74). The enone (75) gave only carbonyl cycloaddition, whereas enone (76) yielded only olefin adduct. Interestingly, both modes of cycloaddition were observed with the enone (77). The ynone (78) also cycloadds exclusively at the carbonyl function [34]. 

In the case of substituted cyclic ketones, particularly cyclohexanones, the stereochemical outcome of an addition reaction is determined by the predominance of either equatorial or axial attack of the nucleophile, leading to axial or equatorial alcohols, respectively 25 -27 (Figure 8). 

For cyclic ketones conformational factors also come into play in determining enolate composition. 2-Substituted cyclohexanones are kinetically deprotonated at the C(6) methylene group, whereas the more-substituted C(2) enolate is slightly favored... 

Determining the Enantiomer Composition of Chiral Glycols or Cyclic Ketones... 

The first application of NMR diffusion measurements to determine the aggregation state of a transition metal catalyst concerned the chiral, tetranuclear Cu(i) catalysts 130-132, used in the conjugate addition reactions of anions to a,p-unsatu-rated cyclic ketones. Compounds 130-132 react wdth isonitriles to form 133-135, and do not degrade to lower molecular weight species (see Eq. (20)) [109]. 

The Baeyer-Villiger process for conversion of open-chain ketones to esters, or cyclic ketones to lactones by a peracid involves an intermediate a-hydroxyperester (235) step, as shown in equation 83. Determination of 235 in the reaction mixture involves selective reduction of the peroxyacid with diphenyl sulfide and reduction of 235 with excess iodide, followed by titration of the liberated iodine. The presence of various transition metal ions may affect the determination by accelerating the final step of the synthetic process, thus... 

The solubility of DDT in twenty materials—ketones, petroleum fractions, and several miscellaneous solvents—over the temperature range —30° to 76° F. was determined by the rapid density method developed by Mauke and Sheard. DDT was found to be most soluble in cyclohexanone and less soluble in aromatic petroleum fractions, but the solvent cost per unit of DDT dissolved with them was only one half that for cyclohexanone. Cyclic ketones were better solvents than acyclic ketones with the same number of carbon atoms and the solubility in ketones was found to decrease with increasing molecular weight. 

Of mechanistic interest is the question of whether these cyclic ketones come directly from conjugated diene intermediates or from PdCl2 complexes of carboxyoctadecenoates. Yields of cyclic ketones 4 are actually of the same order of magnitude from linoleate as from its conjugated diene isomers (Runs 7 and 8, Table I). Studies were also made to determine if yields of cyclic ketones can be influenced by the amount of H20 used. However, in experiments using no added H20 and one-tenth the stoichiometric amount of H20, only 10 and 8% ketones and conversions (diene disappearance) of only 58 and 78% were obtained, respectively. 

There are several examples of similar reactions of enaminonitriles [9,10,11, 12, 13, 14]. Katsuyama et al. [9] determined that refluxing 3-aminobut-2-enenitrile 16 with fluorinated unsaturated ketone 17 in ethanol leads to high yields of dihydropyridines 18 (Scheme 3.6). The reaction of 16 with fluorinated cyclic ketone 19 leading to heterocycle 20 can be carried out in glacial acetic acid and does not need any additional catalyst or reagent [14] (Scheme 3.6). On the other hand, treatment of aminobutenenitrile 16 with ketones without strong... 

Reductive lithiation of the vinylsulfide 67 derived from a cyclic ketone provides a valuable alternative to the Shapiro reaction (section 8.1),84 and the sequence of events leading to 68 or 69 determines the regioselectivity. 

The cyclic ketone has a fixed conformation controlled by the determination of the f-butyl group to be equatorial. Reduction can be controlled to give almost exclusively either the axial or the equatorial alcohol as we explained in Chapter 18. Large reagents prefer to approach equatorially while small reagents like to put the new OH group into an equatorial position. These are stereo-selective reactions, and, because the two different outcomes are diastereoisomers, we can call them diastereoselective. 

Allylic azides, e.g., 1, were produced by treatment of the triisopropylsilyl enol ethers of cyclic ketones with azidotrimethylsilane and iodosobenzene78, but by lowering the temperature and in the presence of the stable radical 2,2,6,6-tetramethylpiperidine-/V-oxyl (TEMPO), 1-triso-propylsilyloxy-l,2-diazides, e.g., 2, became the predominant product79. The radical mechanism of the reaction was demonstrated. A number of 1,2-diazides (Table 4) were produced in the determined optimum conditions (Method B 16h). The simple diastereoselectivity (trans addition) was complete only with the enol ethers of unsubstituted cycloalkanones or 4-tert-butylcy-clohexanone. This 1,2-bis-azidonation procedure has not been exploited to prepare a-azide ketones, which should be available by simple hydrolysis of the adducts. Instead, the cis-l-triiso-propylsilyloxy-1,2-diazides were applied to the preparation of cw-2-azido tertiary cyclohexanols by selective substitution of the C-l azide group by nucleophiles in the presence of Lewis acids. 

Several factors such as the structure of the substrate, the catalyst, the solvent, the reaction temperature, the pressure of hydrogen and other reaction conditions determine the stereochemistry of the catalytic hydrogenation of cyclic ketones, and it is sometimes difficult to predict the major pn uct of catalytic hydrogenation. One reason for the complexity of the stereochemistry of the hydrogenation of cyclic ketones, at least in part, is related to the isomerization of the products under the reaction conditions. Some cyclohexanols were isomerized in the presence of platinum or nickel catalysts at room temperature or at higher temperature under a hydrogen atmosphere, and the isomerization reached a cis-trans equili-brium. For example, rranj-3,3,5-trimethylcyclohexanol isomerized in the presence of a nickel catalyst. 

The irradiation of phenylcyclohexenyl ketone (146) under argon in methanol results in its conversion to the cyclic ketone (147) by the well known Nazarov reaction. A careful study of this reaction by n.m.r. spectroscopy in deuteriated solvent shows that the enol (148), a long suspected intermediate, is the initial photochemical product. This is transformed readily by a thermal reaction into the final product (147). If non-protic solvents are used for the irradiation two new products (149) and (150) are formed. The structure of the stable compound (149) was determined by X—ray crystallography. The formation of the compound (149) is... 

---