Simple Cyclic Ketones

For simple cyclic ketones (Cn) the barrier for syn-anti isomerization of BF3 was shown to decrease in the order Cs > C = Ce > C4, a trend which closely follows the order of their basicities towards BF3 (vide supra). 

In contrast to simple cyclic ketones, some strained, and also sterically hindered, ketones give the less stable isomer. Thus, reduction of various bicyclo[2.2.1]heptanones4 by alkali metals in liquid ammonia, alone or in combination with proton sources (alcohols or ammonium chloride), gives predominantly the mfo-alcohols, regardless of whether these are thermodynamically favored or not (see Table 2, p 3972). 

Arenesulfonyl azides react at ambient pressure with enol ethers of simple cyclic ketones to give ring contracted arenesulfonylimidate esters in good yields (equation 99)90. The addition-rearrangement is highly stereoselective as shown in equations 100-102. 

The Baeyer-Villiger reaction can be carried out using isolated enzymes or whole cell systems. Biotransformations of simple cyclic ketones are most effective. For example, 4-methylcyclohexanone is oxidized with high enantioselectivity by using cyclohexanone monooxygenase (6.64). 

The Schmidt reaction of a simple cyclic ketone yields lactams with the ring expanded, while the intramolecular Schmidt reaction of cyclic ketone with an azido group at the side chain leads to the formation of bicyclic lactams with nitrogen at the position of fusion. It is interesting that the reaction between a cyclic ketone and 2-azido ethanol can form either a lactam or a lactone by means of the treatment with a different base, in which the lactam is formed when the reaction system is treated with KOH, whereas lactone is generated when NaHCOs is used as the base. Especially, the reaction between 4-ferf-butylcyclohexanone and 3-azido-2-methyl-2-phenylpropanol gives lactam in 19 1 stereoselectivity. ... 

The approximate absorption cross sections for cyclopentanone (in cyclohexane solution) are compared with those of the other simple cyclic ketones in figure IX-E-1. The structure and magnitude seen in this absorption is qualitatively similar to that reported for this compound by Benson and Kistiakowsky (1942). 

Enzymes Sources Coenzyme needed Alde- hydes Acyclic ketones Simple cyclic ketones Bulky cyclic ketones Aromatic ketones Dike- tones Unsaturated ketones 3-Oxo- acid esters 4-Oxo- acid esters 5-Oxo- acid esters... 

By changing from the simplest to larger aliphatic and cyclic ketones, structural factors may be introduced which favor alternative unimolecular primary photoprocesses or provide pathways to products not available to the simple model compound. In addition, both the increase in molecular size and irradiation in solution facilitate rapid vibrational relaxation of the electronically excited reactant as well as the primary products to thermally equilibrated species. In this way the course of primary and secondary reactions will also become increasingly structure-selective. In a,a -unsym-metrically substituted ketones, the more substituted bond undergoes a-cleavage preferentially. 

Iodine fluoride is a more versatile reagent than molecular fluorine in geminal fluorination of other hydrazones and related compounds under milder reaction conditions [55] Substrates fluorinated include hydrazones of simple cyclic or steroidal ketones (e g, 4 tert butylcyclohexanone, 70%, 3 cholestanone, 70%), W methyl and A/N dimethylhydrazones [R2C=NNH(CH3) 70%, R2C=NNC(CH3)2, 50%], semicarbazones (R2C=NNHCONH2, 25-50%), and 2,4-dinitrophenylhy-drazones [R2C==NNH-C6H3-2,4(N02)2, 25-50%]... 

It has been reported that perfluoroisobutylene and perfluorocyclobutene undergo 1,2 cycloaddition with l-(N-morpholino)isobutylene in ether at room temperature to give the corresponding perfluorocyclobutane derivatives ]20a). Enamines of cyclic ketones produce only simple alkylation products when treated with these perfluoroolefins. 

The stereochemical outcome of nucleophilic addition reactions to cyclic ketones is the subject of numerous experimental and theoretical studies, with substituted cyclohexanones and cy-clopcntanones having been intensively studied. In addition reactions to substituted cyclohexanones 1 the problem of simple diastereoselectivity is manifested in the predominance of cither axial attack of a nucleophile, leading to the equatorial alcohol 2 A. or equatorial attack of the nucleophile which leads to the axial alcohol 2B. 

Ordinary ketones are generally much more difficult to cleave than trihalo ketones or p-diketones, because the carbanion intermediates in these cases are more stable than simple carbanions. However, nonenolizable ketones can be cleaved by treatment with a 10 3 mixture of t-BuOK—H2O in an aprotic solvent such as ether, dimethyl sulfoxide, 1,2-dimethoxyethane (glyme), and so on, or with sohd t-BuOK in the absence of a solvent. When the reaction is applied to monosubstituted diaryl ketones, that aryl group preferentially cleaves that comes off as the more stable carbanion, except that aryl groups substituted in the ortho position are more readily cleaved than otherwise because of the steric effect (relief of stain). In certain cases, cyclic ketones can be cleaved by base treatment, even if they are enolizable. " OS VI, 625. See also OS VH, 297. 

Attack by eCN is slow (rate-limiting), while proton transfer from HCN or a protic solvent, e.g. HzO, is rapid. The effect of the structure of the carbonyl compound on the position of equilibrium in cyanohydrin formation has already been referred to (p. 206) it is a preparative proposition with aldehydes, and with simple aliphatic and cyclic ketones, but is poor for ArCOR, and does not take place at all with ArCOAr. With ArCHO the benzoin reaction (p. 231) may compete with cyanohydrin formation with C=C—C=0, 1,4-addition may compete (cf. p. 200). 

In the first reports by Ishii and coworkers , catalytic amounts of both HPI and Co(II)acetylacetonate, Co(acac)2, were employed for the oxidation of alkanes in AcOH at 100 °C, dioxygen being the terminal oxidant. The appeal of this procedure for the oxidative transformation of simple hydrocarbons into carbonyl derivatives is clear. Cycloalkanes were converted into a mixture of cyclic ketones plus open-chain a, )-dicarboxylic acids (Table 11), while linear alkanes yielded the corresponding alcohols plus ketones in significant amounts (40-80%), and alkylbenzenes could be oxidized in almost quantitative yields . 

Chiral sulfinimines 236 are very useful intermediates for the preparation of enantiomer-ically pure primary amines 237 (equation 158) . This reaction has been applied to the synthesis of a-amino acids . For sulfinimines obtained from simple ketones, lithium reagents are preferable for the addition , while for cyclic ketones organomagnesium compounds gave the best results. Addition of alkyl and aryl Grignard compounds to sulfinimines, derived from 3- and 4-substituted cyclohexanones, proceeds with excellent diastereoselectivity, depending on the stereochemistry of the ring substituents rather than the sulfinyl group . 

Aldol reactions are often used to close five- and six-membered rings. Because of the favorable entropy (p. 211), such ring closures generally take place with ease, even where a ketone condenses with a ketone. An important example is the Robinson annulation reaction which has often been used in the synthesis of steroids and terpenes. In this reaction a cyclic ketone is converted to another cyclic ketone, with one additional six-membered ring containing a double bond. The substrate is treated with methyl vinyl ketone (or a simple derivative of methyl vinyl ketone) and a base.551 The enolate ion of the substrate adds to the methyl vinyl ketone in a Michael reaction (5-17) to give a diketone that undergoes or... 

When seemingly simple organic structures defy isolation, this usually stimulates many theoretical and experimental studies in an effort to rationalize anomalous behavior. In the case of cyclopropanone, the possibility was considered that the molecule might preferably exist as an open-chain dipolar structure rather than as the cyclic ketone ... 

The positions of the double bonds in such enamines appear to be controlled by the same factors that affect the stability of simple olefins and not by those which affect the enamines from many cyclic ketones.263 The products of mercuric acetate oxidation of some indolizidines, with yields, are shown in structures 213-217. The double bond positions were ascertained by comparing the IR and NMR spectra with 218 and 219. 

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