Cyclohexanone ring

The superscript e refers to the equatorial position of a substituent (here Br) in that ring of the adamantane which is disubstituted (here the cyclohexanone ring C(l,2,3,4,5,9)]. A superscript "a denotes the corresponding axial position. 

The regio- and diastereo-selectivity of the Michael addition of 2-phenylcyclo-hexanone with a,p-unsaturated ketones are dependent on the reaction conditions. Mixtures of all six diastereoisomers resulting from reaction at either the 2- or 6-position of the cyclohexanone ring can be obtained using solid potassium hydroxide with tetra-n-butylammonium or A-benzylephcdrinium bromide catalysts. At 20°C with tetra-n-butylammonium bromide, the ratio of the 2,2- and 2,6-disubstituted cyclohexanones is ca. 3 2, but at higher temperatures with solid potassium f-butoxide the kinetically formed 2,6-isomer predominates (ca. 5 1) with the (2S,6R, R )-stereoisomer dominant, whereas greater amounts of the thermodynamically preferred 2,2-(2S,lR )-isomer are obtained with the chiral catalyst [61]. 

A very effective method for removal of the chiral auxiliary from cyclohexenones 34 involves treatment with I2 in THF-H2O to give the iodolactones 35 (Scheme 9). These highly functionalized chiral cyclohexanones have figured prominently in the asymmetric synthesis of natural products e.g. Scheme 15. Furthermore, selective cleavage of the cyclohexanone ring in 35... 

Nucleophilic addition to asymmetric carbonyl compounds is stereospecific. For example, most nucleophiles preferentially add to cyclohexanone rings from the more-crowded axial face rather than from the less-crowded equatorial face. 

Table 1. Approximate Increments (3 At.) for Substituents at the n- and -Carbon Atom of a Cyclohexanone Ring in an Octant Projection (I)22...

The n-7t Cotton effects of decalones are approximately the sum of typical he values for a given ring isomer and conformer (Figure 3) and 5Ae increments of any substituent in the cyclohexanone ring (Table 1). 

The isoxazole annelation reaction2,3 is a general method for fusing a new cyclohexanone ring onto an existing system and is complementary to the well-known Robinson annelation.4 It has several major advantages ... 

The cyclohexanone ring is locked in a boat form in 451, in a chair form in 453 while it is flexible in 454. As a result, the bridgehead C3 — H bond in 451 is appropriately aligned to overlap with the x orbital of the carbonyl group, whereas it is not in 453 and 454. On that basis, the facile bridgehead enolization of 451 by comparison with 453 and 454 is readily explained by the principle of stereoelectronic control. This is also supported by the... 

Deuterium atom was neatly incorporated at the bridgehead position C-l in ketone 464, the only compound in which the cyclohexane ring is locked in a boat conformation. Examination of molecular models indicates that the cyclohexanone ring can easily adopt a boat form in 460 and 461. It appears to be more difficult with ketone 462 and almost impossible with ketone 463. 

X-Ray diffraction techniques were used to help in the study of a QSAR of artemisinin 1 <2002JME292>, as well as in the determination of the structure of the artemisinin intermediate a,4-dimethyl-decahydro-7-oxo-l-naphthaleneacetic acid 7, where the cyclohexane ring assumes a chair conformation and the cyclohexanone ring a distorted one <1995JCX473>. 

However, all attempts to activate the a-position of the cyclohexanone ring in order to facilitate a subsequent diazotization, which was to be followed by rhodium carbenoid-mediated aryl C-H insertion onto C-4 [21], were unsatisfactory [22], One of the approaches was based on the generation of the silyl enol ether 35, but attempts to achieve its a-acylation led only to the formation of Paal-Knorr-type cyclization products 36. Chemoselective formylation of 34 to 37 was possible by reaction with ethyl formate in the presence of a large excess of sodium ethoxide, but in situ oxidation of the desired compound 37 to 38, which was the major isolated product, made the reaction impractical (Scheme 6). 

Figure 25 Two stable conformations of the cyclohexanone ring in ABA (HCt, the half-chair conformation with the pseudoaxial side chain HC2, the half-chair conformation with the pseudoequatorial side chain).

Clark and coworkers reported a successful annulation reaction between the dipheny-lacetone dianion and 1,3-dibromopropane, which led to the synthesis of a cyclohexanone ring (Scheme 19)31. On the other hand, neither 1,2-dichloroethane nor 1,2-dibromoethane gave the corresponding cyclic product. In these reactions, the ethylene-bridged compound and the dimerized compound were obtained, respectively. 

St. Jacques and his co-workers 121,122) have found that barriers to ring inversion in some cyclohexanones substituted with gem-dimethyl groups are higher than in the parent compound, that in 2 2,5,5-tetramethylcyclo-hexanone being 8.1 kcal/mol i )-). These workers conclude that the enhanced barriers are due to non-bonded interactions of the substituents in the transition state ), and by a comparison of results with those for methyl-enecyclohexanes (vide infra) place the barrier to inversion of the cyclohexanone ring itself between 4.5 and 5 kcal/mol. 

The physical and chemical properties of cyclopropane are similar to those of olefins, because of the increase in the p-orbital nature of the C-C bonds [50,51]. In bicycIo[4.1.0]heptan-2-one, the cyclopropyl ring is constrained essentially in an axial-like orientation to the plane of the cyclohexanone ring [52,53], Therefore, replacing the 2 -double bond of ABA with cyclopropane would introduce 1,3-diaxial steric repulsion between the cyclopropyl ring and the 6 -methyl group in one conformer, to pull conformational equilibrium towards the other [Fig. (4)]. On the other hand, replacing the C-5 -C-6 single bond with cyclopropane can... 

Ketamine, a dissociative anaesthetic, is administered as a racemic mixture (present in the parenteral preparation) and is initially metabolized by the liver to AT-desmethylketamine (metabolite I), which in part is converted by oxidation to the cyclohexene (metabolite II) (Fig. 1.5). The major metabolites found in urine are glucuronide conjugates that are formed subsequent to hydroxylation of the cyclohexanone ring. As the enantiomers differ in anaesthetic potency and the enantioselectively formed (metabolite I has approximately 10% activity of the parent drug) interpretation of the relationship between the anaesthetic effect and disposition of ketamine is complicated. On a pharmacodynamic basis, the S(+) enantiomer is three times as potent as the R(-) enantiomer (Marietta et al., 1977 Deleforge et al., 1991), while the enantiomer that undergoes N-demethylation (hepatic microsomal reaction) differs between species (Delatour et al, 1991). Based on the observed minimum anaesthetic... 

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