Cyclohexanone derivatives

The intramolecular Claisen condensation of diesters, or Dieckman reaction, occurs readily to give five- or six-membered rings, and it has been extensively used for cyclopentanone and cyclohexanone derivatives. 

Reactions of 6-aminouracils with various 2-substituted cyclohexanones such as the aldehyde (264) give reduced pyrimido[4,5-f ]quinolines (265) (57BRP774095, 58JA3449), and other cyclohexanone derivatives used include the 2-dimethylaminomethyl (Mannich) bases (78AP542) and the 5-benzylidenedimedones (266) formed in situ from dimedone and aldehydes (67KGS395, cf. 67KGS406). 

F E R R I E R Chiral cyclohexanone synthesis Transtormatlon o< unsaturated glycosides into cyclohexanone derivatives by heating in aqueous acetone with mercury (II) salts... 

From the outset, the further O acylation of the initial ketonic products was recognized. Detailed studies have been made of the benzoylation of morpholinoeyclohexene (379-382) and of the effect of the amine moiety of cyclohexanone derived enamines on the ratio of produets (iS5) obtained from acylations. 

The addition of phenylisocyanate (427) to enamines was soon found to lead to double acylation products. In the case of the cyclohexanone derived enamine, the first proposal (428) of a second acylation on nitrogen was... 

Reactions of enamines with selenium dioxide gave low yields of enamino ketones (J8). Aromatization of cyclohexanone derived enamines eould be largely prevented by the use of aeetonitrile as solvent for the reaction. Even then, yields were eonsiderably below the limit of 50%, imposed by the generation of an equivalent of water. 

Tetrahydrocarboline derivatives have recently been synthesized from 2-o-nitroarylated cyclohexanone derivatives. Thus, reductive cyclization of 3-(2,4-dinitrophenyl)-l-methyl-4-piperidone (68) (prepared by the reaction of 2,4-dinitrochlorobenzene with l-methyl-4-A-pyrrolidmo-3-piperideine) gave 7-amino-2-methyl-l,2,3,4-tetrahydro-y-carboline (69). Neither catalytic nor chemical reduction of the... 

As the WT CHMO was known to react (S) selectively with simple four-substituted cyclohexanone derivatives [84—87], it was logical to test mutant 1-K2-F5 as a catalyst in the BV reaction of other ketones. For example, when 4-methoxycyclohexanone (38) was subjected to the BV reaction catalyzed by mutant 1-K2-F5, almost complete enantioselectivity was observed in favor of the (S)-lactone (39) (98.5% ee), in contrast to the WT, which is considerably less selective (78% ee) (see Scheme 2.11) [89]. 

In general, the mutants are different from those that were previously identified as hits in the BV reaction of prochiral cyclohexanone derivatives, which is not surprising. In contrast, mutant 1-K15-C1, which leads to 98.7% ee in favor of (R)-41, is characterized by amino acid exchange F432S. It is therefore identical to mutant... 

The principles involved in the conformational analysis of six-membered rings containing one or two trigonal atoms, for example, cyclohexanone and cyclohexene are similar. The barrier to interconversion in cyclohexane has been calculated to be 8.4-12.1 kcal mol . Cyclohexanone derivatives also assume a chair conformation. Substituents at C2 can assume an axial or equatorial position depending on steric and electronic influences. The proportion of the conformation with an axial X group is shown in Table 4.4 for a variety of substituents (X) in 2-substituted cyclohexanones. 

Laube and Hollenstein [21, 61] studied the single crystal structures of cyclohexanone derivatives complexed with a Lewis acid and found pyramidalization of the carbonyl carbon (4, Fig. 4), in agreement with the observed selectivity [61]. 

An alternative to monooxygenation is realized in the hydration of the substituted cyclohexanone derived from the fission product of 1,2-dihydroxynaphthalene during the degradation of 1,2,3,4-tetrahydronaphthalene (tetralin) (Hernaez et al. 2002) (Figure 7.35). 

The data below give the ratio of equatoriahaxial alcohol by NaBH4 reduction of each cyclohexanone derivative under conditions in which 4-r-butylcyclohexanone gives an approximately 85 15 ratio. Analyze the effect of the substituents in each case. 

The amine-catalyzed Diels-Alder dimerization reaction of a, 3-unsaturated ketones in water was developed by Barbas et al. to form cyclohexanone derivatives (Eq. 12.12). They believe that the reaction proceeds via the in situ formation of 2-amino-1,3-butadiene and iminium-activated enone, as the diene and dienophile, respectively. 

The stereoselective intramolecular Henry reactions have been reported by Seebach. The Michael addition of doubly deprotonated acetyl acetaldehyde to l-methylenedioxyphenyl-2-nitroethene followed by subsequent intramolecular nitro-aldol cyclization leads to the diastereomerically pure cyclohexanone derivative, where the nitro and OH groups are cis as shown in Eq. 3.73.114 This reaction is applied to the synthesis of l-desoxy-2-lycorinone as shown in Eq. 3.74.115... 

Zirconium enolates of various carbonyl compounds have also been investigated for Mannich-type reactions with different electrophiles. According to Shibasaki s method,148 the coupling reaction between a 3-acetoxy-4-alkyl-/3-lactam and the in r(/ -generated zirconium enolate 96 of a cyclohexanone derivative was realized as a key step during the total synthesis of an anitibiotic (Scheme 42).117,149... 

Aliphatic c a -dibromo ketones, such as 2,4-dibromopentan-3-one (262), react with primary amines RNH2 (R = Me, Et, Pr, /-Pr or t-Bu) to give mixtures of imines 263 and lesser amounts of diimines 264. l,3-Dibromo-l-phenylpropan-2-one yields only the amide 265, the product of a Favorskii rearrangement. The nature of the products from aliphatic amines and cyclic a,a -dibromo ketones depends on ring size the cyclohexanone derivative 266 gave Favorskii amides 267 (R = Pr, /-Pr or t-Bu), while trans-2,5-dibromocyclopentanone afforded the enamines 268 (R = /-Pr or t-Bu) (equation 95)296. 

Indicate the stereochemistry of the major alcohol that would be formed by sodium borohydride reduction of each of the cyclohexanone derivatives shown ... 

Ketamine is a cyclohexanone derivative whose pharmacological actions are quite different from those of the other IV anesthetics. The state of unconsciousness it produces is trancelike (i.e., eyes may remain open until deep anesthesia is obtained) and cataleptic it has frequently been characterized as dissociative (i.e., the patient may appear awake and reactive but does not respond to sensory stimuli). The term dissociative anesthesia is used to describe these qualities of profound analgesia, amnesia, and superficial level of sleep. 

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