Carbon functionalized cyclohexanones

In 1999 Trost and Schroder reported on the first asymmetric allylic alkylation of nonstabilized ketone enolates of 2-substituted cyclohexanone derivatives, e.g. 2-methyl-1-tetralone (45), by using a catalytic amount of a chiral palladium complex formed from TT-allylpaUadium chloride dimer and the chiral cyclohexyldiamine derivative 47 (equation 14). The addition of tin chloride helped to soften the lithium enolate by transmetala-tion and a slight increase in enantioselectivity and yield for the alkylated product 46 was observed. Besides allyl acetate also linearly substituted or 1,3-dialkyl substituted allylic carbonates functioned well as electrophiles. A variety of cyclohexanones or cyclopen-tanones could be employed as nucleophiles with comparable results . Hon, Dai and coworkers reported comparable results for 45, using ferrocene-modified chiral ligands similar to 47. Their results were comparable to those obtained by Trost. 

Cyclohexane can be partially oxidized by just attacking one C-C bond to open the ring with functional groups on each end of the six-carbon chain to produce the six-carbon amino acid or adipic acid. Sketch the intermediates to these products starting with cyclohexanone. 

The procedure reported here provides a convenient method for the a-hydroxylation of ketones which form enolates under the reaction conditions. The reaction has been applied successfully to a series of para-substituted acetophenones, 1-phenyl-1-propanone, 3-pentanone, cyclopentanone, cyclohexanone, cycloheptanone, cyclododecanone, 2-methyl cyclohexanone, 2-norbornanone and benzalacetone. In the case of a steroidal example it was shown that a carbon-carbon double bond and a secondary hydroxyl group are not oxidized. A primary amino function, as in the case of p-aminoacetophenone, is not affected.5 Similarly, a tertiary amino ketone such as tropinone undergoes the a-hydroxy at ion reaction.5... 

Felkin and co-workers model correctly predicts the degree of stereoselectivity as a function of the R group and does not require supplementary hypotheses when applied to cyclohexanones. They suggested that torsional repulsions are important, even between bonds only partially formed. To minimize torsional strain, the chiral carbon atom and the carbonyl adopt a staggered conformation in the transition state. Substituent L is anti to the nucleophile, which can then attack with minimal hindrance. To explain the preference for 1 over 2, Felkin and co-workers suggested that M and S interact more strongly with R than O. 

Isomerization during hydrogenation may alter the functional groups present in the molecule. For instance, reduction of cyclohexen-2-ol over 5% platinum-on-carbon occurred with rapid absorption of 1 mole of hydrogen at substantially constant rate and quantitative formation of cyclohexanol. On the other hand, reduction over palladium ceased abruptly at about two-thirds of a mole, and the product was a mixture of cyclohexanol and cyclohexanone, the latter arising through double bond migration to the enol of cyclohexanone (29). 

The aldol reaction is synthetically useful because it forms new carbon-carbon bonds, generating products with two functional groups. Moreover, the P-hydroxy carbonyl compounds formed in aldol reactions are readily transformed into a variety of other compounds. Figure 24.3 illustrates how the crossed aldol product obtained from cyclohexanone and formaldehyde (CH2=0) can be converted to other compounds by reactions learned in earlier chapters. 

The ring-opening reaction of cyclopropacyclopentanones 17 and -cyclohexanones 19 has proved to be a rather general method for the introduction of methyl groups to a carbonyl function, especially if the j8-carbon is a bridgehead atom. ... 

This experiment describes the lithiation of allyl trimethylsilane and the conversions of the lithio compound with trimethylchlorosilane and cyclohexanone, reactions that proceed with very high y-selectivity. For functionalizations with other electrophiles, e.g., epoxides, alkyl halides, and carbon dioxide, see Ref. [1] and literature cited in this paper. 

Oxidations - Enzymes which functionalize inactivated carbon are often difficult to obtain and handle. Many examples exist of oxidations using microbial fermentations, e.g. for steroids, and recently in olefin oxidation.Such preparative transformations have not been achieved with purified enzymes and are unlikely to be amenable to large-scale in vitro approaches because of instability and complexity of the enzyme systems. Klibanov and coworkers, however, have developed systems with horseradish peroxidase and xanthine oxidase for oxidation of aromatic alcohols and amines, for use in syntheses and waste water treatment. Hydroxyphenyl compounds can be oxidized to dihydroxy derivatives. L-DOPA has been made from L-tyrosine in this manner.Cyclohexanone was oxidized to t-caprolactone with a bacterial oxygenase. 

Cyclohexanone, a six-membered carbon ring with a ketone as functional group, is almost exclusively applied as a precursor for the production of aliphatic polyamides. Pure cyclohexanone is mainly converted, via cyclohexanone oxime and caprolactam, to nylon-6 (also called polycaprolactam) [1]. Mixtures of cyclohexanone and cyclohexanol, often called K4 oil, are converted via oxidation into adipic acid that reacts with hexamethylene diamine (HMDA) to nylon-6,6 (poly-hexamethylene adipamide). Other applications of these products can be found in the field of polyurethane and polyester production. 

Several calix[4]pyrrole molecules containing functional groups appended to the carbon- or C-rim of the calix[4]-pyrrole have recently been synthesized. These were prepared using one of two synthetic strategies. The first involves a direct condensation approach and was used to synthesize )S-octamethoxy-mcio-tetraspirocyclohexylca-lix[4]pyrrole 7 from 3,4-dimethoxypyrrole and cyclohexanone. - The resulting electron-rich calixpyrrole was then purified by column chromatography and isolated in 8% yield. 

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