Conjugated Ketone Systems

An example of the calculation of the wavelength of the absorption maximum using Table 5.7 is shown in Example 5.6. In this example, the calculations are similar to those used in the conjugated diene system. Note that in order to affect the absorption maximum, the substituents must 

8 7 P a c = c-c = c-c = o Value assigned to parent a,p-unsatunated six-ring or acyclic ketone, 215 Value assigned to parent a,p-unsatunated five-ring ketone, 202 Value assigned to parent a,p-unsatunated aldehyde, 207 Increments Added for Shift to Longer X (nm)  

Source Scott, A.I., Interpretation of the Ultraviolet Spectra of Natural Products, Petgamon, Oxford, U.K., 1964, With permission. 

An isomer of the molecule used in Example 5.6 is shown in Example 5.7. The calculated absorption maximum is 286 nm. This spectrum is different in several ways from Example 5.6. For example, the carbon at the 5-position has only one alkyl substitution. The double bond between the y- and 5-positions is exocyclic to a ring in this case and therefore increases the wavelength of the absorption maximum. The conjugated system is not within a ring, and therefore, contributions from ring currents are not observed. These two isomers could be distinguished from each other by their UV spectra. 

Within a ring Double bond extension Exocyclic to a ring Calculated X  

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Myrcene with its conjugated diene system readily undergoes Diels-Alder reactions with a number of dienophiles. For example, reaction with 3-meth.5i-3-pentene-2-one with a catalytic amount of AlCl gives an intermediate monocyclic ketone, which when cyclized with 85% phosphoric acid produces the bicycHc ketone known as Iso E Super [54464-57-2] (49). The product is useful in providing sandalwood-like and cedarwood-like fragrance ingredients (91). 

In a useful modification of this method, la-methyl-A -3-keto steroids are obtained by methylation of the A -3-keto systems (20). However, it is unexpectedly difficult to convert the intermediate la-methyl-A -3-keto compound (21) into the conjugated ketone (22). 

Other nucleophiles add to conjugated systems to give Michael-type products. Aniline derivatives add to conjugated aldehydes in the presence of a catalytic amount of DBU (p. 488). Amines add to conjugated esters in the presence of InCla, La(OTf)3, or YTb(OTf)3 at 3kbar, for example, to give P-amino esters. This reaction can be initiated photochemically. An intramolecular addition of an amine unit to a conjugated ketone in the presence of a palladium catalyst, or... 

The a,P-unsaturated ketone or ester (0.3 mol), Na2CO, (7.95 g) and TBA-C1 (8.334 g, 30 mmol) in DMF (5 ml) are stirred for 10 min at room temperature. Pd(OAc)2 (0.33 g, 1.47 mmol) is then added and the mixture is stirred for a further 5 min before the iodoalkyne (30 mmol) in DMF is added dropwise over 1 h. The mixture is then stirred for 3-6 h at room temperature until GLC analysis indicates the complete consumption of the alkyne. The volatile material is evaporated and Et20 (150 ml) is added. The ethereal mixture is filtered through Celite, washed with H20 (50 ml), dried (MgS04), and evaporated to yield the conjugate carbonyl system (50-60%). 

Conjugated ketones and esters generally react with chloroform under basic conditions by Michael-type addition of the trichloromethyl anion to the C=C bond or by insertion of dichlorocarbene into the C=C bond, depending on the substitution pattern of the conjugated system (see Sections 6.4 and 7.3). The corresponding reaction with bromoform under basic conditions produces 1,1-dibromocyclopropanes. 

Base removes a proton from adjacent to a carbonyl group. We can use a general to represent the base however, we could use hydroxide, since that is released upon dissolving sodium carbonate in water. It does not matter which a-position we choose they are actually all equivalent in this symmetrical substrate. The nucleophilic attack of the enolate anion onto the second carbonyl is followed by base-initiated dehydration, so that a favourable conjugated ketone is the product. As you can see, the size of the ring systems is automatically defined by the reaction. 

The reaction is remarkably specific hydroxyls (even at C-21), saturated as well as conjugated ketones, ketals and even hindered isolated double bonds (e.g., A9(11)) are left substantially unattacked. Another advantage of this sequence is that it produces a A16-20-keto system, readily amenable to further substitution at C-16 or C-17. 

Reactions of this type are referred to in a variety of terms, many of which are rather confusing and nondescriptive. They sometimes are classified as 1,4-additions, implying that addition occurs across the terminal positions of the conjugated system. A synonymous term is conjugate addition. When the nucleophile is a carbanion, the reaction is called a Michael addition. Thus, by this definition, Equation 17-7 represents a Michael addition. Another, perhaps more typical, example is the addition of an enolate to a conjugated ketone ... 

The demonstration that both double bonds of the cross-conjugated dienone system are not necessary for photoisomerization considerably extends the potential utility of these rearrangements because of the greater availability of a,/3-unsaturated ketones. It is safe to predict that photochemical rearrangements of a,/3-unsaturated ketones will be subject to intense investigation in the immediate future. 

Further evidence that this is indeed the case comes from the dehydration under basic conditions of 8-hydroxy ketones (51-54). For example, the dehydration of 147 can yield the ci or the trans conjugated ketones 149 and 151 via the enolate anions 148 and 150 respectively. The formation of the trans product 151 is favored because there is less steric interaction between the planar enolate anion system and the phenyl group at the B-carbon... 

In aprotic solvents, an increase in solvent polarity resulted in an increase in the amount of ds-0-decalone formed. Similar results were also obtained in the hydrogenation of cholestenone and testosterone (see Table I). If, as suggested by McQuillin et al. (3), a more polar aprotic solvent will facilitate complexation of the carbonyl oxygen of an a,j3-unsaturated ketonic system in the same way that it increases its polarization (25), it can be assumed that what is occurring in these polar solvents is a 1,4-addition of hydrogen to the conjugated system. 

The anti-inflammatory activity of curcumin and its derivatives is associated with the hydroxyl and phenol groups in the molecule, which are also essential for the inhibition of prostaglandins, PG synthetase and leucotriene synthesis (LT) (Kiuchi et al., 1982, 1992 Iwakami, et al, 1986). Claeson et al. (1993, 1996) suggested that the antiinflammatory action and the antiparasitic activity were associated with the (3-dicarbo-nylic system with conjugated double bonds (dienes) (Araujo et al., 1998, 1999). The better skin penetration and lipophylicity is attributed to the presence of a diene ketone system. Calebin-A, a novel curcuminoid isolated from turmeric, protects neuronal cells from (3-amyloid insult. The hydroxy group at para-position of this compound is most critical for the expression of biological activity (Kim et al., 2001). 

The acylium ion is then attacked by the aromatic system in the usual way. Multiple substitution is rarely a problem because the deactivated conjugated ketone is much less reactive than benzene. 

Nazarov cyclizations require acid, and protonation of the ketone sets up the conjugated k system required for an electrocyclic reaction. 

The first systematic approaches to cis,syn,cis stereoisomers of this ring system were recently described by Eaton and co-workers.328) To gain access to monoketone 320 (Scheme 49), dicyclopentyl ketone was directly brominated and dehydro-brominated. The resulting cross-conjugated ketone 318 underwent acid catalyzed cyclization to provide the first tricyclic intermediate (319). Catalytic hydrogenation of 319 led stereospecifically to 320. Its six 13C resonance lines require that the molecule have C2 or Cs symmetry. The stereochemistry of this product was ulti-... 

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