Unsaturated cyclic ketone

The 3.8-nonadienoate 91, obtained by dimerization-carbonylation, has been converted into several natural products. The synthesis of brevicomin is described in Chapter 3, Section 2.3. Another royal jelly acid [2-decenedioic acid (149)] was prepared by cobalt carbonyl-catalyzed carbonylation of the terminal double bond, followed by isomerization of the double bond to the conjugated position to afford 149[122], Hexadecane-2,15-dione (150) can be prepared by Pd-catalyzed oxidation of the terminal double bond, hydrogenation of the internal double bond, and coupling by Kolbe electrolysis. Aldol condensation mediated by an organoaluminum reagent gave the unsaturated cyclic ketone 151 in 65% yield. Finally, the reduction of 151 afforded muscone (152)[123]. n-Octanol is produced commercially as described beforc[32]. 

TS-1 zeolites have been used in the presence of H2O2 to perform the BV reaction on cyclic and aromatic ketones . Cyclohexanone and acetophenone can be oxidized at 80 °C with selectivities lower that 60%, due to the formation of a-hydroxyketones and other undesired products. The observed modest results seem to be associated with the poor selectivity of the active Ti-peroxo species. In this respect, Corma and coworkers developed new Sn-based heterogeneous catalysts able to selectively activate the ketone instead of 11202 . Cyclic ketones are transformed into the corresponding lactones and unsaturated cyclic ketones like 110 are oxidized to unsaturated lactones in very high chemoselectivitjf , unusual for other oxidizing systems (equation 75). As expected, the authors failed to detect the presence of metal-peroxo derivatives in their systems . ... 

With saturated, or non-conjugated unsaturated, cyclic ketones, a-cleavage takes place readily in solution on irradiation, usually in a triplet-stale process. The resulting acyl-alkyl btradicals have a num-... 

A mixture of palladium chloride and triphenylphosphine effectively catalyzes carboxylation of linoleic and linolenic acids and their methyl esters with water at 110°-140°C and carbon monoxide at 4000 psig. The main products are 1,3-and 1,4-dicarboxy acids from dienes and tricarboxy acids from trienes. Other products include unsaturated monocar-boxy and dicarboxy acids, carbomethoxy esters, and substituted a,J3-unsaturated cyclic ketones. The mechanism postulated for dicarboxylation involves cyclic unsaturated acylr-PdCl-PhsP complexes. These intermediates control double bond isomerization and the position of the second carboxyl group. This mechanism is consistent with our finding of double bond isomerization in polyenes and not in monoenes. A 1,3-hydrogen shift process for double bond isomerization in polyenes is also consistent with the data. 

A significant portion of the neutral ethyl ether extract from the salts of carboxylated methyl linoleate consists of ,/3-unsaturated cyclic ketones. This material is produced in small but significant amounts (4-10%) (Table I) from the carboxylation of polyunsaturates but not from the corresponding monounsaturated fatty acids and esters (19). These ,/ -unsaturated cyclic ketones were identified spectroscopically (IR, UV, and NMR) as 4. This structural assignment was firmly established by mass spectral analyses before and after hydrogenation of the carbon-carbon double bond. 

The photochemical reactions of three a/3-unsaturated cyclic ketones have been reported. In these cases, it appears that the reaction is that of the olefinic group although the wavelength of the incident radiation is at the ultraviolet absorption of the carbonyl group. Photolysis of 2-cyclo-pentenone (16), carvone (XXXV) (7,12) and y-tropolone methyl ether... 

When nonconjugated dienes react with carbon monoxide and water in the presence of dicobalt octacarbonyl, saturated and unsaturated cyclic ketones are produced (55, 77). This appears to be due to the formation of unsaturated acylcobalt carbonyls followed by cyclization, as discussed in Section II, B,3. 

Benzophenone (Amax = 340 nm, log e = 2.5, n-ir electronic transition) can be used as a photochemical reagent and eq. 4.25 shows a radical Michael-addition reaction with benzophenone. The formed benzophenone biradical (triplet state, Tx) abstracts an electron-rich a-hydrogen atom from methyl 3-hydroxypropanoate (62) to generate an electron-rich a-hydroxy carbon-centered radical [III], then its radical adds to the electron-deficient (3-carbon of a, (3-unsaturated cyclic ketone (63) through the radical Michael addition. The electrophilic oxygen-centered radical in the benzophenone biradical abstracts an electron-rich hydrogen atom from methyl 3-hydroxypropanoate (62) [70]. So, an a-hydroxy carbon-centered radical [III] is formed, and an electron-deficient a-methoxycarbonyl carbon-centered radical [III7] is not formed. 

Chalcone, chromone, flavone, /rans-cinnamaldehyde, cyclopentenone, etc. gave the corresponding products in satisfactory yields [28], The oxidation of some disub-stituted a,j8-unsaturated cyclic ketones, however, gave predominantly hydroxylated products [29], An interesting variation was the synthesis of ds-hydroxyflavanones from 2-hydroxychalcones, e.g. [30] ... 

Another unique compound was found7(g) among the products of the reaction between 3,5,6-tri-O-methyl-D-glucose and acetylmethylene-phosphorane. An inflection at 222 nm in the electronic spectrum, and strong infrared absorption at 5.8 /am, indicated an a,/3-unsaturated, cyclic ketone structure.89 When this compound was allowed to react with methylmagnesium bromide, the product showed7 8 an absence... 

Compound A is a cyclic, nonconjugated keto alkene whose carbonyl infrared absorption should occur at 1715 cm-. Compound B is an a,B-unsaturated, cyclic ketone additional conjugation with the phenyl ring should lower its IR absorption below 1685 cm-1. Because the actual IR absorption occurs at 1670 cm-1, B is the correct structure. 

Similarly, conjugate addition of trimethyisilyllithium to hydrazones of a,/(-unsaturated cyclic ketones, followed by alkylation, gives exclusively fra/w-adducts (>98% de) which on hydrolysis produce the corresponding trans-2-alkyl-3-silyl ketones34. 

Diphenylmethylene)cyclopropane (29b) reacts with a,P-unsaturated cyclic ketones in the presence of [PdCp(Ti -allyl)] and triisopropylphosphine to afford compounds (53) in moderate to high yields (equation 20). ... 

As expected, the monomers that produce isotactic polymers in nonpolar solvents generally give syndiotactic polymers with the same initiators in polar solvents. Linear esters of acrylates always produce amorphous polymers. Polymers of x, -unsaturated cyclic ketones obtained in the presence of Grignard reagents were also amorphous [62]. 

The total synthesis of several amaryllidaceae alkaloids including that of narciclasine was accomplished in the laboratory of T. Hudlicky. The C2 stereochemistry was established by a two-step sequence Luche reduction of the a,(3-unsaturated cyclic ketone followed by a Mitsunobu reaction. The ketone was first mixed with over one equivalent of CeCIs in methanol and then the resulting solution was cooled to 0 °C, and the sodium borohydride was added. In 30 minutes the reaction was done, and the excess NaBH4 was quenched with AcOH. The delivery of the hydride occurred from the less hindered face of the ketone and the allylic alcohol was obtained as a single diastereomer. 

The research team of D.F. Covey developed a synthetic route to convert 5p-methyl-3-ketosteroids into 7(S)-methyl substituted analogues of neuroactive benz[e]indenes. The synthesis began with 19-nortestosterone, in which the a,p-unsaturated cyclic ketone moiety was degraded to afford a tricyclic aldehyde. This aldehyde was unstable and could not be stored. For this reason it was immediately subjected to the Tsuji-Wllkinson decarbonylation to afford the decarbonylated product in high yield. 

Asymmetric synthesis via chiral, nonracemic hydrazones have gained wide acceptance in the community of synthetic organic chemists. Some examples of asymmetric alkylations of acyclic, satu-rated and unsaturated cyclic ketones - and aldehydes, which are applicable in the natural products field, are shown in Scheme 55. Various methods of cleavage of the alkylated hydrazones are also illustrated in Scheme 55. 

Venhuis et al. observed a particularly original oxidative bioactivation mechanism by which an a, 3-unsaturated cyclic ketone is converted to the corresponding catechol and delivered enantioselectively into the CNS (Figure 36.29b). This concept can be generalized and has the potential to lead to new anti-Parkinson treatments. " ... 

Asymmetric conjugate additions of the anions of chiral allyl- and crotylphos-phonamides 1.74 (Y = RCH=CH) to a,p-unsaturated cyclic ketones, lactones and lactams, and to tert-Bu cinnamate are highly stereoselective at -78°C [313] (Figure 7.68). Hanessian and coworkers obtained 1,4-adducts with a high stereoselectivity. The level of selectivity was maintained even when the 3-position of the acceptor was substituted, so quartemary stereocenters can be generated. Both enantiomers of 1.74 are available, so it is possible to obtain either enantiomeric 1,4-adduct. 

Bellus, D., Kearns, D.R., and Schaffner, K., 1969, Photochemistry of a,P-unsaturated cyclic ketones specific reaction of me and rat triplet states of O-acetyltestosterone and 10-methyl-A1 9-octalone(2), Helv. Chim. Acta 52, 971-1009. 

Hydrogenation of diketones and ketones proved to be not very effective (Vermeer et al. ") hydrogenations of the diketones, butane-2,3-dione andhex-ane-3,4-dione, on 6.5% Pt-silica-Cnd at 10 bar and 20 C in CH2CI2 solution produce ee s of only 33% and 38%, respectively, although trifluoroaceto-phenone gave 56% (Bodmer et al. Likewise, Torey et al. found that hydrogenation of the C=C side chain in an unsaturated cyclic ketone over Pd-charcoal catalyst modified with (-)-ephedrine at 0°C in MeCN resulted in a product with an ee of only 36%. 

Isophorone [14.268], [14.269] is an unsaturated cyclic ketone. It consists of a-isophorone [78-59-1] (3,5,5-trimethyl-2-cyclohexen-l-one), which contains about 1-3% of the isomer P-isophorone [471-01-2] (3,5,5-trimethyl-3-cyclohexen-l-one). Isophorone is a stable, water-white liquid with a mild odor that is miscible in all proportions with organic solvents. It dissolves many natural and synthetic resins and polymers, such as poly(vinyl chloride) and vinyl chloride copolymers, poly(vinyI acetate), polyacrylates, polymethacrylates, polystyrene, chlorinated rubber, alkyd resins, saturated and unsaturated polyesters, epoxy resins, cellulose nitrate, cellulose ethers and esters, damar resin (dewaxed), kauri, waxes, fats, oils, phenol-, melamine-, and urea-formaldehyde resins, as well as plant protection agents. However, isophorone does not dissolve polyethylene, polypropylene, polyamides. 

DMP with high purity by the original procedure therefore, a few modifications have been suggested. In addition, DMP has been successfully used in the syntheses of polycyclic heterocyclesand in the removal of thioketals and thioacetals. It should be mentioned that other hypervalent iodine compounds can be used as oxidants as well, especially for the o-iodoxybenzoic acid (IBX), the precursor to DMP, which can oxidize tertiary cyclic allyl alcohol into O, y0-unsaturated cyclic ketones and secondary amines into imines and can convert epoxides or aziridines into corresponding of-hydroxy ketones or Q -amino ketones. 

In 2012, the Bencivenni group reported an AFC alkylation/acetalization cascade of 1- and 2-naphthols with a,p-unsaturated cyclic ketones via iminium catalysis. In this reaction, they found that a stoichiometric amount of water was necessary to obtain high ee values and 1-naphthols showed a better stereochemical outcome than 2-naphthols. Unexpectedly, encumbered l//-inden-l-ones could be applied in this system, furnishing the desired products in high yields (Scheme 6.51). 

Scheme 6.51 AFC-acetalization cascade of 1- and 2-naphthols with a,(3-unsaturated cyclic ketones reported by Bencivenni.

Figure 5. Some branched cycloses, cyclitols and alpha, beta-unsaturated cyclic ketones derived from xylaric acid some acyclic c> /o (8 - 9) and ribo (10) ring precurors.

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