Preparation of cyclic ketones

4-Phenylheptanedioyl dichloride — 3-(l,2,3,4-tetrahydro-4-oxo-l-naphthyl)-propionic acid574 

3-Chloropropionanilide — 3,4-dihydro-2(l/f)-quinolone575 0-(4-Methylbenzyl)benzoic acid — 2-methyl-9-anthrone576 

3-(2-Bromo-5-methoxyphenyl)propionic acid ----- 4-bromo-7-methoxy- 

Other condensing agents used for such ring closures include hydrogen fluoride,576 polyphosphoric acid,578 phosphoryl chloride,581 zinc chloride,582 and mixtures of phosphoryl chloride and zinc chloride.527,528 

When an aromatic compound is treated with a mixture of carbon monoxide and hydrogen chloride in the presence of aluminum chloride and copper(i) chloride, the derived aromatic aldehyde is obtained. Presumably formyl chloride is formed from the carbon monoxide and hydrogen chloride, although it is stable only as the adduct with aluminum chloride. 

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The excellent method for cyclizing o-benzylbenzoic acids to anthranol acetates, by heating the acid in- a mixture of acetic acid, and anhydride with zinc chloride as a catalyst,228 has been used also in the preparation of cyclic ketones of the tetralone type. In this way 7-3-acenaphthylbuty-ric acid has been cyclized in 78% yield 224 Y-2-phenanthrylbutyric acid48 and the 9,10-dihydro derivative97 in 51% and 59% yields respectively and a,j8-dimethyl-Y-2-naphthylbutyric acid in 90% yield.186... 

Tin tetrachloride has often been recommended for the preparation of cyclic ketones 515 it is also advantageous to use it with furan derivatives. 

This reaction has been widely used for the preparation of cyclic ketones. 

For preparation of cyclic ketones from dicarboxylic acids see... 

Methyl ketones are important intermediates for the synthesis of methyl alkyl carbinols, annulation reagents, and cyclic compounds. A common synthetic method for the preparation of methyl ketones is the alkylation of acetone derivatives, but the method suffers limitations such as low yields and lack of regioselectivity. Preparation of methyl ketones from olefins and acetylenes using mercury compounds is a better method. For example, hydration of terminal acetylenes using HgSO gives methyl ketones cleanly. Oxymercuration of 1-olefins and subsequent oxidation with chromic oxide is... 

The present preparation illustrates a general and convenient irethod for ring contraction of cyclic ketones. The first step is the usual procedure for the preparation of enamines. The second step involves 1,3-dipolar cycloaddition of diphenyl phosphorazidate to an enamine followed by ring contraction with evolution of nitrogen. Ethyl acetate and tetrahydrofuran can be used as a solvent in place of toluene. Pyrrolidine enamines from various cyclic ketones smoothly undergo the reaction under similar reaction conditions. Diphenyl (cycloalkyl-1-pyrrolidinylmethylene)phosphoramidates with 5,6,7, and 15 members in the ring have been prepared in yields of 68-76%. 

The reaction of the enamines of cyclic ketones with alkyl isocyanates, acyl isocyanates, phenyl isothiocyanates, and acyl isothiocyanates has also been reported 112). The products are the corresponding carboxamides. The products from the isothiocyanates have been utilized as intermediates in the preparation of various heterocyclic compounds 113). 

This procedure illustrates a new three-step reaction sequence for the one-carbon ring expansion of cyclic ketones to the homologous tt,/3-unsaturated ketones. The key step in the sequence is the iron(III) chloride-induced cleavage of the central bond of trimethyl-silyloxycyclopropanes which me obtained by cyclopropanation of trimethylsilyl enol ethers. The procedure for the preparation of 1-trimethylsilyloxycyclohexene from cyclohexanone described in Part A is that of House, Czuba, Gall, and Olmstead. ... 

The method can be further improved using trimethylsilyl (TMS) enol ethers, which can be prepared in situ from aldehydes and ketones [49]. TMS enol ethers of cyclic ketones are also suitable, and diversity can be enhanced by making either the kinetic or thermodynamic enol ether, as shown for benzyl methyl ketone. Thus, reaction of the kinetic TMS enol ether 10-133 with the amino aldehyde 10-134 and dimethylbarbituric acid 10-135 yielded 10-136, whereas the thermodynamic TMS enol ether 10-137 led to 10-138, again in excellent purity, simply by adding diethyl ether to the reaction mixture (Scheme 10.33). 

Cyclic nitroalkenes are prepared from cyclic ketones via nitration of vinylstannanes with tetranitromethane in DMSO, as shown in Eq. 2.36, where DMSO is a critical choice of solvent for replacing tin by nitro at the unsaturated carbon. The conversion of ketones to vinylstannanes... 

Nitration of the potassium enolates of cycloalkanones with pentyl nitrate81 or nitration of silyl enol ethers with nitronium tetrafluoroborate82 provides a method for the preparation of cyclic a-nitro ketones. Trifluoroacetyl nitrate generated from trifluoroacetic anhydride and ammonium nitrate is a mild and effective nitrating reagent for enol acetates (Eq. 2.41).83... 

The synthetic utility of the carbonylation of zirconacycles was further enhanced by the development of a pair of selective procedures producing either ketones or alcohols [30] and has been extensively applied to the synthesis of cyclic ketones and alcohols, most extensively by Negishi [22—27,29—33,65,87,131—134], as detailed below in Section I.4.3.3.4. The preparation of unsaturated aldehydes by carbonylation with CO is not very satisfactory. The use of isonitriles in place of CO, however, has provided a useful alternative [135], and this has been applied to the synthesis of curacin A [125]. Another interesting variation is the cyanation of alkenes [136]. Further developments and a critical comparison with carbonylation using CO will be necessary before the isonitrile reaction can become widely useful. The relevant results are shown in Scheme 1.35. 

The present procedure is a general method for the preparation of monoalkylated ketones from enamines of aldehydes and ketones with electrophilic olefins. There are many advantages in this method of alkylation. Only monoalkylation occurs, even when such reactive species as acrylonitrile are used and, when a cyclic ketone like 2-methylcyclohexanone is used, reaction occurs only at the lesser substituted center. In a general base-catalyzed reaction, substitution occurs on the more substituted center. 

Most enamines, unfortunately, are sensitive to hydrolysis. The parent enamine, iV,iV-dimethylvinylamine, has in fact been prepared [3], but appears to be unstable. Enamines of cyclic ketones and many aldehydes can readily be isolated, however [4-7]. The instability of enamines might at first appear to diminish the utility of enamines as nucleophiles, but actually this property can be viewed as an added benefit enamines can be readily and rapidly generated catalytically by using a suitable amine and a carbonyl compound. The condensation of aldehydes or ketones with amines initially affords an imine or iminium ion, which then rapidly loses a proton to afford the corresponding enamine (Scheme 1). 

Oxidation of cyclic ketones by H2O2 in the presence of an acid zeolite was used for the preparation of lactones and u-hydroxycarboxylic acids [124]. Thus, for c-pentanone oxidation in the presence of H-ZSM-5, -valerolactone is obtained with 62.3% selectivity at 40% conversion, whereas 5-hydroxy-pentoic acid is obtained with 34% yield in the presence of Zeolon M. 

The photorearrangement of 7V-aryl lactams 34 to the ortho-position offers an interesting possibility for the preparation of cyclic benzo-aza-ketones of type 35, whereas the rearrangement to the para-position should lead to para-cyclophane 144 formation. 7-, 8-, and 13-Membered ring jV-aryl lactams (34, n = 5, 6, and 11) were successfully rearranged in ethanol to 35 in chemical yields of 60, 83, and 80%,13 and in quantum yields of 0.071, 0.11, and 0.082, respectively.14... 

Enantioselective alkylation of ketones. Chiral imines prepared from cyclic ketones and 1 on metalation and alkylation are converted to chiral 2-alkyleyclo-alkanones in 87-100% enantiomeric purity.1 The high cnantioselectivity is dependent on chelation of the lithium ion in the anion by the methoxyl group, which results in a rigid structure. 

Enamines of cyclic ketones may also be used to prepare polyamides in a different type of condensation reaction (67MI11100). This polymerization involves reaction with diisocyanates (Scheme 46), with the enamine functioning as a difunctional reagent. Morpholino- and piperidino-enamines are the most effective monomers. 

Other Peroxyacids. Benzeneperoxyseleninic acid has been prepared in situ from benzeneseleninic acid and hydrogen peroxide and is used to epoxidize terpenic olefins and Baeyer-Villiger oxidation of cyclic ketones. 

The chemical properties of cyclic ketones also vary with ring size. Lower members (addition reactions, than corresponding acyclic ketones. The Cg—C12 ketones are unreactive, reflecting the strain and high enol content of medium-sized ring systems. Lactones are prepared from cyclic ketones by the Bayer-Villiger oxidation reaction with peracids. S-Caprolactone is manufactured from cyclohexane by this process ... 

Representatives of Condensed Pyrroles Prepared from Oximes of Cyclic Ketones... 

Finally, ring expansions of cyclic ketones are an important method for the preparation of carbocyclic systems. Diazoalkanes allow this reaction to occur and involve C—C bond formation. When combined with carefully chosen organoaluminum compounds, this process can be performed in a highly stereoselective fashion (equation 148)541. 

The asymmetric alkylation of cyclic ketones, imines of glycine esters, and achiral, enolizable carbonyl compounds in the presence of chiral phase-transfer organoca-talysts is an efficient method for the preparation of a broad variety of interesting compounds in the optically active form. The reactions are not only highly efficient, as has been shown impressively by, e.g., the synthesis of enantiomerically pure a-amino acids, but also employ readily available and inexpensive catalysts. This makes enantioselective alkylation via chiral phase-transfer catalysts attractive for large-scale applications also. A broad range of highly efficient chiral phase-transfer catalysts is also available. 

Cycloalkenyllithiums.3 Alkenyllithiums are usually prepared by reductive lithiation of trisylhydrazones of ketones with butyllithium, but this method fails with the hydrazones of cyclic ketones. However, the cycloalkenyl sulfides, prepared by reaction of cyclic ketones with thiophenol, can be reductively lithiated with LDBB at -78°. This lithiation fails in the case of cyclopentenyl sulfides, but is useful in the case of the vinyl sulfides obtained from 6-, 7-, and 8-membered cycloalkanones. 

The regioselective attack of nonactivated C-H-bonds by an excited carbonyl group is demonstrated with the transannular cyclization of bicyclic diketones 76, which can easily be prepared from cyclic ketones 75 according to Stetter et al. [61]. Upon irradiation, the selectively excited benzoyl... 

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