7- cycloalkanone

Synthesis from Aldehydes and Ketones. Treatment of aldehydes and ketones with potassium cyanide and ammonium carbonate gives hydantoias ia a oae-pot procedure (Bucherer-Bergs reactioa) that proceeds through a complex mechanism (69). Some derivatives, like oximes, semicarbazones, thiosemicarbazones, and others, are also suitable startiag materials. The Bucherer-Bergs and Read hydantoia syntheses give epimeric products when appHed to cycloalkanones, which is of importance ia the stereoselective syathesis of amino acids (69,70). 

Moreover, fermentation of various a-substituted cycloalkanone enol esters results in optically active six-, eight-, ten-, and twelve-membered ring ketones with 70—96% ee (84). Isolated enzymes catalyze similar transformations, bacillus coagulans and Candida glindracea]i 2Lse OF (Meito Sangyo) hydrolyze a number of cycHc and acycHc enol esters, giving ketones in 40—80% yield and 14—85% ee (85,86). 

Compounds i, ii, and iii can be prepared by an acid-catalyzed reaction of a diol and the cycloalkanone in the presence of ethyl orthoformate and mesitylenesul-fonic acid. The relative ease of acid-catalyzed hydrolysis [0.53 M H2SO4, H2O, PrOH (65 35), 20°] for compounds i, iii, acetonide, and ii is C5 C7 > ace-... 

The photochemistry of cyclobutanones differs from that of less strained larger cycloalkanones. Fragmentation to ethylene and ketene (derivatives), decarbonylation and rearrangement to oxacarbenes predominate here. The oxacarbene formation, which occurs with retention of the configuration of the... 

The vinylogous 3,5-hexadien-2-one (16) adds in a 1,4 cycloaddition with zl -dehydroquinolizidine (17) to form compound 18 (26). A similar 1,4-cycloaddition reaction takes place between pyrylium salts and the pyrrolidine or morpholine enamines of cycloalkanones (26a). 

The reaction conditions (neutral, acidic or basic) do have an affect on the regioselectivity of the reaction. Acidic reaction conditions have also been shown to preferentially provide one regioisomer over basic conditions for reactions of aryl hydrazines. Extensive studies with 2-perfluoroacylcycloalkanones and mono-substituted hydrazines were studied to determine the selectivity of various alkyl-, aryl-, and heteroaryl-substituted hydrazines. Reactions of the aryl hydrazine 21 with the trifluoromethyl-substituted cycloalkanone 22 under neutral conditions (methanol, reflux) gave a mixture of isomers 23 and 24, whereas the reaction of the pyridyl hydrazine 25 was shown to give exclusively 26. 

Ketoesters 9 can be coupled to give enol ethers 10, which may for example be converted to cycloalkanones by hydrolysis. 

A novel ring closure was discovered by Stork (6) in which the pyrrolidine enamine of a cycloalkanone reacts with acrolein. The scheme illustrates the sequence in the case of 1-pyrrolidino-l-cyclohexene, and the cyclopentane compound was found to undergo the reaction analogously. The procedure details the preparation of the bicyclo adduct and its cleavage to 4-cyclooctenecarboxylic acid. 

Nitradon of the potassium enolates of cycloalkanones with pentyl n silyl enol ethers with nitroniiim tetraflnoroborate " provides a method for the preparadon of cydic ct-nitro ketones. Tnflnoroacetyl nitrate generated from tnflnoroacedc anhydnde and ammonium nitrate is a mild and effecdve nitradug reagent for enol acetates fEq. 2.411. ... 

The preparation of several medium- and large-sized 2-carbo-methoxycycloalkanones has been accomplished by treatment of the cycloalkanone with sodium triphenylmethyl, followed by carbonation with dry ice, and esterification with diazomethane. 1 The yields are good but the procedure is laborious. The synthesis of 2-carbomethoxycycIooctanone via the Dieckmann cyclization of dimethyl azelate with sodium hydride yields 48% of this product when the procedure is carried out over a 9-day period.3... 

The reaction described is of general synthetic utility for the preparation of a variety of cyclic /3-keto esters from the corresponding ketones. Using this procedure the 2-carbethoxy-cycloalkanones have been prepared from cyclononanone, cyclo-decanone, and cyclododecanone in yields of 85%, 95%, and 90%, respectively. The procedure is simpler and gives much higher yields than other synthetic routes to these systems. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Lithiated areneacetonitriles react with a,/i-unsaturated ketones at low temperatures using short reaction times to give both 1,2- and 1,4-adducts. The 1,2-addition is reversible and under thermodynamic control (higher temperatures and longer reaction times) only the 1,4-adducts, i.e., <5-oxonitriles, arc obtained. When lithiated arylacetonitrile is added to 2-substituted 2-cy-cloalkenones in THF or in THF/HMPA mixtures at — 70-0°C, followed by protonation or alkylation under kinetically controlled conditions, predominantly cis- or fnms-2,3-disubstitut-ed cycloalkanones respectively, are obtained. 

The Michael additions of chiral cycloalkanone imines or enamines, derived from (FV l-l-phcnyl-ethanamine or (5)-2-(methoxymethyl)pyrrolidine, are highly diastereofacially selective reactions providing excellent routes to 2-substituted cycloalkanones. This is illustrated by the addition of the enamine of (S)-2-(methoxymethyl)pyrrolidine and cyclohexanone to 2-(aryl-methylene)-l,3-propanedioates to give, after hydrolysis, the (2 5,a.S )-oxodicstcrs in 35-76% yield with d.r. (2 S,aS)/(2 S,a/ ) 94 6- > 97 3 and 80-95% ee214. 

When the cyclic enone is unsubstituted, but the resulting enolate is quenched with an electrophile under conditions of kinetic control the irons adduct is formed exclusively303. Particularly successful is the sequential Michael addition/enolate alkylation in diastereoselective routes to frans-a,/j-difunctionalized cycloalkanones and lactones304-308. The key steps in the synthesis of methyl ( + )-jasmonate (3)309-310 (syn/anti diastereoselection) and (-)-khushimone (4) (syn/anti and induced diastereoselection) illustrate this sequence311 (see also Section D. 1.1.1.3.). 

The lithium enolates of cyclopentanone and cyclohexanone undergo addition-elimination to the 2,2-dimethylpropanoic acid ester of ( )-2-nitro-2-hepten-l-ol to give 2-(l-butyl-2-nitro-2-propenyl)cycloalkanones with modest diastereoselection. An analogous reaction of the enolate ion of cyclohexanone with the 2,2-dimethylpropanoic acid ester of (Z)-2-nitro-3-phenyl-2-propenol to give 2-(2-nitro-l-phenyl-2-propenyl)cyclohexanones was also reported. The relative configuration of these products was not however determined6. 

Corey and Chaykovsky were the first to investigate the reaction of dimethyl sulphoxide anion (dimsyl anion) with aldehydes and ketones400,401. They found that the reaction with non-enolizable carbonyl compounds results in the formation of /1-hydroxyalkyl sulphoxides in good yields (e.g. Ph2CO—86%, PhCHO—50%). However, with enolizable carbonyl compounds, particularly with cycloalkanones, poor yields of hydroxyalkyl products are observed (e.g. camphor—28%, cyclohexanone—17%, but... 

The same reaction on a keto ester gives a cycloalkanone. " ... 

Trimethylsilylketene and acyl isocyanates generate 4-trimethylsiloxy-l,3-oxazin-6-ones 12 in situ, which smoothly react with the enamines of cycloalkanones to give bicyclic 2-pyridones 13 <96TL(37)4977>. The heterocycles 12 also undergo the Diels-Alder reaction with dimethyl acetylenedicarboxylate or methyl propiolate to furnish substituted 2-pyridones <96TL(37)4973>. 

The radicals derived by hydrogen abstraction from 1,3-dithianes and 1,3-oxathianes undergo intramolecular addition to ot,P-unsaturated esters and hence facilitate the synthesis of cycloalkanones <96T9713>. 

Reduction, carboxyl groups, 56,83 Reduction of a,0-unsaturated p-toluene-sulfonyl-hydrazones to alkenes, 59,42 Reductive alkylation, 56,52 Reductive cleavage, 56, 101 Resolution of amines, 55,80, 83 Rexyn 201,55,4 Rhodium(III) oxide, 57, 1 Ring contraction, 56, 107 Ring expansion of cycloalkanones to cycloalkenones, 59, 113... 

ONE-CARBON RING EXPANSION OF CYCLOALKANONES TO CONJUGATED CYCLOALKENONES 2-CYCLOHEPTEN-l-ONE... 

Flavoprotein 1,2-monooxygenases are used for the insertion of an atom of oxygen into the ring that is the first step in the degradation of both cyclopentanone and cyclohexanone before hydrolysis of the resulting lactones and dehydrogenation (Figure 3.5). There are two types of cycloalkanone... 

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