Cyclopentanones, cleavage

Keto acids are obtained by acylation of cyclopentanone enamines (see p. I3f.) with acid chlorides and subsequent base-catalyzed mro-aldol cleavage (S. Hdnig, 1960). 

The preparation of long-chain fatty acids has been carried out in this way because cleavage of 115 with strong sodium hydroxide gives the ketoacid (116), which is easily reduced by the Wolf-Kishner method to the saturated acid. A similar sequence of reactions can be carried out starting with the cyclopentanone enamine, and this method allows lengthening the chain... 

It has been shown that hydroxymethylene cyclohexanones, in contrast to their cyclopentanone analogs, can be smoothly converted into a-cyanocyclohexanones by the nucleophilic cleavage of the correspond-... 

The synthetic problem is now reduced to cyclopentanone 16. This substance possesses two stereocenters, one of which is quaternary, and its constitution permits a productive retrosynthetic maneuver. Retrosynthetic disassembly of 16 by cleavage of the indicated bond furnishes compounds 17 and 18 as potential precursors. In the synthetic direction, a diastereoselective alkylation of the thermodynamic (more substituted) enolate derived from 18 with alkyl iodide 17 could afford intermediate 16. While trimethylsilyl enol ether 18 could arise through silylation of the enolate oxygen produced by a Michael addition of a divinyl cuprate reagent to 2-methylcyclopentenone (19), iodide 17 can be traced to the simple and readily available building blocks 7 and 20. The application of this basic plan to a synthesis of racemic estrone [( >1] is described below. 

An important stage in the synthesis has been reached. It was anticipated that cleavage of the trimethylsilyl enol ether in 18 using the procedure of Binkley and Heathcock18 would regiospecifically furnish the thermodynamic (more substituted) cyclopentanone enolate, a nucleophilic species that could then be alkylated with iodo-diyne 17. To secure what is to become the trans CD ring junction of the steroid nucleus, the diastereoisomer in which the vinyl and methyl substituents have a cis relationship must be formed. In the... 

From intermediate 12, the path to key intermediate 7 is straightforward. Reductive removal of the benzyloxymethyl protecting group in 12 with lithium metal in liquid ammonia provides diol 27 in an overall yield of 70% from 14. Simultaneous protection of the vicinal hydroxyl groups in 27 in the form of a cyclopentanone ketal is accompanied by cleavage of the tert-butyldimethylsilyl ether. Treatment of the resultant primary alcohol with /V-bromosuccini-mide (NBS) arid triphenylphopshine accomplishes the formation of bromide 7, the central fragment of monensin, in 71 % yield from 27. 

Commercial food grade water-soluble Cu-chlorophyllin is the most notable among these preparations. Copper chlorophyllins are produced from crude natural chlorophyll extracts followed by the hydrolysis of the phytyl and methyl esters, cleavage of the cyclopentanone (E) ring in dilute alkali, and the replacement of magnesium by copper. ... 

From the reactions presented in this section one can conclude that cyclic acetal formation via addition to a carbene intermediate is a general reaction for type I cleavage of cyclobutanones, tricyclic compounds, and certain bridged bicyclics as minor products. No acetal has been isolated from photolyses of cyclopentanones or cyclohexanones except for the special case of an a-sila ketone previously discussed. 

SAMP-Hydrazones derived from ketones may also be cleaved by treatment with three equivalents of sodium perborate tetrahydrate at pH 7 in water/rert-butyl alcohol at 60 °C. Hydrolysis of aliphatic derivatives is effected in 4-24 hours and reactions yielding aromatic ketones proceed within 2- 3 days. This cleavage reaction furnishes the desired ketones chemoselectively in the presence of olefinic double bonds in 85-95% yield (cyclopentanone 70% yield)30. 

Part of the photorearrangement of cyclopentanone to 4-pentenal cannot be quenched,323,324 nor can most of the analogous reaction of camphor.326 In this regard also, the reaction resembles type I cleavage the more stable the alkyl radical which can be formed by acyl-carbon homolysis, the more such reaction competes with intersystem crossing. 

This type of fragmentation has been observed for a number of compounds, most of them having an exocyclic double bond. The decomposition of cyclopentanone (3) into ethene and carbon monoxide was described as a typical example in Section II. Cleavage of y-thiobutyrolactone (54) into carbon monoxide, ethene, and thioformaldehyde [93JCS(P2)1249] was mentioned in Section V.E. Another typical example is the formation of atomic carbon from 5-diazotetrazole (89JA8784). 

Types of Reaction. The net result of a-cleavage in cycloalkanones is the formation of an unsaturated aldehyde and/or a saturated ketene which subsequently reacts with nucleophiles. These types of reaction can be illustrated by the photochemistry of menthone (Formula 224). Irradiation of menthone in aqueous ethanol gives a saturated acid (Formula 225) and an unsaturated aldehyde which is either Formula 226 or 227 (86). In the absence of nucleophiles, irradiation of cyclopentanone... 

PV2M010O40 has usually been used in the acid form. H5PV2M010O40 catalyzes aerobic oxidative cleavage of cycloalkanes, 1-phenylalkanes, and ketones. For example, the oxidation of 2,4-dimethyl cyclopentanone and 2-methylcyclo-hexanone gives 5-oxo-3-methylhexanoic acid and 6-oxoheptanoic acid, respectively, in yields higher than 90% [285, 286). Bromination of arenes with HBr [287), oxidative dehydrogenation of cyclohexadiene [288, 289) and a-terpinene [290), oxidation of 2,4-dimethylphenol [291) and sulfides [292) are other examples. 

Assuming carbon-carbon bond cleavage occurs in the route leading to ethylene formation, unsuccessful attempts have been made to isolate the bis(ethylene) intermediate by reacting ethylene with titanocene obtained in a way similar to that described above (41). However, car-bonylation of the reaction mixture yielded cyclopentanone, inferring that titanocene intermediates are produced (43). 

There is of course no need to use reconnection if you prefer another strategy but you are advised to try disconnection first. Disconnection of the 1,3-diCO relationship in the spiro-diketone 54 reveals a 1,6-diCO compound that could no doubt be made by oxidative cleavage of 58. But various authors10 preferred to ignore the 1,6-diCO relationship and simply disconnect to the enolate of cyclopentanone 56 and a bromoester 57. 

Prepared by addition of 4-pentenyl magnesium bromide to cyclopentanone, dehydration of the alcohol to l-(4-pentenyl)cyclopentene, epoxidation of the endocyclic double bond, and periodate epoxide cleavage.53... 

Cyclic Ketones. The molecular ion peak in cyclic ketones is prominent. As with acyclic ketones, the primary cleavage of cyclic ketones is adjacent to the C=0 group, but the ion thus formed must undergo further cleavage in order to produce a fragment. The base peak in the spectrum of cyclopentanone and of cyclohexanone (Figure 1.22) is mlz 55. The mechanisms are similar in both... 

Annelation. Cleavage of l-(trimethylsilyloxy)-2-alkoxycarbonylcyclo-propanes (1) with KF-18-crown-6 generates y-oxo-a-ester enolate anions, which can be trapped by electrophiles. Trapping with a vinyl phosphonium salt results in [3 + 2] annelation to provide annelated cyclopentanones (2).1... 

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