Cyclobutanone cleavage

Cyclobutanone cleavage. Benzannulated lactones are obtained from 2-(o-hydroxyphenyl)cyclobutanones as a result of Rh insertion. Whether the benzylic position is fully substituted is a determinant factor for giving rise to -y-lactones or c-lactones. 

The oxidation by chromic acid alone leads to a mixture of cyclobutanone and 4-hydroxybutyraldehyde the existence of an isotope effect for the oxidation of I-deuteriocyclohexanol suggests that Cr(VI) produces the ketone and lower oxidation states of chromium produce the cleavage product. 

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. 

The fragmentation is stereospecifically anti as shown by complementary geometry obtained in the cleavage of the epimeric pair of epoxycyclobutanones 91 and 92 (Eq. 110). The fragmentation product 93 of cyclobutanone 91 is transformable into the dimethyl ester of the pheromone of the Monarch butterfly. Considering the availability of the starting epoxy ketones from enones, the oxasecoalkylation serves to reorient the oxidation pattern with chain extension as summarized in Eq. 111. 

While the haloform reaction normally only cleaves methyl ketones because of the structural requirements for the a,a,a-tribromomethyl ketone to induce fragmentation, the strain release that accompanies cleavage of a cyclobutanone permits extension... 

Treatment of cyclobutanones (232) with NaOMe and diphenyldisulfide in MeOH at reflux temperature led to to-sulfenylation and subsequent ring cleavage to furnish compounds (233) (Table 14)78>. 

The O radical can then undergoNorrish type II cleavage, abstracting H- from Cl in a six-membered TS, to give the cyclobutanone and the ketenol. 

The reaction gave only the rearrangement products 333 and 334, and the side product 335, as expected from the reactivity of alkylidenecyclopropane derivatives (Scheme 49). Compound 333 might arise from the 0-0 bond cleavage followed by the rearrangement of a cyclopropyloxy cation to an oxoethyl cation (Scheme 49, path a). Spiro-hexanone 334 could arise from a different fragmentation of ozonide C-O bond and further cyclopropyloxy-cyclobutanone rearrangement (Scheme 49, path b). Oxirane 335 can eventually derive from the same path b or from other side processes [13b]. 

The Cj - and 54-symmetric tetraesters of tricyclo[3.3.0.0 ]octane (430 and 431) have been prepared by oxidation of diene 429 To access the parent hydrocarbon (435), acid chloride 432 was transformed to the derived ketene which undergoes intramolecular [2+2] cycloaddition The resulting cyclobutanone (433) serves as precursor to perester 434 whose thermal decomposition proceeds with chain transfer in competition with cleavage The unique arrangement of the carbon atoms in 435 is such that the smallest rings are all five-membered. The highly symmetric structure may be viewed as a constrained cisoid bicyclo[3.3.0]octane (as well as the symbol of NATO). 

The photochemistry of cyclobutanone presents a special case since the Norrish type-I cleavage to give an acylalkyl diradical intermediate releases ring-strain energy. Thus the energy available for subsequent reactions is reduced correspondingly, compared to the energy retained in an acyl radical from an acychc ketone, or less strained cyclic ketones. 

The pump-probe-detect arrangements for the femtosecond experiments was similar to those described above. When cyclobutanone was pumped with two photons of a X = 307-nm femtosecond pulse, two consecutive C—CO bond cleavages led to the formation of the trimethylene diradical, detected as an easily ionized transient at 42 amu, with buildup and decay times of 120 20 fs. The decay presumably involves isomerizations to cyclopropane and to propylene— structures not ionized by the probe pulse and thus undetected during the experiment. 

This femtosecond study confirmed the involvement of the oxytetramethylene diradical as a reactive intermediate, and found that the trimethylene formed from it had the same hfetime as the trimethylene generated through the photodecarbonyl-ation of cyclobutanone. For tetrahydropyran, the oxypentamethylene drradical (86 amu) is formed readUy and the 85 amu transient, from the p-cleavage of a C H bond, is the dominant fragmentation product. 

Further examples of oxidative cleavage of alkylidenecyclobutanes to cyclobutanones are collected in Table 5. 

A synthetic study has revealed that the combination of anhydrous hydrogen chloride and zinc(II) chloride in the presence of a nucleophile, e.g. benzenethiol, promotes the ring cleavage of cyclobutanones such as bicyclo[3.2.0]heptan-6-one (28) to provide / -sulfanyl ketones such as 3-phenylsulfanylcycloheptanone (27).63 Alternatively, iodotrimethylsilane in the presence of either mercury/water or zinc(II) iodide also converts cyclobutanones to /i-iodo ketones 29.64 The synthetic applications of these transformations are summarized in Table 5. 

Cyclobutanone has been prepared by (1) reaction of diazomethane with ketene,4 (2) treatment of methylenecyclobutane with performic acid, followed by cleavage of the resulting glycol with lead tetraacetate,5 (3) ozonolysis of methylenecyclobutane, (4) epoxidalion of methylene-cyclopropane followed by acid-catalyzed ring expansion,7 and (5) oxidative cleavage of cyclobutane trimethylene thioketal, which in turn is prepared from 2-(cu-chloropropyl)-l,3-dithiane.8... 

I. Hanna, J. Pan, and J. Y. Lallemand, Optically active cyclobutanones from glycals Preparation and regioselective cleavage, Synlett p. 510 (1991). 

Linkers that enable the preparation of y-lactones by cleavage of hydroxy esters from insoluble supports are discussed in Section 3.5.2. Resin-bound y-lactones have been prepared by Baeyer-Villiger oxidation of cyclobutanones [39], by intramolecular addition of alkyl radicals to oximes [48], by electrophilic addition of resin-bound sele-nenyl cyanide or bromide to 3,y-unsaturated acids (Figure 9.2 [100]), and by palladium-mediated coupling of resin-bound aryl iodides with allenyl carboxylic acids (Entry 10, Table 5.7 [101]). 

Alternatively, an anion stabilizing group alpha to the carbonyl group of the cyclo-butanone provides a pathway for cleavage by attack of a nucleophile on the cyclo-butanone carbonyl carbon. C-Acylation creates the familiar 1,3-dicarbonyl system which, by deacylation involving attack at the cyclobutanone carbonyl group, leads to a geminal alkylation as shown in Eq. 115 b 47,79). 

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