Cyclobutane-1,3-dione ring

Within the cubane synthesis the initially produced cyclobutadiene moiety (see p. 329) is only stable as an iron(O) complex (M. Avram, 1964 G.F. Emerson, 1965 M.P. Cava, 1967). When this complex is destroyed by oxidation with cerium(lV) in the presence of a dienophilic quinone derivative, the cycloaddition takes place immediately. Irradiation leads to a further cyclobutane ring closure. The cubane synthesis also exemplifies another general approach to cyclobutane derivatives. This starts with cyclopentanone or cyclohexane-dione derivatives which are brominated and treated with strong base. A Favorskii rearrangement then leads to ring contraction (J.C. Barborak, 1966). 

Cycloadditions are in general an effective way of constructing cyclobutane rings. A wide variety of heterocyclic systems dimerize in this way. 1,3-Diacetylindole, for example, affords the head-to-tail dimer 242 on irradiation in ethanol.185 Ethyl 2-ethoxy-l,2-dihydroquinoline-l-carboxy-late is similarly converted in diethyl ether into the trans head-to-head dimer.186 Notable among many analogous photodimerizations are those reported in 1,4-dihydropyridines,187 in furo[3,2-b]pyridin-2(4//)-ones,188 in 8-methyl-s-triazolo[4,3-a]pyridine,189 and in 2H-2-benzazepine-1,3-diones.190 The [ 2 + 2] dimerization of amidopyrine is the first reported example of a photocycloaddition in a 4-pyrazolin-3-one.191... 

An interesting possibility for the construction of a tetracyclic system 174 with two cyclobutane rings arises by addition of lithiated alkoxyallenes 120 to 173 followed by two consecutive electrocydic reactions. Products such as 174 are useful precursors for benz[a]anthracene-7,12-diones (Scheme 8.43) [110]. 

Attempts to prepare a bicyclobutane by reductive cydization of cyclobutane-1,3-diones have been unsuccessful [114]. a,o)-Dibenzoylalkanes are reduced at a mercury cathode to cycloalkanediols only when a ring size of 5 or 6 results. These reactions have been achieved using either aqueous ethanolic sodium hydroxide [115] or acetonitrile containing tetramethylammonium tetrafluoroborate [113] as electrolyte. Attempts to extend the process to formation of 7-membered rings lead only to oligomeric materials. 

Due to the ring strain in the cyclobutane ring, /(-carbonyl cyclobutanones made by oxidation of methylenecyclobutane in methanol will readily undergo retro-Claisen-type reactions. For ozonolysis, this can be avoided by changing the solvent from methanol to dichloromethane treatment of 6-methyl-8-methylene-m-3-oxabicyclo[4.2.0]octan-2-one with ozone in methanol gave methyl 2-(4-methyl-2-oxo-4-tetrahydropyranyl)acetate (1), while the same treatment in dichloromethane gave 6-methyl-m-3-oxabicyclo[4.2.0]octane-2,8-dione (2).16... 

Hydrogenation of dione 21 with 10% palladium on charcoal gave the cyclobutane-ring cleaved compound 22 in 47% yield. 

Pinacol rearrangement driven by the release of the ring strain of a cyclobutane ring has been employed in an extremely efficient manner to form cyclopentanone derivatives. Experimentally. the Lewis acid mediated aldol condensation of benzaldehyde with l,2-bis(trimethyl-siloxy)cyclobutcne at —78 C gave the pinacol 1 in its silylated form.35,36 Subsequent treatment of this pinacol with trifluoroacetic acid at room temperature afforded 2-phenyl-cyclopentane-l,3-dione (2) in 97% yield.35,36... 

With 1,4-diketones the distribution of the reduction products is dependent on the stereochemical situation of the two carbonyl functions. In acyclic derivatives, with no stereochemical interaction between the two carbonyl functions, the ketone groups are independently reduced to give methylene products in the usual manner. On the other hand, cyclic 1,4-diketones react differently. For example, cyclohexane-1,4-dione (22) suffers ring opening to give hexane-2,5-dione and hex-5-en-2-one derivatives, and products of further reduction are also detectable (equation 11). A 1,4-diketone (23) in which the two carbonyls are stereochemically close, gave the diketone (24) under relatively mild conditions (Zn/AcOH, 25 C), formed by the same C—C bond cleavage as seen in cyclohexane-1,4-dione. Under Clemmensen conditions this derivative was then converted to cyclobutane-1,4-diol (25 equation 12) in 98% yield, which is closely related to the aforementioned cyclopropanediol intermediate. ... 

Because of their instability, cyclopropanones have been isolated in only a few cases, and methods for preparing the pure ketones are very limited. Among these are the addition of diazoalkanes to ketenes at low temperature ", potassium t-butoxide elimination of highly substituted a-bromoketones , photochemical decarbonylation of cyclobutane-1,3-diones " and ring-closure of 1,3-dihalo ketones Other methods exist for formation... 

The [2+2]photocycloaddition of 5-arylfuran-2,3-diones (496) to trimethylsilyl-oxyethylenes (495) occurs with high regio- and stereoselectivity to efficiently yield polyfunctionalised cyclobutanes (497). ° A convenient four step stereoselective synthesis of ( + )-norasteriscanolide (500) has used the [2+2]photoadduct (499) from 2-cyclopentenone and the trimethylsilyl enol ether (498) to assemble the 5/8 ring system present in many terpenoids. 2-Naphthaldehyde undergoes regio-and stereoselective [2+2]photoadditon to the cyclic ketene silyl acetals (501) to... 

Acyloin-type cyclization of dimethyl 2,3-di-tert-butylbutanedioate by sodium in refluxing toluene gave the 3,4-di-/erf-butyl-2-hydroxycyclobutanone (1) in 90% yield.Oxidation with dimethyl sulfoxide and acetic anhydride - gave 3,4-di-tm-butylcyclobutane-l,2-dione (2, 55%). Irradiation of this a,/1-diketone gave 2,3-di-terf-butylcyclopropanone (3) and a polymeric product. (For the base- or acid-induced ring contraction of cyclobutane-1,2-diones, see Section 4.1.2.2.7.). 

Photolysis of dimethylketene, which underwent thermal dimerization into tetramethyl-cyclobutane-1,3-dione, gave tetramethylcyclopropanone 1, together with 2,3-dimethylbut-2-ene (from dimethylcarbene dimerization) and carbon monoxide (from ketene photodissociation). Formation of the three-membered ring most probably arises from the addition of dimethylcarbene to dimethylketene. ... 

Ring contraction of a cyclobutane-1,2-dione was first postulated in order to account for the formation of an a-oxo acid 2 from 2-phenylcyclobutane-1,2-dione (1). ... 

The parent compound cyclobutane-1,2-dione itself was proposed as an intermediate in the acid- or base-catalyzed ring contraction of l,2-dichlorocyclobutyl-l,2-diylcarbonate (5), adduct of dichlorovinylene carbonate with ethene under photolysis, which on dissolution in cold dilute potassium hydroxide and subsequent acidification or on dissolution in hydrochloric acid, gave the 1-hydroxycyclopropanecarboxylic acid (6) as a single product. (For other examples of such a reaction, see ref 70.)... 

Cyclobutane-l,2-dione has been isolated from the bromination of 1,2-bis(trimethyl-siloxy)cyclobutene, prepared by sodium induced acyloin cyclization of butanedioate in the presence of chlorotrimethylsilane . The acyloin cyclization of 1,4-, 1,5- and 1,6-diesters to give four-, five- and six-membered rings and the cyclization of )9-chloro esters to three-membered rings in the presence of chlorotrimethylsilane, which usually requires highly dispersed sodium, has been recently simplified by the use of sonochemical activation. The ring contraction of cyclobutane-1,2-diones to 1-hydroxyeyclopropanecarboxylic acid (7) and derivatives may be catalyzed by aqueous acid or base, by methoxide anion, amines or hydrazines and even takes place, though more slowly, in pure water or ethanol. ... 

For the photochemical ring contraction of cyclobutane-1,2-diones with carbon monoxide elimination, see Section 4.1.1. 

Photochemical ring contraction of various substrates, e.g. cyclobutane-1,3-diones and 1 -pyrazolin-4-ones - gives either isolable cyclopropanes or cyclopropanones as intermediates which are usually intercepted as adducts or which fragment to alkenes and carbon monoxide. The photoextrusion process most often leads to fragmentation products. 

The de Mayo addition resxtion continues to be of considerable value for the formation of precursors for further synthesis. One example of this is the formation of the photoadducts (42, 43), prepared by photoaddition of isoprene to the enol of the dione ester (44), and have been used in a general synthesis of cyclopentenes. The photoadducts (42, 43) are produced in the standard fashion by the formation of a labile cyclobutane which subsequently ring opens. Takeshita et al. have reported the... 

Benzocyclobutenedione and other cyclobutane-l,2-diones also undergo such ring expansions (Eq. 118). 

The base-catalysed ring contraction of substituted cyclobutanes continues to attract attention and has been used for the synthesis of bicyclo[n,l,0]alkyl derivatives (n = 3 or 4) of known configuration. However, when applied to chlorotrialkylcyclobutane-1,3-diones, cyclopropanone-2-carboxylates are not obtained instead, ring cleavage occurs to give y-chloro-P-keto-esters, perhaps because of the ring strain associated with cyclopropanone. The dione (31), a photoproduct from bicyclo[2,2,l]hept-5-ene-... 

The difference between the photoreactivities of cyclobutanone and cyclohexanone has been discussed using Salem theoretical diagrams for coplanar a-cleavage in each ketone. Kimura and co-workers " have studied the effect of ring size on the photochemical reactions of a series of dispiro-cyclobutane-l,3-diones and the derived cyclohexylimines. Funke and co-workers have photolysed a series of cycloalkane carboxaldehydes including cyclobutane carboxaldehyde. 

The 1,4-diones (428) and (429) with an interposed cyclobutane ring are cleaved by reaction with zinc and zinc chloride in protic solvents. The presence of both carbonyl groups is necessary for the reaction. The ketone (430) is inert under the reaction conditions. 

Ring closures with bis(trifluoromethyl)ketene Cyclobutane-1,3-diones from ketenes... 

Effect of solvent. A soln. of dimethylketene in cyclohexane frozen in liq. Ng, bis(trifluoromethyl)ketene condensed on it, allowed to liquify in a Dry Ice-acetone bath, then distilled -> 2,2-dimethyl-4,4-bis(trifiuoromethyl)cyclobutane-l,3-dione. Y 81%. - In a more polar solvent, a mixture of the dione with the isomeric y -lactone is obtained. F. e. s. D. C. England and C. G. Krespan, J. Org. Chem. 35, 3322 (1970) ring closures with bis(trifluoromethyl)thioketene cf. M. S. Raasdi, ibid. 35, 3470. 

Scheme 2.51 Oxovanadium-induced ring-opening oxidation of 1,1,3,3-tetramethyl cyclobutan-2,4-dione...

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