Cubane derivative, Favorskii

No Favorskii rearrangement products are produced when a-halocyclopentanones are treated with base, and products of aldol, substitution and dehydrohalogenation reactions are produced. However, when an a-halocyclopentanone is part of certain condensed systems, cubane derivatives may be obtained (see Section 3.7.3.5). 

At this point, it is interesting to compare the absence of reactivity of a-halocyclopentanones under Favorskii rearrangement conditions, with the ring contraction observed when such a-halocyclopentanones are included in cage structures used as precursors of cubane derivatives. We will show in what follows that this marked difference in reactivity can be explained by the equatorial stereochemistry of the halogen in the cage a-cyclentanone derivatives. 

SCHEME 18.10. Cubane derivative through Favorskii rearrangement. 

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). 

The three types of compounds reported in Table 6 are more strained than those in Table 3. This factor, as well as others, such as the differences in reactivity and in experimental conditions, the steric and electronic factors, are all much more favorable for a semibenzilic rather than for a cyclopropanone mechanism. For derivative 67 of the cubane series, Eaton and Cole proposed such a mechanism. For the bicyclo[2.2.1]heptane derivatives, with the exception of 76, no a or a hydrogens are available, so that the semibenzilic mechanism is the only one possible (quasi-Favorskii). However, in the latter compounds, the aa -dihalogenated or the polyhalogenated derivatives can undergo ring opening. We will now discuss the influence of the steric and electronic factors on this secondary reaction. 

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