Cyclobutane, from fragmentation

This work has been compared with analogous cyclobutane thermolytic decompositions. The siletanes were found to fragment more readily than the cyclobutanes. Although fragmentation via propene formation (most substituted C—C bond) was favored in both classes of compounds, it was more dominant with the siletanes. These effects are apparent from the kinetic data in Table IV.144-147... 

Generally, the yields of cyclobutanes are low and byproducts, resulting from fragmentation or rearrangements of intermediate 1,4-diradicals, are produced to a large extent. Additionally, the syntheses of the starting azo compounds are difficult, so that the synthetic applicability of this reaction is limited. 

Conlin and co-workers have also studied the fragmentation of a siletane (silacyclobutane). In this case, both the E- and Z-isomers of 1,1,2,3-tetra-methylsilane 45 were prepared and thermolyzed (Scheme 8).144 Both E-and Z-isomers of 45 led to the same products in slightly different ratios the major products were propene with silene 46, and E- and Z-2-butenes with silene 47. Silene formation was inferred from detection of the disila-cyclobutane products. During these processes, the stereochemical integrity of the compounds was largely preserved. 

Of the wide array of platinum derivatives, carboplatin is the only compound except cisplatin that is used in medical practice, and it differs from cisplatin in the replacement of two chlorine atoms with a cyclobutan-l,l-dicarboxylic acid fragment. Like cisplatin, carboplatin also reacts with DNA to form both internal and external cross-bonds. The range and indications of use are practically analogous to cisplatin. Synonyms of this drug are paraplatin and others. 

The decay of the tetramethylene diradical derived from 2,2,5,5-t/4-cyclopenta-none is much slower than seen for the C4Hg diradical. Both principal decay modes, fragmentation to two ethylenes and ring-closure to cyclobutane, may be dependent dynamically on torsional motions of the terminal methylene groups. 

Few syntheses of cyclobutanes by the five minus one strategy starting from a metallacyclopen-tane by elimination of the metal fragment have been reported. Such metallacarbocycles have been postulated as intermediates in the cyclodimcrization of alkenes to give cyclobutanes as an alternative mechanistic interpretation for the orbital symmetry forbidden thermal [2 -1- 2] cycloadditions of alkenes (Houben-Weyl, Vol. E18, pp 843 - 873). 

A fragmentation reaction which appears to proceed via the generation of 1,4-diradicals is the decomposition of 1,1-tetramethylenediazenes. Unlike the more stable 1,2-diazenes (tetrahy-dropyridazines, see Section 4.2.1.), the 1,1-isomers are not usually isolated or characterized by physical methods but are proposed as intermediates in the thermal decomposition of iV-phenyl-sulfonamidopyrrolidines 1, giving 1,4-diradicals which recombine to yield cyclobutanes 3 and 4. 39 These intermediates are also formed in the photochemical decomposition at low temperature of 1,1-tetramethylenediazenes, prepared in situ from 1-aminopyrrolidines and /er/-butyl hypochlorite.141... 

Reaction with OH also leads to the splitting of the dimer (-30% efficiency), and there is evidence that one-electron oxidants such as S04 may also induce the splitting of the dimer (Heelis et al. 1992). The NO -radical-induced splitting of the tetramethyl-substituted Ura cyclobutane dimer has been investigated in acetonitrile (Kruger and Wille 2001). The -N03 radical has been generated photo-lytically from a Ce(VI) salt (Chap. 5.2). Under theses conditions, the 5-5 -linked intermediate is also trapped, possibly by a deprotonation or a Ce(IV)-mediated oxidation that competes with 3-fragmentation [reactions (310)—(313)]. 

Compared with the parent system and those with identical substitution in all four carbons, the structure of other derivatives should be affected by the substitution pattern and by the nature of the substituents. For 1,2-disubstituted derivatives, structure type C, in which the doubly substituted cyclobutane bond is weakened (and lengthened), or a related structure type in which the bond is cleaved, should be favored. This is born out by several observations mentioned earlier. For example, the geometric isomerization of 1,2-diaryloxycyclobutane (Sect. 4.1) can be rationalized by one-bond rotation in a type C radical ion. Similarly, the fragmentation of the anti-head-to-head dimer of dimethylindene (Sect. 4.4) may involve consecutive cleavage of two cyclobutane bonds in a type C radical ion. The (dialkylbenzene) substituents have a lower ionization potential (IP 9.25 eV) [349] than the cyclobutane moiety (IP 10.7 eV) [350] hence, the primary ionization is expected to occur from one of the aryl groups. 

The stereochemistry of the addition reactions to the alkene of a-pinene is dominated by the geminal methyl groups of the four-membered ring, which hinder addition from the same face. These methyl groups hinder the approach of a nucleophile to the rear of the epoxide. The fragmentation to form sobrerol also involves the release of the strain of the cyclobutane ring. 

The benzo version of the cyclopropyl- ir-methane rearrangement has been reported for substrate (16). The products are shown in equation (19), of which cyclobutane (17) corresponds to the cyclopropyl- n-methane product. The two alkenes are secondary products from the cyclobutane, while the last two products derive from photocycloreversion of the starting material (Griffin fragmentation), the diphenylcarbene being trapped by the solvent (BuKDH) in the form of the ether. 

The interpretation of these two schematic views confronts some difficulties. Option (1) requires the extrusion of a hydrogen from a methylene hardly active in acidic medium (acetic acid). Under basic conditions, it would be necessary first to convert the sulfide to a sulfoxide such as V to achieve sufficient activation of this methylene. This oxidation may be accomplished by LTA as indicated previously. Nevertheless, the ensuing cyclobutane fragmentation in VI— the actual oxidative step—by concurrent attack of acetate and departure of Pb(II) diacetate (X = PbOAc2 in Scheme 27.1) has no precedent in LTA-amine chemistry, although it is electronically balanced. Besides, the final product of this sequence would be sulfoxide VII. Having no reductive work-up procedure, this sulfoxide should survive until the isolation step. Since this is not the experimental fact, option (1) must then be discarded. 

The occurrence of methylene elimination by reaction (7) is suggested by the presence of traces of cyclopropane in the products, as well as allene which may result from C3H6 decomposition. The decrease of propene yield with increasing pressure is attributed to a pressure-dependence of reaction (8). The direct decomposition of cyclobutane by reaction (9) is thought not to occur, but is equivalent to (2)-I- (5) or to (6) if C4H7 decomposes to the appropriate fragments. 

Figure 4.16. Derivation of the correlation diagram for the concerted fragmentation of cyclobutenophenanthrene from the orbital energy-level scheme of biphenyl and the orbital correlation diagram for the fragmentation of cyclobutane into two ethylenes. (The additional double bond has been neglected in the simplified treatment.) The arrows indicate the magnitude of orbital interactions between the two superimposed systems (by permission from Michl, 1974b).

The sequence of intramolecular photocycloaddition-cyclobutane fragmentation has been used by Crimmins in an excellent manner for the synthesis of pentalenenes and the even more sophisticated lauren-l-ene (27). The latter synthesis was accomplished in 27 steps from cyclopentenone U66). One of the key steps is the reductive cleavage of the tetracyclic cyclobutane (167), followed by hydrogenation of the resulting P,7-unsaturated ester to give keto ester (168 Scheme 57). 

In Norrish type II cleavage, the O radical abstracts H from the y-carbon in a six-membered TS, and the 1,4-diradical then fragments to give an alkene and an enol, the latter of which tautomerizes to the ketone. Sometimes, the 1,4-diradical undergoes radical-radical combination to give a cyclobutane, instead. The Norrish type II cleavage is closely related to the McLafferty rearrangement that is often seen in the mass spectra of carbonyl compounds. 

The above powerful effect has been shown to have its origin in the superior orbital overlap in 4a-like TS wherein the breaking ctc n bonds are aligned parallel to the orbital axes of the cyclopropane ring (dashed lines in 4a). In the alternate 4b-like TS, orbital overlap is unsatisfactory because the axes of the involved orbitals are essentially perpendicular. Thus, the cyclopropane has synthetically compelled the choice of one pathway and controlled the stereochemical course of the reaction at the sites of the two newly generated it bonds. Such a feature was observed from the cyclobutane derivative 7 as well as it fragmented to the .y, .y-diene 8 with a stereospecificity that was too high to measure. However, the reaction 7 8 was... 

Cycloaddition. Reaction of the 1,3-dipolar species derived from methyl 2-phenylthiocyclopropyl ketone with silyl vinyl ethers furnishes functionalized cyclopentanes. A related reaction is the trapping of a fragmented cyclobutane. ... 

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