Formation of Cyclobutanes

Cyclobutanes are usually more difficult than cyclopropanes to prepare by cyclization. Although their ring strain is as high as that of cyclopropanes, more bonds must assume a suitable conformation for cyclobutane formation, resulting in a higher entropic barrier (Table 9.1). 

The relative rates given in Table 9.2 should be used as a rough guideline only, because small structural variations or different reaction conditions can alter the cyclization rates significantly. 

1 Baldwin, J. E. Rules for ring closure./. Chem. Soc. Chem. Commun. 1976, 734—736. 

2 Baldwin, J. E. Cutting, J. Dupont, W. Kruse, L. Silberman, L. Thomas, R. C. 5-Endo-trigo-nal reactions a disfavoured ring closure. 

3 Johnson, C. D. Stereoelectronic effects in the formation of 5- and 6-membered rings the role of Baldwin s rules. Acc. Chem. Res. 1993, 26, 476 182. 

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The facile formation of cyclobutane products is indeed another important contribution of enamine chemistry (302-306). The formation of cyclobutanes has also been found in the closely related reactions of amino acetal derivatives of ketenes with acrylic esters (307). 

Fig. 1. Geometry of the formation of cyclobutane from two ethene molecules.

Zhang RB, Eriksson LA (2006) A triplet mechanism for the formation of cyclobutane pyrimidine dimers in UV-irradiated DNA. J Phys Chem B 110 7556-7562... 

Figure 10.1. Reaction scheme for the formation of cyclobutanes (S) and (9) and vinylcyclohexene (13) from butadiene.

Eq. 34 is included so that the possibility of synchronous concerted formation of cyclobutanes may be considered. This step is formally a forbidden triplet to singlet process, but several workers have taken the position that this may not be an inhibiting factor for concerted reactions. 31,38,99)... 

So summarizing we see that in thermal [2 + 2] cycloaddition, a supra-supra process is geometrically possible but symmetry forbidden. But in supra-antar process, symmetry is allowed but geometrically difficult. Now we have to explain how the photochemical formation of cyclobutane takes place from 2n components. 

The cyclodimerisation of fluorinated alkenes and formation of cyclobutane from alkenes activated by electron withdrawing groups has formed great application in laboratory and industry... 

Scheme 4 Stacking of diolefin compounds and the formation of cyclobutane, cyclophane, and polymers as the photoproducts...

This is so, as shown by Grubbs reports of the reactions of metallacycles of type L Ni(CH2)4 It is reported that the preferred decomposition pathway depends on the degree of coordination (Scheme 2). Here the formation of cyclobutane from... 

Treatment of propargyl alcohols with phosphorus trichloride gives chloroallenes and these can undergo dimerization under the reaction conditions, as in the case of the formation of cyclobutanes 15 and 16.30... 

Mechanistically, it is reasonable to regard metallacyclopentanes as intermediates in the formation of cyclobutane derivatives from two alkene substrates.5 It has been established that nickelacyclopentane not only acts as an intermediate in such a reaction but also as a catalyst.6... 

Analogous reactions of 3-diazobicyclo[2.2.1]heptan-2-one with perchloric acid in alcohols, such as ethanol, gave the corresponding ethers, e rfo-3-ethoxybicyclo[2.2.1]heptan-2-one (34%),, n -2-ethoxybicyclo[3.1,1]hcptan-6-onc (41%) and methyl cyclohex-3-enecarboxylate.69 Further examples of the formation of cyclobutanes from cyclopentanes via Wagner-Meerwein-type rearrangements are given in Table 2. 

Further examples of the formation of cyclobutanes via Norrish type I cleavage of cyclopen-tanones are given in Table 4. 

The formation of cyclobutanes from transition metal complexes is possible by reductive elimination and has been extensively described in Section 7.A. 1.3.1.2. Coordination compounds in which cyiobutanes act as ligands are unknown. 

Much less information is available about [2 + 2]-cycloadditions. These allow the formation of cyclobutane derivatives in the reaction between two alkenes, or that of cyclobutenes from alkenes and alkynes. The reaction can be achieved thermally via biradical intermediates,543 by photoreaction,544 and there are also examples for transition-metal-catalyzed transformations. An excellent example is a ruthenium-catalyzed reaction between norbomenes and alkynes to form cyclobutenes with exo structure ... 

Let us take as a given that gaseous cyclobutane has an enthalpy of formation either ca 25 or 35 kJ mol"1 lower than gaseous cyclopropane, the two values differing by which value is taken for the enthalpy of formation of cyclobutane. It was seen that regardless of elec-... 

See R. Fuchs and J. H. Hallman, op. cit. (Reference 74). We share these authors conclusion that the sole calorimetric study of the enthalpy of formation of cyclobutane is somehow incomplete , and so invites suspicion that it is also inaccurate. [See S. Kaarsemaker and J. Coops, Reel. Trav. Chim. Pays-Bas, 71, 261 (1952).]... 

For simplicity in both writing and reading the chapter, it has been assumed the archival value for the enthalpy of formation of cyclobutane is correct. 

Exercise 28-10 Write a mechanism for formation of cyclobutane from the photolysis of cyclopentanone, and ketene from the photolysis of cyclobutanone. 

It has been observed that the formation of the olefin and carbon monoxide, 45, is ten times more important than the formation of the bicyclic hydrocarbon and carbon monoxide, 46, at 80° and 80 mm. pressure even at 3130 A. The formation of the strained bicyclic hydrocarbon is evidently not a favorable reaction although this may not be the only consideration. In the case of camphor it should be interesting to find out if an optically active isomer of the ketone on photolysis will give rise to an optically active trimethyl bicyclo [2.1.1] hexane (XXVI). A concerted reaction, analogous to the formation of cyclobutane from cyclopentanone, may lead to only an optically active product. 

Like many ionic cyclizations, the formation of cyclobutane rings by radical cyclizations is very slow, and powerful accelerating effects will be required for any synthetic applications (see Scheme 7).2 These cyclizations are again reversible, and, in the absence of any other effects, the equilibrium lies to the side of the open radical due to ring strain. The fragmentations of simple cyclobutyl carbinyl radicals are slow,... 

Stepwise reactions by way of diradical intermediates are also possible they often require rather high temperatures, but they are probably involved in the formation of cyclobutanes by the thermal coupling of alkenes like the halogenated alkene 2.161 with themselves or with dienes like butadiene giving the cyclobutane 2.163. The radical centres in the intermediate 2.162... 

Recently, the distinction between electrophilic and ion radical (electron-transfer) mechanisms of addition reactions to the vinyl double bond of aryl vinyl sulfides and ethers has been achieved by studying substituent effects (Aplin Bauld 1997). Specifically, the effects of meta and para substituents on the rates of electrophilic addition correlate with Hammett cr values, while ionization of the substrates to the corresponding cation radicals correlates with cr+. The significance of the respective correlations was confirmed by statistical tests. The application of this criterion to the reaction of aryl vinyl sulfides and ethers with tetracyanoethylene revealed that formation of cyclobutanes occurs via direct electrophilic addition to the electron-rich alkene and not via an electron-transfer mechanism. 

Scheme9.20. Formation of cyclobutanes by intramolecular addition of organometallic reagents to C-C double bonds [60, 82-84],...

Scheme 9.22. Formation of cyclobutanes from enolates and metalated imines [91-94].

Several intramolecular [2 + 2] cycloadditions with formation of cyclobutane rings have been observed. For example, the tetracyclic diolefin (3), in which two double... 

The electron transfer induced cleavage of cyclobutane systems is of interest also in connection with photoreactivation, a repair mechanism for photo-damaged DNA. Upon exposure to UV light, DNA may be damaged by the formation of cyclobutane links between adjacent thymine units. The resulting dimers are cleaved, and DNA is restored, by a photoreactivating enzyme in the presence of near UV or visible light. The mechanism of reactivation may involve electron transfer, either to or from the pyrimidine dimer [258-260]. 

Confirmation of the preferred coupling of the primary carbon atom of the alkyl-substituted 1,3-diene has been referred to earlier, e.g., in the formation of cyclobutane derivatives from frawr-piperylene. 

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