Cyclobutenes 2 + 2 + 2 cycloaddition reactions

The reaction of ethyl 2,2-diethoxyacrylate with alkynylalkoxycarbene complexes affords 6-ethoxy-2H-2-pyranylidene metal complexes [92] (Scheme 48). The mechanism that explains this process is initiated by a [2+2] cycloaddition reaction (see Sect. 2.3), followed by a cyclobutene ring opening to generate a tetracarbonylcarbene complex. This complex can be isolated and on standing for one day at room temperature renders the final 6-ethoxy-2Ff-pyranylidene pentacarbonyl complex. This last transformation requires the formal transfer of one carbonyl group and one proton from the diethoxy methylene moiety to the metal and to the C3 2H-pyranylidene ring, respectively, with concomitant cyclisation. Further studies on this unusual transformation have been extensively performed by Moreto et al. [93]. 

In a similar process, tertiary enaminones react with alkynylcarbene complexes to give the corresponding pyranylidene complexes following a reaction pathway analogous to that described above. First, a [2+2] cycloaddition reaction between the alkynyl moiety of the carbene complex and the C=C double bond of the enamine generates a cyclobutene intermediate, which evolves by a conrotatory cyclobutene ring opening followed by a cyclisation process [94] (Scheme 49). 

Intermolecular [4C+2S] cycloaddition reactions where the diene moiety is contained in the carbene complex are less frequent than the [4S+2C] cycloadditions summarised in the previous section. However, 2-butadienylcarbene complexes, generated by a [2+2]/cyclobutene ring opening sequence, undergo Diels-Alder reactions with typical dienophiles [34,35] (Scheme 59). Also, Wulff et al. have described the application of pyranylidene complexes, obtained by a [3+3] cycloaddition reaction (see Sect. 2.8.1), in the inverse-electron-demand Diels-Alder reaction with enol ethers and enamines [87a]. Later, this strategy was applied to the synthesis of steroid-like ring skeletons [87b] (Scheme 59). 

Aumann et al. have observed an unusual formal [6S+2C] cycloaddition reaction when they performed the reaction between an alkynylcarbene complex and 1-aminobenzocyclohexenes. The solvent used in this reaction exerts a crucial influence on the reaction course and products of different nature are obtained depending on the solvent chosen. However, in pentane this process leads to cyclooctadienylcarbene complexes in a reaction which can be formally seen as a [6S+2C] cycloaddition [117] (Scheme 71). The formation of these compounds is explained by an initial [2+2] cycloaddition reaction which leads to a cy-clobutenylcarbene derivative which, under the reaction conditions, undergoes a cyclobutene ring opening to furnish the final products. 

The cationic pathway allows the conversion of carboxylic acids into ethers, acetals or amides. From a-aminoacids versatile chiral building blocks are accessible. The eliminative decarboxylation of vicinal diacids or P-silyl carboxylic acids, combined with cycloaddition reactions, allows the efficient construction of cyclobutenes or cyclohexadienes. The induction of cationic rearrangements or fragmentations is a potent way to specifically substituted cyclopentanoids and ring extensions by one-or four carbons. In view of these favorable qualities of Kolbe electrolysis, numerous useful applications of this old reaction can be expected in the future. 

The meso-ionic 1,3-oxazol-S-ones show an incredible array of cycloaddition reactions. Reference has already been made to the cycloaddition reactions of the derivative 50, which are interpreted as involving cycloaddition to the valence tautomer 51. In addition, an extremely comprehensive study of the 1,3-dipolar cycloaddition reactions of meso-ionic l,3-oxazol-5-ones (66) has been undertaken by Huisgen and his co-workers. The 1,3-dipolarophiles that have been examined include alkenes, alkynes, aldehydes, a-keto esters, a-diketones, thiobenzophenone, thiono esters, carbon oxysulfide, carbon disulfide, nitriles, nitro-, nitroso-, and azo-compounds, and cyclopropane and cyclobutene derivatives. In these reactions the l,3-oxazol-5-ones (66)... 

Warrener and co-workers (25) exploited a 1,3-dipolar cycloaddition reaction to synthesize a 7-azanorbornane 124 (Scheme 9.25). The cyclobutene-1,2-diester 121 underwent smooth cycloaddition with benzyl azide to give the triazohne 122, which... 

The construction of the tricyclo[5.2.0.02,6]nonane (26, n = 1) and tricyclo[6.2.0.02,7]decane (26, n = 2) frameworks involved the [2 4- 2] cycloaddition of readily accessible31,32 l,2-bis(trimethyl-siloxy)cyclobutene and cnone 25, n = 1 or 2, respectively.33 The yields (75-80%) were good for adducts 26a, c, e, and g. Lower yields (40-50%) were observed for adducts 26b and 26f, while adduct 26d was only isolated in a trace amount. The most interesting and important reaction, related to the total synthesis of eudesmane sesquiterpenes, was the photochemical reaction of (-)-piperitone (25g) with l,2-bis(trimethylsiloxy)cyclobutene, which gave c/.v,(5wf/u W-2/j,7/i-dimethyl-4/ -isopropyl-l f ,8Jf -bis(triniethylsiloxy)tricyclo[6.2.0.0z 7]dec-3-one (26g) with the relative cis configuration of the methyl (R2) and isopropyl (R3) groups.33,34 Some of the other photochemical [2 + 2] cycloaddition reactions utilizing l,2-bis(trimethyl-siloxy)cyclobutene are shown by the formation of 2735,36 and 28.37... 

If the motion had been disrotatory, this would still have been evidence for a cyclic mechanism. If the mechanism were a diradical or some other kind of noncyclic process, it is likely that no stereospecificity of either kind would have been observed. The reverse reaction is also conrotatory. In contrast, the photochemical cyclobutene—1,3-diene interconversion is disrotatory in either direction.368 On the other hand, the cyclohexadiene—1,3,5-triene interconversion shows precisely the opposite behavior. The thermal process is disrotatory, while the photochemical process is conrotatory (in either direction). These startling results are a consequence of the symmetry rules mentioned in Chapter 15 (p. 846).Vl,As in the case of cycloaddition reactions, we will use the frontier-orbital and Mdbius-HQckel approaches.37"... 

A number of examples of photoaddition to alkynes has been described. Dimethyl acetylenedicarboxylate has been found to add to methyl-substituted 3-benzoylthiophens301 and to thiophen and 2,5-dimethylthiophen302 on irradiation. Benzo[f>]thiophen also undergoes cycloaddition reactions with alkynes,303 and in the case of dimethylacetylene dicarboxylate, product formation has been shown to be wavelength dependent.304 Intramolecular [ 2 -(- 2] cycloaddition has been observed on both direct and triplet-sensitized irradiation of the alkyne (353) and gives the cyclobutene (354)305 the isomer (355) is formed on prolonged irradiation. 

Pericyclic reactions are commonly divided into three classes electrocyclic reactions, cycloaddition reactions, and sigmatropic rearrangements. An electrocyclic reaction forms a sigma bond between the end atoms of a series of conjugated pi bonds within a molecule. The 1,3-butadiene to cyclobutene conversion is an example, as is the similar reaction of 1,3,5-hexatriene to form 1,3-cyclohexadiene ... 

Table 6. Fluorinated Cyclobutenes by [2 + 2]-Cycloaddition Reactions of Fluoroalkenes with Alkynes...

Fluorinated cyclobutenes synthesized from the cycloaddition of fluoroalkenes with non-fluorinated alkynes (vide supra) undergo pyrolysis to give fluorinated butadienes, e.g. the pyrolysis of 3,3.4,4-tetrafluorocyclobut-l-ene gives l,1,4,4-tctrafluorobuta-l,3-diene (15) almost quantitatively. Tetrafluorodienes of this type undergo [2-F 2]-cycloaddition reactions with alkenes to give fluorinated cyclobutancs. ... 

The chiral titanium reagent (6) also catalyzes the [2 + 2] cycloaddition reaction of 1,3-oxazolidin-2-one derivatives of a,(3-unsaturated carboxylic acids and ketene dithioacetals in the presence of MS 4A to give cyclobutanone dithioacetal derivatives with high optical purity (eq 10). Vinyl sulfides, alkynyl sulfides, and 1,2-propadienyl sulfides can also be employed in this reaction to give the corresponding cyclobutanes, cyclobutenes and methylenecyclobutane derivatives with high optical purity (eqs 11 and 12). ... 

Lewis acid catalyzed reactions of allenes with alkenes generally give cyclobutanes rather than ene adducts. AlCb catalyzed reactions of alkylallenes with alkenes give alkylidenecyclobutanes. Similarly, AICI3 catalyzed reactions of alkynes with alkenes give cyclobutenes. These reactions are believed to occur by stereospecific cycloaddition of the alkene with the vinyl cation formed by complexation of AICI3 to the allene or alkyne. 

One of the more obvious synthetic uses of cyclobutenes which has already been mentioned is for the preparation of specifically substituted 1,3-dienes, often to be used in subsequent [4 -t- 2] cycloaddition reactions. 

If the cyclobutene-vinylketene equilibrium is established in the presence of a 1,3-diene such as cy-clopentadiene, cyclohexadiene or ( )-l,3-pentadiene, the ketene is trapped via a [4 + 2] cycloaddition reaction to furnish a 2,3-divinylcyclobutanone (127). When such reactions are carried out above 120 C a further 3,3-sigmatropic rearrangement takes place to yield cyclooctadienones (128) in overall yields ranging from 30-90%. The intermediate divinylcyclobutanes can also be obtain by dehydrohalogenation of crotyl chloride in the presence of the dienes. ... 

Although thermal [2 + 2]-cycloaddition reactions are essentially hmited to the cases described above, many (although by no means all) double-bond compounds undergo such reactions when photochemically excited (either directly or by a photosensitizer, see p. 340), even if they are not in the above categories. Simple alkenes absorb in the far UV (p. 332), which is difficult to reach experimentally, although this problem can sometimes be overcome by the use of suitable photosensitizers. The reaction has been applied to simple alkenes (especially to strained compounds, such as cyclopropenes and cyclobutenes), but more often the double-... 

The product is formed via a [2+2]-cycloaddition de Mayo reaction) between cyclopentenone (2) and cyclobutene. The reaction is carried out under photochemical conditions, because the thermal process is symmetrically forbidden. A cw-cyclobutane is formed as is expected for de Mayo reactions with cyclopentanone (see Key Chemistry). 

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