Substituted cyclobutanes

Sila- and Germa-cyclobutanes Substituted with Oxygen, Sulfur, Nitrogen or Phosphorus 596... 

Treatment of diester 10 with diethyl oxalate in the presence of base gave the disodium salt 11, which was thereafter alkylated to afford the tetrasubstituted thiophene 12. This material was subsequently used as a precursor for preparation of 3,4-dimethoxythiophene 9 <04T10671>. In a similar series of reactions involving glyoxal and suitable sulfides, several cyclobutane substituted 2,5-diacylthiophenes were synthesized <04HC26>. 

It is interesting to see the pressure dependence of hot tritium reaction in cyclobutane C4H8. Recoil tritium attacks this molecule to give tritiated cyclobutane (substitution reaction) in an excited state, which either stabilizes by collision with a third body or decomposes into two molecules of ethylene. This is shown in the following scheme ... 

Methane ethane and cyclobutane share the common feature that each one can give only a single monochloro derivative All the hydrogens of cyclobutane for example are equivalent and substitution of any one gives the same product as substitution of any other Chlorination of alkanes m which the hydrogens are not all equivalent is more com plicated m that a mixture of every possible monochloro derivative is formed as the chlo rmation of butane illustrates... 

The photosensitized dimerization of isoprene in the presence of henzil has been investigated. Mixtures of substituted cyclobutanes, cyclohexenes, and cyclooctadienes were formed and identified (53). The reaction is beheved to proceed by formation of a reactive triplet intermediate. The energy for this triplet state presumably is obtained by interaction with the photoexcited henzil species. Under other conditions, photolysis results in the formation of a methylcydobutene (54,55). 

Thermal decomposition of cis- and frans-3,6-dimethyl-3,4,5,6-tetrahydropyridazines affords propene, cis- and frans-l,2-dimethylcyclobutanes and 1-hexene. The stereochemistry of the products is consistent with the intermediacy of the 1,4-biradical 2,5-hexadienyl. The results indicate that thermal reactions of cyclic azo compounds and cyclobutanes of similar substitution proceed with similar stereospecificity when compared at similar temperatures 79JA2069). 

Thus the reactions of cyclic or acyclic enamines with acrylic esters or acrylonitrile can be directed to the exclusive formation of monoalkylated ketones (3,294-301). The corresponding enolate anion alkylations lead preferentially to di- or higher-alkylation products. However, by proper choice of reaction conditions, enamines can also be used for the preferential formation of higher alkylation products, if these are desired. Such reactions are valuable in the a substitution of aldehydes, which undergo self-condensation in base-catalyzed reactions (117,118). Monoalkylation products are favored in nonhydroxylic solvents such as benzene or dioxane, whereas dialkylation products can be obtained in hydroxylic solvents such as methanol. The difference in products can be ascribed to the differing fates of an initially formed zwitterionic intermediate. Collapse to a cyclobutane takes place in a nonprotonic solvent, whereas protonation on the newly introduced substitutent and deprotonation of the imonium salt, in alcohol, leads to a new enamine available for further substitution. 

The alkylation of enamines with nitroolefins, which gives intermediates for reductive cyclization (6S2), also provided an example of a stable cycliza-tion product derived from attack of the intermediate imonium function by the nitro anion (683). A previously claimed tetrasubstituted enamine, which was obtained from addition of a vinylsulfone to morpholinocyclohexene (314), was shown to be the corresponding cyclobutane (684). Perfluoro-olefins also gave alkylation products with enamines (685). Reactions of enamines with diazodicarboxylate (683,686) have been used diagnostically for 6-substituted cyclohexenamines. In a reaction of 2-penten-4-one with a substituted vinylogous amide, stereochemical direction was seen to depend on solvent polarity (687). 

Wehle, D. Fitjer, L. Tetrahedron Lett., 1986, 27, 5843, have succeeded in producing two conformers that are indefinitely stable in solution at room temperature. However, the other five positions of the cyclohexane ring in this case are all spiro substituted with cyclobutane rings, greatly increasing the barrier to chair-chair interconversion. 

Alkenes with electron-withdrawing groups may form cyclobutanes with alkenes containing electron-donating groups. The enamine reactions, mentioned above, are examples of this, but it has also been accomplished with tetracyanoethylene and similar molecules, which give substituted cyclobutanes when treated with alkenes of the form C=C—A, where A may be... 

Substituted cyclobutanes or benzene rings are formed by the reaction of imidazolides with suitable double-bond systems. 

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... 

This chapter contains a review of some photodimerizations and photo-condensations leading to the formation of substituted cyclobutanes. Since the literature in this field is indeed vast, it would be impossible to present here a comprehensive review of all the reactions reported to lead to such products. Instead, it is our goal to present a general survey of the various types of compounds known to produce cyclobutane compounds upon irradiation and to discuss mechanisms which have been proposed to account for some of these products. 

Some years ago we began a program to explore the scope of the palladium-catalyzed annulation of alkenes, dienes and alkynes by functionally-substituted aryl and vinylic halides or triflates as a convenient approach to a wide variety of heterocycles and carbocycles. We subsequently reported annulations involving 1,2-, 1,3- and 1,4-dienes unsaturated cyclopropanes and cyclobutanes cyclic and bicyclic alkenes and alkynes, much of which was reviewed in 1999 (Scheme l).1 In recent days our work has concentrated on the annulation of alkynes. Recent developments in this area will be reviewed and some novel palladium migration processes that have been discovered during the course of this work will be discussed. 

A trifluoromethyl group attached to a cyclohexane ring is unremarkable with respect to its chemical shift, absorbing at -75 ppm, with a 3/fh = 8Hz (Scheme 5.2). There are no data available for trifluorometh-ylcyclopentane or cyclobutane. The chemical shift for trifluoromethyl-cyclopropane reflects additional shielding, such CF3 groups appearing the farthest upheld of any CF3-substituted hydrocarbon. 

In all the latter cases the easier dimerization reaction is connected with the particular stability of the intermediate diradical species. This is also the reason for the recently found facile dimerization of the 1-donor substituted allylidene-cyclopropane 136a (Scheme 66) [127]. Allylidenecyclopropane 136a cyclodimer-izes to the expected cyclobutane 467 in very mild thermal conditions, due to the stabilization of the intermediate 466. At higher temperature (120 °C) both 136a and 467 give a more complex mixture of products, with the cyclooctadiene dimer 468 being the prevailing one (Scheme 66) [127],... 

The cycloadditions in entries 1-3 are still believed to occur via a diradical stepwise pathway, as confirmed by obtaining a thermodynamic 78 22 trans/cis mixture of dispirooctanes 536 from frans-dicyanoethylene (533) (entry 3) [13b, 143], The cycloaddition to tetracyanoethylene (131) in the absence of oxygen gives only low yields of the [2 + 2] adduct, due to the simultaneous formation of products 542 and 543 (Scheme 74) [13b]. Still, the formation of the cyclobutanes 537 and 542 is noteworthy, since the reactions of TCNE with phenyl substituted MCPs exclusively afford methylenecyclopentane derivatives [37,144], The reaction is thought to occur via dipolar intermediates 539-541 formed after an initial SET process (Scheme 74) [13b]. The occurrence of intermediates 540 and 541 has been confirmed by trapping experiments [13b]. 

It is noteworthy to point out that the rate of retro-aldol reaction is enhanced by ring strain. Thus, suitably substituted 3-oxygenated carbonyl cyclobutanes would... 

The following cleavage reactions depict the importance of these hetereoatom substituted cyclobutanes in organic synthesis. 

In 1988 Heinze and Burton reported a facile synthesis of various a,p,P-trifluorostyrenes.15 These trifluorostyrene compounds were reported to be unstable to cyclodimerization at room temperature when stored neat, especially the compounds that were /lura-substituted with electron-donating substituents. They described the preparation of one compound, l,4-bis(trifluorovinyl)benzene with the observation that the material gelled when allowed to stand neat overnight. They offered the explanation that the gel was a polymer network connected with flnorinated cyclobutanes. Burton later went on to utilize this dimerization reaction for the cross-linking of polyimide thermoplastics.16... 

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