Bicyclobutane derivative

The synthesis of the peri methyl substituted benzo[6]thiepins, 58 and 59, was conveniently accomplished via the corresponding bicyclobutane derivatives 56 and 57 starting from 4-methyl-2 H-thiachromene (55). 

Obviously, the advantages of this new synthetic method are i) valence isomerization can be performed under very mild conditions and ii) due to the fairly strong acidity of the bridgehead hydrogens of a bicyclobutane moiety, some substituents can be introduced regioselectively. Nevertheless, one serious disadvantage of this synthesis is the limitation of its applicability Thus, the formation of the precursor bicyclobutane derivatives is limited only to 46 and 56, and many attempts to prepare bicyclobutane precursors from other thiapyran derivatives have been unsuccessful so far. 

Transition-metal catalyzed decomposition of alkyl diazoacetates in the presence of acetylenes offers direct access to cyclopropene carboxylates 224 in some cases, the bicyclobutane derivatives 225 were isolated as minor by-products. It seems justified to state that the traditional copper catalysts have been superseded meanwhile by Rh2(OAc)4, because of higher yields and milder reaction conditions217,218) (Table 17). [(n3-C3H5)PdCl]2 has been shown to promote cyclopropenation of 2-butyne with ethyl diazoacetate under very mild conditions, too 2l9), but obviously, this variant did not achieve general usage. Moreover, Rh2(OAc)4 proved to be the much more efficient catalyst in this special case (see Table 17). 

Bicyclobutane derivatives react with rhodium complexes to give products which convincingly implicate metallocycles and metal-carbene species (72). 

Gem-Dihalocydopropanes belong to the most readily available cyclopropane derivatives known today. They have been shown to be extremely valuable starting materials for the preparation of cyclopropanes and cyclopropenes, they may be converted to bicyclobutane derivatives and spiropentanes, can lead to allenes and the higher cumulenes, cyclopentenes and cyclopentadienes, and many other classes of compounds, both hydrocarbon systems and derivatives with valuable functional groups. The article summarizes the preparative developments in the area of gem-dihalocyclopropane chemistry during the last decade. 

In the case of bicyclobutane derivatives, the coupling constant for the central C-C bond, which should have very little s character,122 ranged from — 6 to — 17 Hz.123 The sign of the coupling is reversed with respect to other C-C bonds. Clearly, the %s character is not the only factor controlling the magnitude of these coupling constants. 

Accordingly, Gassman and co-workers have shown that cyclic bicyclobutane derivatives can be activated by photoexcited 1-cyanonaphthalene, eq. 40 (115) ... 

When the carbene or carbenoid resulting from a dihalocyclopropane is unable to rearrange to the al-lene due to steric or other factors, insertion or addition reactions characteristic of carbenes take place. Thus dibromonorcarane on reaction with methyllithium gives a bicyclobutane derivative by insertion of the carbene into a 0-C—H bond (equation 57).178 Allene formation is sterically unfavorable in this case. Similarly, dibromotetramethylcyclopropane gives l,2,2-trimethylbicyclo[1.1.0]butane instead of tetra-methylallene (equation 58).179 181 An example involving a tricyclic dibromocyclopropane is given in equation (59).182... 

The unique bonding in the bicyclobutane system, which is reflected in its unusual chemistry, has also spurred an interest in its radical cation. For example, the photoinduced electron transfer chemistry of bicyclobutane derivatives has been investigated in detail (cf. Sect. 4.4). The product distribution obtained under a variety of reaction conditions suggests a radical cation structure in which the transannular bond is substantially weakened. This structure type has been confirmed by CIDNP results for several derivatives [248, 249] and by ESR results for the parent system [340]. 

FIGURE 30. Electron density surface contours for the occupied orbitals of bicyclobutane derived from an SCF calculation The individual figures are in order of energy, the highest at the top... 

The electrochemical reduction " of 1,1,3,3-tetramethylcyclobutanedione (14) exhibits two one-electron waves in DMF. Macroscale electrolysis at the plateau of its second wave afforded the keto-alcohol 15 and not the bicyclobutane derivative. 

The cathodic reduction of 2,2,4,4-tetramethylcyclobutanedione leads to the formation of the l-hydroxy-3-cyclobutanone derivative. It was proposed that this product is formed via the intermediacy of a bicyclobutane derivative (82). 

The question of two rings going-on one is also seminal to the study of homoaromaticity. For n odd, the set of [(CH) CH2] ions demonstrate a delicate balance between mono and bicyclic structures (see Ref 133 and numerous references cited therein to both the experimental and theoretical literature). In the case of n = 3, one can imagine a planar cyclobutenyl cation (63) and a markedly non-planar, highly puckered bicyclobutyl cation (64). Both calculational theory on the parent and experiment on derivatives show the latter geometry to be preferred. However, as in the case of the other purported bicyclobutane derivatives characterized by the 2,4-carbons trigonally coordinated that were discussed earlier in this section, formal theory shows there is no 1,3-bond. The ion is not homoaromatic and there is no cyclopropane ring. In the case of n = 5,... 

Although bicyclobutane is not known to be a natural product or a cornerstone in any synthesis of commercial value, this fascinating molecule has attracted enormous attention from the scientific community. The chemistry of bicyclobutane officially started in 1959 with the formation of its first derivative by Wiberg and Ciula (previous claims for the successful preparation of bicyclobutane derivatives have been shown to be in error ). 

Compound 30 undergoes a photochemical transformation producing a bicyclobutane derivative (equation 32). This is a 7C2a + 2a reaction, in which the formation of the central bond is accompanied by the migration of the anhydride bridge. 

It should be pointed out, however, that in other cases an electrophilic reaction cannot be totally excluded. By virtue of the substituent effect, such a mechanism was invoked for the reactions of the highly electrophilic triazolinedione with bicyclobutane derivatives (equation 68) ... 

Electrochemical oxidation constitutes one of the two methods used to produce the radical cation of bicyclobutane derivatives. The radical cation obtained in this way undergoes nucleophilic addition of MeOH followed by a second oxidation step leading finally to 64 (equation 88) ... 

In most cases, thermolysis of bicyclobutane derivatives yields compounds containing a 1,3-butadiene moiety. Substituents originally located at the bridgehead position assume positions 2 and 3 in the butadiene product, indicating that in the course of the reaction the central bond remains intact. Selected examples are given in equations 118-121. 

Equations 127-130 are several additional interesting examples of pyrolytic reactions of bicyclobutane derivatives. 

Compared to many other hydrocarbons, bicyclobutane derivatives undergo a relatively facile hydrogenation reaction. Depending on substituents and reaction conditions, one or two moles of hydrogen can be absorbed. This is exemplified in equation 132 . ... 

The lithium salts of bicyclobutane derivatives are relatively stable. X-ray analysis of lithium bicyclobutane prepared in the presence of N,N,N, iV -tetramethylethylenediamine showed that the salt exists as a dimer having structure 96 . 

In light of the similarity between the bridge bond in bicyclobutanes and the n bond in olefins, it is not surprising that bicyclobutanes undergo relatively facile polymerization. In fact, in many cases it is highly recommended to store bicyclobutane derivatives either below - 50° C or with radical inhibitors to prevent undesired polymerization. The majority of the data in the literature relates to radical polymerization reactions. While anionic polymerization has been observed, it seems that bicyclobutanes in general do not undergo effective cationic polymerization. 

In order to introduce groups which cannot effect the elimination reaction, sterically hindered non-nucleophilic bases such as lithium diisopropylamide , lithium 2,2,4,4-tetramethylpiperidide or even t-BuO" can be used. Employing this technique, Szeimies and coworkers introduced thio and amino groups into the bridgehead position of bicyclobutane derivatives ... 

Since cyclopropanes are known to cleave heterolytically in photochemical reactions, bicyclobutanecarbonitrile was photolyzed in methanol in an attempt to generate the ionic bicyclobutane via an alternative route . However, this and other photochemical reactions of bicyclobutane derivatives (see Section V.K), yield no evidence of an ionic bicyclobutane. 

Irradiation (Vycor filter) of 1,2,3-trimethylsilylated cyclobutenedicarboxylic anhydrides in dichloromethane gave the corresponding trimethylsilyl-substituted bicyclobutane derivative 6, which was partially desilylated with tetrabutylammonium fluoride in chloroform. Complete desilylation to give 7 required treatment with sodium hydroxide for seven days at room temperature and with acetic anhydride. ... 

Another situation in which the chemically robust nature of the 4-methyI-l, 2,4-triazole-3,5-dione adducts has been exploited is in the synthesis of bicyclobutane derivatives.Addition of 4-methyl-l,2,4-triazole-3,5-dione to bicyclo[1.1.0]butane gave the urazole 20, which was converted to 2,3-diazabicyclo[2.1.1]hex-2-ene and by thermolysis or photolysis back to bi-cyclo[1.1.0]butane. While this is not in itself a useful synthetic sequence, the urazole intermediates in such a sequence can be chemically modified in ways that would be impossible for the bicyclobutanes themselves. Hence for the adduct 21 of dimethyl bicyclo[1.1.0]butane-l,3-dicarboxylate, the ester groups can be modified into ethyl, vinyl, substituted vinyl, hydroxymethyl, bromo and other substituents and this was used to prepare, for example, 1,3-divinylbicyclo[1.1.0]butane (22) and l-ethyl-3-vinylbicyclo[1.1.0]butane. ... 

Process (a) is characteristic of the photolysis of cholesta-3,5-diene (R = H), which gave bicyclobutane derivative in at least 75% yield. Subsequent treatment with water or alcohol provided a homoallylic carbenium ion, in which the protonation had occurred stereoselective-ly. Coordination with solvent then provided either cyclopropylmethyl ethers and alcohols (R = H, Et) or cyclopentylmethyl ethers and alcohols. 

Irradiation of pleiadiene (9) either at Sj (< 460 nm) or 2 (> 280 nm) gave a product mixture which was mainly polymeric material plus less than 15% of the bicyclobutane derivative 11. A plausible mechanism involves the intermediacy of a cyclopropylmethyl diradical 12. ... 

As a rare example of nortricyclene formation by metals other than palladium (tri-methylamino)tetracarbonyliron is found to react with norbornadiene and a tricyclic bicyclobutane derivative, in the presence of carbon tetrachloride, to form an addition product 46 with a nortricyclene skeleton. ... 

Transition-metal catalyzed decomposition of alkyl diazoacetates in the presence of acetylenes offers direct access to cyclopropene carboxylates 224 in some cases, the bicyclobutane derivatives 225 were isolated as minor by-products. It seems justified to state that the traditional copper catalysts have been superseded meanwhile by RhjCOAc), because of higher yields and milder reaction conditions (Table 17). 

Finally it should be mentioned that strained ring compounds bearing C—H bonds with high s character can be dilithiated although the corresponding dianions are not resonance stabilized. Examples are 1,2-dilithiocyclopropene 22 and certain bicyclobutane derivatives e.g. 767 . ... 

In a study using a bicyclobutane derivative, Hogeveen and coworkers showed that no skeletal rearrangement occurred and concluded that a carbene was not an intermediate in this reaction (80JOC4337). 

However in aprotic media the reactions of R are more varied. Thus in the presence of carbon dioxide, benzyl halide reduction in aprotic solvents produces some phenyl acetate. In aqueous solutions only toluene is formed at negative potentials. Rifi has reported the synthesis of bicyclobutane derivatives from the corresponding 1,3-dihalo-cyclo butanes at a mercury pool cathode in DMF containing LiBr e.g. 

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