Cyclobutene 3.3- dimethyl

Since 3-methylenecyclobutane-l,2-dicarboxylic anhydride is easily converted to 3-methyl-2-cydobutene-l,2-dicarboxylic acid, it is an intermediate to a variety of cyclobutenes. The dimethyl ester of 3-methylenecyclobutane-l,2-dicarboxylic acid is also a versatile compound on pyrolysis it gives the substituted allene, methyl butadienoate, and on treatment with amines it gives a cyclobutene, dimethyl 3-methyl-2-cyclobutene-l,2-di-carboxylate. ... 

At elevated temperatures perfluoro-3,4-dimethyl (or -diethyl) cyclobutenes equilibrate with isomeric perfluorobutadienes [138, 139] via nonstereoselective... 

A similar sequence of reactions takes place with the enamlnes of cyclic ketones (55-57) the initially formed unstable cyclobutene rearranges with insertion of two carbon atoms into the ring. A wide variety of cyclic ketones have been allowed to react in this way. For instance, the enamine (75) gave 76 on reaction with dimethyl acetylenedicarboxylate in refluxing toluene (55) and the heterocyclic enamine (77) obtained from dihydro-3-(2H)-... 

Enamino ketones and esters also react with dimethyl acetylenedicarboxylate (67). Again cycloaddition appears to occur and the unstable cyclobutene intermediates rearrange to give insertion of two carbon atoms. 

Dimethyl acetylenedicarboxylate (80) undergoes initial 1,2 cycloaddition with acyclic enamines to form cyclobutene intermediates which immediately decompose into acyclic dienaminodiesters (94,95). When an acyclic n/c-enediamine is used instead of a simple acyclic enamine, a dienediamino-diester is produced via a cyclobutene intermediate (95a). A cyclization reaction of dimethyl acetylenedicarboxylate with an acyclic enaminoketone... 

CYCLOBUTENE, 46, 34 Dicyclohexylcarbodiimide in oxidation of cholane-24-ol with dimethyl sulfoxide and pyridinium trifluor-oacetate, 47, 25... 

Reinhoudt et al.53) have reported the first synthesis of a monocyclic thiepin stabilized by electronic effects of the substituents. This synthesis utilizes the idea described in Section 2.3.3. 3-Methyl-4-pyrrolidinothiophene (85a) was treated in deuteriochloroform at —30 °C with dimethyl acetylenedicarboxylate. H-NMR monitoring of the reaction indicated that a [2 + 2]cycloaddition proceeded slowly at this temperature giving the 2-thiabicyclo[3.2.0]heptadiene (86a) which rearranged via ring opening of the cyclobutene moiety to the 4-pyrrolydinylthiepin (87a). At the... 

Finally, a reaction should be mentioned in which a nucleophile gives support to another reacting species without appearing in the final product. Diphenyl cyclopropenone interacts with 2,6-dimethyl phenyl isocyanide only in the presence of tri-phenylphosphine with expansion of the three-ring to the imine 344 of cyclobutene-dione-1,2229,230 Addition of the isocyanide is preceded by formation of the ketene phosphorane 343, which can be isolated in pure formss 231 it is decomposed by methanol to triphenyl phosphine and the ester 52. 

Dimethyl 7-10-tetrahaptotricyclo[4.2.2.02 5]deca-3,7,9-triene-7,8-dicarboxy-late tricarbonyliron reacted readily with several 1,3-dipoles nitrile oxides, at the cyclobutene double bond, to give adducts from which the tricarbonyliron group could be easily removed by oxidative decomplexation with trimethylamine N-oxide (237). 

Irradiation of a mixture of dimethyl cyclobutene-1,2-dicarboxylate (372) and 3-methyl-2-cyclohexenone (373) gave the adduct (374), which was then pyrolyzed to give the diene (375). Hydrogenation afforded the keto diester (376). On the other hand, when the compound (374) was reduced by NaBH4, y-lactone (377) was... 

One such example is a sequence of solution reactions starting from the dimer 91, which has a cis-1,2-dicarboxylic acid arrangement and is obtained by irradiation of monomethyl fumarate, 90, in the crystal (137). This isomerically pure dimer may be oxidatively decaiboxylated, by a variety of methods, to the thermally unstable cis-disubstituted cyclobutene 92, whose smooth disrotatory ringopening leads to the isomerically pure dimethyl c/s, frans-muconate, 93 (167). 

With acyclic dienes, the quantum yield for cyclobutene formation (4>cb) rarely exceeds ca 0.1, the expected result of the fact that the planar s-trans conformer normally comprises the bulk (96-99%) of the conformer distribution at room temperature. However, 4>cb is often significantly larger than the mole fraction of s-cis form estimated to be present in solution. For example, 1,3-butadiene, whose near-planar (dihedral angle 10-15°105 106) s-cis conformer comprises ca 1% of the mixture at 25 °C, yields cyclobutene with < >cb = 0.04140, along with very small amounts of bicyclo[1.1.0]butane141. A second well-known example is that of 2,3-dimethyl-l,3-butadiene (23 ca 4% gauche s-cis at 25 °C107), which yields 1,2-dimethylcyclobutene (25) with < >cb = 0-12 (equation 16)111. Most likely, these apparent anomalies can be explained as due to selective excitation of the s-cis conformed under the experimental conditions employed, since it is well established that s /raw.v... 

Dimethyl tricyclo[4.2.2.02 -5]deca-3,7-diene-9,10-dicarboxylate adds bromine and iodine only to the less hindered double bond to give the syn 1,2-addition product of the cyclobutene moiety79. The product composition from this compound depends on the temperature and the solvent. At high temperatures, the 1,2-addition predominates over the transannular reaction, but this predominance is small in a solvent like chloroform and is lost in a protic solvent such as acetic acid (equation 47). 

Dimethylbenzene-1,2-dithiol disodium salt reacted with trans-1,2-dichlorocycloocta-3,5,7 triene and then dimethyl acetylenedicarboxylate in a sequence (Scheme 17) that finally resulted in 99, which on heating lost cyclobutene and gave the thianthrene diester 100 (78CC57). 

Several reactions of enamines with acetylenic esters are reported. " In general, [2 + 2] mode of addition leads to cyclobutene intermediates, which undergo ring opening, yielding dienamines. (V,A(-Dimethyl-isobutenylamine (227) with DMAD, for example, gives the dienamine... 

Asymmetric deprotonation of monocyclic cycloalkanones is not restricted to cyclohexanones. Thus, deprotonation of 3-phenylcyclobutanone with lithium bis[(S)-l-phenylethyl]amide in THF at — 100 °C in the presence of chlorotriethylsilane affords (—)-(/ )-3-pheny 1-1 -(triethylsi-lyloxy)-l-cyclobutene with 92% ee in 70% yield59d. Interestingly, with lithium (/ )-2,2-dimethyl-A-[( / )-2-(4-methyl-l-piperazinyl)-l-phenylethyl]propylamidc in THF/HMPA an ee value of only 47 % for the enol ether is recorded. 

Cyclobutenes are effective dienophiles.19-21 The stereochemistry of these reactions has been studied by employing 2,5-dimethyl-3,4-diphenylcyclopenta-2,4-dienone as the diene. Thus, r/.v-3,4-dich 1 orocyclobutene reacted with the dienone to give the anri,exo- and the anti,endo- so-mers 15 in a ratio of 4 1.22 Similar cycloaddition of the dienone with dimethyl tricy-clo[4,2,2.02 5]dcca-3,7,9-triene-7,8-dicarboxylatc gave the exo- and the rwfo-isomers 16 in a ratio of 6 1.22 The exo stereoselectivity is attributed to steric factors.22... 

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... 

Base-catalyzed ring expansion has heen observed vit i cyclo propyInictliy p-toluenesulfonate and bromide.205 Treatment with potassium rert-butoxide in dimethyl sulfoxide induced competing y- and -elimination yielding cyclobutene (14) and methylenecyclopropane (15), respectively. An initial a-elimination was ruled out by deuterium-labeling studies. 

Nonacarbonyldiiron in the presence of activated zinc as well as disodium tetracarbonylferrate have both been utilized to dechlorinate dimethyl cispransjransA,2,3,4-tetrachlorocyclobutane-1,2-dicarboxylate (41), which leads to [dimethyl l,2,3,4- 7-l,3-cyclobutadiene-l,2-dicarboxy-latejiron tricarbonyl (42) in 1 and 35-40% yield, respectively.15 As a result of the better leaving tendency of the bromide anion, the yield of 42 can be improved to 70% by reaction of the analogous dibromide with nonacarbonyldiiron in dimethylformamide.16 In another experiment, debromination with activated zinc in tetrahydrofuran converts cyclobutane-1,2-di-carboxylate 43 to cyclobutene-1,2-dicarboxylate 44 in 58% yield.15... 

Several cyclobutenes can be synthesized by elimination of selenoxides from the corresponding methyl- or phenylselanyl derivatives 58 or by elimination of dimethyl selenide from the corresponding selenonium salts 60. The results of these conversions are summarized in Table l.23 The cyclobutenes have been used as precursors for substituted butadienes.23... 

Cyclobutene has been prepared (1) by pyrolysis of cyclobutyl dimethyl amine oxide4"6 and cyclobutyltrimethylammonium hydroxide4,6 (50-73% yield), which were prepared 1n eight steps from malonate esters (2.0-2.1% overall yield of... 

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