Cyclobutenes preparation

Cyclobutenes prepared by the Ramberg-BScklund reaction are almost always unsubstituted at the vinylic positions. In 1974, Paquette introduced a related and complementary ring contraction which is particularly suitable for the synthesis of 1,2-dialkylcyclobutenes. The reaction takes place when carbanions of five-membered cyclic sulfones are treated with LAH in refluxing dioxane (Scheme 19). The mechanism of the reaction is not clear. Good yields are obtained only when the sulfone is 2,5-dial-kylated in the absence of these groups, simple reduction of sulfone to sulfide becomes a serious side reaction. Dibenzyl sulfone is converted into a mixture of stereoisomeric stilbenes (56%) and dibenzyl sulfide (23%) under the same conditions. ... 

Cyclobutane-l,2-dione has been isolated from the bromination of 1,2-bis(trimethyl-siloxy)cyclobutene, prepared by sodium induced acyloin cyclization of butanedioate in the presence of chlorotrimethylsilane . The acyloin cyclization of 1,4-, 1,5- and 1,6-diesters to give four-, five- and six-membered rings and the cyclization of )9-chloro esters to three-membered rings in the presence of chlorotrimethylsilane, which usually requires highly dispersed sodium, has been recently simplified by the use of sonochemical activation. The ring contraction of cyclobutane-1,2-diones to 1-hydroxyeyclopropanecarboxylic acid (7) and derivatives may be catalyzed by aqueous acid or base, by methoxide anion, amines or hydrazines and even takes place, though more slowly, in pure water or ethanol. ... 

The bis(silyloxy)cyclobutenes are also subject to a variety of special reactions. Probably the most interesting is the observation that they readily undergo a ring-opening reaction leading to a butadiene derivative. This reaction has already been used to prepare large-ring diketones from cyclic 1,2-diesters. 

Fluorinated cyclobutanes and cyclobutenes are relatively easy to prepare because of the propensity of many gem-difluoroolefins to thermally cyclodimerize and cycloadd to alkenes and alkynes. Even with dienes, fluoroolefins commonly prefer to form cyclobutane rather than six-membered-ring Diels-Alder adducts. Tetrafluoroethylene, chlorotrifluoroethylene, and l,l-dichloro-2,2-difluoroethyl-ene are especially reactive in this context. Most evidence favors a stepwise diradical or, less often, a dipolar mechanism for [2+2] cycloadditions of fluoroalkenes [S5, (5], although arguments for a symmetry-allowed, concerted [2j-t-2J process persist [87], The scope, characteristic features, and mechanistic studies of fluoroolefin... 

Fluorinated bicyclo[2 2 0]hex 5-en 2 ones prepared from Dewar benzene derivatives serve as synthons of cyclobutenes [269] Photochemical cleavage of fluonnated azacyclohexadiene in the gas phase also gives fluorinated cyclobutene [270] (equation 41)... 

Displacement of Vinyl fluorine or chloride by secondary amines has given some unusual enamines as illustrated for the preparation of 1,1-difluoro-2-piperidino-3-phenyl-2-cyclobutene (151) (US), l,l-difluoro-2,4-dipiperidino-3-phenyl-2-cyclobutene (152) (114), and 2-phenyl-3-(l -aziridinyl)-2-cyclohexenone (153) (115). 

The benzo-fused derivative 8 of l,4-dimethyTl,4-dihydro-l,4-diazocine can be prepared by gas phase thermolysis of the cyclobutene derivative 7,31 a reaction that can be reversed photo-chemically. In contrast to the parent system, the heterocyclic ring of the benzannulated compound displays no aromatic character. 

Preparation of l,2-bis(trimcthylsilyloxy)cyclobutene from diethyl succinate (Riihlmann condensation using Na and TMSC1), and of 2-hydroxycyclo-Ibutanone. 

The synthesis of 2-chloro-2,3,3-trifluorocyclobutyl acetate illustrates a general method of preparing cyclobutanes by heating chlorotrifluoroethylene, tetrafluoroethylene, and other highly fluorinated ethylenes with alkenes. The reaction has recently been reviewed.11 Chlorotrifluoroethylene has been shown to form cyclobutanes in this way with acrylonitrile,6 vinylidene chloride,3 phenylacetylene,7 and methyl propiolate.3 A far greater number of cyclobutanes have been prepared from tetrafluoroethylene and alkenes 4,11 when tetrafluoroethylene is used, care must be exercised because of the danger of explosion. The fluorinated cyclobutanes can be converted to a variety of cyclobutanes, cyclobutenes, and butadienes. 

A number of the bicyclic ozonides 12 were prepared in good yield (45-65 %) by diimide reduction of furan singlet oxygenates (Eq. 9) 23>. Again, low temperature were essential because the furan endoperoxides readily transform into 1,2-diacyl-ethylenes. Of course, the bicyclic ozonides 12 can alternatively be prepared via ozonolysis of the appropriate 1,2-disubstituted cyclobutene 24). 

Thiopyranopyrrolizines can be prepared readily from the enamine 170 upon treatment with DMAD. Alternatively, heating of the thiacyclooctadiene derivative 171 in methanol gives the same tricycle 172, but this time as a 5 2 mixture with the (Z,E)-isomer of the precursor 171. These reactions probably involve the the intermediacy of an unstable cyclobutene and/or a zwitterionic diene, as shown in Scheme 51 <1984JA1341>. 

In 1995 the first examples of ring-opening cross-metathesis reactions for the preparation of functionalised monomeric products using the Grubbs ruthenium vinylalkylidene catalyst 4 were published by Snapper and co-workers [47]. Reaction of a variety of symmetrical cyclobutenes with simple terminal alkenes... 

If the alkenes and acetylenes that are subjected to the reaction mediated by 1 have a leaving group at an appropriate position, as already described in Eq. 9.16, the resulting titanacycles undergo an elimination (path A) as shown in Eq. 9.58 [36], As the resulting vinyltitaniums can be trapped by electrophiles such as aldehydes, this reaction can be viewed as an alternative to stoichiometric metallo-ene reactions via allylic lithium, magnesium, or zinc complexes (path B). Preparations of optically active N-heterocycles [103], which enabled the synthesis of (—)-a-kainic acid (Eq. 9.59) [104,105], of cross-conjugated trienes useful for the diene-transmissive Diels—Alder reaction [106], and of exocyclic bis(allene)s and cyclobutene derivatives [107] have all been reported based on this method. 

Bis(trimethylsiloxy)cyclobutene, a very useful building block, is easily prepared by the modified acyloin condensation of diethyl succinate with sodium in xylene in the presence of trimethylsilylehloride 62). 

The [3.3.3]propellane skeleton could also be prepared from the cyclobutene (282), which provided the product (283). The propellane (283) was an intermediate compound in the synthesis of modhephene (284) 96K... 

The ozonolysis of cyclobutene derivatives in the preparation of 1,4-diketones was also applied to the total synthesis of eyclopentanoid antibiotics 161 162k The oxidative cleavage of (470) by ozone and reductive work-up yielded the diketone (471) in 73 % yield. Diketone (471) underwent intramolecular aldol cyclization to give the key intermediate (472), which was used to synthesize ( )-xanthocidin161,162), (+)-epi-xanthocidin 162), ( )-p-isoxanthocidin161,162) as well as ( )-desdihydroxy-4,5-didehydroxanthocidin162). 

An interesting application was described by Liebeskind and Stone, who prepared l-(methoxy-l,2-propandienyl)-2-cyclobuten-l-ols 62 by treatment of cyclobutenones 61 with lithiated methoxyallene 42 (Scheme 8.16) [59]. The authors used these primary adducts in a subsequent acid-catalyzed ring-enlargement providing 5-hydroxy -5 -vinyl- 2 -cyclopenten-1 -ol s. 

The few reported [2 + 2] cycloadditions of alkoxyallenes illustrated in Eqs 8.29 and 8.30 are probably of less synthetic importance. Cyclobutene derivative 162 could be prepared in good yield by cycloaddition of tetramethoxyallene 39 and acetylenedicar-boxylate 161 [105], whereas the reaction of 1,1-diethoxyallene 163 and phenylisocya-nate (164) gave the expected /3-lactam 165 [106]. Another example for a [2 + 2] cycloaddition is the dimerization of 39 described by Saalfrank et al. [107]. 

The thermal [2 + 2]-cycloaddition of allenyne 68 was used for the preparation of a naphtho[a]cyclobutene skeleton 69 [66]. 

The procedure described is a modification of that developed by Diels and Criegee. Bicyclo[2.1.0]pentane has been prepared by the pyrolysis of 2,3-diazabicyclo[2.2.1]hept-2-ene, the photolysis of 2,3-diazabicyclo[2.2.1]hept-2-ene, the pyrolysis of N-phenyl-2-oxo-3-azabicyclo[2.2.1]heptane, and the addition of methylene to cyclobutene. ... 

As an application of this procedure, Snapper succeeded in the formal total synthesis of (+)-astericanolide. Treatment of iron complex 62, which is prepared from cyclopentenol derivative 60 and iron complex 61, with MeaNO gives fused cyclobutene derivative 63. ROM of cyclobutene of 63 using Ig under ethylene gas smoothly proceeds to produce an eight-membered ring of 64 via Cope rearrangement. The resulting product 64 is converted into Wender s intermediate for the synthesis of (+)-astericanolide ... 

Strained alkenes, including cyclobutenes 29 [120] and benzcyclobutadiene derivatives 30 [121], can be prepared by this route. Particularly advantageous is the wide range of reduction potentials for 1,2-dibromides, which allows some selective reactions. The dibromide 26 can be purified from any of the isomer 25 by reduction at -0.86 V vs. see when the diequatorial bromide remains unchanged and the diaxial compound is converted to the alkene [110], Bromination of dialkenes followed by selective debromination to recover one alkene leads to protection of the other alkene as the dibromide. Subsequently the second alkene can be recovered by reduction at more negative potentials [122],... 

The four-, five-, and six-membered analogs (178,180, and 182) were also obtained from the diprotonation of squaric acid (3,4-dihydroxy-3-cyclobutene-l,2-dione, 177), tri-O-protonation of croconic acid (4,5-dihydroxy-4-cyclopentene-l,2,3-trione, 179), and tetra-O-protonated rhodizonic acid (5,6-dihydroxy-5-cyclohexene-l,2,3,4-tetraone, 181), respectively. These ions were prepared in either Magic Acid (1 1 FSOsH-SbFs) or fluorosulfuric acid at low temperature and characterized by NMR. Ab initio/IGLO calculations showed that di-O-protonated squaric acid (178) is planar and aromatic, whereas the polyprotonated croconic and rhodizonic acids (180 and 182) have more carboxonium ion character, and no indication was obtained for any significant contributing homoaromatic structures. 

The double )5-scission pathway becomes dominant in bicyclic systems (Equations (7)-(9) and Scheme 13). Thus, cyclopentene ozonide (69) gives cyclopropane (Equation (7)) <68TL329l>. Photolysis of the ozonide derived from 1,4-benzodioxins (70) provides a method for the preparation of labile o-benzoquinones (71) (Scheme 13) <87JOC56l6>. Photolysis can also provide a route to unstable compounds and transient species such as the aziridine-2,3-dione (72) (Equation (8)), identified at 77 K using infrared spectroscopy <80JA6902>. Relatively unstable azacarbapenems (73) have been prepared by photolysis of tricyclic compounds containing a cyclobutene ozonide (Equation (9)). On silica, the 1,2,4-trithiolane (74) underwent photo-equilibration (Equation (10)) with the 1,3-dithetane (75) and sulfur. 

Wiseman and coworkers have succeeded in preparing tricyclo[5.3.0.0 ]decane (393), a CioHig hydrocarbon which unlike adamantane is chiral. Their elegantly simple approach entails Diels-Alder addition of cyclobutene to l,4-dihalocyclohexa-l,3-dienes, catalytic hydrogenation of the adduct, reaction with aluminium triiodide, and ultimately di- -butyltin dihydride reduction. 

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