Cyclobutene derivative

Cycloaddition of norbornadiene with allene takes place to yield the cyclobutene derivative 10[5], Cyclodimerization of 1,2-cyclononadiene (11) affords a mixture of stereoisomers of the cyclobutane derivatives 12[6,7],... 

The Electrocyclic Ring Operung of Fluonnaled Cyclobutene Derivatives Dolbier, W R, Jr, Koroniak, H Mol Struct Energ S, 65-81 51 o... 

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. 

Polyether-type structures such as 6/3-38 are frequently found in bioactive compounds (e. g., maitansine). Nicolaou and coworkers [239] have developed a new, efficient approach to these compounds, which is based on a domino ROM/RCM using the second-generation Grubbs catalyst 6/3-15. Thus, the cyclobutene derivative 6/3-37 could be transformed into 6/3-38 in 80% yield (Scheme 6/3.10). 

The sesquiterpenes (+)-10-epijuneol466, (4.54) and ( )-calameon467) (4.55) have been obtained via addition of 6-isopropyl-3-methyl-2-cyclo-hexenone to cyclobutene derivatives. A similar sequence has been applied for the synthesis of an eudesmane precursor (4.56)468). 

Another convenient entry to fused cyclobutene-1,2-diesters was via site selective modification of the norbomene rt-bond in Smith s fe-alkene 49, e.g. treatment with 3,6-di(2 -pyridyl)-s-tetrazine 51 followed by DDQ oxidation afforded the cyclobutene-derivative 53 <97AA119>, while direct coupling with 3,5-f> (trifluoromethyl)-l,3,4-oxadiazo]e 54 furnished the tas(cyclobutene-l,2-diester) 55 (Scheme 6) <97SL196>. 

Titanated vinylallenes generated from the coupling of acetylenes and propargyl carbonates [38] undergo facile, unidirectional electrocyclization to give cyclobutene derivatives under extremely mild reaction conditions as shown in Eq. 9.17 [39]. 

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. 

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). 

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]. 

Halogen-substituted allenes undergo [2 + 2]-homodimerization under relatively mild conditions to afford l,2-bis(halomethylene)cyclobutene derivatives in good yields [9]. 

With the silyl-substituted difluoroallene 245 and molybdenum hexacarbonyl, the expected [2+ 2+ 1] cycloaddition is not observed. CO is not incorporated and the cyclobutene derivatives 246 can be isolated in good yields (Scheme 15.77) [148]. 

Scheme 20.41 Enyne-allene via rearrangement of a cyclobutene derivative.

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 ... 

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)... 

If quinoline derivatives are expected to be synthesized by this procedure, the starting cycloalkene should contain a cyclobutene ring. When cyclobutene derivative 65c is reacted with Ig under ethylene gas, isoquinoline derivative 66c is obtained in 60% yield. Furthermore, cyclic amino acid ester 66d is obtained from glycine derivative 65d in 75% yield by a one-step reaction. Various isoquinolone derivatives 66e-66i are also synthesized from cyclobutenyl amides... 

Very recently, the same group reported skeletal reorganization of enynes to 1-vinylcycloalkene by GaCls-Reaction of 78f, for example, proceeds in toluene at 0 °C and is completed within 1 h to give 79f. It is interesting that highly strained cyclobutene derivative 82 is obtained from 1,7-enyne 78g (Scheme 33). 

Cyclobutanes can be conveniently prepared from cyclobutene derivatives through electrophilic addition, catalytic hydrogenation, nucleophilic addition, cycloaddition as well as light-induced addition reactions. 

A practical preparation of cyclobutane derivatives involved, as the key step, the hydrolysis of l,2-bis(triinethylsiloxy)cyclobutene derivatives in hydrochloric acid, which was then followed by acetylation to afford a-acetoxycyclobutanone derivatives.42 Some useful examples are given in Table 2. 

In some cases the nature of the products resulting from photolysis of dienes and trienes depends on whether the reaction occurs from the excited singlet state or the triplet state. The triplet states can be populated exclusively by suitable sensitizers. For example, 3-methylene-1, 5-hexadiene gives a cyclobutene derivative (A) from the singlet state and tricyclo ring compound (B) from triplet state ... 

Study of the photochemistry of myrcene, 23, a triene containing both a conjugated diene system and a remote, unconjugated double bond, has been exceptionally informative. Direct excitation produces a cyclobutene derivative 24, /S-pinene, and a host of minor products287 including 25. In contrast, indirect excitation using a number of sensitizers gives only a derivative of bicyclo[2.1.1]hexane, 25.288... 

The products obtained upon direct excitation of butadiene,291 norbornadiene,292 cyclohexadiene,293 and other dienes294 are also completely different from those obtained by photosensitization, again demonstrating quite different chemical reactivity of excited singlet and triplet dienes. However, 1,l -bicyclohexenyl295 and 1,3-cycloocta-diene298 represent exceptions, undergoing both direct and sensitized photoisomerizations to cyclobutene derivatives. 

The triplet states of maleic anhydrides and maleimides add to olefins and to acetylenes to yield cyclobutane and cyclobutene derivatives.436,437 A host of sensitizers are effective in promoting the reaction,436 and in some cases the reaction does not proceed at all unless sensitized. Interestingly enough, many such additions have been reported to be stereospecific.438... 

In certain polyfluorinated cyclic compounds difiuoromethylene groups are hydrolyzed to carbonyl groups relatively easily.141 This is usually associated with the formation of cycloalkene intermediates, since the proximity of a C = C bond notably increases the reactivity of a difluoro-methylene group towards hydrolytic reactions. Thus, easy conversion of such groups to oxo groups has been observed in many cyclobutene derivatives. 2-Chloro-l,l,2-trifluoro-3-phenyl-cyclobutane is converted by potassium hydroxide into cyclobutene 1 and cyclobut-2-enone 2.141... 

Double bonds and electron-donating groups in the 1-position of fluorinatcd cyclobutene derivatives enhance the hydrolysis of fluorine in position 3.143... 

The Elcctrocyclic Ring Opening of Fluorinated Cyclobutene Derivatives ... 

Roberts and coworkers, investigating the ionization reactions of cyclobutene derivatives, found that the resulting cyclobutenyl ions were unusually stable10-113. They suggested that rather than regarding these ions as simple allyl cations, their properties were consistent with a C(1 ),C(3) interaction and cyclic delocalization of the 7t-electrons. As such, these 27r-electron systems were considered to be the homoaromatic counterparts of the well established, aromatic cyclopropenium ions39. 

Some of the bicyclo[3.1.0]hexene zirconocene derivatives, especially those containing a phenyl group, rearrange quantitatively to the corresponding 4-vinyl-l-metalla-2-cyclobutene derivatives when heated in toluene to 60-80 °C for several hours (equation 131). The 6,6-dimethyl-2,3-diphenyl-2-zirconabicyclo[3.1.0]hex-3-ene derivative prefers ring-opening to the isomeric j/. -allylic complex upon thermolysis. 

Attempted conversion of gew-dibromotriangulanes 68 and 71 to the corresponding vinylidene derivatives, e.g. 69 was also accompanied by an unusual rearrangement, yielding cyclobutene derivatives (equations 46 and 47)89. On the other hand, a similar reaction of dibromide 71 gave the desired allene 72 in 85% yield (equation 48)71. 

Irradiation of the sulfone (39) in benzene gave, not the strained cyclobutene derivative, but the pleiadene dimer (40).39... 

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