Cyclobutane derivatives

Many synthetic methods enabling the preparation of cyclobutane derivatives are similar to those previously described for the cyclopropane-containing compounds. Nevertheless, their diversity seems to be less extensive than in the case of the cyclopropane-forming reactions. 

Within the cubane synthesis the initially produced cyclobutadiene moiety (see p. 329) is only stable as an iron(0) complex (M. Avram, 1964 G.F. Emerson, 1965 M.P. Cava, 1967). When this complex is destroyed by oxidation with cerium(IV) in the presence of a dienophilic quinone derivative, the cycloaddition takes place immediately. Irradiation leads to a further cyclobutane ring closure. The cubane synthesis also exemplifies another general approach to cyclobutane derivatives. This starts with cyclopentanone or cyclohexane-dione derivatives which are brominated and treated with strong base. A Favorskii rearrangement then leads to ring contraction (J.C. Barborak, 1966). 

Simple cyclobutanes do not readily undergo such reactions, but cyclobutenes do. Ben-zocyciobutene derivatives tend to open to give extremely reactive dienes, namely ortho-quinodimethanes (examples of syntheses see on p. 280, 281, and 297). Benzocyclobutenes and related compounds are obtained by high-temperature elimination reactions of bicyclic benzene derivatives such as 3-isochromanone (C.W. Spangler, 1973, 1976, 1977), or more conveniently in the laboratory, by Diels-Alder reactions (R.P. Thummel, 1974) or by cycliza-tions of silylated acetylenes with 1,5-hexadiynes in the presence of (cyclopentadienyl)dicarbo-nylcobalt (W.G. Aalbersberg, 1975 R.P. Thummel, 1980). 

The thermal ring opening of l,2-bis(trimethylsiloxy) cyclobutenes (from acyloin condensation of 1,2-dicarboxylic esters) was used in ring expansion prodecures (see p. 53f.). 

Only relatively few examples of interesting target molecules containing rings are known. These include caryophyllene (E.J. Corey, 1963 A, 1964) and cubane (J.C. Barborak, 1966). The photochemical [2 + 2]-cycloaddition applied by Corey yielded mainly the /ranr-fused isomer, but isomerization with base leads via enolate to formation of the more stable civ-fused ring system. 

Thermal electrocyclizations of perhalogenated 1,3-butadienes yield perhalogenated cyclobutenes which can be solvolysed to 3,4-dihydroxy-3-cydobutene-l,2-dione ( squaric acid ) and its derivatives (G. Maahs, 1966 H. Knorr, 1978 A.H. Schmidt, 1978). Double CO extrusion from fused cyclobutenediones has been used to produce cycloalkynes, e.g., benzyne from benzocyclobutenedione by irradiation in an argon matrix (O.L. Chapman, 1973) and cyc/o-Ci8, cyclo-Cn, etc. by laser desorption mass spectroscopy of appropriate precursors (see section 4.9.8). 

---

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],... 

A point m a molecule is a center of symmetry if any line drawn from it to some element of the structure will when extended an equal distance m the opposite direction encounter an identical element The cyclobutane derivative m Figure 7 4 lacks a plane of symmetry yet is achiral because it possesses a center of symmetry... 

Cyclobutane derivatives are formed after exposing a mixture of alkenes and maleic anhydride to light. Photoadducts are formed by reaction of maleic anhydride with ethylene [74-85-1] and benzene (50). 

By using freshly preeipitated copper powder at 200 °C, perfluroallenes can be prepared by the elimination of bromine fluoride or iodine fluoride from the corresponding starting matenals [70] The reaction is carried out at low pressure, 1-2 mm of Hg, and the products quickly dimenze into cyclobutane derivatives (equation 39)... 

Enamines having a hydrogen on the enamine carbon also undergo cycloaddition to give cyclobutane derivatives. The latter are less stable, so that the reaction must be carried out under milder conditions in order to obtain... 

The addition of p-quinone to enamines normally produces furan derivatives, especially when the enamine possesses a 3 hydrogen (see Section III. A). 1,2 Cycloaddition is claimed to take place to give a cyclobutane derivative when p-quinone and an enamine with no jS hydrogens are allowed to react at low temperatures (51). However, little evidence is reported to verify this structural assignment, and the actual structure probably is a benzofuranol (52). Reaction of a dienamine (formed in situ) with p-quinone in the presence... 

Unsaturated sulfoncs (314,315) and nitroolcfins (303,315-317) also give alkylation products with enamines. In the latter reactions the formation of nitroethyl or cyclobutane derivatives has been found (316) to depend on the reaction medium as well as steric and electronic parameters which determine the fate of zwitterionic intermediates. Thus no enamine products could... 

Metallacycles as intermediates in redox rearrangements of cyclopropane and cyclobutane derivatives 96MI10. 

Thermal cycloadditions of butadiene to 3-bromo- 133 and 3-methoxy-5-methylene-2(5//)-furanones 220 were studied (95TL749). These systems contain substituents at C3 capable of stabilizing also a possible radical intermediate, influencing hereby the rate and/or the course of the reaction. Thus, the reaction of 133 and 220, respectively, with butadiene at 155°C afforded mixtures of the expected 1,4-cycloadducts 221 and 222, respectively, and of the cyclobutane derivatives... 

According to the Woodw ard-Hofmann rules the concerted thermal [2n + 2n] cycloaddition reaction of alkenes 1 in a suprafacial manner is symmetry-forbidden, and is observed in special cases only. In contrast the photochemical [2n + 2n cycloaddition is symmetry-allowed, and is a useful method for the synthesis of cyclobutane derivatives 2. 

From a preparative point of view, the photochemical [2 + 2] cycloaddition is the most important of the photochemical reactions especially the cycloaddition involving enones. The [2 + 2] cycloaddition is the method of choice for the construction of cyclobutane derivatives as well as cyclobutane units within larger target molecules. 

The overall reaction includes allylic transposition of a double bond, migration of the allylic hydrogen and formation of a bond between ene and enophile. Experimental findings suggest a concerted mechanism. Alternatively a diradical species 4 might be formed as intermediate however such a species should also give rise to formation of a cyclobutane derivative 5 as a side-product. If such a by-product is not observed, one might exclude the diradical pathway ... 

The thermal reaction between two molecules of aUcene to give cyclobutane derivatives (a 2 + 2 cycloaddition) can be carried out where the aikenes are the same... 

A strong acceptor TCNE undergoes [2+2] rather than [4+2] cycloaddition reactions even with dienes. 1,1-Diphenylbutadiene [20] and 2,5-dimethyl-2,4-hexadiene (Scheme 5) [21] afford mainly and exclusively vinyl cyclobutane derivatives, respectively. In the reactions of 2,5-dimethyl-2,4-hexadiene (1) the observed rate constant, is greater for chloroform solvent than for a more polar solvent, acetonitrile (2) the trapping of a zwitterion intermediate by either methanol or p-toluenethiol was unsuccessful (3) radical initiators such as benzyl peroxide, or radical inhibitors like hydroquinone, have no effect on the rate (4) the entropies of activation are of... 

Another explanation has been offered to explain the large proportion of cyclobutane derivatives produced by low-energy sensitizers, especially for the anthracene derivatives.<17) This is that energy transfer to diene occurs from the second excited triplet state of the sensitizer rather than the first. Experiments using a large number of anthracene derivatives as sensitizers... 

Many examples of photocycloaddition reactions of olefins and polyenes yielding cyclobutane derivatives have been reported. Irradiation of mixtures of butadiene and 1,1-dichloroethylene in the presence of a... 

Photodimerization reactions of some other simple alkenes and dienes follow/39-30 36-182 Although not a dimerization reaction, photochemical ring closures to yield cyclobutane derivatives are analogous and are included in this section 31-35 ... 

Irradiation of a mixture of hexadiene isomers in 1,1-dichloroethylene with /J-acetonaphthone gave four cyclobutane derivatives<54) ... 

Again, only oxa-propellanes, not dispirans, were formed when 1,1,2,2-cyclobutane derivatives were used as starting materials 4d). The tetratosylate 37 was formed by esterification of the corresponding tetrol 36 with p-TsOH accompanied by the bicyclic... 

The observation that the overwhelming product from the cycloaddition of 3 to 1,3-butadiene (12) is a cyclobutane derivative 31 and the proportion of the [4 -I- 2] adduct increases in the order 12 < 26 6 is in accord with the increasing diene reactivity in this series. Whereas cyclopentadiene readily combines with most dienophiles at low temperatures, 1,3-butadiene, mainly owing to its predominant s-trans conformation, enters into [4 + 2] cycloadditions only at elevated temperatures. 

This article will only discuss two particular kinds of photocycloaddition reactions, the photodimerization or cross-cycloaddition of two olefins to yield a cyclobutane derivative, and the photoreaction of an olefin with a carbonyl compound to give an oxetane, Eq. 1 and Eq. 2. The inportance of substituent effects in reactions of these types is pointed... 

The reaction of ethylene with steroidal a,/ -unsaturated ketones yields both cis and trans cyclobutane derivatives as illustrated in Eq. 55. 145)... 

Radialenes represent the biggest and best known subset of the radialene family this is not surprising in view of the fact that more methods to prepare them exist than for any other class of radialenes. The major strategies are the transformation of appropriate cyclobutane derivatives, the thermal or Ni(0)-catalyzed cyclodimerization of butatrienes or higher cumulenes and the cyclotetramerization of (l-bromo-l-alkenyl)cuprates. 

Cyclobutane derivatives are involved in all known syntheses of the parent [4]radialene (Scheme 8). The first approaches used /1-elimination reactions on compounds 5836, 5936 and 6036- 38 to introduce all four exocyclic C=C bonds in one operation. 

---