Cyclobutanes stepwise

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... 

The cycloadditions in entries 1-3 are still believed to occur via a diradical stepwise pathway, as confirmed by obtaining a thermodynamic 78 22 trans/cis mixture of dispirooctanes 536 from frans-dicyanoethylene (533) (entry 3) [13b, 143], The cycloaddition to tetracyanoethylene (131) in the absence of oxygen gives only low yields of the [2 + 2] adduct, due to the simultaneous formation of products 542 and 543 (Scheme 74) [13b]. Still, the formation of the cyclobutanes 537 and 542 is noteworthy, since the reactions of TCNE with phenyl substituted MCPs exclusively afford methylenecyclopentane derivatives [37,144], The reaction is thought to occur via dipolar intermediates 539-541 formed after an initial SET process (Scheme 74) [13b]. The occurrence of intermediates 540 and 541 has been confirmed by trapping experiments [13b]. 

Unlike thermal [2 + 2] cycloadditions which normally do not proceed readily unless certain structural features are present (see Section 1.3.1.1.), metal-catalyzed [2 + 2] cycloadditions should be allowed according to orbital symmetry conservation rules. There is now evidence that most metal-catalyzed [2 + 2] cycloadditions proceed stepwise via metallacycloalkanes as intermediates and both their formation and transformation are believed to occur by concerted processes. In many instances such reactions occur with high regioselectivity. Another mode for [2 + 2] cyclodimerization and cycloadditions involves radical cation intermediates (hole-catalyzed) obtained from oxidation of alkcnes by strong electron acceptors such as triarylammini-um radical cation salts.1 These reactions are similar to photochemical electron transfer (PET) initiated [2 + 2] cyclodimerization and cycloadditions in which an electron acceptor is used in the irradiation process.2 Because of the reversibility of these processes there is very little stereoselectivity observed in the cyclobutanes formed. 

Modified Wolff-Kishner methods work well on ordinary cyclobutanones. Generally, the hydrazones are made at fairly mild reaction temperatures, base is added and the cyclobutane is distilled directly from the hot reaction mixture.237,272 279-284 The hydrazone can also be isolated prior to the reduction.285 The relatively facile reduction of cyclobutanones which occurs before that of larger ring ketones can be utilized in the selective reduction of cyclobutanones in the presence of, for example, a cyclohexanone, i.e. pentaspiro[3.1.3.3.3.3]heneicosane-5,11,19-trione was reduced in a stepwise manner to pentaspiro[3.1.3.3.3.3]heneicosane-5-one.237... 

The pyrolysis of pinenes is mechanistically similar to that of cyclobutane, giving initially a 1,4-diradical. Subsequent C-C bond fission of this 1,4-diradical thus generates a diene. The stepwise cycloreversion of 7,7-dimethylbicyclo[3.1.1]heptan-2-one (20) at 600 °C is a good example.100 106... 

In the case of the fluorinated ethylenes, it is known through work of Bartlett and his collaborators that the reaction is stepwise by way of a biradical intermediate.17 Much of the evidence supporting this conclusion has been obtained from the study of additions of l,l-difluoro-2,2-dichloroethylene, abbreviated 1122, to dienes. Scheme 1 outlines six possible general routes, each of which has several potential stereochemical variations, that addition of an olefin to a diene could follow. When 1122 reacts with butadiene and simple substituted butadienes, the products are entirely cyclobutanes consequently, we may restrict attention... 

Stepwise reactions by way of diradical intermediates are also possible they often require rather high temperatures, but they are probably involved in the formation of cyclobutanes by the thermal coupling of alkenes like the halogenated alkene 2.161 with themselves or with dienes like butadiene giving the cyclobutane 2.163. The radical centres in the intermediate 2.162... 

The cycloreversion of the cyclobutane radical cation Pyr +oPyr could proceed in either a concerted or stepwise manner, and many attempts were made to determine the mechanism of this cleavage step. Because the radical cation is delocalized, it is not unreasonable that both the C(5)-C(5 ) and the C(6)-C(6 ) bonds are weakened by oxidation of PyroPyr. The observation of a substantial secondary deuterium isotope effect for the cleavage of the first bond [C(6)-C(6 )] and a small isotope effect for the cleavage of the second bond [C(5)-C(5 )] in various deu-terated uracil-derived cyclobutane dimers was, however, taken as an indication of a stepwise splitting mechanism via the distonic radical cation Pyr+-Pyr [9]. Theoretical studies performed by Rosch, Michel-Beyerle et al. also strongly support the assumption of a successive cycloreversion [10]. 

Bauld and coworkers studied the [2+2] cycloaddition of A-vinyl carbazoles 86a and electron-rich styrenes 86b catalyzed by iron(III) catalysts A or B in the presence of 2,2 -bipyridine as a ligand, which was reported originally by Ledwith and coworkers (Fig. 21) [142, 143]. Deuterium-labeling studies provided support for the stepwise nature of the process, consisting of reversible SET oxidation of the electron-rich olefin to a radical cation 86 A. Nucleophilic addition of excess 86 leads to distonic radical cation 86B, which cyclizes to cyclobutane radical cation 86C. Back electron transfer affords cyclobutanes 87 and regenerates the catalyst. Photoelectron transfer catalysis gave essentially the same result, thus supporting the pathway. 

From organic chemistry it is known that cycloaddition reactions leading to cyclobutanes are required to be stepwise reactions, according to the Woodward-Hoffmann rules [131]. A bond is formed between the two olefins, leading to a tetramethylene intermediate (T). In a subsequent step, the second bond is formed, yielding the cycloadduct. Depending on the reactants, either zwitterionic or diradical tetramethylenes can be proposed as intermediates [132, 133]. 

In recent years, more and more photochemists consider that many photocycloaddition reactions take place stepwise, that is, one bond is first formed. The formed tetramethylene intermediate may close to a cyclobutane or initiate the polymerization. We will leave this discussion to Sect. 4. 

Stepwise reactions by way of diradical intermediates are also possible, as in the coupling of the halogenated alkene 6.102 with butadiene 6.103. As we saw in Chapter 2 (see pages 67-68), any group, C, Z or X, stabilises a radical. Both radical centres in the intermediate 6.104 are stabilised, the one at the top by the o-chlorines and the /3-fluorines, and the one below because it is allylic. These combine rapidly 6.104 (arrow on the upper drawing) to give the cyclobutane 6.105. 

The stepwise, oxidative cycloaddition mechanism [particularly with d metal systems 1 )] could intervene in the valence isomerizations of strained, cyclobutane ring systems where energy factors and difficulties in attaining bidentate coordination work in its favor. For the other processes, however, where bidentate coordination is either very favorable or guaranteed, its contribution to catalytic chemistry would seem to be significantly less. 

The [2 + 2] cycloaddition represents the most general and direct pathway for the formation of a cyclobutane structure from two alkene moieties, as outlined in Scheme 2.126. This process may occur as a concerted reaction via a cyclic transition state (mechanism a), as a stepwise reaction involving the formation of an acyclic biradical (mechanism b), or through bipolar (mechanism c) intermediates. Depending upon the structure of the reactants, cycloaddition may occur by any of these mechanisms. 

Its thermal stability was explained by invoking the forbidden concerted thermal fragmentation of a cyclobutane ring. In such a rigid molecule even stepwise cleavage beginning with the conjoining bond would closely resemble a concerted process. Nor is a... 

Now are there such reactions as [2 + 2] cycloadditions Can, say, two molecules of ethylene combine to form cyclobutane The answer is yes, but not easily under thermal conditions. Under vigorous conditions cycloaddition may occur, but step-wise—via diradicals—and not in a concerted fashion. Photochemical [2 + 2] cycloadditions, on the other hand, are very common. (Although some of these, too, may be stepwise reactions, many are clearly concerted.)... 

Cyclopropylidene-l,3-dioxanes or -1,3-dioxolanes are ketene acetals and examples of bis-donor-substituted methylenecyclopropanes which undergo facile cycloaddition with electron-deficient alkenes 12. Thus, spiro[2.3]pentanone acetals 13 were obtained after reaction in an aromatic solvent either at room temperature or 40 C. Upon subsequent aqueous workup, hydrolytic cleavage of a C-C bond of the cyclobutane ring took place rather than the expected acetal hydrolysis (Table 7). This cycloaddition was found to proceed in a stepwise fashion as reaction of the dimethyl ( )-but-2-enedioate gave a cisj tram mixture of cycloadducts on further heating, this ratio changed. 

Photoinduced [2 + 2] cycloaddition (Section 4.9) of alkenes (alkynes) to form cyclobutane (cyclobutene) derivatives is one of the best studied reactions in photochemistry.680 682 According to the Woodward Hoffmann orbital symmetry rules,336 the cycloaddition of one singlet excited (Si) and one ground-state alkene is allowed by a suprafacial suprafacial concerted stereospecific pathway (Scheme 6.45) 695 699 700 Rare concerted [4 + 2] and [4 + 4] photocycloadditions of conjugated singlet excited dienes must occur in a suprafacial antarafacial and suprafacial suprafacial manner, respectively.690 Since the suprafacial antarafacial reactant approach is geometrically difficult to achieve, [4 + 2] reactions usually proceed stepwise (involving biradical intermediates). [2 + 2] or [4 + 4] photocycloadditions can occur in either a concerted or stepwise fashion. 

A beautiful illustration of a delicate balance between a stepwise and a concerted reaction has been found in the reactions of 1,1-dimethylbutadiene 6.133.716 This diene rarely adopts the s-cis conformation necessary for the Diels-Alder reaction with tetracyanoethylene giving the cyclohexene 6.136. However, it can react in the more abundant s-trans conformation in a stepwise manner, leading to a moderately well stabilised zwitterion 6.134. The intermediate allyl cation is configurationally stable, and a ring cannot form to C-l, because that would give a trans double bond between C-2 and C-3 in the cyclohexene 6.137. Instead a cyclobutane 6.135 is formed. All this is revealed by the solvent effect. In the polar solvent acetonitrile the stepwise ionic pathway is favoured, and the major product (9 1) is the cyclobutane 6.135. In the nonpolar solvent hexane, the major product (4 1) is the cyclohexene 6.136 with the Diels-Alder reaction favoured. 

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