Cyclobutanes => alkenes

Peterson alkenation cyclobutane synthesis and cyclopentane annulation via l-lithio-l-(trunethylsilyl)cyclopropane)... 

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). 

Thermal decomposition of unsubstituted 3,4,5,6-tetrahydropyridazine at 439 °C in the gas phase proceeds 55% via tetramethylene and 45% via a stereospecific alkene forming pathway. The thermal decomposition of labelled c/s-3,4,5,6-tetrahydropyridazine-3,4- f2 affords cfs-ethylene-l,2- f2, trans-ethylene-l,2-if2, c/s-cyclobutane-l,2- f2 and trans-cyclo-butane-1,2- /2 (Scheme 57) (79JA3663, 80JA3863). 

A special case of fragmentation is that of 1,4-diradicals where fragmentation can lead to two stable molecules. In the case of 1,4-diradicaIs without functional-group stabilization, reclosure to cyclobutanes is normally competitive with fragmentation to two molecules of alkene. 

The complementary relationship between thermal and photochemical reactions can be illustrated by considering some of the same reaction types discussed in Chapter 11 and applying orbital symmetry considerations to the photochemical mode of reaction. The case of [2ti + 2ti] cycloaddition of two alkenes can serve as an example. This reaction was classified as a forbidden thermal reaction (Section 11.3) The correlation diagram for cycloaddition of two ethylene molecules (Fig. 13.2) shows that the ground-state molecules would lead to an excited state of cyclobutane and that the cycloaddition would therefore involve a prohibitive thermal activation energy. 

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 types of cycloadditions discovered for enamines range through a regular sequence starting with divalent addition to form a cyclopropane ring, followed by 1,2 addition (i) of an alkene or an alkyne to form a cyclo-cyclobutane or a cyclobutene, then 1,3-dipolar addition with the enamine the dipolarophile 4), and finally a Diels-Alder type of reaction (5) with the enamine the dienophile. 

Olefins conjugated with electron-withdrawing groups other than a carbonyl group undergo reactions with enamines in a manner similar to the carbonyl-conjugated electrophilic alkenes described above. Namely, they condense with an enamine to form a zwitterion intermediate from which either 1,2 cycloaddition to form a cyclobutane ring or simple alkylation can take place. 

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. 

In contrast with the [4 + 2]- --electron Diels-Alder reaction, the [2 + 2 thermal cycloaddition between two alkenes does not occur. Only the photochemical [2 + 2] cycloaddition takes place to yield cyclobutane products. 

Bradshaw et al. 67) were the first to propose a reaction pathway that is compatible with a transalkylidenation scheme. They suggested that the reaction proceeds via a quasi-cyclobutane intermediate. Applied to linear alkenes, this is pictured as follows ... 

Many authors assume that the reaction indeed proceeds in such a way, with the specification that the quasi-cyclobutane intermediate corresponds with a complex of cyclobutane with C4-symmetry (3, 13, 2%, 46, 49, 68-72). The role of the catalyst is described by these authors in terms of the forbidden-to-allowed concept of Mango and Schachtschneider 73, 74), in which the assumption is made that the formation of the cyclobutane complex is the result of a concerted fusion of two alkenes. In the following this will be considered in more detail. 

It is clear that a detailed mechanism for the metathesis reaction of alkenes cannot yet be given with certainty. In view of the fact that, for similar reactions which are formally cyclobutane-dialkene transformations, a nonconcerted reaction pathway has been demonstrated, a concerted fusion of two alkenes to form a cyclobutane complex and its decomposition in the same way with a change in the symmetry plane is less probable. On the basis of the information on the two other mechanisms to date, the mechanism involving a metallocyclic intermediate is more plausible than a mechanism involving carbene complexes. 

Another possibility might be a complex involving more than two alkene molecules e.g., analogous to the cyclobutane complex, a cyclohexane complex can be imagined. In the literature, evidence concerning these possibilities has not been provided so far. 

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. 

We have emphasized that the Diels-Alder reaction generally takes place rapidly and conveniently. In sharp contrast, the apparently similar dimerization of alkenes to cyclobutanes (15-61) gives very poor results in most cases, except when... 

Alkenes with electron-withdrawing groups may form cyclobutanes with alkenes containing electron-donating groups. The enamine reactions, mentioned above, are examples of this, but it has also been accomplished with tetracyanoethylene and similar molecules, which give substituted cyclobutanes when treated with alkenes of the form C=C—A, where A may be... 

Thermal dimerization of ethylene to cyclobutane is forbidden by orbital symmetry (Sect 3.5 in Chapter Elements of a Chemical Orbital Theory by Inagaki in this volume). The activation barrier is high E =44 kcal mof ) [9]. Cyclobutane cannot be prepared on a preparative scale by the dimerization of ethylenes despite a favorable reaction enthalpy (AH = -19 kcal mol" ). Thermal reactions between alkenes usually proceed via diradical intermediates [10-12]. The process of the diradical formation is the most favored by the HOMO-LUMO interaction (Scheme 25b in chapter Elements of a Chemical Orbital Theory ). The intervention of the diradical intermediates impfies loss of stereochemical integrity. This is a characteric feature of the thermal reactions between alkenes in the delocalization band of the mechanistic spectrum. 

Cyclobutanes can also be formed by nonconcerted processes involving zwitter-ionic intermediates. The combination of an electron-rich alkene (enamine, enol ether) and an electrophilic one (nitro- or polycyanoalkene) is required for such processes. 

Intramolecular [2 + 2] photocycloadditions of alkenes is an important method of formation of compounds containing four-membered rings.184 Direct irradiation of simple nonconjugated dienes leads to cyclobutanes.185 Strain makes the reaction unfavorable for 1,4-dienes but when the alkene units are separated by at least two carbon atoms cycloaddition becomes possible. 

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 ... 

Some years ago we began a program to explore the scope of the palladium-catalyzed annulation of alkenes, dienes and alkynes by functionally-substituted aryl and vinylic halides or triflates as a convenient approach to a wide variety of heterocycles and carbocycles. We subsequently reported annulations involving 1,2-, 1,3- and 1,4-dienes unsaturated cyclopropanes and cyclobutanes cyclic and bicyclic alkenes and alkynes, much of which was reviewed in 1999 (Scheme l).1 In recent days our work has concentrated on the annulation of alkynes. Recent developments in this area will be reviewed and some novel palladium migration processes that have been discovered during the course of this work will be discussed. 

As pericyclic reactions are largely unaffected by polar reagents, solvent changes, radical initiators, etc., the only means of influencing them is thermally or photochemically. It is a significant feature of pericyclic reactions that these two influences often effect markedly different results, either in terms of whether a reaction can be induced to proceed readily (or at all), or in terms of the stereochemical course that it then follows. Thus the Diels-Alder reaction (cf. above), an example of a cycloaddition process, can normally be induced thermally but not photochemically, while the cycloaddition of two molecules of alkene, e.g. (4) to form a cyclobutane (5),... 

It can be assumed that, upon irradiation, tautomer 5-40-II reacts with the alkene 5-41 in a highly regioselective [2+2] cycloaddition to give the cyclobutane 5-42 as an intermediate. Subsequent retro-aldol-type reaction and hemiacetal formation produces 5-44 via 5-43. After addition of the Lewis acid (BF3-Et20), cyclization takes place to give the desired products. It should be noted that the excess of alkene must be removed under reduced pressure before addition of the Lewis acid in order to avoid polymerization. 

Mechanistic evidence indicates 450,451> that the triplet enone first approaches the olefinic partner to form an exciplex. The next step consists in the formation of one of the new C—C bonds to give a 1,4-diradical, which is now the immediate precursor of the cyclobutane. Both exciplex and 1,4-diradical can decay resp. disproportionate to afford ground state enone and alkene. Eventually oxetane formation, i.e. addition of the carbonyl group of the enone to an olefin is also observed452. Although at first view the photocycloaddition of an enone to an alkene would be expected to afford a variety of structurally related products, the knowledge of the influence of substituents on the stereochemical outcome of the reaction allows the selective synthesis of the desired annelation product in inter-molecular reactions 453,454a b). As for intramolecular reactions, the substituent effects are made up by structural limitations 449). 

The Lewis acid catalyst 53 is now referred to as the Narasaka catalyst. This catalyst can be generated in situ from the reaction of dichlorodiisopropoxy-titanium and a diol chiral ligand derived from tartaric acid. This compound can also catalyze [2+2] cycloaddition reactions with high enantioselectivity. For example, as depicted in Scheme 5-20, in the reaction of alkenes bearing al-kylthio groups (ketene dithioacetals, alkenyl sulfides, and alkynyl sulfides) with electron-deficient olefins, the corresponding cyclobutane or methylenecyclobu-tene derivatives can be obtained in high enantiomeric excess.18... 

When alkenes are allowed to react with certain catalysts (mostly tungsten and molybdenum complexes), they are converted to other alkenes in a reaction in which the substituents on the alkenes formally interchange. This interconversion is called metathesis 126>. For some time its mechanism was believed to involve a cyclobutane intermediate (Eq. (16)). Although this has since been proven wrong and found that the catalytic metathesis rather proceeds via metal carbene complexes and metallo-cyclobutanes as discrete intermediates, reactions of olefins forming cyclobutanes,... 

As depicted in Scheme 11, ylides 39 derived from 4-methyl-[l,2,3]triazolo[l,5- ]pyridine react with Michael acceptors, which, upon nucleophilic attack at C3 and ring opening, lead to nucleophilic displacement of nitrogen. The intermediate diradical led to a mixture of compounds, including alkenes and a cyclobutane derivative when methyl acrylate was used, and the indolizine 40 with methyl propiolate as the electrophile <1998T9785>. Heating 4-methyl triazolopyridine with benzenesulfonyl chloride in acetone also confirmed decomposition via a radical pathway. 

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