Alkenes cyclodimerization

The electronic state of the metal center basically determines reactivity and selectivity. When, for example, the 27t-component is strongly electron deficient, as in maleic anhydride, acrylal-dehyde or acrylonitrile, it tends to be firmly coordinated to the metal thus forming a stable, unreactive complex. When, however, the alkene is only weakly bound, e.g. in the case of some nonactivated alkenes, cyclodimerization of methylenecyclopropane may occur predominantly or exclusively instead of cocyclodimerization. The same is true for phosphorus-free catalyst systems even in the presence of electron-deficient alkenes. A precoordination of the alkene to the metal center is thus necessary in order to accomplish both co- and the homocyclodimerization reaction. 

In the 1960 s Ledwith found the [2 + 1] alkene cyclodimerization (review Ledwith, 1972), which is based on the generation of small concentrations of chain-carrying cation radicals from n donor molecules, such as electron-rich alkenes, conjugated... 

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 first stannenes were obtained as reactive intermediates that were identified by their reaction products.570,571 For example, Me2Sn=C(SiMe3)2 (Scheme 20) was prepared by the 1,2-elimination of LiBr, or by a retro-Diels-Alder reaction, and was characterized by cyclodimerization, by ene reactions with alkenes, and by cycloaddition with 1,4-dienes.572... 

Of conrse, the cyclic cation-radical formed should be less stable than the alkene cation-radical (which contains a double bond that is favorable for the spin-charge scattering). However, the cation-radical product and corresponding nentral species are generated in a concerted process. The process involves simultaneous covalent bond formation and one-electron reduction of the cyclic product (Karki et al. 1997). Similar to other branched-chain processes, the cation-radical dimerization is characterized by an activation enthalpy that is not too high. These magnitudes are below 20 kJ mol for the pair of cyclohexadiene and trani-anethole (p-MeOCgH4CH=CHCHMe, Z-form Lorenz and Bauld 1987). It is clear that the cation-radical variant of cyclodimerization differs in its admirable kinetic relief. For cyclohexadiene and tran -anethole, catalytic factors are 10 and 10, respectively (Bauld et al. 1987). 

Pronounced rate and selectivity enhancements had previously been observed for Ni(0)-catalyzed cyclodimerizations as well as rhodium-catalyzed alkene hydroformylation reactions. For related references see (Ni) van Leeuwen, P.W.N.M. Roobeek, C.F. Tetrahedron 1981, 37, 1973. (Rh) van Leeuwen,... 

The thermal cyclodimerization of fluoroalkenes represents a route to fluorinated cyclobutanes. In most cases the neat alkene is heated in a sealed tube for prolonged periods of time. For symmetrical fluoroethenes head-to-head dimerization predominates. For instance, 1.1-dichloro-2,2-difluoroethene (1) undergoes thermal dimerization (180°C, 14 days) to give the hcad-to-hcad dimer 2 although no yield was reported.1... 

Alkenes substituted by capto-dative groups such as 5 and 7 undergo cyclodimerization under milder conditions. Mixtures of head-to-head stereoisomers are also obtained in these cases.5,6... 

Strained alkenes undergo thermal cyclodimerization often spontaneously. For instance, the fl t/-Bredt bicycloalkenes 9 and 10 formed as transients give the cyclodimers 11 and 12, respectively, along with oligomeric substances.7... 

Cyclobutadienes represent very reactive alkenes that undergo both [2 + 2] as well as [4 + 2] cycloadditions. Both the cyclodimerizations, mixed [2 + 2] cycloadditions and Diels-Alder reactions of these reactive species have been reviewed (see Houben-Weyl, Vols. 4/4, p 231 and E 17 f, Section 10B). In most instances the initially formed cyclodimer is tricyclo[4.2.0.02-5]octa-3,7-diene (36) and has the all cis-syn configuration. This is attributed to the concerted [4n -I- 2n] cycloaddition mechanism in which stereochemical control is affected by secondary orbital interactions. 

Metal-catalyzed cyclodimerization has been restricted to buta-1,3-dienes, norbornadienes (see Houben-Weyl, Vol. 4/4, pp 295-299) and more recently to strained alkenes such as cyclopropenes and methylenecyclopropanes (see Sections, 3., l.B.2.2.2. and 2.B.2.4.2.). 

Although hole-catalyzed (cycloaddilions involving radical cation intermediates) and PET (photochemical electron transfer) mixed [2 -I- 2] cycloadditions have been reported from electron-rich alkenes, the only report of a cyclodimerization is that of (E)-4-(prop-l-enyl)anisole which gives stereoisomeric mixtures of the head-to-head dimers 1 and 2.12... 

Metal-catalyzed cyclodimerizations of cumulenes can often result in different regiochemistry compared to their thermal counterpart. For example the nickel-catalyzed dimerization of the cumulene 22 gives exclusively the 4-radialene 23 whereas the thermal reaction gives the symmetrical 4-radialene 24.29 Metal-catalyzed cyclodimerizations of alkenes as seen in this and other examples often proceed under mild conditions. However, as the result of the intervention of metal-complexcd intermediates, regio- and stereochemistry may differ from their thermal counterparts. 

The photoinduced electron transfer (PET) initialed cyclodimerization was first studied with 9-vinylcarbazole as substrate1 and characterized mechanistically as a cation radical chain reaction.2 The overall reaction sequence3-4 consists of a) excitation of an electron acceptor (A), b) electron transfer from the alkene to the excited acceptor (A ) with formation of a radical ion pair, c) addition of the alkene radical cation to a second alkene molecule with formation of a (dimeric) cation radical, and d) reduction of this dimeric cation radical by a third alkene molecule with formation of the cyclobutanc and a new alkene cation radical. Steps c) and d) of the sequence are the chain propagation steps. The reaction sequence is shown below. 

For synthetic purposes, the conversion of diallyl ether (11, X = O) to 3-oxabicy-clo[3.2.0]heptane (12, X = O),11 of ethyl JV,7V-diallylcarbamate (11, X = NC02Et) to A7-car-boethoxy-3-azabicyclo[3.2.0]heptane (12, X = NC()2Et)12 and of 4-hydroxyhepta-l,6-diene (13) to 3-hydroxybicyclo[3.2.0]heptane (14)13 have become the most useful copper(I)-photocat-alyzed (intramolecular) cyclodimerizations of alkenes. 

Another reactive alkene which undergoes cycloaddition with nonactivated ethenes is hexafluo-ropropene 12.22 Again these cycloadditions give mixtures of stereoisomeric cyclobutanes. It is interesting to note that regiospecificity is observed in these cyclodimerizations with head-to-head dimers being formed exclusively. 

One of the problems associated with thermal cyclodimerization of alkenes is the elevated temperatures required which often cause the strained cyclobutane derivatives formed to undergo ring opening, resulting in the formation of secondary thermolysis products. This deficiency can be overcome by the use of catalysts (metals Lewis or Bronsted acids) which convert less reactive alkenes to reactive intermediates (metalated alkenes, cations, radical cations) which undergo cycloaddilion more efficiently. Nevertheless, a number of these catalysts can also cause the decomposition of the cyclobutanes formed in the initial reaction. Such catalyzed alkene cycloadditions are limited specifically to allyl cations, strained alkenes such as methylenccyclo-propane and donor-acceptor-substituted alkenes. The milder reaction conditions of the catalyzed process permit the extension of the scope of [2 + 2] cycloadditions to include alkene combinations which would not otherwise react. 

Evidence for the inclusion of such species in the catalytic cyclodimerization of alkenes has resulted in their isolation from the reaction of nickel(O) compounds with strained alkenes or 1,4-dihalobutanes. and by their displacement with activated alkenes, such as maleic anhydride or corresponding alkenes to yield the four-membered cyclodimers, which are also produced in the catalytic reaction.120... 

In a different, biological context the photochemical cyclodimerization of carbonyl-conjugated alkenes is important as a major source of ultraviolet-induced damage to living cells. Thymine (2.77)... 

When thioketones are irradiated alone, a cyclodimerization may occur to give a 1,3-dithietane (4.98). In the presence of an alkene, different cycloadducts are found, usually thietanes. If visible radiation is used, electron-rich alkenes are especially effective as addends, and the products can be rationalized on the basis of a two-step mechanism involving the more highly stabilized biradical intermediate (4.99). Sometimes a 1,4-dithiane accompanies foe thietane (4.100) as a result of foe trapping of the biradical by a further molecule of ground-state thioketones (unlike ketones, thioketones react with radicals quite readily, which is one of foe causes of... 

For cyclodimerization of fluoroalkenes to occur the alkencs must contain at least two geminal fluorine atoms, for example, tetrafluoroethene(l), trifluoroethenes, substituted trifluoroethenes, and l,l-dihalo-2.2-difluoroethene. These reactions require high temperatures and pressures. When the alkene is unsymmetrical. as in the case of l,l-dichloro-2,2-difluoroethene (3), two diflPerent orientations of addition can be envisaged to occur, hcad-to-head addition and head-to-tail addition,Generally, only the head-to-head adducts and not the head-to-tail adducts arc formed under kinetic control (Tabic 3, see also Houben-Wcyl, Vol. E17e, p85 however, see Table 3 and Houben-Weyl, Vol. 5/3. p 250 for rare examples of accompanying head-to-tail adducts). 

Many of the complexes discussed in the previous sections are catalysts for alkyne oligomerization. In fact, alkyne dimerization and trimerization (see Cyclodimerization -tri-merization Reactions) at a cobalt center is recognized as one of the most synthetically useful catalytic reactions mediated by a homogeneous transition metal complex. The cobalt complexes most useful and extensively studied are CpCoL2, where L is CO, alkene, diene, or phosphine. The complex types... 

Another mechanism for the 2n -f 27t ) photocycloaddition of alkenes via electron transfer is the reaction that proceeds via a triplet state which is produced by a back-electron transfer from a radical anion of the electron acceptor to a radical cation of the electron donor. The triplet state alkenes generated by this way can undergo the cyclodimerization (Scheme 22). Farid showed that the DCA-sensitized (2n 3- 2n) photocyclodimerization of 1,2-diphenylcyclo-propene-3-carboxylate occurs via the triplet state of the cyclo-propene in acetonitrile [84]. In this photoreaction, two types of the (An -(- 27t) photocycloaddition reactions take place between DCA and the cyclopropene depending upon solvents. One type of the cycloadduct is produced in benzene via exciplex and the other type of the photocycloadduct is produced in... 

An excess (5 1 mole ratio) of ethyl diazoacetate is used in these reactions to suppress cyclobutadimerization or Diels-Alder cyclodimerization. In difunctional molecules which have non-equivalent ionizable functionalities, cyclopropanation is highly selective for the more easily oxidized functionality. The latter selectivity is perhaps the most attractive aspect of the reaction. In contrast to transition metal (e.g. rhodium) catalyzed cyclopropanations, cation radical additions to electron deficient alkene moieties do not occur at all. The reaction is relatively sensitive to... 

In a large number of carbene and carbenoid addition reactions to alkenes the thermodynamically less favored syn-isomers are formed 63). The finding that in the above cyclopropanation reaction the anti-isomer is the only product strongly indicates that the intermediates are organonickel species rather than carbenes or carbenoids. Introduction of alkyl groups in the 3-position of the electron-deficient alkene hampers the codimerization and favors isomerization and/or cyclodimerization of the cyclopropenes. Thus, with methyl crotylate and 3,3-diphenylcyclopropene only 16% of the corresponding vinylcyclopropane derivative has been obtained. 2,2-Dimethyl acrylate does not react at all with 3,3-dimethylcyclopropene to afford frons-chrysanthemic add methyl ester. This is in accordance with chemical expectations 69) since in most cases the tendency of alkenes to coordinate to Ni(0) decreases in the order un-, mono-< di- < tri- < tetrasubstituted olefines. 

Ni(cod)2 or mixtures of Ni(cod)2 with an electron deficient alkenes (e.g. dialkyl fumarate or maleic anhydride) have been found to be the most efficient catalysts for the cyclodimerization of methylenecyclopropane and 2-methylmethylenecyclopropane no. i7i) Ni(cod)2 the combined yields of cyclodimerization products afe lower, but the ratio or four-membered to five-membered rings is higher. The reverse holds for the modified catalysts (Eq. 66). 

These codimerization reactions are mainly limited by the degree of n-bond strength of the electron deficient alkenes to Pd(0). Strongly bonded ligands may prevent any interaction of the metal with the methylenecyclopropane. Typical examples of too strongly bonded alkenes are maleic anhydride, acrolein and acrylonitrile. On the other hand, too weak interactions may result in cyclodimerization of the methylenecyclopropane rather than codimerization. 

The last observations automatically lead to the conclusion that non-activated alkenes also could undergo these reactions. Indeed it was found that ethylene, norbornene, norbomadiene198) and allene 199) react with methylenecyclopropane to give cycloadducts (Scheme 7). The reason for the limitation to these alkenes lies in the ability of methylenecyclopropane to compete successfully with alkenes in it-complexation to the metal. Thus cyclodimerization of methylenecyclopropane is much faster than codimerization with other alkenes, which give less stable ic-com-plexes with Pd(0). 

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