Reactions of Methylenecyclopropanes

Due to their tendency to dimerize in different thermal conditions, the formal [2 + 2] cycloaddition reaction of methylenecyclopropane derivatives and their... 

Albeit the transition metal catalysed reactions of methylenecyclopropane derivatives have already been thoroughly reviewed [2], it should be noted here that the cyclodimerization of these compounds can also be achieved by catalysis with Ni or Co complexes. The regioselectivity of the process is surprising and opposed to that of the thermal reaction, giving dispiro[2.1.2.1]octane derivatives (Scheme 69) [2],... 

The reaction of methylenecyclopropane with azides is the earliest 1,3-dipolar cycloaddition reported so far on this system [53,54]. 

Thermal cyclodimcrization of methylenecyclopropane results in head-to-head cycloaddition (see Section 1.3.1.1.). By contrast the bis(cycloocta-l,5-diene)nickel(0) catalyzed reaction of methylenecyclopropane gives the head-to-tail dimerization product 6 in 9% yield in addition to a [3 + 2] dimer 7.20... 

The reaction of methylenecyclopropanes with transition metal complexes is well known to promote a catalytic a-ir cycloaddition reaction with unsaturated compounds, in which a trimethylenemethane complex might exist71-76. Recently, much interest has been focused on the interaction of strained silicon-carbon bonds with transition metal complexes. In particular, the reaction of siliranes with acetylene in the presence of transition metal catalysts was extensively investigated by Seyferth s and Ishikawa s groups77-79. In the course of our studies on alkylidenesilirane, we found that palladium catalyzed reaction of Z-79 and E-79 with unsaturated compounds displayed ring expansion reaction modes that depend on the (Z) and (E) regiochemistry of 79 as well as the... 

The palladium-catalyzed Heck-type reaction of methylenecyclopropane 66 in the presence of soft nucleophiles such as sodium diethylmalonate gives a mixture of isomeric alkenes 70 and 71 (Scheme 8.32) [77]. In this process, there is first a carbopalladation of the double bond of 66 giving the cyclopropylcarbinylpalladium in-... 

Table 1 Reactions of Methylenecyclopropane and Electron Deficient Alkenes in the Presence of Nickel(O) or...

Ni(0) catalysis is able to induce reactions of methylenecyclopropane with olefins activated by electron-withdrawing groups (equation 193). These cycloadditions work with the utmost efficiency in the case shown, whereas more substituted components might give lower yields due to competing side reactions such as cyclo- and codimerization. These problems could be circumvented by employing new Ni(0) systems with triarylphosphines as cocatalysts (equation 193). Similar conditions lead to the smooth addition of dialkylmethylenecyclopropanes to electron-deficient olefins. ... 

While a, a -diphenylmethylenecyclopropane undergoes ring enlargement into 2,2-diphenylcyclobutanone upon treatment with selenious acid ", reaction of methylenecyclopropane with thallium(III) nitrate or mercury(II) hypochlorite leads mainly to ring fission products besides a low percentage (18 %) of cyclobutanone In addition to their formation by epoxidation of cyclopropylidene compounds, oxaspiropentanes are... 

Scheme 7. Reactions of methylenecyclopropane with non-activated alkenes (catalyst Pd(0)/P(iPr)3)...

Hydrobromic and hydrochloric acid undergo addition to the exocyclic double bond of methylenecyclopropanes following the Markovnikov rule. The reaction of methylenecyclopropane with hydrochloric acid alone or in the presence of a Lewis acid such as tin(IV) chloride gave... 

The reaction of methylenecyclopropane with 4-nitroperoxybenzoic or 3-chloroperoxyben-zoic acid in dichloromethane afforded oxaspiropentane (1) which is readily converted to cyclobutanone. " ... 

Methylenecyclopropanes undergo a variety of [2 + 3] cycloadditions (1,3-dipolar cycloadditions) across the double bond. Examples of the addition of diradicals are some of the dimerization reactions of methylenecyclopropane vide infra). Small quantities (< 5%) of an addition product of a 1,3-diradical to methylenecyclopropane with preservation of the three-membered ring were isolated from the thermal reaction of dispiro[2.2.2.2]deca-4,9-diene with methylenecyclopropane. ... 

The Diels-Alder reaction of methylenecyclopropane with cyclohexa-1,3-diene at 120°C gave the spirocyclopropanebicyclooctene in 50% yield.When cyclopentadiene and spiro[2.4]hepta-4,6-diene were used as dienes the respective spirocyclopropanenorbornenes were obtained. At 190°C, (chloromethylene)cyclopropane underwent [2 + 4] cycloaddition reactions with cyclopentadiene, furan and cyclohexa-1,3-diene to give the respective Diels-Alder adducts. The reaction of buta-1,3-diene and cyclohexa-1,3-diene with bicyclopropylidene as dienophile gave predominantly the [2 + 2] cycloadduct in addition to a small quantity of the Diels-Alder product. Cyclopentadiene, however, formed exclusively the dispirocyclo-propanenorbomene as result of a formal [2 + 4] cycloaddition. 

Substituted 1,2,4-triazines and 1,2,4,5-tetrazines are known to undergo [2-1-4] cycloaddition with inverse electron demand when reacted with alkenes. The primary bicyclic product loses nitrogen to give dihydropyridines and dihydropyridazines, respectively. The reaction of methylenecyclopropane with dimethyl-1,2,4,5-tetrazine-3,6-dicarboxylate at room temperature gave the spiro-dihydropyridazine 2 in 80% yield. ... 

The dimerization of methylenecyclopropane to 5-methylenespiro[2.4]heptane 2 was usually observed during the palladium(0)-catalyzed reaction of methylenecyclopropane with alkenes which involved the cleavage of the three-membered ring giving 6. °... 

This section reviews the reactions of methylenecyclopropanes functionalized at the double bond generating cyclopropane derivatives. 

Di- and oligomerization reactions of methylenecyclopropanes are also the most important competing side reactions in many of the codimerization reactions employing methylenecyclo-propane (MCP), which are summarized in Section 2.2.2.3. They are specially favored if the cosubstrate, i.e. the alkene in a [3-I-2]-cycloaddition reaction, is only weakly bound to the metal center thus allowing it to be replaced by a second molecule of MCP. 

Table 2. [3 -I- 2] Cycloadducts from the Nickel(0)-Catalyzed Reaction of Methylenecyclopropane with Chiral Acrylic Ester Derivatives ...

For reviews of transition metal-catalyzed reactions of methylenecyclopropanes (a) Binger P, Biich HM (1987) Top Curr Chem 135 77 (b) Nakamura I, Yamamoto Y (2002) Adv Synth Cat 344 111... 

A. de Meijere, A. Leonov, T. Heiner, M. Noltemeyer, M. Terosobes, Eur. J. Org. Chem., 2003,472. For previous examples of Diels Alder reactions of methylenecyclopropane derivatives under normal or high pressure conditions, see ref 7 of the paper. 

Dipolar cycloadditions. The reaction of methylenecyclopropane with nitrones generates spirocyclic isoxazolidines that are prone to thermal rearrangement. Thus 4-piperidones can be prepared in a two-step process. 

According to the data in Table 3 the reactivity of methylenecyclopropanes should lie somevi here between that of norbomene and a cyclopropene. In practice, the situation is even more complex (and sometimes puzzling) because there are three different strained bonds within a methylenecyclopropane C(l)-C(4), C(2)-(3) and C(l)-C(3). Moreover, little is known about the strain energies of the organo-metallic intermediates involved in transition metal catalyzed reactions of methylenecyclopropanes. 

The latter are of special synthetic interest since they result in the formation of two new C—X bonds (X = C, N). As shown in Scheme 3, thermally induced cycloadditions can only be achieved at high temperatures or when the methylenecyclopropane or the cosubstrate are activated by strong electron-withdrawing groups, such as halogen or CN. As will be outlined in the following chapters, a number of cycloaddition reactions of methylenecyclopropanes can be achieved under moderate conditions and in satisfactory to good yields in the presence of suitable transition metal catalysts. 

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