Cycloaddition reactions of methylenecyclopropanes

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

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. 

A catalytic asymmetric cycloaddition reaction between norbomadiene and methylenecyclopropane can also be achieved in the presence of a [Ni(cod)2]-(—)-benzylmethylphenylphosphine catalyst to give the cycloadduct (72) in an optically active form. This reaction may proceed via a metallocyclopentane intermediate. The reactions of methylenecyclopropane with [Ni(cod)2l-phosphine systems do not appear to involve cleavage of the three-membered ring. However, the bis(acrylonitrile)nickel-catalysed cycloaddition reaction of methylenecyclopropane with methyl acrylate, which yields 3-methoxy-carbonylmethylenecyclopentane (73), does involve C—C bond cleavage. Reaction with the deuterium-substituted compound CHD=CDC02Me gives the cyclopentane derivative (74). An intermediate of the type (75) may be involved in this reaction. 

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 cycloaddition reactions of captodative olefins all are considered to proceed through the intermediacy of a 1,4-diradical, due to the captodative stabilization of the terminal radicals. In cross-cycloadditions captodative olefins easily give cyclobutanes when heated with fluoroolefins [141]. They also react with allenes to give methylenecyclobutanes [142], and with methylenecyclopropane to give spiro[2.3]hexanes [143]. 

The Pd -catalyzed [3 + 2] cycloaddition reactions of (97) exhibit very different selectivities from those of the corresponding methylenecyclopropane codimerizations. One major distinction is the chemoselec-tivity only electron-deficient alkenes will react to form methylenecyclopentane. The nucleophilic nature of this TMM synthon is indicated in the exclusive annulation of the electron-poor double bond of 2,3-di-methoxycarbonylnorbomadiene (equation 109). - No such differentiation of alkenes is evident in the methylenecyclopropane codimerization with the same diene (equation 65). 

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. ... 

Eq. 117. Since breaking this C—C bond requires more energy, it is not necessarily so that the most energetically favoured TMM-Pd species act as intermediate, TMM-Pd-complexes with a higher energy level may be reasonable intermediates if they react immediately with a second olefin. We believe that in the cycloaddition reaction with methylenecyclopropane the first metalorganic intermediate is a complex in which both olefins are coordinated to the metal and so held in proximity to each other. Further reaction may involve a direct or a stepwise coupling as shown in Eq. 118. It is unknown at the present time which process occurs and whether it also depends on the nature of the metal and of the second olefin. 

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. ... 

When bicyclopropylidene was treated in the same way only trimers of the initially formed 8,9-diazadispiro[2.0.2.4]deca-7,9-diene were isolated.The cycloaddition reaction of the unsym-metrical dimethyl 3-cyano-l, 2,4-triazine-5,6-dicarboxylate with methylenecyclopropane was re-gioselective. The primary product was the 2-cyanospiro-3,4-dihydropyridine system (with C3 as spirocenter) which hydrolyzed readily upon chromatography. Dimethyl 4-oxo-5-aza-spiro[2.5]oct-5-ene-6,7-dicarboxylate was isolated as a stable product in 8%> yield. ... 

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. 

If the [3-h 2]-cycloaddition reaction of a methylenecyclopropane is performed with a remote alkene or alkyne moiety within the same molecule, products 2 of the bicyclo[3.n.0]-type (n < 3) or the bicyclo-[n.3.0]-type (n > 3) can, in principle, be obtained. The former of these product types can be considered as unhkely, as an alkene or alkyne separated by only one or two atoms from the methylenecyclopropane would give rise to a strained annulated ring, i.e. a cyclopropane or a cyclobutane. It is known from investigations of photochemically initiated intramolecular [2 3-2] cycloadditions of alkenes that the minimum size required for a spacer between 7t-systems is three atoms in a reaction of a non-crossed type. There are actually a few examples of photoinduced intramolecular cycloadditions of the crossed type involving substrates with short spacers (n =... 

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. 

Olah et al. reported the triflic acid-catalyzed isobutene-iso-butylene alkylation, modified with trifluoroacetic acid (TFA) or water. They found that the best alkylation conditions were at an acid strength of about//q = —10.7, giving a calculated research octane number (RON) of 89.1 (TfOH/TFA) and91.3 (TfOH/HaO). Triflic acid-modified zeohtes can be used for the gas phase synthesis of methyl tert-butyl ether (MTBE), and the mechanism of activity enhancement by triflic acid modification appears to be related to the formation of extra-lattice Al rather than the direct presence of triflic acid. A thermally stable solid catalyst prepared from amorphous silica gel and triflic acid has also been reported. The obtained material was found to be an active catalyst in the alkylation of isobutylene with n-butenes to yield high-octane gasoline components. A similar study has been carried out with triflic acid-functionalized mesoporous Zr-TMS catalysts. Triflic acid-catalyzed carbonylation, direct coupling reactions, and formylation of toluene have also been reported. Tritlic acid also promotes transalkylation and adaman-tylation of arenes in ionic liquids. Triflic acid-mediated reactions of methylenecyclopropanes with nitriles have also been investigated to provide [3 + 2] cycloaddition products as well as Ritter products. Tritlic acid also catalyzes cyclization of unsaturated alcohols to cyclic ethers. ... 

Cycloaddition of COj with the dimethyl-substituted methylenecyclopropane 75 proceeds smoothly above 100 °C under pressure, yielding the five-membered ring lactone 76. The regiocheraistry of this reaction is different from that of above-mentioned diphenyl-substituted methylenecyclopropanes 66 and 67[61], This allylic lactone 76 is another source of trimethylenemethane when it is treated with Pd(0) catalyst coordinated by dppe in refluxing toluene to generate 77, and its reaction with aldehydes or ketones affords the 3-methylenetetrahy-drofuran derivative 78 as expected for this intermediate. Also, the lactone 76 reacts with a, /3-unsaturated carbonyl compounds. The reaction of coumarin (79) with 76 to give the chroman-2-one derivative 80 is an example[62]. 

The last [2 + 2] cycloaddition performed onto methylenecyclopropane itself consists of the use of ketene derivatives, particularly of dimethylketene 508 (Table 40, entry 1) [133]. The result is an almost equimolar mixture of the two possible regioisomers 511, albeit no yield has been reported. Anyway, the particular reactivity of methylenecyclopropane was confirmed, since it was found to be around 15 times more reactive than isobutene [133]. The scarce regioselectivity of this cycloaddition was confirmed by the reactions of the same ketene 508 with 2,2-disubstituted methylenecyclopropanes (entries 2 and 3) [134], BCP has also been shown to be reactive towards chloro-substituted ketenes 509 and 510, affording the expected cycloadducts 514 and 515 in mild conditions (entries 4 and 5) [13b],... 

These reactions of 1-Me resemble that of (dichloromethylene)cyclopropane [31] and radicophilic alkenes with a capto-dative substitution pattern [32]. Thus, it is not surprising that 1-Me reacts with a-ferf-butylthioacrylonitrile (18), yielding the two isomeric cyclobutane derivatives 19a, b (ratio 2.2 1) as a mixture of two diastereomers each [29] (Scheme 5), and this reaction occurs under milder conditions than the [2-1-2] cycloaddition of 18 onto methylenecyclopropane. 

Metalations with organolithium compounds, 8, 6 26, 1 27, 1 Methylenation of carbonyl groups, 43, 1 Methylenecyclopropane, in cycloaddition reactions, 61, 1... 

The highly strained double bond in methylenecyclopropane displays enhanced reactivity in cycloaddition reactions. In addition to normal [4+2] cycloaddition to 1,3-dienes (e.g. equation 13)32, methylenecyclopropane and its derivatives have a pronounced tendency to undergo thermal [2+2] cycloaddition reactions. For example, thermal dimerization of methylenecyclopropane in the gas phase results in formation of isomeric dispirooctanes 16 and 17 (equation 14)33. This unusual cyclization is considered to proceed via a stepwise radical mechanism involving the intermediacy of biradical 18 (equation 15)34. Equation 15 demonstrates that methylenecyclopropanes possessing substituents capable of stabilizing intermediate radicals undergo efficient [2+2] dimerization even... 

Cycloaddition of methylenecyclopropane with alkenes.1 This reaction when catalyzed by Ni(COD)2 and triphenylphosphine can result in either 2,3- or 3,4-disubstituted methylenecyclopentanes depending on the electronic properties of the alkene. 

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