Cycloaddition reactions methylenecyclopropanes

Cycloaddition reactions. Methylenecyclopropanes (1) undergo very slow [2 + 2] cycloaddition of the exocyclic double bond with PTAD to give 1 1 adducts (2).3... 

A positive feature of the reaction is that nitrile oxides are more regioselective, in cycloadditions to methylenecyclopropanes, compared to nitrones. Only traces (up to 5%) of the 4-spirocyclopropane regioisomers are generally observed with methylenecyclopropanes unsubstituted on the exocyclic double bond. The yields are only moderate, but higher with more stable nitrile oxides (Table 27, entries 5, 6, 10-12). 

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

Two other [2 + 2] cycloadditions on methylenecyclopropane have been carried out with particular alkenes. The first one is the reaction with the capto-datively substituted olefin 496a, which affords the spirohexane cycloadduct 497a in modest yields (Table 39, entry 1) [126]. The low yield is partially... 

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. 

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). 

Bicyclic ketones are prepared by cycloadditions of methylenecyclopropanes with cyclic a,P-unsatu-rated carbonyl compounds. c J-Bicyclo[3.3.0]octan-2-ones (50), (51) and (52) are obtained in good yields by phosphine-nickel(0)-catalyzed cross coupling reactions of 2-cyclopentenone with methylenecyclopropanes in the presence of 0.1-1 equiv. of triethylborane as a Lewis acid (equations 18 and 19 and... 

Nickel(0)-catalyzed [3 + 2] cycloadditions of methylenecyclopropanes with A(-substituted maleimides (56 equation 22) lead almost exclusively to 5-alkylidenehexahydro-l//-cyclopenta[c]pynolo-l,3-diones (57) and (58 equation 23). A similar reaction occurs in the presence of a palladium(O) catalyst, but with lower selectivity. Unsubstituted maleimide and maleic anhydride do not undergo this cycloaddition. Ozonolysis of (57) and (58) into the corresponding ketone derivatives (62-78% yield) followed by reduction of both carbonyl groups gives l//-cyclopenta[c]pynoles, which are of interest with regard to their pharmacological activity (98% yield). ... 

Methylenecyclopropane (69) has been shown to rearrange in the presence of Ni(0) to butadiene. When olefinic ligands are present in solution, the intermediate is trapped in a cycloaddition reaction (equation 46) . ... 

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 methylenecyelopropanes can be achieved under moderate conditions and in satisfactory to good yields in the presence of suitable transition metal catalysts. 

Whereas the transition metal catalyzed cyclotrimerization and cyclotetramerization of alkynes leading to benzene or cyclooctatetraene and their derivatives is a rather common reaction, there exist only a few examples of cooligomerizations between alkynes and alkenes or 1,3-butadienes leading to 1,3- or 1,4-cyclohexadiene derivatives20S). It is therefore surprising that the [3+2]-cycloaddition between methylenecyclopropanes and alkynes, catalyzed by triarylphosphite modified Ni(0) compound, is a rather convenient method to synthesize 4-methylenecyclopentenes 206). A wide range of methylenecyclopropanes and alkynes, in the latter case mainly 1,2-disubstituted ones, can be used for these reactions (Eqs. 98-100, see p. 127-128). 

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. 

Cyclopropene, methylenecyclopropane and their derivatives have proved to be valuable reagents in transition metal-catalyzed cycloaddition reactions. Small and medium carbocycles can be prepared by this method. The chemoselectivity observed in some of these reactions is quite remarkable. In addition, high degree of regio- and stereoselectivity is obtained in most cases. In particular the new [3+2] cycloaddition described here and which involves methylenecyclopropane and its derivatives as trimethylenemethane synthones, shows great synthetic promise as a method for constructing fivemembered rings. 

An example for a [2 + 2+1] cycloaddition of methylenecyclopropane is its reaction with hexa-carbonyldicobalt complexes of various alkynes leading to spiro[2.4]heptenones (Pauson-Khand reaction). With monosubstituted alkynes the insertion of the carbonyl moiety occurred predominantly between the methylene group and the substituted carbon atom of the alkyne giving spiro[2.4]hept-6-en-5-ones 27. The proportion of the isomeric spiro[2.4]hept-5-en-4-ones 28 was about 20% in the product mixture. ... 

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. 

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. 

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