Palladium cycloaddition reactions, methylenecyclopropanes

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... 

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). ... 

Methylenecyclopropanes 9 with geminally disubstituted alkene moieties undergo palladium-catalyzed [3-1-2] cycloaddition reactions with carbon dioxide under pressure. Besides cycloadduct 10 arising from formal distal cleavage of the MCP, furan-2(5//)-one 11, resulting from double-bond isomerization, is formed in variable amounts, depending on the substrate as well as the specific catalyst used. ... 

Methylenecyclopropane is also a convenient TMM precursor for the cycloaddition reaction. Both nickel(O) and palladium(O) complexes can catalyze the [3 + 2] cycloaddition of aUcylidenecyclopropanes with aUcenes and alkynes (Scheme 12). ° Unlike the Ni-catalyzed reaction, the regioselectivity in the Pd-catalyzed reaction with alkene is independent of the structure of the starting aUcylidenecyclopropanes, which indicates that this reaction also proceeds via TMM-Pd as mentioned above. The TMM-Pd generated from aUcylidenecyclopropanes can undergo a stereoselective intramolecular cycloaddition with alkynes,and the regiochemistry is different from the Ni-catalyzed reaction... 

A further noteworthy side reaction of palladium-catalyzed methylenecyclopropane cycloadditions is the isomerization of 2-(n-alkyl) methylenecyclopropanes to isoprene-type dienes, and subsequent reaction of the latter with electron-deficient alkenes to form cyclohexenes in a Diels — Alder reaction, rather than providing [3 + 2]-addition products. 

Interestingly, when l,l-dimethyl-2-methylenecyclopropane is employed instead of (1-methyl-ethylidene)cyclopropane, no reaction is observed in the palladium(0)-catalyzed reaction with 77-phenyldiphenylketenimine. This is in line with the general observation that ring-substituted methylenecyclopropanes are less reactive in cycloadditions. 

A single example is known for a palladium(0)-catalyzed cotrimerization reaction involving two molecules of an alkene and a methylenecyclopropane molecule, leading to the formation of a seven-membered-ring product.The reaction is limited to unsubstituted allene and, along with the cyclotrimer, l,3,5-tris(methylene)cycloheptane (3), 1,3-bis(methylene)cyclopen-tane (2), the product of a [3 + 2] cycloaddition, is also obtained. The product ratio 2/3 is markedly dependent on the catalyst composition. Additionally, the allene trimer, 1,2,4-tris(methyl-ene)cyclohexane (4), and the methylenecyclopropane homodimer, 5-methylenespiro[2.4]hep-tane (5), are formed. 

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