3- Methylenecyclopentanecarboxylic

The nickel(0)-catalyzed codimerizations of methylenecyclopropane (26) or 2,2-dimethylmethylene-cyclopropane with the chiral derivatives of acrylic acid lead to optically active 3-methylenecyclopen-tanecarboxylic esters or amides (39 equation 16) in good yields (Table 3). When (-)-camphorsultam acrylate is used, 3-methylenecyclopentanecarboxylic amides are obtained in up to 98% de. °... 

The reaction of MCP (1) with methyl acrylate has been intensely studied by several researchers. The cycloadduct methyl 3-methylenecyclopentanecarboxylate (2) is formed... 

With /1-substituted unsaturated esters, e.g. methyl ( )-crotonate or dimethyl maleate, the stereochemistry at the alkene group is predominantly retained in the products, i.e. methyl rra7i -2-mcthyl-3-methylenecyclopentanecarboxylate (3) and dimethyl 3-methylenecyclopen-tane-1,2-dicarboxylate (4), when phosphane-free nickel catalysts are employed at temperatures slightly above room temperature. When equimolar amounts of MCP and dimethyl maleate are used, approximately equal amounts of homocyclodimers of MCP and [3 + 2] cycloadducts arc obtained, even if the MCP is added dropwise to the catalyst solution in dimethyl maleate, indicating that the cycloaddition is a relatively slow reaction. When the maleate/MCP substrate ratio is increased to 3 1, the yield of the codimers 4 is raised to 78%.Dialkyl fumarates and maleic anhydride do not undergo cycloaddition under these conditions. 

Cycloaddition.2 In the presence of this nickel catalyst, methylenecyclo-propanes undergo an unusual cycloaddition across carbon-carbon double bonds. Thus methylenecyclopropane (1) when heated in a sealed tube (60°, 48 hrs.) with excess methyl acrylate in the presence of bis(acrylonitrile)nickel(0) gives the 1 1 adduct, methyl 3-methylenecyclopentanecarboxylate (2), in 82% yield. Methyl vinyl ketone or acrylonitrile is also a suitable substrate. The reaction provides a useful synthesis of methylenecyclopentane derivatives. 

Addition of cyclopropane to activated olefins to form cyclopentanes is catalyzed by a zero-valent nickel complex, S41. Thus methylenecyclopropane and methyl acrylate react in the presence of a catalytic amount of bis(acrylonitrile nickel) to give methyl 3-methylenecyclopentanecarboxylate in 82% yield. 

A suitable approach to the synthesis of spiro[2.3]hexanes is the [2-1-2] cycloaddition of alkenes to the double bond of methylenecyclopropanes. This reaction is often described as a codimerization and usually requires catalysis by a nickel(O) complex such as bis(cycloocta-l,5-diene)nickel. l,l-Dimethyl-2-methylenecyclopropane reacts with alkyl acrylates to give a mixture of alkyl cis- and tranj-l,l-dimethylspiro[2.3]hexane-5-carboxylates 1 (19-40%) and alkyl 3,3-dimethyl-4-methylenecyclopentanecarboxylate 2 (60-81 %). The proportion of spiro [2.3]hexane derivative was highest when rer/-butyl acrylate was used as the activated alkene. 

Whereas palladium(0)-catalyzed reactions of dialkyl fumarate and dialkyl maleate yield reaction products identical to those obtained from the phosphane-modified nickel-catalyzed reactions (vide supra), analogous palladium(0)-catalyzed reactions with ( )-but-2-enoic or (E)-cinnamic acid derivatives lead to different products to the nickel-catalyzed reactions, i.e. in the palladium-catalyzed reactions formal distal cleavage of but-2-enoic MCP occurs to provide methyl tra i-2-methyl-4-methylenecyclopentanecarboxylate (12, R = Me) and methyl trans-4-methylene-2-phenylcyclopentanecarboxylate (12, R = Ph), respectively." Yields and stereoselectivities are slightly higher with palladium(O) catalysts. When R = Me, 7.4% of the C-C double bond isomerization product, methyl traM -2,4-dimethylcyclopent-3-enecarboxylate (13, R = Me), is additionally obtained, raising the combined yield of cyclocodimers to 49.9%. With methyl (jE )-cinnamate, analogous isomerization only occurs upon workup, i.e. distillation of the crude product. 

Vinyl carbanions derived from acrylic esters and their jS-phenyl derivatives react with several carbon electrophiles to give a-substituted and a,/8-disub-stituted derivatives. While /8>alkyl substituted acrylates have been shown to dimerize in the presence of potassium catalyst at 110 C. Three simple unsaturated esters undergo palladium(0)-catalysed codimerization with methylenecyc-lopropane to furnish methylenecyclopentanecarboxylic esters in reasonable yield. An efficient procedure for the oxidation of isatins to anthranilic acid esters has appeared. Methyl 2,4,6-tri-isopropylbenzoate forms a dipole-stabilized carbanion on reaction with Bu Li, which then reacts with carbon electrophiles [e.g. E = Bui, (CH3)2C0, or CH3CHO] to give a range of ester derivatives in good yield (Scheme 52). ... 

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