Palladium-catalyzed trimethylenemethane reaction to form methylenetetrahydrofurans. Reactions of substituted TMM precursors and mechanistic interpretation

Article abstract of DOI:10.1021/ja00157a061

Alkyl-, phynyl-, vinyl-, and acetoxy-substituted palladium-trimethylenemethane (Pd-TMM) complexes react with aldehydes in the presence of organotin cocatalysts such as trimethylin acetate and trimethylin p-toluenesulfonate to give cycloadducts. The reactions of methyl-substituted TMM precursors 2a, 3, and 12 were studied most extensively. Two methylenetetrahydrofuran regioisomers, 10k and 10t, were produced in mixtures varying from 31:1 to 1:200 depending upon the TMM precursor, aldehyde, and cocatalyst. Conjugating substituents decrease the reactivity of the Pd-TMM complex, and only isomer 10t is available. The acetoxy substituent increases the reactivity of the organometallic and generated only 9k; however, the products cannot be isolated due to their lability. Electron-withdrawing substituents cause the complexes to be unreactive. Carveol-derived TMM precursors 23 and 2j give fused bicyclic products. Stereochemical analysis of these products showed that, contrary to olefin acceptors, aldehydes can, in some cases, attack the Pd complex on either face of the TMM moiety. These results indicate that trimethyltin chloride can be a very potent cocatalyst. The mechanism of the cycloaddition of aldehydes and, in particular, cocatalysis by organostannanes is discussed. The cocatalyst is believed to act by (1) aiding ring closure through the intermediacy of a stannyl ether and (2) acting as a Lewis acid to increase the rate of nucleophilic addition to the aldehyde.