Cycloaddition Reactions of Ketene Diethyl Acetal toward the Synthesis of Cyclobutene Monomers

The [2+2]-cycloaddition reactions of ketene diethyl acetal with methyl acrylate and acrylonitrile were optimized. Highly efficient ketal cleavage to either 2-cyano-1-cyclobutanone or 2-methoxycarbonyl-1-cyclobutanone was achieved using formic acid. Among the numerous reduction methods attempted, only sodium cyanoborohydride in acidic medium led successfully to the corresponding alcohols, but isolation of the desired products was not achievable. We show that the anomalous cyclobutanone chemistry is due to the acidic α-proton and the electron-withdrawing substituent in the α-position. Substitution of the α-proton by a methyl group results in a turnaround back to textbook chemistry.