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Thermal Hetero [3 + 2] Cycloaddition of Dipolar Trimethylenemethane to O -Alkyloximes. Straightforward Synthetic Routes to Substituted Pyrrolidines and Prolines

1998; American Chemical Society; Volume: 63; Issue: 5 Linguagem: Inglês

10.1021/jo972302y

1520-6904

Shigeru Yamago, Masaharu Nakamura, Xiao Qun Wang, Masao Yanagawa, Shuzo Tokumitsu, Eiichi Nakamura,

Synthesis and Catalytic Reactions

Thermal hetero [3 + 2] cycloaddition reaction of a dipolar trimethylenemethane 2 with an O-alkyloxime produces a substituted pyrrolidine. Thus, heating of a mixture of an alkylidenecyclopropane 1 an anti-O-alkyloxime 3 proceeds smoothly in good yield to give a substituted pyrrolidine 4 bearing a ketene acetal group in its 3-position, which upon hydrolysis under mild conditions gives a 3-alkoxycarbonylpyrrolidine 5 in quantitative yield. On the other hand, the cycloaddition to a syn-oxime is extremely slow. The cycloaddition reaction can be achieved by starting with nearly equimolar quantities of the two starting materials, and the reaction is quite insensitive to the choice of solvent and to the presence of oxygen and water. In the reaction of a substituted methylenecyclopropane 1 (R ≠ H), the reaction may take place with high regio- and stereoselectivity, which is in consonance with the concerted nature of the cycloaddition reaction. The present synthesis represents one of the rare examples of the imine-based route to pyrrolidines, which have been much less explored than the 1,3-dipolar cycloaddition route using olefin and azomethine ylide.