Synthesis of 2-Pyrrolidinones by Palladium-Catalyzed [3+2] Cycloaddition of Isocyanates

Abstract

Pd/DPEphos catalyzes the [3+2] cycloaddition of various alkyl isocyanates with 2-acetoxymethyl-3-allyltrimethylsilane as a synthetic equivalent of trimethylenemethane (TMM). Taking advantage of 2-acetoxymethyl-3-allyltrimethylsilane acting both as nucleophile as well as electrophile this reaction gives a convenient access to 5-ring lactams with an exocyclic alkene moiety. The formation of the β,γ-unsaturated 2-pyrrolidinones occurs without olefin isomerization and without epimerization of the stereogenic centers. Mechanistic investigations suggest an initial N-allylation of the isocyanate followed by nucleophilic ring closure furnishing the desired 2-pyrrolidinones.

Key words

allyl silanes - cycloaddition - heterocycles - isocyanates - lactams - palladium - Tsuji–Trost allylation

• References and Notes

• 1 Institute of Pharmaceutical Chemistry, University of Marburg, Marbacher Weg 6, 35032 Marburg, Germany.

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