Synthesis of Functionalized Cyclohexenes through a Vinyl Alkenylation-Initiated [4 + 2] Cycloaddition Reaction

Notwithstanding the prevalence of functionalized cyclohexene skeletons in natural products and pharmaceuticals, concise synthetic protocols for their effective assembly from simple starting materials are still scarce. Herein, we present a highly efficient and sustainable access toward functionalized cyclohexenes based on the cascade reaction of N-methoxyacrylamides with allenyl acetates. The formation of the product involves an initial vinyl C-H metalation of acrylamide, followed by allene insertion and β-oxy elimination to afford a vinyl alkenylation product as a key intermediate. Under the reaction conditions, this in situ formed 1,3-diene derivative undergoes self [4 + 2] cycloaddition to give the final product. In general, the reaction is accomplished under mild conditions with a benign solvent and is compatible with a number of labile functional groups. In addition, the potential of this method is further showcased by a gram-scale application scenario.