Asymmetric Diels-Alder and Inverse-Electron-Demand Hetero-Diels Alder Reactions of β,γ-Unsaturated α-Ketoesters with Cyclopentadiene Catalyzed by N,N′-Dioxide Copper(II) Complex

Highly enantioselective Diels-Alder (DA) and inverse-electron-demand hetero-Diels-Alder (HDA) reactions of beta,gamma-unsaturated alpha-ketoesters with cyclopentadiene catalyzed by chiral N,N`-dioxide Cu(OTf)(2) (Tf = triflate) complexes have been developed. Quantitative conversion of beta,gamma-unsaturated alpha-ketoesters and excellent diastereoselectivities (up to 99:1) and enantioselectivities (up to > 99% ee) were observed for a broad range of substrates. Both aromatic and aliphatic beta,gamma-unsaturated alpha-ketoesters were found to be suitable substrates for the reactions. Moreover, the chemoselectivity of the DA and HDA adducts were improved by regulating the reaction temperature. Good to high chemoselectivity (up to 94%) of the DA adducts were obtained at room temperature, and moderate chemoselectivity (up to 65%) of the HDA adducts were achieved at low temperature. The reaction also featured mild reaction conditions, a simple procedure, and remarkably low catalyst loading (0.1-1.5 mol%). A strong positive nonlinear effect was observed.