Asymmetric Cycloaddition of β,-Unsaturated -Ketoesters with Electron-Rich Alkenes Catalyzed by a Chiral Er(OTf)₃/N,N′-Dioxide Complex: Highly Enantioselective Synthesis of 3,4-Dihydro-2?H-pyrans?

摘要

The asymmetric inverse-electron-demand hetero-Diels–Alder (HDA) reactions of β,-unsaturated -ketoesters with electron-rich alkenes were investigated, with an N,N′-dioxide/erbium(III) complex employed as the catalyst. Quantitative conversion of the β,-unsaturated -ketoesters and excellent enantioselectivities (up to >99 % ee) and diastereoselectivities (up to >99:1 d.r.) were observed for a broad range of substrates by using a 0.5–0.05 mol % catalyst loading under mild reaction conditions. The reaction could be scaled up to the gram scale with the same results. In addition, this was the first application of Er(OTf)₃ to the asymmetric inverse-electron-demand HDA reaction and it behaved as an efficient catalyst. Moreover, the synthetic utility of this methodology was demonstrated with the synthesis of key intermediates of some natural products.