Asymmetric cycloaddition of β,γ-unsaturated α-ketoesters with electron-rich alkenes catalyzed by a chiral Er(OTf)3/N,N'- dioxide complex: Highly enantioselective synthesis of 3,4-dihydro-2H-pyrans

Abstract

The asymmetric inverse-electron-demand hetero-Diels-Alder (HDA) reactions of β,γ-unsaturated α-ketoesters with electron-rich alkenes were investigated, with an N,N'-dioxide/erbium(III) complex employed as the catalyst. Quantitative conversion of the β,γ-unsaturated α-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. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.