Asymmetric synthesis of multi-substituted spiro[5,5]undecane-1,5,9-triones via organocatalytic three-component reaction

The asymmetric domino three-component Knoevanagel-Diels-Alder addition (ATCDA) reaction, as an important methodology, has been utilized to construct complex product from ordinary starting materials. In this report, many typical organoamine catalysts were investigated to achieve highly efficient asymmetric three-component reaction of enones 2, aldehydes 3 and Meldrum's acid 4. Various pharmacological multi-substituted spiro[5,5]undecane-1,5,9-triones promoted by 9-amino-9-deoxy-epi-quinine 1 g in one-pot, were obtained in moderate to good yields (up to 81%) with excellent diastereo-(>99:1 dr) and enantioselectivities (up to 97% ee). Meanwhile, based on the controlled experiments and analytical data, a reasonable mechanism of dual-activity for this reaction has been proposed. (C) 2011 Elsevier Ltd. All rights reserved.