Enantioselective Organocatalytic Multicomponent Synthesis of 2,6-Diazabicyclo[2.2.2]octanones


  • We warmly thank Dr. N. Vanthuyne and M. Jean for HPLC analyses on a chiral stationary phase, Dr. M. Giorgi for X-ray diffraction analyses, and the whole team of the Spectropole (http://www.spectropole.u-3mrs.fr). S. Goudedranche and H. Du are acknowledged for the preparation of some starting materials. Financial support from Aix Marseille Université, the CNRS, the ANR (project CIL-MCRs, ANR-07-CP2D-06), and the COST action CM0905 ORCA is acknowledged.


original image

Three-star compounds: The title reaction of β-ketoamides, acrolein, and aminophenols, catalyzed by a bifunctional thiourea-tertiary amine organocatalyst, enables the preparation of an enantioenriched diazabicyclo[2.2.2]octanone (2,6-DABCO) scaffold. The chemoselective reaction sequence installs five new bonds and three stereocenters, two of which are contiguous tetrasubstituted centers, with excellent yields and high levels of stereocontrol. M.S.=molecular sieves.