Organocatalytic Synthesis of Substituted Spirocyclohexane Carbaldehydes via [4+2] Annulation Strategy between 2-Arylideneindane-1,3-diones and Glutaraldehyde

An organocatalytic domino reaction between 2-arylideneindane-1,3-diones and glutaraldehyde has been devised that gives functionalized spirocyclohexane carbaldehydes with an all-carbon quaternary center. The reaction proceeds through a Michael/Aldol sequence in good-to-high chemical yields and with high levels of stereoselectivity (up to >95:5 dr and 99% cc) in the presence of the alpha,alpha-L-diphenylprolinol trimethylsilyl ether 3 (20 mol %) and DIPEA (20 mol %) in ether at 0 degrees C.