Organocascade Synthesis of Bicyclo[3.3.1]nonan-9-ones Initiated by an Unusual 1,6-Addition of Cyclohexanones to (E)-2-(3-Arylallylidene)-1H-indene-1,3(2H)-diones

An efficient organocatalytic cascade reaction for the synthesis of the bicyclo[3.3.1]nonan-9-one skeleton is reported. The cascade reaction proceeds smoothly between prochiral 4-substituted cyclohexanones and (E)-2-(3-arylallylidene)-indene-1,3-diones involving a 1,6-/γ-protonation/1,4-addition sequence to construct bicyclic products that contain five stereogenic centers in good to high chemical yields and excellent diastereo- and enantioselectivity (up to >20:1 dr and 97% ee) in the presence of a thioether-linked l-prolinol-camphor-derived organocatalyst at ambient temperature. An interesting organocatalytic three-component triple cascade reaction has been performed to produce a bicyclo[2.2.2]octan-2-one in a favorable chemical yield and stereoselectivity (>19:1 dr and 97% ee) starting from 1,3-indanedione, an enal, and cyclohexenone in the presence of a primary amine organocatalyst. (Figure presented.).